Ed Friedlander, M.D., Pathologist

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Welcome to Ed's Pathology Notes, placed here originally for the convenience of medical students at my school. You need to check the accuracy of any information, from any source, against other credible sources. I cannot diagnose or treat over the web, I cannot comment on the health care you have already received, and these notes cannot substitute for your own doctor's care. I am good at helping people find resources and answers. If you need me, send me an E-mail at Your confidentiality is completely respected. No texting or chat messages, please. Ordinary e-mails are welcome.

I am active in HealthTap, which provides free medical guidance from your cell phone. There is also a fee site at

If you have a Second Life account, please visit my teammates and me at the Medical Examiner's office.

Freely have you received, give freely With one of four large boxes of "Pathguy" replies.

I'm still doing my best to answer everybody. Sometimes I get backlogged, sometimes my E-mail crashes, and sometimes my literature search software crashes. If you've not heard from me in a week, post me again. I send my most challenging questions to the medical student pathology interest group, minus the name, but with your E-mail where you can receive a reply.

Numbers in {curly braces} are from the magnificent Slice of Life videodisk. No medical student should be without access to this wonderful resource.

I am presently adding clickable links to images in these notes. Let me know about good online sources in addition to these:

Freely have you received, freely give. -- Matthew 10:8. My site receives an enormous amount of traffic, and I'm still handling dozens of requests for information weekly, all as a public service.

Pathology's modern founder, Rudolf Virchow M.D., left a legacy of realism and social conscience for the discipline. I am a mainstream Christian, a man of science, and a proponent of common sense and common kindness. I am an outspoken enemy of all the make-believe and bunk that interfere with peoples' health, reasonable freedom, and happiness. I talk and write straight, and without apology.

Throughout these notes, I am speaking only for myself, and not for any employer, organization, or associate.

Special thanks to my friend and colleague, Charles Wheeler M.D., pathologist and former Kansas City mayor. Thanks also to the real Patch Adams M.D., who wrote me encouragement when we were both beginning our unusual medical careers.

If you're a private individual who's enjoyed this site, and want to say, "Thank you, Ed!", then what I'd like best is a contribution to the Episcopalian home for abandoned, neglected, and abused kids in Nevada:

I've spent time there and they are good. Write "Thanks Ed" on your check.

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Especially if you're looking for information on a disease with a name that you know, here are a couple of great places for you to go right now and use Medline, which will allow you to find every relevant current scientific publication. You owe it to yourself to learn to use this invaluable internet resource. Not only will you find some information immediately, but you'll have references to journal articles that you can obtain by interlibrary loan, plus the names of the world's foremost experts and their institutions.

Alternative (complementary) medicine has made real progress since my generally-unfavorable 1983 review. If you are interested in complementary medicine, then I would urge you to visit my new Alternative Medicine page. If you are looking for something on complementary medicine, please go first to the American Association of Naturopathic Physicians. And for your enjoyment... here are some of my old pathology exams for medical school undergraduates.

I cannot examine every claim that my correspondents share with me. Sometimes the independent thinkers prove to be correct, and paradigms shift as a result. You also know that extraordinary claims require extraordinary evidence. When a discovery proves to square with the observable world, scientists make reputations by confirming it, and corporations are soon making profits from it. When a decades-old claim by a "persecuted genius" finds no acceptance from mainstream science, it probably failed some basic experimental tests designed to eliminate self-deception. If you ask me about something like this, I will simply invite you to do some tests yourself, perhaps as a high-school science project. Who knows? Perhaps it'll be you who makes the next great discovery!

Our world is full of people who have found peace, fulfillment, and friendship by suspending their own reasoning and simply accepting a single authority that seems wise and good. I've learned that they leave the movements when, and only when, they discover they have been maliciously deceived. In the meantime, nothing that I can say or do will convince such people that I am a decent human being. I no longer answer my crank mail.

This site is my hobby, and I do not accept donations, though I appreciate those who have offered to help.

During the eighteen years my site has been online, it's proved to be one of the most popular of all internet sites for undergraduate physician and allied-health education. It is so well-known that I'm not worried about borrowers. I never refuse requests from colleagues for permission to adapt or duplicate it for their own courses... and many do. So, fellow-teachers, help yourselves. Don't sell it for a profit, don't use it for a bad purpose, and at some time in your course, mention me as author and William Carey as my institution. Drop me a note about your successes. And special thanks to everyone who's helped and encouraged me, and especially the people at William Carey for making it still possible, and my teaching assistants over the years.

Whatever you're looking for on the web, I hope you find it, here or elsewhere. Health and friendship!


More of Ed's Notes: Ed's Medical Terminology Page

Perspectives on Disease
Cell Injury and Death
Accumulations and Deposits
What is Cancer?
Cancer: Causes and Effects
Immune Injury
Other Immune
HIV infections
The Anti-Immunization Activists
Infancy and Childhood
Environmental Lung Disease
Violence, Accidents, Poisoning
Red Cells
White Cells
Oral Cavity
GI Tract
Pancreas (including Diabetes)
Adrenal and Thymus
Nervous System
Lab Profiling
Blood Component Therapy
Serum Proteins
Renal Function Tests
Adrenal Testing
Arthritis Labs
Glucose Testing
Liver Testing
Spinal Fluid
Lab Problem
Alternative Medicine (current)
Preventing "F"'s: For Teachers!
Medical Dictionary

Courtesy of CancerWEB

Violence is the antithesis of creativity and wholeness. It destroys community and makes brotherhood impossible.

We have fed the heart on fantasies,
The heart's grown brutal from the fare;
More substance in our enmities
Than in our love.

No matter what you do, somebody is going to hate you. Look around. See who hates you. Make sure it's the right people.

Forgiveness is a powerful tool. Use it.

Razors pain you / Rivers are damp /
Acids stain you / And drugs cause cramp /
Guns aren't lawful / Nooses give /
Gas smells awful / You might as well live.

Go not in and out at the courts of law, that thy name may not stink.

How many Americans does it take to screw in a light bulb?
Five. One to do it, and four to fill out the environmental impact reports.

The truth is incontrovertible. Malice may attack it. Ignorance may deride it. But in the end -- there it is.

There is a doctrine whispered in secret that a human being is a prisoner who has no right to open the door and run away.

Quis, quid, ubi, quidubus auxiliis, cur, quomodo, quando?
What was the crime, who did it, when was it done, and where,
How done, and with what motive, who in the deed did share?

Confucius said, "In hearing litigation, I am no different from any other judge. But if you insist on a difference, it is, perhaps, that I try to get the parties not to resort to litigation in the first place."

People will never stop committing atrocities until they stop believing absurdities.

Did you hear about the hippie who mixed LSD and prune juice?
He started a whole new movement!

If you never encounter anything in your community that offends you, then you are not living in a free society.

IMOGEN: O, do not make me laugh.
Laughter dissolves too many just resentments,
Pardons too many sins.

IACHIMO: And saves the world
A many thousand murders.

Forensic Pathology Video -- Victorian Institute

KCUMB Students
"Big Robbins" -- Environmental / Nutritional
Lectures follow Textbook


    Physical injury (all)
    Chemical injury (all)
    Forensic (all)

Bringing out the Dead
"Bringing Out the Dead"

Forensic Medicine for Medical Students
British site
Primarily meant to stimulate interest

Trauma / Environmental / Nutritional
Iowa Virtual Microscopy
Have fun

First Section
Chaing Mi, Thailand

Second Section
Chaing Mi, Thailand

Third Section
Chaing Mi, Thailand

Fourth Section
Chaing Mi, Thailand
Sometimes has an
image bank available

Forensic Pathology
Notes and links to photos
Midwest Forensic Path

Atkin Investigations
Site by a cyberbuddy

U. of Dundee
Forensic Medicine
Introductory notes

Crime Scene Investigator's Resources
Site by a cyberbuddy


    Describe how the medical examiner's office operates, what deaths must usually be referred there, and how bodies may be identified.

    Properly complete a death certificate, avoiding the usual pitfalls. Distinguish the various manners and mechanisms of death.

    Tell how a rural primary care physician called to a crime scene can estimate the time of death.

    Describe the most common findings in physical child abuse, and mention the various medical conditions that may simulate it.

    Distinguish predictable and unpredictable medication side effects. Give the anatomic pathology seen with the common serious drug side-effects.

    Describe the extent of the illegal drug problem in the US. Recognize needle marks, and describe the internal anatomic pathology and pathophysiology of injectable drug abuse. Give the "two principles" rule for all drug testing that will have medicolegal implications.

    Suspect poisoning by thallium, arsenic, mercury, and lead when appropriate. Describe their pathophysiology and distinctive anatomic lesions as applicable.

    Describe the anatomic pathology and pathophysiology of cocaine use. Give an account of death through excited delirium.

    Give a short account of the physiology and health effects of absinthe, cannabis, and the recreational inhalants.

    Describe the anatomic pathology and pathophysiology, as applicable, of poisoning by paraquat, organophosphates, and dioxin.

    Describe what we know about the health consequences of caffeine use.

    Give a full account of what we know about the pathophysiology and anatomic pathology of acute and chronic alcohol abuse, including the quantitative aspects.

    Describe what happens to people who ingest methanol, isopropanol, and ethylene glycol.

    Ambrose Pare
    Ambrose Paré, surgeon
    Describe the common types of firearms, and how gunshot wounds do their damage. Given a gunshot wound, tell whether it is an entry wound or an exit wound. If it is an entry wound, determine what you can about the range.

    Distinguish abrasions, contusions, lacerations, and the various kinds of sharp-force wounds. Given a weapon or proposed scenario, decide whether it could have produced illustrated pathologic changes. Avoid the common pitfalls. Describe the usual ways in which blunt trauma causes death.

    Distinguish suffocation, smothering, strangulation, mechanical asphyxia, and choking. Describe the common scenarios, and how you would use pathology to confirm or discredit a scenario. Explain what happens during hanging.

    Give accounts of the common chemical asphyxiants. Especially, describe what you would see in illness and death due to carbon monoxide toxicity.

    Describe injuries from extreme heat, and how various kinds of burns do their damage.

    Describe the pathology of drowning. Explain how pathologists deal with drowning cases.

    Give a full account of the pathology of blast, decompression, and electrical injuries. Describe how death occurs, and what the pathologist might see, in heat stroke, heat exhaustion, and hypothermia.

    Explain how a physician might help evaluate the claim of someone seeking asylum and claiming to have been tortured.

    Explain how ionizing radiation injures living tissue. Know the various definitions for quantitating radiation and its effects on people. Give the pathology of radiation sickness of varying degrees of severity.

    Discuss briefly how the nature and impact of war have changed since the beginning of the twentieth century.

    Describe the usual situations that lead to homicide.

    Describe the usual situations that lead to suicide.

    After you've reviewed the pathology of violence, talk with your friends about the following often-heard claims. Reasonable people will differ about all of them.

      "The United States is an unusually violent society."

      "We are all born good. Criminals are products of their environments."

      "Violence in the U.S. is largely the result of the entertainment industry."

      "A physician has a duty to urge people not to keep firearms in their homes."


{07130} violent death, don't try these at home

    Nothing that pertains to human suffering and death is outside the larger domain of human pathology. Knowing what motives underlie most homicides and suicides is as important for a student physician as knowing which special stain helps the lab define a hemangiopericytoma.

    Most of this unit is about violence. Like most other mammals, when we human beings are HURTING AND CONFUSED at the same time, we have a natural (though lamentable) tendency to lash out against (blame, physically attack) someone else, regardless of the realities of the situation. We've all seen individuals do this, and perhaps we've even done this ourselves.

    Especially, groups of people who are HURTING AND CONFUSED will lash out against neighbors who are slightly (but not too much) different from themselves. This behavior begins with "extremists", who of course can explain to you why they are right, what past injustices they are redressing, how they are "doing God's work", "cleansing the evil", and so forth. Soon the savvy politicians follow, and next, many "normal" people are doing things that most will regret when they come to their senses, if they themselves survive. This happens around the world, and in the "developed world's" slums and prisons.

    * Physical anthropologists examining human remains from ancient cultures find rates of violent death (most often from head trauma) vary considerably, from lows of around 5% to far higher. As one would expect, there's far more violence when there is poverty, social stress, and population pressure (Am. J. Phys. Anthro. 130: 60, 2006).

    George Orwell wrote, "We sleep safe in our beds because rough men stand ready in the night to visit violence on those who would do us harm." Like it or not, this is the truth.

Omaha Beach, Saving Private Ryan

Force, or the credible threat of force, will always govern human affairs. The best for which we can hope is that this will be the force of good laws.

Even the great pacifists of our era (Gandhi, Martin Luther King, others) knew this. To their credit, they were able to bring about change with as little violence as possible, by placing their own lives on the line.

I wish this kind of personal courage from "the world's leaders" and "grievance-group spokespersons" was the norm today.

    Of course, neither I nor anybody else has any quick fix for a world that is still too violent. You already know the right-wing and left-wing crackpot solutions; these would be funny if only....

    The public does not see, or think about, military combat as it really is, and has always been. The "Iliad" and "All Quiet on the Western Front" are much closer to the reality than the movies or the newspapers. Even those who survive combat uninjured return with memories of beloved companions having limbs and faces blown off, having guts gush out over their hands, being burned to cinders, screaming for hours, bleeding to death per rectum, etc., etc. Returning to civilian life, combatants find that those for whom they fought do not want to hear about these experiences or their impact. Most of them decide that this is knowledge from which their loved ones must be protected. Remember this when you care for people who have been in combat.
The Price -- eyewitness WWII painting
The Price
Eyewitness World War Two painting

    Especially since the rise of guerilla warfare, political violence has been directed primarily against civilians. Soldiering, once the honorable life of a brave man, has become largely a matter of armed thugs killing (or starving) civilians and trying to leave no witnesses to the actual violence. In a war zone, the opposite sides take turns, and the soldiers (government, guerillas, child recruits) are often safer than the non-combatants.

      * Your lecturer is a man of peace. He predicts that this historical trend will reverse when, and only when, ordinary people in the poor nations have plenty of private firearms. Whatever your own feelings about firearms, if you actually talk with these people, I think they'll tell you the same thing.

    THERE HAS NEVER BEEN A WAR BETWEEN TWO GENUINE DEMOCRACIES. When a democracy and a non-democracy go to war, it has become the norm for the non-democratic side deliberately to place their own non-combatants, especially children, in harm's way so as to generate misguided sympathy.

    People with agendas (especially the Left: J. Pub. Health. Pol. 19: 289, 1998) deluge us with claims that the United States is an extraordinarily violent society. (Our homicide rate is now 4.7 / 100000 people, 14827 homicides in 2013, along with non-fatal injuries from violence down by about half from the 1990's but still higher than the other developed nations -- update JAMA 314: 478, 2015 -- from age 1 to age 44, homicide is the most common cause of death among non-Hispanic blacks.) This ignores the fact that the violence is concentrated in underclass communities. These communities, for whatever reason, are lawless and ridden with substance abuse, and the "code of the streets" requires posturing ("keeping respect") that ultimately invites re-injury (Am. J. Pub. Health 95: 816, 2005). Monitoring serial admissions of "penetrating trauma recidivists" shows "it only gets worse", and that the manner (shooting, stabbing) usually stays the same until death occurs (J. Trauma 61: 16, 2006). Where there is not a culture of lawlessness, dependency, individual non-achievement, and despair, and where illegal drugs are not being dealt, people in the US are as safe as anywhere in the world (and safer than most places). Among "indigenous peoples" and in the slums of the poor nations, violence and murder are far more prevalent. Despite the "noble savages" claims of the Left, the evidence of archeology is every bit as horrorific (for example, Sci. Am. 289(2): 33, 2003).

      * The left-wing fringe still uses terms like "nontraditional violence" and "implied violence" for any criticism whatsoever directed against a leftist individual, leftist agenda, or grievance-group. Despite what can still happen on a left-wing campus, United States law has consistently refused to recognize such things either as "violence" or "hate speech" or "hate crimes".

    Some episodes of mass killing (past / present) get a great deal of attention in the US media and schools; others get ignored. Cambodia

    In the late 1800's, the Belgians under megalomaniac King Leopold II looted the Congo, killing around 10 million people and enslaving, torturing and mutilating many more. This prompted massive outrage at the time in the US and Britain but has now been mostly forgotten. The genocide in Armenia (about 6 million dead) in the early 1900's rarely gets mentioned. (In 1939, Hitler, preparing to "kill without pity or mercy all men, women, and children of Polish race or language", said, "Who still talks today about the Armenians?") We almost never hear about the slaughter of millions of civilians, especially in China, by the Japanese military as the empire was expanding. And they almost certainly did experiment with germ warfare, including plague and anthrax, on civilian populations (for example,Lancet 360: 857, 2002; Clin. Microb. Inf. 8: 450, 2002). Stalin's policy of slaughtering every Soviet citizen who had ever made a profit by farming never seems to get mentioned, even though he killed millions of his own people. The greatest mass-murderer of all time (about 20 million people executed, not counting over 35 million more who died in his famine) was Mao Zedong, who is now remembered in many circles primarily as the popularizer of cute unisex jackets. Pol Pot's death in 1998 got a few sentences in the news; he killed at least a million people in Cambodia, engaged in systematic electrical torture (Tuol Sleng, elsewhere), began his attempt to realize his left-wing, anti-Western, back-to-nature organic-food fantasy by shooting everybody who wore eyeglasses, and then banned all institutions (schools, hospitals banks, stores, and even the family). Of course a famine followed with about 2 million more deaths. What has been happening in Central Africa for decades got noticed only when the "Rwanda genocide" heated up in the mid-1990's; it is now being ignored once again. The world's largest ongoing war since 1998 has been centered on the Congo (Zaire -- "The Second Congo War") where "the national crude mortality rate is 2.1 deaths per 1000 per MONTH (Lancet 367: 44, 2006). It has caused more deaths than any other war since WWII, but only occasionally gets mentioned in the media. (The fighting has been less since 2003 but is ongoing in the eastern part of the nation.) As in other wars in which the purpose is to wreck the economy, most deaths are from easily-treatable illness or hunger. I saw no real US press coverage of the long civil war in pre-earthquake Haiti, where there have been around 4000 political murders of civilians, and widespread rape, alternating among the national police, the rebels, and even the very frustrated "UN peacekeepers" (Lancet 368: 864, 2006.)


    Nothing else can possibly work.


    If we make peaceful revolution impossible, we make violent revolution inevitable.

        --Jack Kennedy

    Whatever your politics, and whatever your specialty, you'll see the contents of this lecture during your practice. People who abuse alcohol, do drugs, choose a violent lifestyle, and/or do tobacco consume a grossly disproportionate amount of health care. You'll be very impressed when you go on rotations. When insurance-company talk of "health care cost control" turns to excluding sports injuries (as it sometimes does "because you assumed the risk"), I think of the incredible irony and stupidity.

    * In the era of mass-media, where entertainment rather than truth-seeking brings in the money for the broadcaster, political demonstrations are a major means of influencing public opinion. Nowadays, a terminology seems to be emerging. Decide if this squares with your own observations.

      PEACEFUL DEMONSTRATION: The participants will conduct themselves like decent human beings. They will not shout filthy abuse, block traffic, interfere with business operations, disrupt religious services, vandalize property, etc., etc. Gandhi and Martin Luther King generated great sympathy for their causes by keeping their demonstrations strictly peaceful; the government violence directed against them further increased sympathy for their causes.

      NON-VIOLENT DEMONSTRATION: The participants will do whatever they can to get attention and ideally provoke a VIOLENT response from the people that they want the public to see, fairly or not, as "the bad guys." You've seen plenty of this from extremists and demagogues at both ends of the political spectrum. Often, it works.


    Especially if you choose rural medicine, you're likely to be called to the scene when a dead body is discovered.

    The first problem in any examination of death is find out whose body it was. Remember that identification of remains by distraught relatives is notoriously unreliable. The police will almost always do fingerprinting and/or dental identification. For skeletonized remains, the forensic anthropologist (a Ph.D. specialty allied to pathology) and the DNA lab (get the DNA from tooth pulp) can be extremely helpful.

        Death is a great disguiser. -- Shakespeare.

        * Heads-up to country doctors called for a consult by the police -- it is quite common to find a partly-decomposed bear's paw in the woods. On x-ray, the bones look quite human except that the bear has several sesamoid bones that we do not.

    Next, you may be asked to estimate the time of death. This is not an exact science.

      Even estimates of the rate of body cooling (probably best, in the absence of such evidence as bloodstains on the morning paper) are only moderately useful, as both temperatures at death and rates of cooling vary widely.

        You can enjoy reading about this if you like. For the first half-hour or so, the core temperature of the body can actually increase because on ongoing, inefficient anaerobic metabolism coupled with no blood circulating to the skin to remove heat.

        * Post-mortem rectal temperature time of death nomogram: For. Sci. Int. 54: 51, 1992; the actual ranges vary hugely; post-mortem hypoxanthine For. Sci. Int. 51: 139, 1991; vitreous potassium For. Sci. Int. 46: 277, 1990 & AMFJP 18: 158, 1997; CSF chemistry J. For. Sci. 38: 603, 1993. All about post-mortem chemistry: Am. J. For. Med. Path. 14: 91, 1993.

        Ed's time-of-death program gets thanks from police and prosecutors around the world.

        * A man convicted (very likely wrongly) of a godawful rape-murder based on unreliable estimates of how fast you digest dinner: AJFMP 12: 344, 1994. Scientific pathologists hate charlatans as much as scientific clinicians hate health-care quacks.

      For bodies found in the great outdoors, maggots are the medical examiner's little friends (more than you want to know about maggots: J. For. Sci. 38: 702, 1993).

        * Maggots near a skeletonized corpse died of the secobarbital she consumed (AJFMP 21: 59, 2000). A forensic entomologist proves that the neglectful parents kept the child so filthy that maggots began consuming the child's anogenital area for a week preceding death: For. Sci. Int. 120: 155, 2001.

      We fat (i.e., fatten) all creatures else to fat us, and we fat ourselves for maggots.

{07024} maggots

Post-mortem animal bites -- gnaw-marks at edges
Ed Lulo's Pathology Gallery

    In forensic pathology, histologic study of the tissues plays a very limited role.

    * Forensic nursing is an up-and-coming field. Nurses focused on forensics can pick up procedural errors in the hospital, and can excel at describing wounds at the time of presentation (which can be very helpful at trial).


    If the law does not require a medical examiner's inquest, or if you are the medical examiner, keeping the following in mind will help you avoid the usual pitfalls.

    The CAUSE OF DEATH is your best opinion, as a physician, with or without an autopsy. You list this on the death certificate.

      CAUSE OF DEATH: Thromboembolus in right main pulmonary artery (circa 1 minute)

      SECONDARY TO: Thrombophlebitis of leg vein (circa 5 days)

      SECONDARY TO: Adenocarcinoma of the pancreas (circa 6 months)

      NOTE: You may call the most important (to the lawyers) item on your list the "proximate" cause of death, i.e., what set the fatal chain of events in motion. "Cancer of the breast" is okay; "coronary artery atherosclerosis" probably isn't (why not?)

      NOTE: Please don't write "cardiopulmonary arrest" as the cause of death. We already knew that....

    The MECHANISM OF DEATH is your story. "The Trousseau pulmonary embolus strained the right ventricle and a rhythm disturbance developed." Once again, this is your best opinion.

    The MANNER OF DEATH is for the lawyers. You might list your opinion on your death certificate, too. There may be future disagreement. In the above instance...

      MANNER OF DEATH: Natural

    Here are your choices:

      HOMICIDE: Death because of the hostile or illegal act of another. At the very least, someone else did something out-of-the-ordinary that set in motion a process that resulted in the person's death. (The lawyers may decide on "first-degree murder", "second-degree murder", "voluntary manslaughter", "involuntary manslaughter", "justifiable homicide", or "excusable homicide.")

        Extremely poor medical care is coming to be treated and prosecuted as homicide. There are now small series: AMFJP 30: 18, 2009.

        Traffic fatalities are a special case; they are usually treated as "vehicular homicides" only if the killer is intoxicated and/or leaves the scene of a fatality.

      This is the kiss of Tosca!
      Justifiable homicide.
      This is the kiss of Tosca!

      SUICIDE: At the very least, the person did something that resulted in his or her death, and this was more or less what the person intended.

        From the mid-1960's to the mid-1990's, the reported suicide rates hovered just below 1 in 10,000 people/year, and the reported homicide rates just above this number. In the mid-1990's there was a drop in both overall crime (still mysterious) and in suicide rates (due to the internet / cell phones?) For people of working age, suicide rates increase when the business cycle is down (Am. J. Pub. Health 101: 1139, 2011).

      ACCIDENT: These deaths resulted from some kind of unplanned, unintended injury. They include most "therapeutic misadventures" (i.e., mishaps at the doctor's or dentist's). Notoriously, if sporotrichosis from a rose-thorn prick were to lead to death, it would be an accidental death. Among the grayest areas are "accidents" in the workplace due to employer negligence; many prosecutors now consider these to be homicides (Am. J. Pub. Health 90: 535, 2000). Animal attacks are accidents (fatal dog attacks are very rare Am. J. For. Med. Path. 32: 50, 2011).

      NATURAL: Death due entirely to disease or birth defect. (NOTE: "Unnatural death" means homicide, suicide, or accident.) Some medical examiners find the "naturals" most interesting... much like in a big university hospital, the clinical history enables the pathologist to guess the cause correctly before autopsy 65% of the time (J. Clin. Path. 61: 124, 2008). I'll accept "death from old age" if the person is over 90 and there's no signs of violence -- the cardiac ventricles are supposed to be more subject to rhythm problems.

      UNDETERMINED: You're an honest doctor and you know you can't really tell. This is a great category for normal-looking, 300-year-old skeletons found in the desert with negative toxicology, most cases of "sudden infant death syndrome" with no proper death-scene workup, substance abusers or organic-brain-syndrome people found at the bottom of the stairs ("did they fall or were they thrown?"), etc., etc.

      NOTE: If I wrongfully bite you, and you go to the hospital and are rightly treated with penicillin, and you die of anaphylaxis as a result of the penicillin injection, your death is probably a homicide -- my wrongful act set this unfortunate series of events in motion.

      NOTE: If a guy shoots himself, and spends six months in the hospital recovering, and dies of a pulmonary embolus from being at bed-rest for so long, it's still a suicide.

      NOTE: By common practice, if a guy has bad emphysema and blows out his lung trying to inflate his kid's balloon, it's "natural", not "accidental".

      NOTE: The good medical examiner always asks "Why today rather than yesterday?" especially when the only finding is serious-but-stable atherosclerotic coronary disease.

      NOTE: "Therapeutic misadventures" do not include the deaths that result from expected risks of today's powerful therapies. If someone dies of pseudomonas sepsis while undergoing a bone marrow transplant for leukemia, death is "natural", i.e., an not-unanticipated consequence of the illness and its treatment.

      NOTE: Physician-assisted suicide will be part (though hopefully still an infrequent part, thanks to more humane terminal care in general) of mainstream medicine when you're in practice. These deaths (along with today's discreet acts of euthanasia) will be registered as natural deaths.

      NOTE: If you find me dead in front of the TV, with a half-eaten greaseburger dripping over my fat paunch, stinking of tobacco, with a medicine cabinet full of statins and anti-hypertensives that you can tell from the dates on the bottles that I didn't take, and I have known 3-vessel coronary disease and have been complaining of angina, and you don't know something's amiss or see anything curious on examining my body or the scene, go ahead and sign me out as "natural; cause of death is atherosclerotic coronary artery disease". Yeah, a few tricky homicides probably get missed.

      NOTE: Although there is no need to point out the irony, deaths from oat cell carcinoma, heroin-shooter's endocarditis, cocaine heart, and Laennec's cirrhosis are "natural deaths". In particular, your lecturer would like to see a sixth category, "Illegal-drug abuse-related", because separating accidents, homicides, and suicides here is close to impossible.

{07135} morbid obesity, another contributor to "natural" death

    IMMEDIATE CAUSE OF DEATH is what happened just before, regardless of the manner of death or the proximate cause. For example, a person who is accidentally burned and dies three weeks later of pseudomonas sepsis has sepsis as immediate cause of death, the burn as the proximate cause.

    * MODE OF DEATH is an unpopular word for what was apparent without a physician's full workup ("shock", "coma", "pulmonary edema", "sudden cardiac arrest", "pneumonia").



      30 minutes... I can already see lividity on a light-skinned person. Rigor may be present. The body may or may not feel slightly cool.
      3 hours... Lividity is usually obvious.
      5 hours... Rigor is usually obvious.
      10 hours... The body feels cold.
      12-18 hours... Rigor is usually maximum.
      24 hours... Rigor is usually starting to lyse; this can be later if it's hot out
      2 days... Green discoloration (sulfurated hemoglobin) on the flanks
      2-3 days... Green discoloration on the abdomen
      3-4 days... Marbling of the skin begins (red discoloration of surface veins)
      5-6 days... Epidermis separates from dermis
      2 weeks... Bloated, lots of gas in tissues
      3 weeks... Gas causes bursting of the organs, eyes bulge, tissues are soft
      4 weeks... Semi-liquid, slime

      After a near-plateau of variable duration (as above, heat generated by anaerobic metabolism approximately matches heat loss), the body cools at one degree celsius per hour in the first 12 hours, then 1/2 degree celsius for however long it takes to get to room temperature. Circumstances (clothing, obesity, ambient temperature, mystery factors) alter this rate of cooling tremendously.

      Things happen very differently in bodies deposited in the water. There are frequent surprises.

      A newborn with near-zero internal body flora, and some other folks, may not putrefy.

      * Jack Kevorkian's original claim to fame was his attempts to use the optic fundi to determine time of death in very early cases: J. For. Sci. 6: 261, 1961; Am. J. Path. 32: 1253, 1956.

    You are already familiar with RIGOR MORTIS, one-time stiffening of the body after death. In addition to the conventional teaching that this is due to depletion of ATP with subsequent binding of actin to myosin, I suspect this is due at least in part to the influx of calcium through injured membranes.

    You also know LIVOR MORTIS (I say LYE-vorr; others say "LEE-vorr"; "lividity", settling of the blood; this becomes fixed/patterned after a while, and can tell you if the body has been moved.)

      Blood settles. When the lividity becomes fixed (i.e., the red cells are no longer freely mobile in the capillaries, probably because the surrounding tissues have cooled and are more firm) the membranes have become permeable; as decomposition proceeds, the erythrocytes turn to ghosts.

        * Leave the arcana of decomposition ("adipocere grave wax burns like candle wax and accounts for the fragrant smell sometimes reported when certain old burials are re-opened") and the identification of decomposed bodies to us. Check the "electrolytes" handout for more on determining electrolyte status at the moment of death from analyzing the vitreous humor. Approach to the dismembered body: AJFMP 12(4): 291, 1991.

    "Cadaveric spasm" is instantaneous rigor, seen when death occurs with considerable muscular exertion (gripping something, as a branch in someone falling down a mountain) and/or major motor seizure and/or emotion (battlefield, torture).

{07558} livor mortis
{07195} found in the woods
{07021} found in the pond
{07576} post-mortem roach bites (see also AMFJP 18: 177, 1997) -- post-mortem mouse bites look similar

Decomposed body

Decomposed body

Rigor mortis


    The MEDICAL EXAMINER is a physician who autopsies, or has a pathologist autopsy, certain dead bodies. It is a government-appointed position.

      In big cities, the medical examiner is likely also to have his/her subspecialty boards in forensic pathology, i.e., have chosen to devote most of his/her career to this activity.

      Plenty of medical examiners are general pathologists. And in rural communities, physicians who are not pathologists can do this work, getting consultation as needed.

    By contrast, the CORONER is a government official who makes official rulings about the natures of particular deaths.

      In some jurisdictions, the coroner is the medical examiner.

      Elsewhere, the coroner may simply be a college student whose real job is completing routine paperwork, rubber-stamping the medical examiner's conclusions.

      And in others, it may be a funeral director, or way out in the country, whoever owns a truck and is willing to transport dead bodies.

      Laws involving coroners can be interesting, and in some jurisdictions, it's also the coroner's job to arrest the sheriff should he/she misbehave.

      Coroner systems have been gradually giving way to medical examiner systems over the past few decades, (JAMA 279: 870, 1998). Call me old-fashioned, but for a rural county, the familiarity of a police coroner may perhaps work better.

    If you, the licensed physician, are caring for someone and he or she dies of his or her disease, you fill out the death certificate and you needn't even notify the Medical Examiner's office.

    Certain deaths must be referred to the medical examiner / coroner. These include:

    • anyone dying with no physician to complete the death certificate;
    • any death from something other than disease; this includes apparent suicides, homicides, trauma, radiation, poisoning, heat exposure, cold exposure, electrocutions, and complications of illegal abortion;
    • any death in which homicide, suicide, or accident might be the manner, even if there is intercurrent disease as the actual mechanism of death;
    • any death that might provide important information about a public health problem;
    • any death of someone thought to be in good health, or without known disease;
    • anyone dying in police custody, jail, or prison, a detox center, or a halfway-house;
    • anybody dying under age 18;
    • any death thought perhaps to be due to occupational disease or injury (this is routinely ignored in the pneumoconioses and many other situations);
    • any death during surgery;
    • any death thought to perhaps be due to illegal drugs;
    • anyone dying in an "unusual or suspicious manner";
    • deaths from "therapeutic misadventure" (i.e., really unfortunate, unexpected iatrogenic disease)
    • deaths in the first 24 hours following admission to the hospital.

    If there is a bullet in the body, even from long ago and unrelated to the death, the medical examiner (or perhaps a surgeon) should remove it for ballistics examination.

    In a typical community, around 15% of deaths will fall under the medical examiner's jurisdiction, and of these, maybe 35-45% will get autopsied.

      All homicides and suspected homicides get autopsied.

      Where it's an obvious, non-questionable suicide, the medical examiner will at least attempt to obtain the bullet if there is one. I used to do more extensive autopsies when I could, in the hopes of finding some hidden physical disease (i.e., cancer of the pancreas, brain tumor) and if a woman, determine whether she was pregnant. It's only an hour or two extra work for me, and would make a lot of difference for the family.

      For deaths in fires, the medical examiner will at least examine the airways. Soot there says "alive at the time of the fire". No soot says "dead at the time of the fire" or "flash fire".

      If a driver dies after losing control of the car or bicycle, or a swimmer is observed to go under, I always did a complete autopsy in search of natural disease.

      If a body is discovered in the water, usually there will be a complete autopsy. The pathologist may take blood from both sides of the heart and check electrolytes.

      Of course, even without an autopsy, we'll usually take urine (by suprapubic puncture) and blood (femoral vein puncture is best) and check for drugs and alcohol. Where time of death is an issue, or there's a suspicion of diabetes or drugs, vitreous humor will be sampled. Hair samples (roots and all, please) are helpful for the drug history and more. Vaginal swabs and smears will be obtained on all possible homicides of women; oral and anal swabs from everyone.

    Terminology: Whether the person is killed with a firearm or some other weapon, the pathologist examining the wounds will be asked, "Could this weapon have caused this injury?" The pathologist will examine CLASS CHARACTERISTICS ("Rope used in strangling will produce a bruise-abrasion like this one") and INDIVIDUALIZING CHARACTERISTICS ("This rope's twists and thickness exactly match the impression left on the victim's neck.")


    * The great forensic pathologist Ambrose Tardieu wrote an extensive account of physical findings in child abuse in 1860. It was ignored. The story of how we came to recognize the existence of "the battered child syndrome", and the decades of denial that such things could actually happen, is chronicled in Clin. Lab. Med. 3: 321, 1983. ("Isn't it strange how fragile some kids' bones were in life, but not after death?" "When you question the family, be sure not to say anything that might make them feel guilty." "This syndrome of 'osseous discontinuity' can be mistaken for trauma.")

    There is much appropriate discussion of "the battered child syndrome" with evidence of repeated past injury. But the majority of infanticides are the result of sudden anger by a frustrated parent ("I thought at least my BABY would love and comfort me"), and you will not find old trauma.

    Thanks to increased recognition by physicians, and increased awareness perhaps including parents themselves, deaths from child abuse have clearly decreased since the mid-1970's in the developed world (UK Arch. Dis. Child. 97: 193, 2012).

    In the "shaken baby syndrome" (review NEJM 338: 1822, 1998), an acute subdural hematoma follows avulsion of the subdural bridging veins. Look also for retinal bleeds and cerebral edema. You may or may not see a bruise (if the head has been struck; or the striking of the head caused the bleed.) One would think it'd be unnecessary, but it's not -- the worldwide "Don't Shake the Baby" media campaign of the early 1990's: Br. Med. J. 310: 344, 1995. Retinal hemorrhages are common enough just from getting born or even c-sectioned, but are almost always gone by 4 weeks (Ophthalmology 108: 36, 2001).

    Worth knowing:

      Of course, two fractures of different ages in a kid is probably child abuse. And any history that obviously doesn't fit the physical findings is pretty much diagnostic. There is no such thing as "temporary brittle bone disease".

      Babies simply don't get accidental fractures until they start walking by themselves.

      It's now clear that household / playground accidents can and do cause serious / fatal head injury -- very rarely (Dr. Plunkett, AJFMP 2001). This article provoked a firestorm of criticism from the ideologically-minded, but no scientific rebuttal so far, and it seems open-and-shut.

      Don't miss a torn frenulum, in life or at autopsy.

    Future clinicians: Don't mistake any of these for child abuse:

    • Osteogenesis imperfecta with pathological fractures
    • Mongolian spot. "Bruise" on the small of the back that doesn't change. Kids have been taken away from parents and people prosecuted for this.
    • Common and not-so-common rashes. (You'd be surprised what some ignorant folks will mistake for "child abuse.")
    • AV malformation in the brain (this one's real)
    • Brain atrophy with resulting subdural hematomas (this is probably the origin of stories about "this-or-that inborn error of metabolism produces subdural hematomas")
    • * Glutaric aciduria (GA-1. Defense lawyer folklore, though nothing I could find in the literature, claims this grim, vanishingly-rare mostly-motor syndrome, which can come on suddenly, is a cause of retinal hemorrhages and subdural hematomas. Type II is the infamous disease in which the entire body smells like stinky feet.)
    • * Alagille's and Byler's syndromes (if neglected, vitamin K malabsorption can cause a bleeding tendency)
    • Vitamin K resistance syndromes (tricky call)
    • Vitamin D deficiency is rampant among America's junk-food-fed, play-indoors children; "rickets" is now a defense, and you'll need to decide for yourself whether this has merit
    • Other easy-bruising disorders (not-so-tricky calls, but again you'd be surprised). Remember the fragile vessels of Ehlers-Danlos, the coagulopathies of von Willebrand's and the hemophilias, and the thrombocytopenias and platelet dysfunctions.
    • Fractures in preemies. The pathology community was amazed when Acta Paed. 101: 587, 2012 published a series of 71 fractures sustained over a decade in Cardiff's neonatal intensive care units, simply because these kids are so fragile. If the caregivers (who we must assume are not violently abusing the preemies) had been parents, they would have been (probably wrongly) prosecuted.
    • No pathology whatsoever. The McMartin "satanic abuse" school trial got started when one single schizophrenic parent made a crazy assertion and a foolish physician then overcalled a slightly-red irritated backside. Other trials were similar -- once an accusation is made, no matter how foolish, people tend to see abuse.

Shaken baby
Instructional materials
WebPath Photo

Shaken baby syndrome
Retinal bleeds
WebPath Photo

Shaken baby
Axonal retraction spheroids
WebPath Photo

    * Occasionally, psychotherapy helps violent people live better lives, but it's an uphill battle. Review of psychiatry and the treatment of violent patients: Arch. Gen. Psych. 49: 493, 1992.

    Chilling reading: The neurology of violence (Arch. Neurol. 49: 595, 1992). It is simplistic to attribute all violence either to biologic or sociologic factors.

    Major trauma cases (from Sherwin B. Newland, How We Die):

      35%... automobile riders
        7%... motorcyclists
        7%... pedestrians
      10%... gunshot wounds
      10%... stabbings
      17%... falls
      14%... other (bicycles, industrial accidents, botched suicide attempts, etc.)


    ... and all poisons are (potentially) drugs. "Big Robbins" provides a sampler of drug side-effects ranging from the annoying to the lethal.

      There is a pop-claim that "120,000 deaths per year in the United States are caused by medical error". Anyone who has been around medicine will recognize this is obviously false. There are around 2,500,000 deaths annually in the United States and if you are ready to believe that 1 in 20 of these is caused by a clinician's blunder, you are living in a mean-minded fantasy world. Especially, your lecturer remains skeptical (at best) about the widely-reported 2006 suggestion by the Institute of Medicine (academic number-crunchers totally-removed from the real practice of medicine) that 44,000 to 98,000 deaths in the USA every year result from medication errors. Instead, your lecturer believes most of these are due to 20/20 hindsight and use of the retrospectoscope (which isn't fair), and the Institute's willingness to see as cause of death anything that happened during the course of an illness that wasn't textbook-perfect (which is silly). Today's computer programs generate many warnings of improbable drug interactions, making a difficult task even more challenging. The claim that the pharmacy / the nurses giving the wrong medication kills 7000 Americans yearly (JAMA 296: 384, 2006) seems far-fetched; it's hard to study. Having a pharmacist in the ICU seems to help prevent "adverse drug events" (no surprise: JAMA 282: 267, 1999).

    Certain drug effects are PREDICTABLE, and will occur in most people (given a high enough dose), or in those predisposed to problems (i.e., from disease, other drug therapy, or genes). The following are worth remembering always:

    Wizard of Oz
    The Wizard of Oz -- Poppy Field

      Thalidomide caused the shortening of the limbs ("phocomelia") of unborn children.

      Cancer chemotherapy in general is rough on the bone marrow, causing neutropenia and thrombocytopenia. You'll learn about specific agents in "Pharm". For now: Bleomycin, in high doses predictably cause pulmonary fibrosis. Cyclophosphamide causes a vicious urinary bladder inflammation. Adriamycin causes a cardiomyopathy. Vincristine produces a dysautonomia and painful, disabling peripheral neuropathy.

      Reserpine, a great anti-hypertensive drug, causes depression, and even suicide. Methyldopa and propranolol are also depressing.

      Phenytoin and cyclosporine produce hyperplasia of the fibrous tissue of the gingiva.

      Phenytoin and coumarin are notable teratogens.

      The mono-amine oxidase inhibitors can render a person highly susceptible to tyramine in strong cheese and wine, resulting in hypertensive crisis, brain hemorrhage, and so forth.

      The side-effects of glucocorticoids range from immunosuppression to osteoporosis to Cushingoid body habitus. What's more, going off glucocorticoids quickly is a good way to die of addisonian crisis (the adrenal cortex atrophies while exogenous corticosteroids are being taken).

      Several good anti-malarial drugs are oxidizers and will cause hemolysis, especially in patients with G6PD deficiency.

      Aspirin is rough on the gastric mucosa, renders all circulating platelets largely and permanently ineffective (until replaced in 7 days or so, of course), and (in overdose settings) produces a famous sequence of respiratory alkalosis followed by metabolic acidosis.

      The benzodiazepines are amnesic agents. (PLEASE don't prescribe these "to help people study.") So is scopolamine (and perhaps atropine).

      Caffeine produces a mild physical dependency, and withdrawal is accompanied by headache, drowsiness and lots of REM-rebound (sweet dreams....); see below.

      Penicillin at very high doses (i.e., meningitis) causes a non-immunologic hemolysis of red cells.

      If bromsulphthalein dye or adriamycin infiltrate out of the vein, you'll need a skin graft.

      Amphotericin B regularly causes acute tubular necrosis, which is so bad it tends to calcify. Cyclosporine, for renal and other transplants, is also a renal glomerular and tubular poison.

      Man problems often result from drugs (ask): Methyldopa, the classic anti-hypertensive, and opiates (prescribed, street) prevent erections. Clomipramine and the other selective serotonin-reuptake inhibitors make ejaculation much more difficult (dudes, this has its uses....) Thioridazine causes retrograde ejaculation, which can scare the guy. Anabolic steroids are fun but will (at least) accelerate your hair loss (more about gym steroids later). Spanish fly (cantharidin) is supposed to be an aphrodisiac for both you and her, but it's not safe (Forens. Sci. Int. 56: 37, 1992, or ask the Marquis de Sade, who was put away after poisoning some CSW's with it).

      Woman problems: Estrogens have a host of side-effects, the most alarming being the increased risk of atypical hyperplasias and (generally low-grade) carcinomas of the endometrium. Deep-vein thrombosis is an unpredictable but serious complication.

      The alterations in lipid metabolism and fat distribution of the highly-effective anti-HIV drugs are now famous.

      In the past, "clever" murderers used digitalis / oleander extract, succinylcholine, sodium fluoride, or insulin to commit "the perfect crime". Today's savvy medical examiner can detect all this foul play.

    Here's this pathologist's personal list of "the most infamous" UNPREDICTABLE drug side-effects (i.e., nobody knows who will get them, the dose doesn't matter, and it's likely that the chaos of the immune system plays a role). "Are you allergic to any medications?"

      Penicillin is a great antibiotic and a great IgE sensitizer. Anaphylaxis following injected penicillin in a noteworthy complication.

      Quinidine, a good anti-dysrhythmic, causes sudden cardiac death in maybe 1% of people who start taking it.

      Clozapine (the epoch-making anti-schizophrenic drug) and phenylbutazone are noteworthy causes of agranulocytosis. Remember this risk for any drug you prescribe!

      Gold (for arthritis) and penicillamine (for Wilson's, scleroderma, etc.) are notable causes of glomerular protein leakage, often with devastating long-term effects.

      Nitrofurantoin, cyclophosphamide, bleomycin, busulfan, azathioprine, and amiodarone are lung poisons, producing ARDS or chronic interstitial pneumonitis, often at low doses. Methotrexate is prone to do the same; if you see non-caseating granulomas, suspect the methotrexate.

      WebPath Photo

      Amiodarone, griseofulvin, and isoniazid (ask the pharmacologists about "fast acetylators") are liver poisons. (Lots of other drugs can do the same.) The histopathology can mimic alcoholism. (Amiodarone is a horrid lysosome poison.)

      The non-steroidal anti-inflammatory agents are the most common cause of outpatient renal failure nowadays. The old sulfonamide drugs crystallized in the glomerular filtrate and cut up the tubules, while the classic NSAID-prototype phenacetin caused frank necrosis of the renal papillae.

      Halothane is a classic cause of massive hepatic necrosis in unlucky individuals. Overdosing on acetaminophen will do the same thing (big doses overload the safe metabolic pathway via glutathione, and a bizarre, toxic free-radical metabolite then forms by a second pathway -- update Clin. Tox. 50: 27, 2012).

      Hydralazine, procainamide and isoniazid often produce lupus (anti-histone disease, etc.) The first two are the worst.

      Methysergide occasionally causes retroperitoneal fibrosis, with obstruction of the ureters.

      Certain anti-malarial agents will blind occasional patients by causing a retinopathy.

      Abacavir, a very important anti-HIV medication, causes a frightening hypersensitivity syndrome; having a particular HLA allele seems to be required to get this, and antiretroviral therapy is now planned around this.

      Pretty much anything can give you a rash. Types range from IgE, type-I immune injury-mediated urticaria, to type IV mediated phenomena that follow presentation of the drug by Langerhans cells in the epidermis, to the serious vasculitis syndromes, to the dread toxic epidermal necrolysis.

      In the future, we'll know more biomarkers (i.e., genetic alleles) that correlate with different drug allergies (there are about ten known as of 2008: NEJM 358: 637, 2008.)

{53779} phenytoin-induced birth defect, trust me
{53781} phenytoin-induced birth defect

    If all this alarms you, remember that Dr. Hippocrates had no specific drug prescription for any specific disease. Dr. Still and Dr. Osler didn't have a whole lot more. The three of them, unlike many of their contemporaries, realized the situation and had the integrity to say as much. Today's physician must weigh the benefits and risks of any prescription.

      NOTE: "The Physician's Desk Reference" lists side effects of drugs for the judge and jury, ranging from the probable to the improbable. Pretty much everything can supposedly cause "headache", "dizziness", etc., etc.


Pathology of Illegal Drug Use
WebPath Tutorial

I see the Truth, when I'm all stupid-eyed...

          -- Nine Inch Nails, "The Perfect Drug"

    There's no room here for a major treatise on recreational drug abuse, but when you start seeing patients, you'll be impressed with the problems they cause.

      Uncle Sam (1994) reported that usage peaked in 1975, with 23 million users (i.e., people who'd taken a recreational drug in the previous month). Now that the public is more savvy (maybe), and people can lose their jobs if they flunk random drug tests (definitely), the count is down to maybe 11 million, but this is the hard-core.

    Your lecturer has been observing the drug scene since the sixties. IN MY HONEST, CONSIDERED OPINION, THE RECREATIONAL USE OF TODAY'S ILLEGAL DRUGS HAS NOTHING TO RECOMMEND IT.

    * I can't explain to you why people do the illegal drugs or drink heavily.

      Of course, every culture, from stone-age to high tech, has parties where a bunch of people get goofy on the same drug. The same anthropologists who praise this as a "cherished cultural tradition" among primitives may not carry this over to America's illegal drug culture (Subst. Abuse 37: 853, 2002). How are the situations alike, and how are they different?

      Especially, decide how much of this behavior is identity-group membership. This might explain why minority groups (racial minorities, "disenfranchised youth") usually prefer different intoxicants and/or patterns of consumption than the majority culture.

      Not surprisingly, cognitive-behavioral treatment for depression seems to help intractable drug-abusers (Arch. Gen. Psych. 68: 577, 2011).

Sportin' Life
Bess and Sportin' Life: "Happy Dust"

    Some of the essential pathophysiology remains mysterious. We don't even know why pulmonary edema is usual in opiate overdoses, or why people who do street drugs tend to have a hepatic triaditis and enlarged portal lymph nodes. Talc or whatever crystalline substance was present in the injected mixture often finds its way to the portal macrophages, which may also be pigmented.

      No one questions that the use of the addictive drugs induce long-term cellular changes of some sort in the brain; this is reflected in the behavior and is what makes drug abuse such a notoriously relapsing illness.

      * The most interesting work in this area, an examination of gene expression profiles in the nucleus accumbens, tends to discredit the recently-popular idea that the various addictive drugs work through a common pathway ("the addicted brain..."). See Neuropsychopharmacology 31: 2304, 2006.

      * The amygdalas (brain areas that have to do with self-control) in the experienced cocaine-user afflicted with craving seem much smaller than those of normal folks (Neuron 44: 729, 2004). Cause (weak-willed in the first place / stupid enough to try cocaine) or effect (damage from cocaine) or both? We are eagerly awaiting an answer.

    Likewise, the medicolegal evaluation of the deaths of drug-users is fraught with pitfalls.

      The physical findings at autopsy in deaths due to drugs are usually non-specific.

      Tolerance, i.e., decreasing drug effect as the dose is held constant, makes it difficult to say whether the amount that the person took could / could not have been lethal.

      Illegal drugs and their metabolites are easily measured in blood and tissue after death, but post-mortem drug levels must not be over-interpreted.

      Especially, drugs redistribute after death in ways that so far have baffled the best forensic scientists (J. For. Sci. 44: 10, 1999). It's common for a drug, especially if it's lipophilic and there's a fair postmortem level, to be even 10x more concentrated in heart's blood than in femoral vein blood (Am. J. Clin. Path. 133: 447, 2010) as the drug dissociates from the molecules to which it's bound and enters the blood -- and if you see preposterously high levels of any drug after a long postmortem interval, consider this may be involved. Obviously as body proteins denature and temperature and pH change, affinities for the molecules change and drugs diffuse. Most forensic pathologists will simply tell you, "This lab result means the person did this drug."

      The specificities of your screening tests may be insufficient to detect particular drugs. For example, today's "opiate screen" is likely to miss fentanyl.

      And of course, the drugs that were at the scene at the time of overdose are likely to be gone by the time that the police arrive.

      Terms to know:

        BODY PACKER: Someone who swallows containers of the drug to smuggle it across a border.

        BODY STUFFER: Someone who conceals the drug in a packet in the body before being arrested.

        Both types can show up in the emergency room very, very sick (J. Tox. Clin. Tox. 42: 987, 2004; Ann. Emerg. Med. 55: 190, 2010.)

Less Than Zero
* Centers or wooden frames are put under the arches of a bridge, to remain no longer than till the latter are consolidated, and then are thrown away or cast into the fire. Even so, sinful pleasures are the devil's scaffolding to build a habit upon; and once formed and fixed; the pleasures are sent for firewood, and hell begins in this life.

        -- Samuel Taylor Coleridge, opium addict


      Today, this euphoriant-anesthetic substance needs no introduction. Taken by needle, through the nasal mucosa, or smoked in heat-resistant form as "crack" (from the cracking sound made by the crystals), it's has long been major evil presence. There's a mild physiologic withdrawal syndrome. More seriously, once the drug is sampled, the psychologic craving is intense.

        Even experimenting a little with cocaine, even "to help you study", is extremely dangerous. Apparently cocaine use destroys your capacity to be happy without the drug. The cocaine addict will do anything to get more of the drug.

        In the 1980's, the introduction of a cheap, smokable form ("crack", from the sound of the blocks breaking as they burn in the pipe) caused a striking increase in use. According to Sci. Am. 290: 82, Feb. 2004, the use of crack dropped precipitously in the early 1990's. The author's explanation was that community leaders recognized that the danger to their communities' health was too great to accept as "politics and profits as usual", and "extra-judicial street justice" removed the crack dealers. Today's social scientists attribute the tremendous increase in crime between the late 1980's and the mid-1990's largely to the rise and fall of crack.

      Cocaine kills people in at least five different ways:

      • Massive overdose, with blocking of the sodium channels in the heart ("cocaine is a local anesthetic"), bradyarrhythmias and death. Body packers, "stuffers" who swallow the evidence, accidents, probably suicides
      • Stroke (infarct or hemorrhage)
      • Excited delirium (see below)
      • Myocardial infarction / ischemia (cocaine coronary vasoconstriction) / cardiomyopathy (notably left-ventricular diastolic dysfunction (Am. J. Card. 97: 1085, 2006); sudden death (of course; Am. J. Card. 99: 822, 2007). Chest pain of cardiac origin following the ingestion of cocaine is now so familiar in the emergency room that internists even do equipoise studies to determine the best treatment (Arch. Int. Med. 170: 874, 2010) and the best follow-up medications for subclases ("cocaine-induced heart attack people who also have asthma": Am. J. Med. Sci. 342: 56, 2011). The contribution of cocaine and other stimulants to "myocardial infarction with normal coronaries" is tremendous: J. Clin. Path. 65: 512, 2012.
      • Tachyarrhythmias ("sudden arrhythmic death", the most common). A group at Columbia got a group of habitual crack smokers to smoke their stuff while hooked up to EKG's; the changes (tachycardia, much-prolonged QTc interval, etc.) are similar to those for other sympathomimetic agents (Am. J. Card. 97: 1244, 2006). Treatment Clin. Tox. 47: 14, 2009.

      Cocaine and the heart: NEJM 345: 351, 2001; Am. J. Card. 100: 1040, 2007. It is adrenergically mediated and potentiated by both ethanol and tobacco. Cocaine depletes dopamine receptors on the coronary arteries, and renders them super-sensitive to alpha-adrenergic stimuli. This is most likely the cause of the vasospasm (Am. J. Card. 86: 1054, 2000) and symptoms and signs of cardiac ischemia. The cocaine-induced fibrohyaline thickening of the intramyocardial arteries was demonstrated early in this century.

        * The most surprising article I've seen on the taser stun gun is from a group that found that cocaine actually protects the heart from ventricular fibrillation upon getting tasered. It applies to pigs, anyway... (J. Am. Coll. Card. 48: 805, 2006).

      Less well-known is smoked cocaine's ability to produce damage to the pulmonary microvasculature (Chest 121: 1231, 2002). Even if the patient does not have hemoptysis, this is one cause of a lung's being full of hemosiderin-laden macrophages. Check the blood for cocaine in any young person with unexplained hemoptysis.

        * Why cocaine inhalers so often present with pneumothorax (collapsed lung) is a minor mystery of medicine; they generally recover on their own (Am. J. Med. Sci. 339: 65, 2010).

      Remember that even though the brain rapidly develops tolerance to the euphoriant effects of the drug, the sodium channels of the heart never develop tolerance to the effects of cocaine. This triggers rhythm disturbances and death.

      * People with one of the monoamine oxidase A alleles get impressive atrophy of the orbitofrontal cortex if they do a lot of cocaine (Arch. Gen. Psych. 68: 283, 2011).

      Pathologists look for these findings, which are typical of heavy cocaine users and to a lesser extent other stimulant users: (1) Replacement of single cardiac myocytes by fibrous tissue (probably why we get the diastolic dysfunction of the left ventricle; this is distinctive for "chronic catecholamine cardiomyopathy" of which cocaine heart is the chief example); (2) Medial hypertrophy, hyalinization, and/or fibrosis of the small coronary resistance arteries. (For a review with photos see South Med. J. 98: 794, 2005).

      Tachyarrhythmias probably result from the underlying anatomic changes in the heart, since (unlike myocardial infarction), they won't happen during the first experimenting.

      Brain hemorrhages happen even if the vessels in the head are "normal": Neurology 46: 1741, 1996; brain vessel constriction can also produce stroke: JAMA 279: 376, 1998.

      "Crack lung" produces a spectacular anthracosis.

      * You may be told that cocaine produces a vasculitis, especially in the brain (Neurology 40: 1092, 1990). I don't know whether this is true; most cocaine users get no vasculitis from the drug. So far as I've been able to find out, there's no distinctive lesion; it may be just a rare Stevens-Johnson drug-allergy vasculitis.

      Future medical examiners:

        Cocaine's serum half-life is 1 hour. The post-mortem cocaine levels in people whose deaths are attributed to cocaine overlap nearly with those in which cocaine's presence was judged to be an incidental finding. There seems to be a consensus today that whether a particular cokehead dies has little to do with blood levels or dose taken (South. Med. J. 98: 794, 2005). Your lecturer is happy to diagnose cocaine as cause of death if there is ANY of the stuff on board and there is no other obvious cause of death.

        Cocaine is metabolized into benzoylecgonine (serum half life 6 hours, urine half-life 12 hours) and ecgonine methyl ester (serum half-life 4 hours); both degrade into ecgonine which is stable indefinitely. If there is also alcohol on board, about 10% of the cocaine will be turned into cocaethylene, a psychoactive compound with a half-life of 3 hours.

      Watch for post-mortem studies on brain receptors in cocaine addicts, to demonstrate and understand tolerance.

      Crack lung
      Lung pathology series
      Dr. Warnock's Collection

      The famous perforation of the nasal septum is simply an ischemic infarct from vasoconstriction. Cocaine can also kill unborn children by abruption of the placenta or direct toxicity to the fetus (For. Sci. Int. 47: 181, 1990; still clearly true Am. J. Ob. Gyn. 204: 340, 2011), or make babies small and/or premature. Today's "crack babies" need no description (ask a pediatrician, or see Pediatrics 97: 851, 1996; these babies are significantly smaller Pediatrics 101: 229, 1998; Although the most dire predictions have not held up and non-crack-exposed underclass kids also have special problems (Pediatrics 98: 938, 1996; J. Ped. 132: 291, 1998), the "crack babies" do seem to have been damaged permanently by the drug (Pediatrics 120: e1017, 2007).

      * One future hope is a vaccine, i.e., a cocaine analogue that is immunogenic, producing antibodies that bind cocaine and prevent its having an effect. Hope it works. See Nature 378: 727, 1995; Proc. Nat. Acad. Sci. 98: 1988, 2001. Vaccines are also "under development" for nicotine, methamphetamine, phencyclidine, etc., etc., but after a decade there's been nothing really promising (Curr. Psych. Rep. 9: 381, 2007).

      EXCITED DELIRIUM is a curious phenomenon in which a person (most often on cocaine or amphetamines, though the blood levels need not be high and it's seen sometimes without drugs on board) requires physical restraint, then stops struggling and shows labored / agonal breathing and immediately goes into cardiopulmonary arrest. The syndrome is defined to be each of these in succession: (1) hyperthermia, (2) delirium, (3) respiratory arrest; (4) death. Nobody really knows the mechanism (Am. J. Emerg. Med. 19: 187, 2001).

        The phenomenon is so familiar to forensic pathologists and to the police that I have no serious doubt that it's real. The autopsy molecular signature is now reported to be elevated HSPA1B and much-diminished dopamine transporter (For. Sci. Int. 190: e13, 2009).

        Of course, excited delirium generates a lot of bogus "police brutality" lawsuits. Update on excited delirium deaths in custody, viewed with 20/20 hindsight back to 1939: AMFJP 30: 1, 2009. Of course, some of these people die WITHOUT being taken by police, in the way described above (J. Anal. Tox. 33: 557, 2009). Your lecturer suspects that excited delirium, rather than "police brutality", is an important mechanism of death when someone who the police hog-tie dies suddenly (Am. J. For. Med. Path. 31: 107, 2010), though it's possible that a fat person hogtied with a police officer on his back might have his guts pushed upward into his chest cavity, restricting breathing.

      Dr. Halsted, the famous surgeon, and his cocaine addiction: NEJM 352: 966, 2005. It turned him from a great man into a jerk.

Lacerations and incisions
Cocaine "excited delirium"
WebPath Photo

Dead body packer
WebPath Photo

    DOWNERS (barbiturates, others)

      Overdoses can be fatal, especially if you've had a drink. (NOTE: Your lecturer doesn't believe that it's common for people to "forgetfully" take the rest of the bottle of sleepers while groggy from taking just one.) For big-time abusers, there's a physical tolerance and withdrawal syndrome (excitement, seizures) that can kill you. Remember skin blisters in people in "barb" coma; nobody knows why they happen.

      Gamma-hydroxybutyrate (gamma hydroxyburytic acid), gamma-butyrolactone, and 1,4-butanediol (the latter is an industrial solvent, yuck) are popular yuppie downers. Gamma-hydroxybutyrate mimics GABA, the inhibitory neurotransmitter, and crosses the blood-brain barrier easily. Again, there's a physical dependence and the risk of acute toxic death (NEJM 344: 87, 2001).

        * GBH is also a product of decomposition following death, so post-mortem levels are less helpful. We do not test for it routinely (J. For. Sci. 133: 17, 2003); finding it in a dead person's urine is more helpful than in the blood. It also is produced in citrated blood samples simply as they stand. Antemortem blood samples taken in fluoride tubes, and post-mortem urine are more helpful specimens (Am. J. For. Med. Path. 22: 266, 2001).

      Even old-fashioned sedatives such as chloral hydrate still kill people.

Anna Nicole Smith
Chloral hydrate overdose
Coexisting morbidities

      The benzodiazepines ("Valium", etc.) are amnesic drugs. You won't learn well while you're taking the stuff "for test anxiety" or anything else. Today's "more sophisticated" exam-takers are choosing propranolol, a drug with effects on the heart that are not always salutary. Put that stuff away, too.

      * Even the anesthetic propofol is now being used by people seeking a relaxant; it turns out tobe addictive (Clin. Tox. 48: 165, 2010).


      The amphetamines ("speed"; most-used right now is methamphetamine; update Mayo Clin. Proc. 81: 77, 2006) are rough on the heart (sudden death is famous; also "meth cardiomyopathy" Am. J. Med. 120: 165, 2007; disturbingly common Am. J. Card. 102: 1216, 2008), brain, and kidneys, and may incline their users to do foolish, hurtful things. However, sudden deaths from these substances are uncommon, and tend to mimic cocaine's anatomic pathology.

        In particular, intracerebral hemorrhage from doing "meth" is very well-known (AJFMP 25: 334, 2004.)

        Compared with the other drugs of abuse (except ethanol), "meth" is much more likely to lead to death or serious injury by making its users violent and reckless. Of course, we are in the midst of a "meth" epidemic, and folks in the emergency room in San Diego are more likely to be on "meth" than even marijuana (J. Trauma 63: 531, 2007).

        Probably no one was surprised to learn that cocaine and methamphetamine users get horny and do reckless sexual things (Am. J. Psych. 164: 157, 2007).

        The famously-bad tooth decay and fractured teeth seen in the methamphetamine user is caused by a combination of xerostomia, the noxious smoke ("crystal meth" / "ice"), bruxism, and a craving for sugar (Am. J. Health-Syst. Pharm 63: 2078, 2006; Gen. Dent. 54: 125, 2006). It's hard to show in the lab, but your lecturer believes that vasoconstriction from the drug probably infarcts the mouth tissues -- your lecturer thinks this is the main cause of "meth mouth".

        Like "crack babies", "meth babies" born to women who did methamphetamine are much smaller than their counterparts. We await follow-up (Pediatrics 118: 1149, 2006; confirmed Ob. Gyn. 116: 330, 2010; J. Ped. 157: 337, 2010).

        Phencyclidine's pathology is being worked out. It's been a challenge as specific lesions haven't been found, and it's hard to know who's been using. The NIH finally starts looking at folks' "true addiction history" by hair samples, but this isn't feasable for your limited-budget medical examiner (Addiction Biology 13: 105, 2008).

        Mephedrone is an amphetamine available as tablets; it famously causes bruxism (tooth grinding); it's resurfaced and is now being made illegal. (For. Sci. Int. 206: e93, 2011).

      3,4-methylenedioxymethamphetamine ("Ecstasy" / MDMA) is a familiar yuppie drug whose problems are now being studied intensively.

        The drug probably damages serotoninergic axons, with some long-term effects on thinking (old work that impressed me Pharm. Tox. 84: 261, 1999; the idea of real brain damage from casual use is supported Arch. Gen. Psych. 64: 728, 2007; and specifically damage to the serotoninergic axons is now a robust finding Am. J. Psych. 161: 1181, 2004).

        A curious effect is hyponatremia, as the drug seemes to cause both inappropriate secretion of ADH and inappropriate water drinking. This is now a robust finding (Am. J. Med. Sci. 326, 89, 2003; Ann. Emerg. Med. 49: 164, 2007), and can be lethal.

        Use of MDMA is common, deaths from MDMA are rare, and they usually resemble other amphetamine-type deaths (Legal Med. 9 185, 2007).

      * In 2011, synthetic chemicals were marketed in stores as "bath salts", supposedly to be put in your bathwater rather than be consumed as the amphetamine-like drugs that street people knew they were. They killed a few people, caused some appalling senseless violent outbreaks, resulted in quite a few speed-like emergency-room visits, and are now being made illegal (Clin. Tox. 49: 499, 2011; MMWR 60: 624, 2011; NEJM 365: 967, 2011). Compare New Zealand's "party pills" (piperazines): Clin. Tox. 49: 131, 2011.

      * Not really uppers: KETAMINE has caused surprisingly few deaths in recreational users, who are likely to be medical types. See Int. J. Leg. Med. 116: 113, 2002.

      * Not really uppers: LSD and mescaline are seldom encountered today (which is good); there is no known anatomic pathology (Clin. Tox. 48: 350, 2010.)

{07615} tattoo on public-spirited person

Montana Meth Project
Drug-ed ads.


      You're studied heroin, morphine, meperidine, codeine, oxycodone, hydrocodone and the others in your pharmacology class. All are treacherously addictive.

      Heroin, morphine, and meperidine are usually taken by needle (intravenous or skin-popping; there are ways of inhaling "the dragon" heroin). Codeine, hydrocodone, and oxycodone are taken orally.

      Your lecturer is not impressed with the adverse personality or health consequences of opiate use itself (well, it's constipating and bad for the libido).

      However, the stuff is addictive, expensive, and illegal (which causes some of the problems) and overdose is very lethal. Stories from eyewitnesses describe collapse, gurgling, and a massive gush of foam from the mouth. Taken with ethanol, the risk of dying of an overdose is increased.

opium poppies being harvested
Poppies are Also Flowers

      Sid Vicious Unlike cocaine, heroin is not known to have any direct tissue toxicities. There are maybe 4000 deaths from heroin overdose in the US each year, and plenty more from other opiates (oxycodone, hydrocodone). Those dying of opiate overdose either (1) stopped breathing from medullary depression, or (2) got pulmonary edema (nobody knows why opiates can do this, but it's likely that it's neurally-mediated, because of tolerance and because brain injury itself can produce similar edema). Of course, there are plenty of heroin-related deaths due to lifestyle and/or unsanitary injection practices.

      Appallingly, one out of every 65 or so newborns in the United States starts life off in opioid withdrawal ("neonatal abstinence syndrome")(NEJM 372: 2118, 2015).

      It's commonplace for an "accidental" overdose to have been preceded by a critical life-event, and many of these "unfortunate tragic accidents" are probably suicides (Forens. Sci. Int. 62: 129, 1993) while others may have had a recent brush with the law and the dealer gives the buyer an uncut dose of drug to produce the death of a possible business liability.

      * Confusingly, there is an illness seen only in people who snort cooked heroin, and that much be due to some other poison generated in this way. It looks clinically and anatomically like prion disease, but some patients recover; it's called "heroin spongiform encephalopathy" and is recognizable now on MRI scans: For. Sci. Int. 113: 435, 2000.

      Social scientists tell us that heroin was responsible for the upsurge of crime, especially robberies, from the mid-1960's to the mid-1970's. Methadone maintenance as a readily-available treatment proved a great help (thanks very much for that one, Mr. Nixon).

      Methadone / suboxone maintenance keeps drug addiction, which is a relapsing problem, under partial control with great savings to society. There are about 100,000 people on methadone maintenance in the US, and only about 500 deaths per year from overdosing. Most deaths result from increasing the initial dose too rapidly.

      You'll review the various molecules in "Pharm". It's worth remembering that heroin is diacetylmorhine and is metabolized to morphine. Don't try too hard to interpret a post-mortem morphine level, either to decide whether "it's enough to kill the person", or how much of the drug was taken. Tolerance varies tremendously, and attempts to second-guess tolerance by high-tech assays of brain receptors have been non-helpful: For. Sci. Int. 113: 423, 2000. During life, 98% of a dose of opiate is in the tissues; as the body decomposes, much of it will return to the bloodstream. Review J. For. Sci. 46: 1138, 2001. Redistribution is less of a problem than for other drugs: J. For. Sci. 45: 843, 2000.

        * Future medical examiners: The S-enantiomer of methadone is inert but is measured by some of the toxicology techniques.

        * Don't forget to look for pupa cases from the maggots that fed on the body. Morphine can be analyzed from here: For. Sci. Int. 120: 127, 2001.

      "Big Robbins's" statement that a third of heroin addicts had diluted their drug with water from the toilet comes as no surprise to this physician. Heroin may be cut with Baby's talcum powder (stays in the lungs forever), quinine (rough on the heart), or whatever else is handy (who knows?) Heroin addicts seldom use sterile technique, and abscesses and endocarditis (notably on the tricuspid valve, notably staphylococcal) are commonplace, as is the bad retrovirus. "Heroin nephropathy" is usually FSGS (also amyloidosis A, from the abscesses.)

      It's worth remembering that tolerance to opiates is lost VERY fast. One common scenario is a fatal overdose after a 2-3 day stay in jail; the addict simply took the customary dose and died as a result (for example, the death of Sid Vicious). Savvy medical examiners are now estimating these people's tolerance history using hair samples.

      Ultra-rapid detoxification, which ends the addiction during a few hours of artifical sleep and naloxone treatment, has been available since the 1990's and the military (i.e., reality-based) now uses it for burn victims (J. Trauma 71(1S): S-114, 2011).

Drug abuser "works"
WebPath Photo

Heroin-cocaine death
Note foam around mouth
Supposedly Chris Farley

      Ask a forensic pathologist to show you needle marks ("tracks"). These are scars, often pigmented (carbon, hemosiderin), overlying veins and often arranged in a line (savvy dopesters start distal). One reason addicts get tattoos is to make it harder to see their injection sites. "Skin poppers" are often covered with old craters.

        * A long-overdue review on the dermatology of injected drug abuse, emphasizing the long-term problems: Arch. Derm. 143: 1305, 2007.

        * An outbreak of anthrax among skin-poppers whose heroin was mixed with dirt: Science 288: 1941, 2000; Lancet 356: 1574, 2000.

{08170} heroin tracks

Starch granules in tissue
Warning: Gross out
Dino Laporte's PathosWeb

Subcutaneous bleed
Needle user
WebPath Photo

Needle scars
WebPath Photo

        People who inject "Ritalin", "Talwin" or methadone from powdered tablets are also certain to get interesting stuff in their lungs. Talcum powder and pill-fillers both produce little granulomas, which can eventually cause fatal cor pulmonale.

Crystals in the lungs of drug abusers
Lung pathology series
Dr. Warnock's Collection

Talc in the lungs
WebPath Photo

        * Buprenorphine implants for the treatment of opiate dependence: JAMA 304: 1576, 2010.

        The management of patients with chronic pain is only now receiving the recognition it deserves from the medical profession, and is still restricted by laws that don't make sense (a fact that is finally getting media attention). Heroin may perhaps have some use in the management of chronic pain, but the discussion is totally dominated by ideological concerns. Today, however, most users chose heroin not for a physical analgesic but as a powerful anesthetic against deplorable living conditions. It works (and this would lead me to ask why so many people feel they need it -- perhaps the cause is having to live around other substance-abusers, criminals, and mean people), but the problems only begin with impotence, constipation, and infections.

        * For the not-pretty picture of both TB and morphine addiction in the pre-illegal era, read or see Eugene O'Neill's autobiographical "Long Day's Journey into Night".

{07062} talc in heroin-abuser's lung


      "The green muse" was a liqueur distilled from wormwood and sometimes other herbs, was popular in the late 1800's. It affected its users more radically than did other alcoholic beverages, producing a different kind of acute intoxication, then addiction, brain damage, and psychosis. Review Br. Med. J. 319: 1590, 1999.

      Baudelaire, Toulouse-Lautrec, Van Gogh, and Rimbaud were devotees of the drug, which raises the question (for me anyway) whether their devotion to the drug was the cause of, or the result of, their particular outlooks on life. The movie "Moulin Rouge" (2001) celebrates the hallucinations generated by absinthe. A Jayhawk argues that VanGogh's psychosis was at least exacerbated by his absinthe: JAMA 260: 3042, 1988; more by this author on absinthe: Sci. Am. 260(6): 112, June 1989.

      The special ingredient that produced the weird intoxication is supposedly thujone. If you believed everything you read about this, you'd be reading uncritically. Despite its molecular resemblance to the active ingredient of marijuana, it doesn't work on the cannabinoid receptors. More credible is work showing that it acts on the GABA type A receptors (Proc. Nat. Acad. Sci. 97: 3826 & 4417, 2000). This suggests excitotoxicity as the cause of the permanent brain damage.

      * The sad story of a man who drank wormwood obtained via the internet: NEJM 337: 827, 1997.

Van Gogh
After the first glass you see things as you wish they were. After the second, you see them as they are not. Finally, you see things as they really are, and that is the most horrible sight in the world.

        -- Oscar Wilde

    CANNABIS (marijuana, pot, grass, hashish, etc.; "I did not inhale" -- Bill; "Life is way too short to be self-absorbed" -- Ed)

The Case Against Marijuana
For the fraternity
By Ed

What did the two stoners say to each other when they finally ran out of marijuana?

"Hey, this music sounds terrible!"

      The familiar weed, which archeologists tell us goes back at least to the 6th millennium BC, binds to particular receptors in the brain, as do most other drugs. Today, there are as many marijuana smokers as tobacco smokers in the USA (JAMA 307: 173, 2012). The active agent is delta-9-tetrahydrocannabinol. Ask a neuropharmacologist about the "cannabinoid receptors", and the endogenous cannabinoids, notably N-arachidonoylethanolamine (charmingly named "anandamide", ananda being Sanskrit for "bliss.")

        Your lecturer predicts that the brain receptors responsible for the nausea of chemotherapy will turn out to be the CB1 receptors, which use anandamine. CB1 blockers exist and produce severe nausea. For years, nobody looked at clinical uses for these blockers "to help fight the drug problem", which tells me that nobody really believed that marijuana smoking is a major menace to individuals or to society. Further, cannabis is the one common drug of abuse for which the National Academy of Clinical Biochemistry doesn't recommend stat testing in the emergency department (tests for "club drugs" aren't readily available).

          Of course, marijuana also gives stoners the munchies. The CB1 blocker rimonabant for dieters has come (Lancet 365: 1389, 2005; Am. J. Card. 100(12A): 27P, 2007) and gone (didn't work very well; caused depression and suicide).

      * Formerly the hemp plant was cultivated widely in the US for rope and canvas (same word as "cannabis"). People seeking rational explanations for our curious marijuana laws have suspected the political influence of the cotton industry ("King Cotton"; canvas clothes are less comfortable but more durable) and of course the big liquor companies. Or (and this seems right to me) this is just another example of "the law of alien poisons", i.e., that every dominant culture abhors the mind-altering substances preferred by its minority groups, and cannabis was primarily used by Hispanics who called it "Mary Jane" (Substance Use and Misuse 37: 853, 2002: from Nova Southeastern COM). Something on this history of the international ban on marijuana, with a reminder that it was largely driven by a disinformation campaign by a single US politician: Lancet 313: 344, 2004. The "medical marijuana" laws are inadequate to provide the obvious benefits the drug offers (NEJM 362: 1453, 2010); but even the Bush administration (October 2009) reversed itself and stopped sending the Feds after people using the drug in accordance with their states' medical marijuana laws.

      There is a mild withdrawal syndrome seen only in heavy users (i.e., four or more joints per day) that lasts less than a month, with the ex-stoner losing weight, sleeping fitfully, and being crabbier ("increased aggression" shows only on lab tests that seem to measure irritability): Am. J. Psych. 161: 1967, 2007.

      In one long-term study, stoners who weren't already crazy were somewhat more likely to go crazy ("exhibit psychotic symptoms") than non-stoners -- cause and effect, or effect and cause? You decide (BMJ 342: d738, 2011).

      Right or wrong, the government crusade against marijuana has long been a part of "politics as usual". Marijuana smoking was a "political" act during the 1960's, when the government's several "credibility gaps" were obvious and many people were given absurdly long prison terms simply for possessing a joint or two. It seemed to make its known users unmotivated, and your lecturer suspects this means it causes subtle brain damage that may or may not be reversible. If the latter is really true, it has resisted scientific demonstration.

      * Ironically, at the same time that marijuana was the drug of choice for the 1960's, mostly anti-Vietnam-war "counterculture", it was also the drug preferred by front-line troops during the war, who preferred it to alcohol since they wanted to be able to fight effectively in case of surprise attack.

      * Government and government-promoted (D.A.R.E.) material for young people about the supposed risks of marijuana includes obvious, preposterous untruths. For example:

      It is known that marijuana undermines the immune system so it is likely that in another 20 years, if use continues to escalate, the death toll from side effects of long-term marijuana use will equal those of longer-term tobacco use.

      * Of course, this undermines the credibility of warnings about dangers of heroin, cocaine, methamphetamine, and the other genuinely-life-threatening drugs. In the US, politics-as-usual includes the maintenance of an illegal drug culture among the poor and the stupid, with marijuana as the gateway drug. Draw your own conclusion.

      Your lecturer makes yearly medline searches that always reveal exactly nothing plausible about serious health consequences of marijuana smoking (beyond an ultra-rare, Buerger-like "cannabis arteritis" (Br. J. Derm. 152: 166, 2005; J. Am. Acad. Derm. 58(5S1): S65, 2008; the Germans reviewed the data and decided there was no such thing Vasa 39: 43, 2010).   NOR CAN THIS WRITER IMAGINE HOW THE NEUROLOGIC "AMOTIVATIONAL" SYNDROME (if it is real) COULD BE CLEARLY DISTINGUISHED FROM THE APATHY AND ENNUI OF SPOILED MODERN-DAY U.S. KIDS.   This includes the effort in JAMA 287: 1123, 2002, in which Aussies who smoke weed daily for decades have progressive impairment of memory and attention (thanks for trying). Even the Canadians, not known for liberalism, found that the supposed stupidity (i.e., lowered IQ) of stoners is measurable only in those smoking five or more joints weekly, and that looking at past users, "we conclude that marijuana does not have a long-term negative impact on global intelligence" (CMAJ 166: 887, 2002). A mega-study involving imaging of the brain of young teens found smaller brains in those exposed to alcohol, to cocaine, and to tobacco -- but there was no demonstrable effect from marijuana (Pediatrics 121: 741, 2008). In 1999, Bethesda funded a huge study on medical marijuana; it is reviewed in Arch. Gen. Psych. 57: 547, 2000 -- after a lot of hearings and calls for more research, the one solid recommendation was a metered inhaler rather than just letting the patient smoke the weed as a joint. (No, this doesn't make sense to me, either). Studies showcasing the common-sense idea that marijuana helps with chronic painful illnesses continue to be published in major journals (Neuro. 68: 515, 2007 -- the patients are now allowed to smoke the stuff; CMAJ 184: 1143, 2012 finds smoking cannabis much superior than placebo for difficult-to-manage pain and spasticity in multiple sclerosis.) The 2002 claim that cannabis smoking causes 30,000 deaths in Great Britain seems built on faulty assumptions -- you decide: Br. Med. J. 327: 165, 2003. Contrast this with a study from JAMA 299: 525, 2008 indicating more periodontal disease in stoners independent of tobacco use -- without considering that perhaps stoners do not brush-floss their teeth so often as non-stoners or perhaps even eat more candy. How frankly nonsensical the world marijuana laws are: Lancet 363: 344, 2004 (again, not a bastion of liberalism). Mayo's rightly points out that the ongoing hoopla is driven by politics without huge, rigorous studies on either side (Mayo Clin. Proc. 87: 172, 2012) -- but how could science NOT take a back seat to something that has been an important part of our culture for the past sixty years?

      You should not smoke cannabis and then drive a car (reminder BMJ 344: e536, 2012). This was "prove-able" only after blood assays for marijuana smoking became available. See Lancet, April 24, 1976, page 884. A group of Canadian academicians conducted a phone survey asking (1) "Do you drive your car when you are high on marijuana?" and (2)  "How many fender-benders have you had?" They discovered that people who drive stoned average twice as many wrecks (no surprise: Traffic Injury Prevention 11: 115, 2010).

      * In 1997, a team in Italy noticed that cannabis and heroin both activated mesolimbic dopamine transmission by a common receptor mechanism. The subsequent claim that this suggested marijuana was addictive met with guffaws; it seems to me that it simply reflects the fact that both drugs make people happy while they're high (Science 276: 1967, 1997; this would not be worth mentioning except that it got published, somehow, in this distinguished journal and you may hear about it.) Nobody seems to have trouble stopping marijuana smoking.

      Of course, marijuana use results in very few domestic-violence calls. Contrast alcohol. It's also very widely reported to be easily the best way to overcome the dreadful subjective side effects of cancer chemotherapy. This is intensely politicized (your chemotherapy patients will try it themselves, and probably not tell you). Even Canada, not known for radical social politics, legalized medical marijuana in 2001.

      Your lecturer hasn't seen anyone physically sick or dead from marijuana, and believes that claims of grave health threats, birth defects, and so forth are simply disinformation. The few people who are actually getting sick smoked stuff that's been adulterated (for example, by levamisole: Arth. Rheum. 63: 3998, 2011 -- we can't prevent this as long as it remains illegal). Nor has your lecturer heard of dreadful harm from countries where marijuana is available legally at convenience stores. Even the new edition of "Big Robbins" trimmed its warnings against marijuana down to concern about smoke damaging the lungs and being stoned making your thinking fuzzy. Smoking several joints daily is somewhat rough long-term on the lungs but occasional marijuana use seems not to cause lung troubles (JAMA 307: 173, 2012) and using a water-bong is probably safer (JAMA 307: 1796, 2012 -- but where are we going with this?) JAMA 287: 1172, 2002 confirms what everybody knows -- even 17 hours after getting zonked on marijuana, your head's not quite clear. The JAMA editors, not known for being left-wing, also pointed out that most current work does NOT really support the idea that marijuana causes long-term brain damage, and that it's also impossible to tell in any case whether people who smoke a lot of dope are stupider to begin with. (You think?) Science takes a back seat to politics, and truth be told, almost nobody's doing meaningful scientific work with marijuana use itself today. This is a shame, since (for good or ill) the drug is a well-established part of U.S. culture, and (because it is illegal) might be purchased from the same kind of folks as the much more dangerous drugs (i.e., kids learn how to buy from drug dealers). Plus, the brain systems on which it works are evidently quite important (Nat. Med. 9: 1227, 2003). A review of adverse health effects of non-medical cannabis use (Lancet 374: 1383, 2009) emphasized the lack of any real science. The one strong recommendation is to not drive a car when stoned.

      * Synthetic cannabinoids ("Spice herbal incense") that actually do work on the cannabinoid receptors (Eur. J. Pharm. 659: 139, 2011) are now being made illegal (For. Sci. Int. 208: 47, 2011).

        Why do you THINK they call it "dope"? -- Ed

    THE INHALANTS ("glue sniffing", etc.)

      Some people have fun inhaling solvents (acetone, ethyl acetate), gasoline, isobutane (cigaret lighter fluid Int. J. Leg. Med. 120: 168, 2006); isobutyl-, amyl- and butyl-nitrites ("pig pokers", etc.), nitrous oxide ("Whippets", from aerosolized whipped cream cans; a yuppie favorite), toluene (airplane glue), and fluorocarbon (J. For. Sci. 38: 477, 1993) propellants.

      Solvents probably act (like general anesthetics) by solubilizing the lipid in nervous tissue and acting on the same proteins as anesthetics do. Use of some of these drugs can be bad for the heart (sensitizes to rhythm disturbances), kidney, and brain. Intoxicated people can die of aspiration or asphyxia.

      Nitrous oxide users are prone to develop a peripheral neuropathy and megaloblastic anemia.

      "Huffing" is now popular, with computer-cleaner sprays and air-conditioning fluid. "A cool way to die." See Am. J. For. Med. Path. 33: 64, 2012.

      * My favorite article from 2007 was the account of the autopsy of a sniffer of toluene from paint. Granules of aerosolized paint in the lungs were magnificently demonstrated on electron microscopy (For. Sci. Int. 171: 118, 2007).

    DRUG TESTING (review Clin. Lab. Med. 18: 781, 1998)   pharmacology

      There's no time or reason to dwell on the arcane, political-legal subject of testing for drugs of abuse.

      Worth knowing: Heroin is metabolized to morphine, and cocaine to benzoylecgonine and ecgonine methyl ester. You measure these.

      RULE: If there's to be a legal impact of your findings, you must confirm all positives using a test based on a different chemical principle.

        * It is possible to test meconium to see whether Mom has used drugs during pregnancy. Early work (J. Ped. 122: 152, 1993) suggested this might become routine, but understandably it's primariy a research tool, though it has finally come into widespread use (Pediatrics 118: 1149, 2006; Arch. Dis. Child F&N 91: F291, 2006; Clin. Chim. Acta 366: 101, 2006; For. Sci. Int. 153: 59, 2005).

      One fact that needs to be understood by a society considering de-criminalization of marijuana is the fact that it remains detectable in the user's urine longer than more dangerous drugs. People who want to party on Friday night but will lose thier jobs if they are found "drug-positive" on a random urine check on Monday know this, and are more likely to use meth or cocaine instead.

    * All about the "war on drugs": NEJM 330: 357, 1994; JAMA 273: 1143, 1995, Lancet 357: 971, 2001; "a quagmire for our times J. Pub. Health Policy 23: 286, 2002; BMJ 341: c3660 & c4610, 2010 Historians regard the draconian anti-heroin laws of the past as a disaster for good citizens and addicts alike (J. Soc. Hist. 44: 71, 2010). It is one of the mainstays of "politics as usual". Talking about this subject is now considered appropriate for the classroom. The war on drugs directly consumes about $17 billion of our tax dollars per year. There are around 3.5-4 million hard-core addicts (cocaine, crack, heroin), mostly underclass, who are doing most of the crime (robbery, shoplifting, low-level dealing, also child neglect and abuse.) Nobody likes people being addicted to drugs like cocaine and heroin. But despite the rhetoric, it is obvious that vested interests are in control of drug policy. Addiction treatment on demand remains unavailable for most people (Am. J. Psych. 151: 631, 1994; Forens. Sci. Int. 62: 129, 1993; Am. J. Pub. Health 89: 657, 1999). The unavailability of treatment is, of course, the result of politics. (Nancy Reagan's "Just Say No!" campaign, the Republican-Right response to conservative suburbanites who wanted the government to focus on preventing their children from smoking marijuana, ended the Nixon-Carter policy of quietly providing detoxification. Conversely, communities that profit massively from the drug trade strongly oppose detoxification -- their left-wing rhetoric is "curious".) Thankfully, cheap detoxification is becoming more available, but for decades, an addict would have to wait months; this satisfies me that neither the "liberal" nor the "conservative" politicians really wanted criminals/addicts off the streets. (You'll hear the current strategy of interdiction compared to the game "whack-a-mole". Notice that neither "liberal" nor "conservative" politicians ever talk about military action against the cocaine and heroin lords. Is this because they both benefit from the status quo? Or is it because they realize that this wouldn't work?) Drug addiction is notorious for relapsing, and no one expects that methadone maintenance patients will really remain free of street drugs, only that the maintenance will diminish their illegal activities (JAMA 281: 1000, 1999). Drug-related crime has turned our inner cities into war zones (there were around 1500 drive-by shootings in 1995 in Los Angeles alone), young children are brought into criminal lifestyles by drug dealers since they will be punished less severely when caught, and drug-related crime is the #1 or #2 concern of Americans in the surveys lately (after the health-care mess of course). Pediatrics 93: 1050 & 1065, 1994 showcases the disastrous effects on black males ages 9-15; this is one you oughta read, though I don't know whether the "multilevel strategies" the left-wing authors propose will solve the problem while the "war on drugs" continues and there's easy money to be made by those who are not "future-oriented". Drug availability is undiminished (because it is illegal, a high school kid has a much easier time getting marijuana than alcohol), and the number of deaths from drug overdose (not to mention the associated crime and that retroviral disease that is still increasing among IV drug abusers) continues to increase. At least we are putting away more drug dealers, who now occupy a third of our penitentiary spaces (additional $$ beyond the $17 billion/year). Parents: If you don't take a personal, friendly interest in your kids and their happiness, then the local drug dealer probably will. And if you have offered your kids nothing credible to feel part-of, then the local drug culture probably will. The case for continued prohibition of the recreational drugs is persuasive for many people (who generally assume that decriminalization / legalization would increase drug use, which you might reasonably doubt). But their arguments could be applied equally well to alcohol and tobacco (Nature 374: 391, 1995) -- but you knew that.

    Interdicters, moralists, "educators", certain (not all) "drug counsellors" (tough-talk, warm peer support, and monitoring costs mega-bucks for rich professionals or medicaid-recipients caught doing drugs; I'm told "alcohol rehab" now costs $30,000 even though AA's / NA's, still the best, is still free), and (of course) drug dealers all have vested interests in keeping this "war" (and addiction itself) going rather than making timely physician-directed treatment available. An issue I have with one-size-fits-all "drug rehab" programs is that they do not address the other life-situations, i.e., an abuser who can't read or has no useful skills won't get help with this, and there's little emphasis on teaching other living skills that might actually make the person independent and not need either drugs or the revolving rehab door as a crutch. If Newt and Bill ("a new advertising campaign against drugs for 1998") had really wanted to end the problem, it would be possible for any strung-out addict to present himself/herself for humane treatment (for example, an ultrarapid opioid detoxification using naloxone and artificial sleep: JAMA 279: 229, 1998). Is this available? Ads for it are just starting to appear. The strung-out addict is going to rob somebody instead. It is easy to recognize politically-motivated, futile escalation (remember Vietnam?), war-profiteering, or how the current policy of ensuring that drugs generate crime (and crime-profits) serves politics-at-its-worst for both right-wingers and left-wingers. Bill Clinton actually talked about "harm reduction" (JAMA 273: 1143, 1995) rather than a "war" we can win, and the British (not known for being soft-hearted) already consider "damage control" and not "fighting drugs" is the only rational option (Br. Med. J. 315: 329, 1997). Stay tuned (Sci. Am. 269(1): 24, 1993; CIBA Found. Symp. 166: 224, 1992.) Jocelyn Elders, M.D., was pilloried for suggesting decriminalization; a few years later, Newt Gingrich said the same thing and no right-wingers got upset.

    Your lecturer, while no expert on social policy, believes that addiction is bad. Yet I would prefer accessible treatment of addiction (how much does humane detoxification and ongoing monitoring, without other frills, have to cost, anyway?), some ongoing public education (it doesn't have to cost much, and by now everybody knows, anyway...), and other reasonable incentives (as with ethanol -- remember Prohibition? alcohol abuse probably went down after it was repealed; and this doctor will give you a urine specimen anytime you like, thank you) instead of the continued emphasis on attempting to enforce laws as a means of containing what is a very serious problem. Other physicians are now coming around to your lecturer's position as well (Acad. Med. 70: 355, 1995). Maybe the "Smokers' Rights" proponents might make the logical step to drug decriminalization. Amsterdam, where drugs are legal and treatment is readily available, hasn't exactly become a horrible place to be.... Even the British Medical Journal (312: 1655, 1996), not exactly a hotbed of radicals, is now calling the "war on drugs" a defeat, and calling for decriminalization and even legalization.

    The British, who speak more candidly about affairs in the US than our own medical press, seem very happy with Mr. Obama's ideas, including (1) ending the ban on federal funding for people who exchange needles; (2) no raids on people growing medical marijuana legal under state law; (3) drug courts for non-violent offenders. See Lancet 373: 1237, 2009. The Obama administration maintained the interdiction policies while focusing on reducing demand for drugs and treatment for drug misuse -- by 2012, Mr. Obama's treatment programs had reached 22 million drug misusers (Lancet 379: 1184, 2012. Decriminalization of the hard drugs isn't discussable in the USA yet, but Mexico and the Central America are seriously considering it given the damage caused by by the drug-driven wars.

    As always, you're welcome to disagree.

Nothing is more destructive of respect for the government and the law of the land than passing laws which cannot be enforced.

      -- Albert Einstein


    Hanging onto bitterness and resentment is like eating poison and expecting somebody else to die.

          -- Author Unknown

    THALLIUM poisoning requires a very high index of suspicion whether or not it has been fatal, unless the distinctive sign has appeared -- hair loss, * perhaps preceded by blackening of the hair roots.

      * Criminal poisoning by thallium and arsenic in an auto manufacturing plant: Ann. Emerg. Med. 39: 307, 2002. A near-miss homicide attempt, described by the victim, who was crippled: South. Med. J. 96: 632, 2003. A case fully worked-up for pathology: Arch. Derm. 143: 93, 2007. Thallium poisoning is now rampant in China, where the well-being of workers is often ignored: Clin. Tox. 50: 65, 2012.

Thallium poisoning
Source unknown

Thallium poisoning
Cyril Wecht


Mad Hatter
    ELEMENTAL MERCURY is the familiar liquid metal ("quicksilver", etc.) People are often exposed at work. (Everybody knows that mercury in old-fashioned felt caused insanity in hatmakers.) It produces a toxic encephalopathy, with difficulty speaking, clumsiness, and behavioral problems. More subtle cases may mimic amyotrophic lateral sclerosis. The worst endemic location is probably the politically turbulent gold-mining areas of Colombia, where miners have no protection and encephalopathy affects at least 10% of adults. (Lancet 379: 1379, 2012).

    INORGANIC MERCURY is also usually met at work. (Mercury poisoning from folk-amulets: Env. Health Persp. 108: 575, 2000; skin-lighteners that should be illegal Clin. Tox. 49: 886, 2011). This is primarily a kidney poison, causing coagulation necrosis of the proximal tubule and subsequent renal shutdown.

      ORGANIC MERCURY is acquired from environmental contamination, particularly in high-on-the-food-chain fishes. "Minimata disease" was a dread neurologic syndrome among Japanese who ate fish caught near a mercury dump site. Selective necrosis of the tips of the granular layers of the cerebellar folia is the signature lesion.

        Despite much effort, nobody's been able to link intake of methylmercury in fish to brain dysfunction, even in the Seychelle islands where exposure is high (Lancet 361: 1686, 2003).

{07026} mercury poisoning

Mercury poisoning
Striking coagulation necrosis
of proximal tubules
KU Collection

    LEAD ("plumbism")

      A widespread, subtle, chronic poison, primarily in industrial exposure (including those who must live near China's lead mines: Am. J. Pub. Health 101: 834, 2011) and Nigeria's new child gold miners (400 deaths so far, crime against humanity -- Lancet 379: 792, 2012), moonshine, and among children who eat the sweet lead paint chips in slum housing (or inhale paint dust from the windowsill -- still a major problem Am. J. Pub. Health 101-S1: S115, 2011).

        An episode in medical history that has been more or less overlooked was the epidemic of lead poisoning from the placement of lead pipes (hence the name, "plumber") to supply water to houses. The dangers were recognized in Europe as early as 1850, but the epidemic of disease in the US was still going strong as late as the 1930's (Science 315: 1669, 2007), thanks primarily to a massive disinformation by the Lead Industries Association (Am. J. Pub. Health 98: 1584, 2008). We are still paying the price.

        Many houses built before 1960, especially those built on the cheap, are full of lead paint. Remodelling can be unhealthy in these homes, even if nobody eats the paint. Beware also of the paint dust around where the windows open. "The environmentalist community" alternates between activism and indifference.

        In countries where there's still leaded gasoline, folks who get high by inhaling the stuff get sick from lead poisoning.

        Lead in the quack calcium supplements: JAMA 284: 1425, 2000. In quack Asian remedies: Clin. Ped. 50: 648, 2011.

        You can also get lead poisoning from a retained bullet / bullet fragments (Pediatrics 117: 227, 2006). Lead poisoning from smoking marijuana adulterated with lead pellets to increase the weight of the bag (NEJM 358: 1641, 2008). "Pencil lead" isn't lead, but graphite.

      The lead accumulates in bone, where it will remain for a long, long time.

      Supposedly, lead acts by scrambling disulfide groups. In any case, it affects many systems.

        In the blood, a hypochromic-microcytic (why?) anemia results from interference with porphyrin synthesis (delta-ALA dehydratase and ferroCHELAtase; old typo in "Big Robbins".) Future pathologists: Look for basophilic stippling, where chunks of ribosomes remain bound in the red cells.

        In the kidney, it produces a Fanconi syndrome. (Future pathologists: Look for acid-fast, hyaline intranuclear inclusions.) It also poisons the ability to the kidney tubule actively to secrete uric acid, producing the famous "saturnine gout". (* The old Roman character "Saturn" was, among other things, patron of lead.)

{07019} lead inclusions in nuclei of renal proximal tubular epithelium

        In dirty mouths, lead joins the mercaptans of bad breath to produce the famous "lead line" at the gums. (Future physical diagnosticians: you can see the "lead line" in bismuth and mercury poisoning, too.)

        Lead produces an encephalopathy. This can range from learning and behavioral problems of young kids, through horrible cerebral edema, seizures and death in older folks.

        Lead also produces a myelin-and-axons peripheral neuropathy. The chronic, colicky abdominal pain of lead poisoning is infamous.

        The mechanism probably has something to do with lead being taken up at the presynaptic terminals through calcium channels.

      In 1991, the CDC recommended screening all one-year-olds and two-year-olds for lead poisoning (Pediatrics 93: 201, 1994). In the poor neighborhoods, no reasonable person would question the value of this screening.

        * The yield among those living in better homes is essentially zero, but universal screening is still the recommendation, probably to avoid charges of "classism".

        * An assertion that subclinical lead poisoning is a major risk factor for hypertension flopped: JAMA 275: 363, 1996.

    ARSENIC (Lancet 347: 1596, 1996)

      Then she began to groan, faintly at first. Her shoulders were shaken by a strong shuddering, and she was growing paler than the sheets in which her clenched fingers buried themselves. Her unequal pulse was now almost imperceptible.

      Drops of sweat oozed from her bluish face, that seemed as if rigid in the exhalations of a metallic vapour. Her teeth chattered, her dilated eyes looked vaguely about her, and to all questions she replied only with a shake of the head; she even smiled once or twice. Gradually, her moaning grew louder; a hollow shriek burst from her; she pretended she was better and that she would get up presently. But she was seized with convulsions and cried outó

      "Ah! my God! It is horrible!"

            -- "Madame Bovary", Flaubert

      Arsenic, the popular crime-fiction poison and spirochete-killer, disrupts oxidative phosphorylation, ties up sulfides, and does other things. Arsenic trioxide is colorless, odorless, and tasteless, and has always been a favorite for homicidal poisonings.

      * When he finished his internship, Michael Swango MD got his revenge on his attending staff using arsenic, but nobody died that time. Swango's long career as a serial killer was enabled mostly (it seems to me) by physicians' fear of being sued.

    Arsenic and Old Lace

    Michael Swango MD
    and how he managed
    to stay in medicine

      Acute poisoning -- when not fatal in very short order -- is most noxious to the gut, causing vomiting, bloody diarrhea, and severe pain in the abdomen. This progresses to death in hours or days.

      Chronic poisoning causes an encephalopathy, neuropathy, and abdominal pain. Look for (1) hyperkeratosis of the skin, particularly the palms and soles; these may turn into squamous cell carcinomas; (2) "Mee's lines", white smooth lines in the fingernails, where arsenic is bound to keratin (you can see these in renal failure after chemotherapy too -- contrast Beau's depressions, after any grave illness); (3) basophilic stippling of the red cells. (4) Look for blackening of the hair roots too.

      Arsenic is normally present in ground water. After deeper wells were drilled in Bangladesh as an intended public service, water rich in arsenic was struck, and much concern resulted -- see Lancet 360: 1757, 2002; J. Tox. 39: 683, 2001; Lancet 376: 213 & 252, 2010.

      * A famous double-death suspected to be arsenic poisoning is proven to be such: BMJ 333: 1299, 2007.

      * "Paris Green", the famous arsenic-based pigment used in wallpaper in the 1800's, released arsene gas when mold grew on it during the damp season. ("Damp weather is unhealthy!");

      * "Holistic medicine!" Dangerous levels of mercury and arsenic in "Chinese herbal medicine" NEJM 333: 803, 1995.

{07121} Mee's lines

Toxicity in Bangladesh
Texas A&M

Arsenical keratoses

Arsenical keratoses

Mee's transverse leukonychia
These were from chemotherapy
New England Journal of Medicine

    * COPPER toxicity, from old-fashioned containers, was almost certainly the cause of an epidemic of childhood cirrhosis in kids who inherited an (autosomal recessive) susceptibility gene (Lancet 347: 877, 1996); I predict this will be found to be the cause of "Indian childhood cirrhosis" as well.


      This famous weed-killer will, if swallowed, causes ARDS ("acute pulmonary fibrosis") and death over days or weeks. This is among the dumbest possible choices as a means of suicide.

      When the Carter administration sprayed it on Mexican marijuana fields, U.S. marijuana smokers became wildly and selectively indignant over the possible threat to their health. (* "We smoke pot! We like it a lot! So stop spraying it with paraquat!") Paraquat murders: AJFMP 18: 33, 1997.

    * Unripe tropical akee fruit contains dicarboxylic acids (remember the pathophysiology of Reye's?) which cause a fatal encephalopathy (Lancet 353: 536, 1999).


        I think that I shall never see /
        A robin, since the DDT...
        -- c. 1962

      The risk-benefit profiles of these chemicals, especially DDT, is the subject of disinformation campaigns by both the Right and the Left. The chemical was virtually banned worldwide in the mid-1970's. Banning DDT altogether became a huge cause in the 1990's for the environmentalist movement, culminating in the Johannesburg agreement. The Clinton administration took up the cause.

      Thanks to spraying with DDT in the 1950's, the United States and Europe no longer have a malaria problem. DDT brought the number of malaria cases in Sri Lanka from the hundreds of thousands down to 18/year in the 1960's. India had a similar experience. The late-1900's resurgence in malaria in these countries was not due to Rachel Carson's campaign against DDT (as the Right is now alleging), but to development of resistance among the mosquitoes (NEJM 308: 875, 1983); in much of the world, the mosquitoes are still sensitive (Am. J. Trop. Med. 86: 140, 2012).

      The supposed health risks of DDT -- even living next to the dumpsite and having the stuff in your water supply (Env. Health. Perspect. 108: 1113, 2000) resist demonstration. The osteoporosis claim flops (Arch. Env. Health 55: 386, 2000). The study that DDT residues triple your breast cancer risk comes from an organization of which I've never heard (Cancer Causes & Control 11: 177, 2000); the NIH study was negative (Cancer Causes & Control 10: 1, 1999), and so was the Johns Hopkins study (Cancer Ep. 8: 525, 1999). The NIH looks at lymphoma and does not find a connection: Occ. Env. Med. 55: 522, 1998. "No convincing evidence that organochlorines cause a large excess number of cancers" --NIH Annual Rev. Pub. Health. 18: 211, 1997. The NEJM wrote a scathing account of "paparazzi science" underlying anti-DDT activism (337: 1303, 1997). Nature Medicine stated bluntly that the ban was driven by rich "green" activists for their own political gain, "balancing risks on the backs of the poor" (Nat. Med. 6: 729, 2000). Most recently, several individuals (all from identify-environmental-poisons organizations I'd never heard of) presented a claim that prolonged industrial exposure to DDT causes brain damage. I can't see this in their own small-sample statistics, in which differences between exposed and non-exposed people are small and on some tests the exposed people did better than the controls, and demonstrably sick people were eliminated from the control group but not the sample group (Br. Med. J. 357: 1014, 2001). Frankly, the corruption is obvious. A bigger study will surely be forthcoming. DDT sometimes acts as an estrogen. You can make a fertilized boy fish egg grow up into a girl fish if you inject a gigantic amount of DDT into it (Env. Health Perspect 108: 219, 2000). But if DDT demasculinizes human or other warm-blooded males, I couldn't find anybody writing about it. Even the World Wildlife Fund's spokesperson (Br. Med. J. 321: 1404, 2000), who claims children need to be protected both from malaria and from DDT, cites no credible recent work to show a real danger from the latter; his major citation is Am. J. Pub. Health 77: 1294, 1987 which found a very weak correlation between DDT levels and shorter duration of lactation which has never found any further support. If you check his reference on "endocrine disruption" (J. Clin. End. Metab. 85: 2954, 2000), that author merely mentions that this is an allegation made by some people. South Africa's DDT workers basically have no troubles with sperm counts or anything else sexual (Env. Res. 96: 1, 2004). An huge attempt to link DDT exposure to low birth weight did not achieve statistical significance (Am. J. Epid. 162: 717, 2005). In 2005, a retrospective study on the mental development of babies exposed in utero that failed to control for other variables (which was probably impossible anyway) gave mixed results (Pediatrics 118: 233, 2006); since DDT is present in breast milk and actually seemed to benefit this cohort, perhaps DDT is not the cause. Everything else is even softer.

      However... the pesticide leaves residues in the environment that stay around for a long time. This can't be wholesome, though an adverse impact on humans (if any) isn't clear so far. Contrary to right-wing claims, university wildlife experts do still believe that the ban on DDT brought the bald eagle back (Env. Health Rep. 103(S4): 51, 1995; also Science 218: 1232, 1982), and the stuff seems to interact specifically with the steroid receptors on the glands that make eggshell.

      Even the World Wildlife activist admits that malaria continues on the rise, killing at least a million people yearly (low guesstimate) and making 300 million people sick. And insecticides are key to its control. But DDT is pretty much out of use anyway in favor of better chemicals, except in the poorest countries. Most of the world uses better, somewhat more expensive chemicals. I suspect this is why the Clinton era saw a chance to look good by calling for a ban on the stuff -- the non-evidence-based environmentalists could make their political capital without being justly accused (that time) of indifference to one of the world's worst genuine health problems.

      Update: Johannesburg is forgotten. By 2006, even Greenpeace and the World Wildlife Fund decided they were in favor of using DDT where it's really needed (India, sub-Saharan Africa). DDT is most useful in spraying homes and on netting. This obviously saves lives and seems to generate much less resistance than widespread spraying (Am. J. Trop. Med. Hug. 71(S2): 214, 2004). Only a few extremists still campagin against this.

    ORGANOPHOSPHATE INSECTICIDES (malathion, parathion)

      Like the chlorinated hydrocarbons, intoxication may be acute or the result of accumulation in body fat.

      These drugs are basically acetylcholinesterase inhibitors, i.e., first you'll twitch, then go limp (why?). You'll find a full discussion in the section of a "Pharmacology" textbook that also deals with myasthenia gravis.

      Some of them are so toxic that a few drops on unprotected skin will kill. (A famous outbreak a few years ago was caused by a bottle spilled during trucking onto blue jeans later sold in a department store.) You'll recognize these patients by their having a mysterious illness with drooling and pinpoint pupils.

      The decreased serum cholinesterase levels seen in life remain reliable during the hours following death, if the cause of a "sudden and unexplained death" is not obvious.

      Worldwide, the most common method of suicide is self-poisoning with pesticides (commonest of course in the poor nations; estimate is around 300,000/year; Lancet 369: 169, 2007; Clin. Tox. 50: 202, 2012).

      * Future pathologists: A point-of-care four-minute test for red cell acetylcholinesterase to check for organophosphate poisoning is now available (Ann. Emerg. Med. 58: 559, 2011).

      GULF WAR SYNDROME, i.e., neuropathies and minimal-brain-dysfunction problems, may have resulted from exposure to chemical weapons, pyridostigmine, flea collars, etc., etc., etc. This will never get sorted out. See JAMA 277: 215, 223 & 231, 1997.

    Organophosphate poisoning
    Pittsburgh Pathology Cases


      If you believed everything you hear about the alleged dreadful effects of these pollutants, you'd be listening uncritically (to put it mildly). Those who work with them don't have any obvious pattern of illness. The disturbing thing, however, is that they almost completely resist degradation in the environment, and it's hard to tell who has how much on board and to control for variables. Stay tuned to find out what real damage (if any) they will do us.

    DIOXINS (nice review: Am. Fam. Phys. 47: 855, 1993; nothing on adverse effects is being published any more)

      These include "agent orange" (the Vietnam herbicide from "Operation Ranch Hand") and the stuff in the West Virginia Nitro and Italian Saveso industrial disasters, and were among the "Love Canal" pollutants. They also are produced in small amounts by most combustion, and they tend to accumulate in the food chain and thus in people (Am. J. Pub. Health 84: 439, 1994 for levels). "Agent orange" contained a trace of * 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which is the semi-poisonous stuff and seems to be a cancer promoter like so many other chemicals. The manufacture of all dioxins is now banned in the U.S. for political reasons.

      * The story about "dioxin" or TCDD being the most poisonous substance known just isn't true. Guinea pigs are allergic to the stuff, which is most of the basis for this claim.

      TCDD is a "carcinogen" (probably just a promoter) and teratogen in some animal systems. In big doses, it can kill an animal soon after administration, but this hasn't been reported in humans.

      A few weeks after heavy exposure, a human's sebaceous gland basal cells undergo metaplasia into keratinocytes, pushing sebum out of the follicle in huge horny blobs ("chloracne"). This gets somewhat better in a few months or years. In 2004, Ukrainian politician Viktor Yushchenko was poisoned during his candidacy, with the intent of rendering him ugly. It worked, and he ended up gaining sympathy votes and getting elected president.

      Most of the Vietnam Vets who were actually exposed took part in a single fiasco ("Operation Ranch Hand"). These folks now turn out to have about 50% more basal cell skin carcinomas than other comparable folks, but no demonstrable increase in anything else so far.

      Nobody's been able to show an increase in birth defects among children of exposed service personnel from Vietnam (or Saveso or Nitro survivors), nor has convincing evidence of an epidemiologic link to human cancers been forthcoming. Studies finding nothing: NEJM 324: 260, 1991; Am. Rev. Resp. Dis. 144: 1302, 1991; JAMA 267: 2209, 1992; Arch. Int. Med. 150: 2845 & 2495, 1990; and those already cited in the Neoplasia chapter. More: Epidemiology 9: 161, 1998 (no increase in preterm babies, infant morality); Epidemiology 6: 4, 1995 (Air Force finds nothing to suggest negative reproductive outcomes); Epidemiology 7: 352, 1996 (no measurable effect on sperm counts, testosterone, etc.); One study does find a link between adult-onset diabetes, and exposure (history, blood dioxin assay; same Air Force lab as above): Epidemiology 8: 252, 1997.

      And it turns out that most Vietnam veterans don't even have any more TCDD on board than do civilian controls (Am. J. Pub. Health. 81: 344, 1991), though some do. The public continues to believe that Agent Orange is a major health hazard. In 1994, the widow of a chain-smoking Vietnam vet was awarded a large, precedent-setting pension because her husband's lung cancer was supposedly caused by agent orange.

      Serious interest in "Agent Orange" among real epidemiologists has dropped spectacularly since the mid-1990's. Some scientists who worked with the EPA on its "1994 dioxin report", which proclaimed that, yes indeed, dioxin was a big danger, denounced the whole thing as politically-motivated junk science (Science 266: 1629, 1994 -- still good reading). As one who honors the warriors (if not every war), I regret the exposure of our people to a carcinogen, and the campaign of fear and obvious misinformation.

      * Love canal: Chemicals from an old toxic waste site resurfaced. The locals were understandably and justifiably upset and angry. Fortunately, nobody has been able to show a statistically significant increase in any health problem (Science 226: 1217, 1984; Am. J. Forens. Med. Path. 3: 343, 1982; Science 212: 1404, 1981). One little-discussed after-effect of this sort of thing, and the legislation and litigation it has spawned, is that if you purchase a plot of land, YOU become liable for cleaning up any real or imagined toxic health hazard that some militant might claim to discover. As a result, certain locations cannot possibly be developed economically, and everybody loses.

    TOADSTOOLS (Pub. Health Rep. 126: 844, 2011)

      AMANITA PHALLOIDES, the "death angel" produces AMINITIN, which inhibits RNA polymerase. Death results from hepatic necrosis. Mostly an old-world mushroom, it's also present in the USA (Clin. Tox. 49: 128, 2011); the Americas have several species of galerina toadstools that also contain the poison.

      AMANITA MUSCARIA produces MUSCARIN(E), prototype of the parasympathomimetic drugs. ("SLUD" strikes again.) Expect to survive.

    TRICHOTHECENE: A potent mycotoxin that binds to the 60-S ribosomal subunit and prevents peptidyl transferase from acting. This was the poison of the yellow rain flap of the early Reagan years.

    * The homicidal poisoner: reviews AJFMP 17: 282, 1996, AJFMP 16: 223, 1995; AJFMP 34: 38, 2013.

    * The "milk sickness" that killed Abraham Lincoln's mother and thousands of other early-USA pioneers resulted from dairy cattle eating white snakeroot, which contains an alkaloid poisonous to humans.


    Black as the devil
    Hot as hell
    Pure as an angel
    Sweet as love.

          -- Talleyrand on coffee

    The most popular of all drugs. A mild CNS stimulant, which works as an antagonist at the adenosine A1 and A2A receptors. It got a tremendous amount of study in the 1990's; lately interest has tapered off. A mega-study in 2012 showed that coffee consumption was "inversely associated with total and cause-specific mortality", i.e., seems to be good for you; no effect whatever on cancer. And to their credit, they did try to control for whether sicker people simply stop drinking coffee. See NEJM 366: 1891, 2012. Coffee and other caffeinated substances DO save lives by preventing long-term truckers from falling asleep and crashing (BMJ 346: f1140, 2013).

    Use caffeine sparingly (if at all). Your enhanced efficiency is bought at the price of greater fatigue and problems resting after the effect wears off. Ask a pharmacologist about the cyclic-AMP connection.

    The drug also increases adrenergic tone (which accounts for its ability to enhance cardiac rhythm problems and the perception of hypoglycemia). When a patient says they are having palpitations (i.e., they're aware of their heartbeat, which may be slow-regular, fast-regular, or irregular), ask about caffeine use (Lancet 341: 1254, 1993); however, even in the setting of an acute myocardial infarct, these rhythm problems are very unlikely to be dangerous (Heart & Lung 21: 365, 1992). In fact, the first question you ask a person who reports the heart doing single flipflops is have the increased their caffeine intake -- caffeine is the most important casue of occasional ventricular ectopic beats (Am. J. Med. Sci. 343: 150, 2012). And coffee's obviously safe even for people with the common known rhythm problems (Am. J. Med. 124: 284, 2011).

1960's rural physician Rural physician
USA, 1960's

    * Fun to know! Tea in China goes back at least to 2700 BC. "The English drink tea" because it was considered patriotic after they displaced the Dutch as chief imperialists in China. As the American Revolution was beginning, tea became a symbolic issue, and ever since, Americans have preferred coffee. Coffee itself was supposedly discovered by an Arab goatherd, who noted the goats became frisky after eating the berries. Its use became popular among Benedictine monks, who needed something to stay awake during marathon prayer sessions. Of course it was considered a drug menace when it became popular in Europe in the late 17th century; England's Charles II tried to ban it without success, and Bach's Coffee Cantata describes a 1730's father's effort to rescue his daughter from coffee-drinking, only to discover that the new beverage is in fact safe and delightful. Chocolate was a gift from the First Americans, while the kola nut came from Africa.

    In spite of what you've heard, caffeine simply does not produce measurable sustained hypertension (Am. J. Card. 73: 780, 1994; and once again Am. J. Clin. Nutr. 94: 1113, 2011). Nobody's been able to show any convincing risk for atherosclerosis, heart attack (Arch. Int. Med. 152: 1767, 1992), stroke, or sudden death.

    * There was a flap in the 1990's over caffeinated coffee drinking (two or more cups per day) and osteoporosis in women. However, the effect vanishes if the woman also drinks a glass of milk each day, and this finding makes me think that some other variable, not coffee drinking, is the cause. See JAMA 271: 280, 1994. Update, finding a risk in older women: Am. J. Clin. Nutr. 74: 694, 2001 (happens if they have the bad vitamin D receptor, which makes sense).

    * There's another longstanding concern over caffeine use and fetal loss. This might be real, but it isn't a huge effect See JAMA 270: 2940, 1993 and Am. J. Pub. Health. 82: 85, 1992 (makes the claim), JAMA 269: 593, 1993 (refutes the claim, and also denies that babies are more likely to be growth-retarded). NEJM 343: 1839, 2000 found a slight effect, but only if the woman is a non-smoker (study shouts "recall bias!"). In another NIH study, only extreme caffeine abuse (as evidenced by massively-high serum paraxanthine levels) was any risk for fetal loss (NEJM 341: 1639, 1999). Baby does experience the same enhanced wakefulness and diminished sleep that Mom does if she takes coffee: Am. J. Ob. Gyn. 168: 1105, 1993. Caffeine use isn't a risk factor for prematurity: Am. J. Pub. Health. 82: 87, 1992). In an update, the effects of caffeine as a cause of miscarriage are anything but impressive (Ob. Gyn. 98: 1059, 2001). The Dutch found that women drinking more than six "caffeine units" per day (seems like a lot) tended to have smaller babies -- real effect or confouding variables (Am. J. Clin. Nutr. 91: 1691, 2010). Of course, to cover yourself you'll still have to warn your patients to stop taking caffeine as soon as they find they are pregnant.

    * Caffeine is used to stimulate preemies to breathe and happily we now know it does NOT cause brain damage (! JAMA 307: 275, 2012). The alleged link with bladder cancer just doesn't hold up (Lancet 341: 1432, 1993). I'm very skeptical about the supposed link to pancreatic cancer, since it's inconstant and tobacco is likely to be a confounding factor. An attempt to show that maternal caffeine consumption during pregnancy causes attention deficit disorder in the child (you can't blame folks for wondering) failed (Am. J. Psych. 160: 1028, 2003). The alleged link with mouth and tongue cancer is anything but impressive (Cancer 70: 2227, 1992). The alleged link to rheumatoid arthritis as refuted (Arth. Rheum. 48: 3055, 2003). The pop claim that caffeine exacerbates fibrocystic change in the breast has consistently failed to hold up to controlled studies (J. Am. Diet. Assoc. 100: 1368, 2000). Caffeine use during pregnancy has been linked to SIDS but only if you fail to control for these women also being smokers, drinkers, and underclass (Arch. Dis. Child. 81: 107, 1999). More recently, the pop claim that it causes atrial flutter / fibrillation flopped (Am. J. Clin. Nutr. 81: 578, 2005).

    The medical community has finally documented what most adults already know: caffeine enhances the jitteriness of falling and low blood glucose (Ann. Int. Med. 119: 799, 1993).

    * Generalized anxiety disorder patients shouldn't take coffee (Arch. Gen. Psych. 49: 867, 1992), but it's okay for panic-disorder patients (ditto).

    We'll talk about the headache of caffeine withdrawal (probably the most common headache) under CNS (Mayo Clin. Proc. 68: 842, 1993). All about caffeine withdrawal, for those not acquainted with this: NEJM 327: 1109, 1992. Yeah, this means there's "a mild physical addiction", but despite occasional excitement about this fact from ideologues, no one has trouble breaking a coffee habit.

ALCOHOL (ethanol, ethyl alcohol, "grain alcohol", etc.)

    When I put my arms around you and kiss you on your mouth,
    Then I am happy even without beer!

          --Ancient Egyptian love song

    Man, being reasonable, must get drunk.
    The best of life is but intoxication.

          --Lord Byron

    I remember a mass of things, but nothing distinctly; a quarrel, but nothing wherefore. O God, that men should put an enemy in their mouths to steal away their brains! That we should, with joy, pleasure, revel, and applause transform ourselves into beasts!

            --Shakespeare's Cassio

The Drunk, by George Bellows
"The Drunk", by George Bellows

    * Noah needed a drink when the flood waters receded, and made an "ass" of himself, becoming the "butt" of his son's joke (Genesis 9:20). And so sin "reared" up once again. See also Matthew 11:18-19 (drink or abstain, people will criticize you).

{37891} wino crossing

    Hogarth, Gin Lane Hogarth's "Gin Lane" It would be difficult to overstate the contribution of excessive alcohol drinking to ill-health, the patient load of a general hospital, or the business of a Medical Examiner's office. The behavioral changes in acute and chronic alcoholism require no description here.

    In your lecturer's opinion, the harm done by alcohol exceeds by an order of magnitude the harm done by actual ingestion of the equally-available illegal drugs. Yet most people who drink alcohol sensibly appear to take no harm and perhaps even derive some healthy pleasure.

    Your lecturer hopes no one takes strong offense from the word "drunkard" for a person who is very drunk. "Alcoholic" implies loss of self-control over the long-term. A non-alcoholic may be very drunk on a particular occasion. Your lecturer remembers; that's why he quit doing it after a few bad experiences! So did most of you. By contrast, a real-life alcoholic won't learn even from a string of bad experiences, which is what makes them different.

      * Your taxes paid for an expensive government anti-alcohol program specifically targeted at fraternity and sorority members. Most of the older Greeks refused even to sit through the eight-hour indoctrination session. Those that did mostly refused to give the answers that the government wanted to prove their program worked. The authors were truthful enough about the fiasco, and this simply confirmed my old Al-Anon wisdom, "You cannot control another person's drinking." See J. Stud. Alcohol 60: 521, 1999.

    "Proof" (whiskey, other hard liquor) is double the percentage of ethanol in the bottle. Eighty proof whiskey is 40% alcohol.

    * We don't know how ethanol produces its buzz; there's only a little work and it involves GABA receptor channels (Proc. Nat. Acad. Sci. 92: 3633, 1995). Older ideas, which still might be right, focused on solubilization of ethanol in the brain lipid and the corresponding physical changes.

    The liver metabolizes alcohol first to acetaldehyde (via alcohol dehydrogenase), then to acetic acid, and ultimately to carbon dioxide and water. (* Microsomes and peroxidase-catalase systems also help handle some alcohol.)

    There is no question any more that heavy alcohol use by itself can and does permanently damage the brain. The problem's not so much that brain cells are destroyed (that's largely bunk) but that they are damaged ("loss of dendritic spines"). Check out Alc. & Alc. 25: 467, 1990; Exp. Neurol. 106: 156, 1989; still valid Brain Res. 1134: 148, 2007.

    Alcohol has traditionally been cited as causing about half of auto fatalities. Thankfully, today it's considered correct and even smart to choose one partygoer as designated driver. This participant remains cold-sober. (Try it. You'll probably enjoy it.)

    It takes about 5 beers or 5 shots of 80 proof liquor in rapid succession for the typical 70 kg man to reach the "legal" level of intoxication (100 mg/dL), but impairment of judgment and coordination occur at much lower levels. Watch for a lowering of acceptable driver's blood alcohol levels to 50 mg/dL or even lower.

    "The books" cite blood alcohol levels of 350-500 mg/dL as "fatal", but there's lots of variability. It's commonplace for a driver to be arrested with a blood alcohol of 300 md/dL or more. A chronic alcoholic may also die with a low blood alcohol "from cardiac rhythm disturbance brought about by alcoholism."

    Most people metabolize alcohol at a rate of 15 mg/dL/hr, using basically zero-order kinetics. That means you burn off about the equivalent of 1 beer or 1 shot of the hard stuff in 1 hour. Habitual drinkers handle the stuff much more rapidly, and there's much variability among people (for example J. For. Sci. 38: 104, 1993).

      * Future pathologists: Post-mortem ethanol levels are a subject of much interest. Worth knowing:

        Blood levels are a bit lower than serum levels because serum has more water, and of course ethanol is distributed through the aqueous phase.

        If the blood alcohol level is higher than the vitreous level, probably death occurred before equilibrium was achieved, i.e., the dead person had not been drunk for long.

        In a putrefied body, the blood alcohol level can be as high as 150 mg/dL; a day or so of decomposition can raise it up to 50&nbdp;mg/dL but usually not higher. For the first day, there will be alcohol production only if bacteria / candida are already flourishing in the bloodstream, i.e., death was due to sepsis / hyperthermia / bowel perforation. Refrigeration slows the process down greatly. Urine will not support the growth of bacteria post-mortem unless there is glycosuria.

        Alcohol passes rapidly through the gastric mucosa, so if there's even 5 g/dL of alcohol in the stomach, the dead person had a drink within an hour prior to death.

        Alcohol in the stomach is prone to diffuse into the nearby heart and great vessels; moving the body may also cause some to be aspirated into the lungs with the same effect. Your best blood to sample for alcohol comes from the femoral vein. Take a sample from the vitreous also.

        The ratio of urine alcohol to blood alcohol can help you guess whether the person was actively drinking prior to death. If the ratio is under 1.2, the blood alcohol was probably rising at the time of death. If it is over 1.3, the person was probably drinking over a longer period of time.

Huckleberry Finn's father
Pap Finn
    Some drinkers (it's probably partly hereditary) eventually reach a point in which they cannot stop drinking once they have started. This is a sure sign that it time to stop drinking, now, altogether, for the rest of your life. You will also need some assistance doing this. This is available. Recovery will happen when, and only when, the person alters their life focus and how they seek meaning. Despite the existence of many profitable-trendy "counselling centers", etc., etc., the best help is probably still "Alcoholics Anonymous" ("Rational Recovery"/"Secular Sobriety" is the alternative for those who don't want AA-mysticism, or some AA members understand the "G--" word to mean "Good Orderly Direction").

      * The long-term results are not salutary for either partner, but every adult knows that alcohol is an extremely effective short-term anesthetic against nagging and verbal abuse. This is a very common step that leads to the chronic domestic violence syndrome. You might be able to teach both parties a few new ways of coping, Doc.

      * One major concern of a drinker and/or druggie considering sobriety is the loss of friendships. Don't worry. Drinking "friends" will be replaced by higher-quality friends in the sobriety movement. This is well-known by now, and makes me wonder whether people drink (do drugs, join stupid political and ideological movements, etc.) because they are really seeking friendship. One thing your lecturer likes about skydiving is that nobody's drunk or on drugs -- and a group of substance-free chums is hard to find among today's grown-ups.

       Subclassification of alcoholism, simplified:

        Type I: Crybabies ("At least I'm not a criminal")

        Type II: Criminals ("At least I'm not a crybaby")

Tippler, from The Little Prince Type I is memorialized in "The Little Prince": "I drink to forget... to forget that I am ashamed... ashamed of drinking!")

Type II tends to run in families and announce itself early.

      * You'll learn on rotations about naltrexone and other agents to reduce craving. Historical article: JAMA 281: 1318, 1999.

      Anyone overcoming alcohol dependence, regardless of kind or type, deserves our heartiest admiration and congratulations.

    For alcohol assays on the living or the dead, send us blood in a gray-top (sodium fluoride anti-bacterial, anti-enzyme) tube. Keep your sample frozen or in the refrigerator.

      Future pathologists: You'll use both (1) alcohol dehydrogenase methods and (2) gas chromatography for alcohol assays. The former detects methanol and isopropanol also; the second does too, but distinguishes them from ethanol. Remember that early decomposition can produce alcohol levels up to 50 mg/dL.

      "Alco-Screen" dipstick to measure the alcohol in spit: Ann. Emerg. Med. 18: 1001, 1989.

    Here's a partial listing of the bad health consequences of prolonged heavy drinking:

    • alcoholic hepatitis and hepatic cirrhosis
    • brain damage (loss of dendritic spines, Wernicke, Korsakoff, cerebellar atrophy)
    • pancreatitis (acute and -- ouch! -- chronic)
    • cancer of esophagus, throat, and larynx
    • GI bleeding from ulcers, varices, gastritis
    • fetal alcohol syndrome (ask a pediatrician; you cannot rehabilitate these kids very well Lancet 341: 907, 1993)
      • The classic kid with fetal alcohol syndrome has a long upper lip, epicanthic folds, a small head, and is mildly mentally handicapped. There's a lot of variability. Alcohol causes apoptosis of fetal neurons: Science 287: 1056, 2000.

    • neuropathy (at AA's, many people complain years later about numb fingers)
    • cardiomyopathy (this isn't common)
    • rhabdomyolysis (seldom dramatic, but probably contributes to long-term wasting)
    • hangover, tremulousness, seizures, delirium tremens on withdrawal ("pink elephants on parade", etc.)
    • losing job, family, friends
    • oh, and by the way, it probably has a slight favorable effect on HDL and coronary atherosclerosis. Gee whiz.

    We're only now figuring out how alcohol affects the brain at the molecular level.

    Post-mortem alcohol levels are fraught with interpretive problems. Alcohol diffuses post-mortem from stomach to heart's blood. Bacteria from the gut reach the bloodstream by 6 hr, or faster if the gut is injured, and ferment glucose, especially if it's warm and/or there's a high blood glucose. This won't exceed 50 mg/dL the first day, and is usually much less, but can get to 200 or more if there are several days for decomposition. Be sure you also get a post-mortem vitreous sample (always possible) and a post-mortem urine sample (usually possible), and draw your blood from the femoral vein rather than the heart.

      * Thanks to the savvy pathologist testing the vitreous, we knew that Henri Paul, who was driving Princess Diana, really DID have a blood alcohol level of around 175 mg/dL when he crashed (Br. Med. J. 316: 87, 1998).

I've been asked if I ever get the DT's. I don't know. It's hard to tell where Hollywood ends and the DT's begin.

                --W.C. Fields

    METHANOL ("wood alcohol", "blind, vomiting, and drunk") is metabolized to formaldehyde (yeah, you know that's gotta be bad for you) and thence to formic acid (which gives the famous high anion gap acidosis). The retina toxicity from formic acid is infamous ("like stepping into a snowstorm") and can be persistent. Part of the treatment involves saturating alcohol dehydrogenase with ethanol.

      * The outbreak in Estonia from illegal alcohol: Clin. Tox. 45: 152, 2007). Fomepizole to prevent / reverse retinal injury in methanol poisoning: Am. J. Ophth. 134: 914, 2002. As an antidote, it is superior to ethanol (J. Tox. 40: 415, 2002).

    ISOPROPANOL ("rubbing alcohol", users are "rubby-dubs", etc.) is about twice as potent an intoxicant as ethanol, but really nasty to the gastric mucosa. Metabolized to acetone via alcohol dehydrogenase, and produces a modest anion gap acidosis.

      The hand sanatizer in the hospital probably contains isopropanol, and a bewildered patient may get sick by drinking it (NEJM 356: 530, 2007).

    ETHYLENE GLYCOL (anti-freeze) is metabolized to glycolaldehyde, glyoxylic acid, and oxalic acid. This stuff produces both a striking anion gap acidosis, and little crystals that carve up renal tubules, meninges, etc. Not a nice way to die.

      By federal law, all US ethylene glycol has added fluorescein, so the urine of an antifreeze-drinker fluoresces under your Wood's lamp. Handy in the emergency room.

      * A locally-produced cough syrup, laced with ethylene glycol, killed around 100 Haitians (JAMA 279: 1175, 1998).

{07016} ethylene glycol fatality; note crystals in the renal tubules

Ethylene glycol poisoning
Kidney crystals
KU Collection

    * As we finish the discussion of substance abuse: More underclass people die unnatural deaths in the days after the end-of-the-month check comes than in the days before the end-of-the-month check comes. The difference is explained by drugs and alcohol (NEJM 341: 93, 1999).

FIREARMS (Arch. Path. Lab. Med. 130: 1283, 2006)

Power grows out of the barrel of a gun.
      --Mao Zedong

An armed society is a polite society.

      -- Robert Heinlein

WebPath Tutorial

{07252} how an abrasion ring forms

Minuteman Statue

Click here for ideas about what is and is not a "just war." No one will agree with all the ideas.

Abrasion ring: Roughing up of the skin as the bullet pulls it inward; when the skin recoils, it will appear as an abraded ring around any entry wound.

Caliber: In the English-speaking countries, diameter of the bore of rifled small arms, in hundredths or thousandths of a inch, i.e., .357 is 357/1000ths of an inch across. Continental Europe uses a different system.

Firing pin: The part of the gun that strikes the cartridge when the trigger is pulled

* Gauge: Venerable term to describe the diameter of a shotgun bore. It's the number of lead balls of the diameter of the shotgun bore that together weigh a pound. Exception: The 0.410 gauge shotgun has a 0.410 inch bore.

Handgun: A low velocity (650-1400 feet/second) rifled hand-held weapon.

* Lands: Ridges ("rifling") on the inside of the barrel, imparting to the bullet a gyroscopic rotation around its long axis which stabilizes its flight

* Tandem bullet: One of the banes of medical examiners. A bullet misfires and remains in the barrel; on the next shot, two bullets enter at the same point.

* Magnum: Means nothing any more. Glamour term.

Primer: Explosive struck by the firing pin, which in turn ignites the gunpowder.

Secondary missiles: Fragments of bone or whatever struck free by a bullet, which then pass through, and damage, tissue as bullets do

Shotgun: A smooth-bore shoulder-arm weapon that fires a bunch of pellets plus plastic wadding.

Around 2/3 of the homicides in the U.S. result from gunshot wounds ("GSW"'s), and the gun is the U.S. male's preferred means of successfully committing suicide.

"The Duke"

Goya, May 3rd 1808
Goya, Execution of the Rioters

Right or wrong, genocide occurs only when the victims are unable to shoot back. European kings got much nicer when peasants were able to pierce armor using crossbows. Paul Revere's ride was prompted by a move by the British redcoats to seize the private arms of the Boston citizen's militia. And like it or not, private ownership of firearms remains a part of life in the US. Heavily-armed societies may have high homicide rates (Brazil, inner-city Los Angeles, South Africa) or remarkably low homicide rates (rural Alaska, Switzerland). Of course, if children or mentally-scrambled people have access to a homeowner's gun, everybody is in extra danger.

    * Currently, the "politically correct" stance for physicians seems to be to urge their patients to give up gun ownership. People even talk about such "firearm counseling" as a duty of the primary care physician (for example, South. Med. J. 103: 151, 2010, which points out the already-obvious fact that a gun in an unstable home is more likely to harm a family member than scare off an intruder). The push for mandating physicians to do anti-gun counselling sparked a media circus in 2011 and a Florida law.... But you already know this. Before you decide this is your duty, please read South. Med. J. 94: 88, 2001 about your possible liability issues should you use your position as a physician to pursue an anti-gun agenda.

If you, as a clinician, understand gunshot wounds, your documenting them may be great help in eventually preventing a miscarriage of justice. It's a topic that's important but gets missed in undergraduate medical education (AJFMP 24: 273, 2003).

    What really comes from the barrel of a gun? Flaming gas, soot (wipes off, "fouling"), unburned gunpowder, and a bullet. These can tell you how far the gun may have been from the victim.

Bruce Willis

      1. The flaming gas travels for a few inches and will produce a BURN. Carbon monoxide from the gas may impart a redness to the tissues surrounding an entry wound.

      2. The soot travels for a few more inches (6-7 with most handguns nowadays) and will produce a SOOT MARK ("fouling"), which you can wipe off. Take your photo, wipe, and re-photograph. Of course, soot may be missed if the body is washed or hair shaved prior to full examination. Future pathologists: Look for soot and blood spatter on the hand that fired the suicidal bullet. If it's not there, this may be a "clever" homicide instead.

        * Bullets are dirty things; a bit of smudge around an entry, most easily seen on light clothing, isn't soot and doesn't help determine the range.

      3. The unburned powder travels for up to a few feet (3 feet is usual for a handgun), and produces the POWER STIPPLING or POWDER TATTOO (not "powder burns", please; these are typically embedded in the skin so you cannot wipe them off). Ball powder gives bigger marks than the more common flake powder.

{07249} powder tattoo around an entry wound

      4. The bullet will enter (or graze) the body. If it enters, it will scratch the surrounding skin, producing the ABRASION RING.

        Obviously if the bullet enters at an angle, the abrasion ring will be thickest in the direction from which the bullet was fired.

    In order to get a reliable estimate of the range, the particular gun and type of ammunition must be test-fired. Future medical examiners: In looking for powder and soot, remember to check the clothing, too. Future pathologists: Silencers absorb much of the smoke and powder. Starship Troopers
    Starship Troopers

    TIGHT CUTANEOUS ENTRANCE WOUNDS: The muzzle is held against skin or clothing so tight that the gas, soot, and powder pass right through the broken skin.

      If the blast enters a confined space (i.e., a tight-contact gunshot wound against the calvarium or zygomatic arch), you'll see a star-shaped ("stellate") entry wound, as the skin is turned backwards and lacerated. There may be a muzzle imprint from recoil of the weapon.

    LOOSE CONTACT CUTANEOUS ENTRANCE WOUNDS: The muzzle is held at the skin, but not pressed hard against it.

      You'll see a small amount of soot at the edges, but there's no room for the powder to spread out for a dispersed tattoo. Again, there may be a muzzle imprint. Stellate bursting is less likely, but can occur.


      If the bullet wound isn't a tight contact wound, and there's no soot, the shot probably came from several inches away. If there's powder stippling, you're probably within a range of three feet or less. The more dispersed the powder, the greater the distance. Test-fire the weapon and ammunition again. The soot and/or powder tattoo may tell you the direction of the shot.

    DISTANT RANGE CUTANEOUS ENTRANCE WOUNDS: No powder, soot, or stellate blow-out. (Of course, if the victim was shot through clothing, check to see if there's powder or soot on the clothes.) French Connection
    The French Connection

    Most entrance wounds are round, or a bit oval if the bullet entered at an angle. An irregular shape suggests that the bullet had lost its spin (i.e., passed through something else before entering the body) and "wobbled" on striking the body.

    EXIT WOUNDS may be produced by primary or secondary missiles.

      Exit wounds can have any shape -- round, stellate, slit, crescent, etc., etc.

      Note that you won't see an abrasion ring here. One pitfall is a "shored exit wound", an abrasion around the exit wound due to the victim was leaning up against a hard surface or the bullet hitting an unyielding piece of clothing, i.e., a leather belt, JFK's collar and necktie knot, etc.) If there's still any doubt about entry vs. exit wound, look at the clothing and check for residue.


      As the bullet passes through the body, its energy is received by the tissues and dispersed in radial fashion. A temporary cavity is created with a diameter many times that of the bullet. Within 5-10 thousandths of a second, the cavity collapses, but the damage has been done. Organs that are not elastic (liver, spleen) are especially likely to be disrupted. The faster the bullet, the worse the damage. In injuries from rifles (except the lower-velocity .22 caliber type), most of the damage is due to the temporary cavity. A permanent cavity may remain behind.

      If the bullet exits the body, it will carry some of its energy with it, sparing the tissues. If the bullet yaws (i.e., tilts) as it enters the body, more energy will be dispersed over a shorter area. The configuration of the bullet, the length of the track, and the nature of the tissue struck all determine the seriousness of a bullet wound.

      Bullets may fracture bones. Wounds to flat bones (skull, sternum, rib) are usually beveled, with the direction of the cone pointing in the direction from which the bullet came (physics, with variations, J. For. Sci. 38: 339, 1993). Fractures of the skull often radiate from the bullet hole, and/or the supraorbital plates shatter like eggshells (the latter leads to "raccoon eyes").

      Note that real-life people who get shot seldom simply fall over, like they do in the movies. Leave medicolegal stuff (direction of fire, range of fire, number and sequence of shots fired, time and degree of disability) to us.
Goya Disasters of War

        As a matter of fact, if you spend time on the medical examiner's service, you'll be impressed how hard it is, generally, to kill a healthy young adult. Your lecturer once autopsied a gentleman who was stabbed through the heart, severing both descending coronary arteries and piercing the septum, and the descending aorta; the gentleman ran four city blocks before he fell down. Supposedly the brain can remain conscious for maybe 15 seconds after blood flow stops (ask Louis XVI).

      "Suicide by cop": J. For. Sci. 45: 384, 2000; Ann. Emerg. Med. 32: 665, 1998. Someone wanting to die does something to cause a police officer to shoot them. It is fairly common, and the reasons for the choice are obvious.

    SHOTGUN INJURIES (you can't just call these "gunshot wounds"; review Am. J. For. Med. Path. 28: 99, 2007)

      A close-range shotgun injury is the most destructive of civilian gunshot wounds. Why? (1) The weight of the pellets, and the energy in the gas, is very great. (2) The pellets almost never leave the body, so their entire energy is used damaging tissue. Close-range shotgun wounds to the head almost always cause it to burst. Close-range shotgun wound elsewhere recall cookie cutters.

      At greater distances, the shotgun pellets fan out. At 3-4 feet or so, the edges will be scalloped. At great distances, many will miss the target. This makes range the key to the severity of the shotgun wound.

      Shotgun pellets fan out on impacting the body, so you cannot tell the range from the x-ray. Look at high tightly-packed the entry wound is instead.

       At distances of two meters or less, the plastic / cardboard-cellulose wadding may end up in the wound. It's easiest to find on CT scan since it is radiolucent.

    * Air guns (bee-bee guns, blanks) can kill people, usually suicide gestures / "jokes": Am. J. For. Med. Path. 27: 260, 2006. A blank pistol, especially the new ones, will usually kill a person who fires it against his head just by the blast.

{07079} abrasion ring
{07080} abrasion ring
{07630} muzzle imprint
{07083} bullet fractured skull, note bevel
{07235} bullet fractured skull, note bevel
{07325} supra-orbital plate shattered
{07089} powder stippling ("tattooing")
{07033} powder stippling
{07090} bullet graze
{07091} shotgun wound, close-up
{07173} shotgun wound
{07229} mechanism of stellate tearing on close-contact entry wound
{07093} suicide, gun in mouth
{07095} powder residue on hand
{07132} gunshot wound and beating
{07102} through and through
{07111} stellate wound
{07231} stellate wound
{07034} exit wound
{07035} bullet through brain
{07171} histology of entry wound, with char
{48999} shot in the heart
Goya, The Same Everywhere
Goya, "The Same Everywhere"

Bullet through shoulder
Forensic autopsy

Bullet entry & shotgun entry wounds
Forensic autopsy

Bullet graze; shot from behind while
falling; abrasion ring inferiorly,
wrinkle wound superiorly

Bullet track through lung
Forensic autopsy

Bullet entry wound
Forensic autopsy

Shotgun wound to abdomen
Forensic autopsy

Beveled skull wound
WebPath Photo

Recovered bullet
WebPath Photo

Grooves from firing
WebPath Photo

Contact wound
WebPath Photo

Tight contact wound
Abrasion ring and muzzle imprint
WebPath Photo

Tight contact wound
Abrasion ring and great muzzle imprint
WebPath Photo

Loose contact wound
Smoke fouling
WebPath Photo

Gunshot wounds
WebPath Photo

Gunshot wound
Powder residue
WebPath Photo

Midrange wound
Powder tattooing
WebPath Photo

Midrange wound
Powder tattooing
WebPath Photo

Entry and exit wounds
WebPath Photo

Exit wound
WebPath Photo

Exit wound

KU Collection

Shotgun suicide

Gunshot residue
X-ray microanalysis
WebPath Photo

Handgun and rifle rounds
WebPath Photo

Rubber bullet impacts
(by history)
Human Rights Watch

Gunshot Wound
Civil War skull
Wikimedia Commons

    Multi-gunshot wound suicides (could have fooled somebody): AJFMP 10(4): 275, 1989. Suicide by gunshot while driving (the author correctly notes that more than a few auto "accidents" are actually suicides; AJFMP 10(4): 285, 1989).


    I've examined various writings from various sides, and have decided there's nothing too puzzling about it, at least from the standpoint of the pathology. "Oswald acted alone" probably isn't provable one way or the other, but the pathology is interesting.

    Lee Harvey Oswald, sharpshooter and left-wing kook, and/or companion(s), fired three shots from the Book Depository.

    The first bullet missed, struck the pavement, and sent a bit of concrete flying, cutting a spectator's face.

    The second bullet passed into the back of President Kennedy's right shoulder, produced a stress fracture of T1, came out the front of his neck just below the larynx (perforating his shirt collar and top of the necktie, which shored the edge leading the inexperienced pathologist to mistake this for the abrasion ring of an entry wound), then went through the right side of Governor Connally's chest, and ended up in the governor's thigh. If you say a single bullet isn't likely to do this kind of thing, you don't know what you're talking about.

    The president's upper body lurched and his arms flexed in reaction to the spinal injury, creating the impression that his head was being forced backwards by a shot from the front.

    The bullet was rolling when it struck the governor, which is why the entry wound was large.

    The third bullet struck the president in the back of the head, sending blood and 70% of the right cerebral hemisphere splattering. The entry wound in the back of the head was small, and the exit wound in the right parietal bone was six inches across. The head was first pushed forward, then the seizure and jet effect of blood and brains forced the head back, again creating the false impression of a shot from the front.

    Nobody looked at the president's back at Parkland, and they didn't notice the head wound until his heart had just about stopped completely. The guy who intubated him saw blood in the trachea, so a Dr. Perry did a tracheostomy. In doing so, he obliterated the neck wound, which he also unwisely speculated to be an entry wound.

    The autopsy was performed at Bethesda amid much excitement. It was a tough job, and it is clear from the report that the pathologists were not really allowed to do their job. Partly because of pressure from Bobby and Jackie, the pathologists did not shave the scalp around the head wound (!), did not examine the spine or describe the kidneys or adrenals (!!) or the clothes (!!!) or the neck organs (!!!!), and failed to note whether there was an abrasion ring around the entry wound from the second bullet. They claimed they could not establish the trajectory of the bullet that caused the back wound, and later speculated that something fell out on the way to Parkland.

      Bits of the parietal bone were later found on Dealey plaza, beveled out, confirming it was an exit wound.

    Back in the early Vietnam era (1963), the federal executive branch was secretive. The Feds impounded the x-rays and autopsy photos, and the pathologists had to rely on their own (faulty) memories for the positions of the head wounds. Some important evidence got shredded early-on. Things are better now with this aspect of government behavior, thanks mostly to the social changes of the later 1960's and early 1970's.

    The conspiracy theorists focus on reporting rumors, claims by cranks, idle speculators, and even obvious crazies, and failing to report other key facts. The single pathologist (Dr. Cyril Wecht) who dissents from the Warren Commission's report was already a longtime conspiracy buff.

    "Unexplained deaths of people connected with the assassination" mostly aren't unexplained. They are the unnatural deaths of crooked or nutty people, or the natural deaths of other people. The conspiracy buffs listed the people who died during the next few years and calculated the odds against all these people dying around the same time. This is a classic misinformation-artist's fallacy: Flip a coin 100 times, select only the times it came up "heads", then figure the odds against a coin coming up heads each of 50-or-so times. Anyway, many of the "unexplained deaths" were of people friendly to the Warren Commission and/or only peripherally involved. And after 30 years, no one has come forward to confess, nobody has been caught murdering witnesses (which according to the some of the conspiracy theorists has continued over the decades), and Oliver Stone produced his farrago of lies ("JFK") without being molested.

    People who know guns tell me that they don't believe that a lone assassin could have gotten off three shots so quickly. For more on the Kennedy assassination, see J. Am. Coll. Surg. 178: 517, 1994 (the governor's coat; the exit bulge was too small to have been produced had the bullet not passed through the president first); JAMA 267: 2791, 1992; JAMA 268: 1736, 1992; JAMA 269: 1540 & 1544, 1993. The neurosurgeons re-examine the case: Neurosurg. 54: 1298, 2004; and examine a new account Neurosurg. 53: 1019, 2003 -- both articles highly recommended. Most recent review reaches the one-shooter conclusion: Plast. Recon. Surg. 132: 1340, 2013.


{00155} coup contusion of brain; note cone shape
{07051} child abuse
{07036} car wreck

Stoning of Stephen
The Stoning of Stephen

Skull fracture
Car wreck
WebPath Photo

Car wreck
WebPath Photo

Depressed skull fracture
Historic specimen
Wikimedia Commons
    Tearing, shearing, and crushing. The amount of damage delivered by a blow from a blunt object varies directly with:

    • the force used in delivering the blow
    • the surface area that takes the blow (i.e., blows to the head do more mechanical damage than blows to the back; blows from a rounded pipe or a knob on a club do more damage than the side of a board)
    • Remember that kinetic energy varies directly with the mass and the square of the velocity. So the capacity to hurt someone is directly proportional to the mass of the object, and to the square of its velocity.

Lucy Liu

    ABRASIONS result from friction removing the epidermis, with little or no damage to the dermis. They heal with no scar. The pathologist will usually see a remnant of the epidermis at one edge.

Student Doc's Soccer Injury
Fibrin covers an abrasion

Motorcycle fatality

Corporal punishment

Corporal punishment

      Ante-mortem abrasions are reddish from inflammation and perhaps minor bleeding.

      Post-mortem abrasions are yellow, with a fibrin coating resembling parchment. A good rule is that if a wound has a yellow edge, it is post-mortem (why?)

{07064} abrasion

      An abrasion may be the only external sign of blunt force injury, which may have done serious internal damage.

      "Pressure abrasions", from vertical force, are common over the zygoma and the side of the nose and orbits when someone falls. "Patterned abrasions" may tell the nature of the object causing the injury (i.e., tire tracks, pipes, rings on a fist), or merely the clothing. "Nail scratches" need no description; "claw marks" are deeper, U-shaped lesions that have penetrated the upper dermis.

      * Future pathologists: Here's a system for dating abrasions under the microscope:

      • 4-6 hr... polys around vessels

      • 8 hr... polys under the scab

      • 12 hr... polys in the scab

      • 12-24 hr... polys finally fill the scab

      • 30-72 hr... epithelial regeneration begins

      • 5-8 days... good granulation tissue

      • 9-12 days... best epithelial reparative hyperplasia

      • 12 days... good collagen, vascularity of granulation tissue is regressing

      * And for hard-core pathologists dating skin wounds... (AJFMP 16: 203, 1995)

      • Fibronectin strings: First few minutes. Proved person was alive when it happened.

      • Fibroblasts positive for laminin or heparan sulfate: 36 hours minimum.

      • Tenascin, type III collagen: 2 days minimum.

      • Type V or VI collagen: 3 days minimum.

      • Type I collagen spots, fibroblasts positive for type IV collagen, basement membrane fragments positive for their typical stuff: 4 days minimum.

      • Type I collagen strings, fibroblasts stain for alpha-smooth-muscle actin: 5 days minimum.

      • Return of the basement membrane: 8 days minimum.

      • Smooth staining of the basal layer of the epidermis for cytokeratin: 13 days minimum.
      • Always present:

        • 13 days: Basement membrane fragments

        • 22 days: Good solid basement membrane.

        • 24 days: Smooth staining of the basal layer of the epidermis for cytokeratin.

      CONTUSIONS are areas of hemorrhage in soft tissue, due to ruptured blood vessels, due to blunt trauma. Same as a "bruise". Usually, we reserve "contusion" / "bruise" for cases in which the overlying skin is not broken. If it's palpable, it's a "hematoma".

        The blood in most skin bruises is mostly in the subcutaneous tissue. Bruises become more prominent with time, because the blood cells themselves (if they stay intact) and their liberated hemoglobin (if the leak or lyse) spread into the overlying dermis.

        Like abrasions, contusions may or may not be patterned. A patterned contusion, unlike most others, has most of its red cells in the dermis from the beginning, because the dermis was forced between protuberances on the impacting surface.

        Some purists say that a bruise is a contusion visible through the skin.

        It's easier to bruise loose tissue (your orbit) than tightly-woven tissue (your palm).

{07065} kid beaten with electric cord

      Don't mistake the "mongolian spot" or other pigmentation for a contusion. Remember that bruises show up better on light-skinned people, and that scalp bruises are often hard to see. If in doubt, incise the lesion.

      Colors of a bruise: Blue/purple --> violet --> green --> yellow --> vanishes. Sadly, the rate of color change is tremendously variable, and you can't use it to estimate the time of a bruise. One recent study (For. Sci. Int. 50(2): 227, 1991) found the only reliable rule is that yellow always means >18 hours. Uh, one of my skydiving bruises showed yellow at 16 1/2 hours.

      Pretty reliable: If the color has clearly not begun to change, it is less than 48 hours. If the color has obviously changed and become variegated, it is more than 48 hours.

      Unless there is a hematoma that will organize, histology will usually only show the presence or absence of hemosiderin in the bleed. (Complement isn't going to be fixed, so neutrophils won't be coming in). Hemosiderin, usually not present until 72 hours, may sometimes be present by 24 hours.

      Even heavy trauma may not produce a bruise. Conversely, bruises can be much larger than the object that produced them, due to stretching and avulsion of nearby vessels.

      A good rule is that a child who isn't walking shouldn't have a bruise. ("No cruise, no bruise.") After that, a kid living a full, happy life will often have several bruises.

      Factors making a bruise more severe:

      • Lax tissue (around eyelids; older people; those genetic connective-tissue syndromes)
      • Delicate tissues (children, older people)
      • Scanty muscle mass / obesity
      • Bleeding tendency (amyloidosis, alcoholism, hemophilia, aspirin-takers, patients receiving anticoagulants)
      • NOTE: Yes, you can produce a bruise on a newly-dead body, though with no blood pressure, it won't be as impressive as one produced by the same force in life. And post-mortem extravasation of blood can simulate bruising: AMFJP 19: 46, 1998.

        * Future pathologists: How to skin a body in search of contusions -- something you'll need to do if the person has died in police or prison custody AJFMP 17: 316, 1996.

      Advanced decomposition and livor mortis can produce lesions indistinguishable from contusions.

    LACERATIONS: Splits and tears of skin and/or soft tissue, due to stretching-shearing or crushing, on the body surface or deep inside.

{07070} blunt-thing wound
{07591} blunt-thing wound

Goya, Fight with Cudgels
Goya, "Fight with Cudgels"


      Don't mistakenly call an incised wound, produced with something sharp, a "laceration".

      To produce a good laceration, there must be something hard (usually bone) close beneath the point of impact. It's easy to lacerate your scalp or shin, hard to lacerate your abdominal wall.

      You can spot lacerations by their irregular, crushed, abraded, undermined, bruised edges, and the presence of elastic and connective-tissue bridges in their depths. It's usually (not always) easy to tell these from incised wounds; lesions produced by very dull knives or the edges of boards may produce difficulties.

      No, the shape of a wound doesn't tell the exact shape of the instrument that produced it. The classic example is the Y-shaped lesion produced by a metal rod.

      An "avulsion" is a laceration in which a portion of soft tissue has been ripped off the underlying fascia or bone, or an organ ripped off its attachments. The overlying skin may be ripped, or sometimes only a pocket of blood is created deep in the tissues.

      * Dog bites: J. For. Sci. 38: 726, 1993. The English lady who slept in the hospital with her pet rat that bit her and gave her abscesses: Br. Med. J. 309: 1694, 1994.


{07040} motor vehicle accident

Transected pulmonary artery
Car wreck
Pittsburgh Pathology Cases

      The costal arches provide more protection to older adults, in whom they have usually calcified. Younger people may have organ damage with little external evidence of injury.

      Ribs fracture because of (1) direct blows over one or more ribs; (2) indirect trauma from front-to-back chest compression (falls from a great height, getting run over, CPR); (3) pathologic fractures (metastatic cancer, primary bone disease); (4) child abuse (especially by today's savvy abuser who knows he/she can "blame the injuries on CPR" -- Am. J. For. Med. Path. 21: 5, 2000).

        For example, death in a "jumper" from a great height most often results from the broken ribs tearing the heart and great vessels to shreds and/or from transection of the aorta between the more mobile thoracic and less mobile abdominal portions.

      Problems caused by fractured ribs:

      • flail chest (i.e., breathing is made very inefficient because of paradoxical movement of a group of broken ribs)
      • lacerated intercostal vessels and hemothorax
      • lacerated lung and pneumothorax / hemopneumothorax (NOTE: A simple fracture of a rib is unlikely to damage the lung. However, at the time of injury, the rib can be displaced and do damage, then return to its normal location. Don't be fooled.)
      • penetration of the heart, great vessels (ribs 1-3), or diaphragm-liver-spleen (ribs 10-12).

      Fracture of the sternum usually results from steering wheel injury, people jumping on the chest, getting run over, or CPR injury.

      Seat belt injuries: J. For. Sci. 38: 972, 1993. You're still better off with it on than with it off. Listen to the safety ads: politicians realize that seat belts save lives, and (of course) money.


      Like indirect rib and sternal fractures, this most often results from steering wheel/dashboard injuries, falls from heights, people jumping on the chest, or getting run over. Blunt trauma to the heart is more common than incised wounds. Crouching Tiger Hidden Dragon

        A bruise to the heart may undergo necrosis, produce rhythm and EKG disturbances, and develop an aneurysm just like an acute MI.

        * The modern police weapon, a beanbag to stun and knock over perpetrators: Ann. Emerg. Med. 38: 383, 2001.

      A laceration of the heart may produce rupture (free wall, septal, papillary muscle, chorda). The left coronary artery or its plaques may be damaged, or a dissecting hematoma may be produced in the aorta or coronary system.

      Forcing the heart downward may rip the ascending aorta transversely. This usually happens in steering wheel injuries. Or the sudden compression of the heart may burst the ascending aorta. Or a sudden deceleration injury can lacerate the descending aorta just beyond the origin of the left subclavian artery. (How do you think that might happen?) If the vertebral column is fractured and dislocated, the aorta may be ripped. Tiny rips in the aorta may bleed late, or develop into post-traumatic "pseudo-aneurysms", with their walls composed only of collagen.

{03224} "steering wheel" aortic transection

Ripped aorta
Car wreck
WebPath Photo


      In addition to the familiar iatrogenic pneumothorax (positive-pressure respirators, needles in the chest), blunt trauma to the chest can rip the tracheo-bronchial tree or the pleura beneath a rib.

      If the lung is compressed while the glottis is closed, there may be several bursting ruptures of the lungs.

      TENSION PNEUMOTHORAX results when a bronchus or portion of pleura is ruptured and the airway communicates with the pleura. During inspiration, air is forced into the pleural cavity. During expiration, the flap closes, and air remains in the pleural cavity. Eventually, the mediastinal structures will be shifted away from the tension pneumothorax, compromising venous return to the heart.

      Rupture of the diaphragm from strong compressive force at or below its level is fairly common, particularly on the left, where the liver affords less protection.

      Future pathologists: In suspected child abuse, one favorite defense is "the child simply stopped breathing / choked and the injuries resulted from CPR". Each case must be considered individually. In-hospital CPR in kids without bleeding problems doesn't seem to cause retinal hemorrhages, and if they occur at all they're tiny (Pediatrics 99: E3, 1997). Old claims about CPR causing serious liver lacerations (NEJM 207: 500, 1962) reflect the era's ignorance about child abuse. CPR occasionally ruptures the stomach of a child, but beyond this, the injuries it causes children seem minor (Am. J. For. Med. Path. 21: 5 & 307, 2000).


      Even when there is no external evidence of trauma to the abdomen, the liver, spleen, or distended stomach or intestine can be lacerated. (The abdominal muscles are much more pliable; empty hollow organs move easily and are very difficult to injure by blunt trauma.)

      The liver is very commonly lacerated, by virtue of its consistency and placement. Any surfaces may be shattered, depending on the direction of the force. If there's fatty change, it's even easier to lacerate. Blunt-force injuries to the gallbladder and bile ducts are uncommon except in conjunction with liver injury.

Lacerated liver
Car wreck
WebPath Photo

{07145} fat embolus (oil red O, glomerulus)
{07148} fat embolus (brain capillary)
{07149} fat embolus (bone marrow in lung artery)


Cranach, Judith Victorious
Cranach, "Judith Victorious"

{07068} sharp-thing wound

No, 'tis not so deep as a well, nor so wide as a church door; but 'tis enough, 'twill serve: ask for me tomorrow, and you shall find me a grave man.

      -- Shakespeare's Mercutio

{07043} stab wound of head
{07072} stab wound
{07066} stab wound
{07071} stab wound
{07131} stab wound
{07031} stab wounds
{07160} stab wound, knife guard went in
{38252} stab wound of chest
{38256} stab wound of chest

Ronald Goldman's Autopsy
Text only
Not for young or sensitive viewers

Shark bite
From one of Uncle Sam's
cautionary websites

Nail gun mishap
Through orbit, no sequelae
Patient x-ray from NEJM

{53702} guy with "behavioral disorder"
{53703} knife swallowed by guy in {53702}

{07388} incised wounds
{07391} incised wounds


Stab wound
Single edged blade
WebPath Photo

Knife wound
Hilt mark
WebPath Photo

{07398} throat was cut
{07399} hesitation wounds

Incised wound

Defense wounds
WebPath Photo

Defense wound
WebPath Photo

Defense wounds
WebPath Photo

{07383} wrinkle wound

Sword Wound of Skull
NIH Historic Collection
Wikimedia Commons


{07045} suffocation

{12354} smothered?

Mechanical asphyxia
Conjunctival petechiae
WebPath Photo

{07213} candy corn occluding airway

Fatal acute aspiration
Bryan Lee

Tracheo-carotid fistula
Bryan Lee

Godfather I Godfather I

STRANGULATION: Occlusion of the blood flow and/or air passages in the neck by external compression. (If there is a contribution from body weight, it is considered hanging rather than strangulation).

{07056} petechiae in strangulation
{07074} manual strangulation

{07046} hanging

In JUDICIAL HANGING, the "client's" upper cervical vertebrae (C2, C3, and/or C4) are supposed to be broken and/or dislocated by a carefully-planned drop (* actually, doing this right is the exception: For. Sci. Int. 54: 81, 1992). The classic "hangman's fracture" is through the pedicles of C2, with hyperextension of the neck pushing C1 and the body of C2 into the spinal cord, causing instant death. Suicides won't be able to do this unless they have cancer, Down's (maybe), rheumatoid arthritis, or osteoporosis weakening the vertebral column.

Goya Hard is the Way
Goya, "Hard is the Way"

Death by Hanging
Dino Laporte's PathosWeb

Suicidal hanging
Source unknown
Not for young or sensitive visitors.

Suicidal hanging
Source unknown
Not for young or sensitive visitors.

Jonbenet's Autopsy Report
Boulder County Coroner
Text only

Hanging of Jewish civilians
Romania under Nazi occupation
WWII era

{07189} ligature strangulation
{10415} ligature strangulation (belt)

Goya interrogation scene
Goya, Interrogation by Mock-Strangulation

* Medical historians! Burke and Hare, old-time Scottish medical school anatomy department provisioners, decided that robbing new graves was too much work. They started obtaining the corpses of poor folks by "burking", i.e., sitting on the chest and occluding nose and mouth with their palms.

{07047} strangled by hand
{07137} strangled by hand

Strangled by hand
Ed Lulo's Pathology Gallery


{07013} carbon monoxide, acute; note the cherry-red livor mortis
{07116} carbon monoxide after-effects on globus pallidus

Carbon monoxide
Cherry red
WebPath Photo

{24922} burn
{46535} burn
{46536} burn

Deep Burn, Histopathology
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

Nanking, 1937

{07186} thermal injuries
{07103} second-degree burn histology
{07184} could be Curling's ulcers

DROWNING (Am. J. For. Med. Path. 27: 20, 2006 deals with children but is just as applicable to adults; NEJM 366: 2012, 2012.)

{07139} drowned; the foam is a mix of pond water and lung surfactant
{07147} drowned
{07027} decomposition speeded by warm water

Petrous bone hemorrhages
WebPath Photo

Plant material in airway
WebPath Photo



    High-voltage alternating current (i.e., 7680 volts, from the generator plant) kills by generating heat.

    Low-voltage alternating current (i.e., 110 volt household current) kills by inducing ventricular fibrillation; or if the amperage is high, the heart simply cannot re-polarize.

    C=V/R, where:

      C is current in amperes
      V is voltage in volts
      R is resistance in ohms

Maryland labor safety

Electrical burns are generally small, gray, charred marks with a grayish-white rim (blood was driven out, then vessels were seared closed). And in the large majority of electrocutions on household appliances, there is NO lesion found on autopsy.

    Death does not occur instantaneously after the shock, and the victim's last act may be to turn off the defective tool or remove the contact, making it much harder to recognize that this is an electrocution.

* {07519} ...and that one word were "Lightning!", I would speak.... -- Lord Byron

{07190} lightning wound
{07513} lightning wound
{07037} electrical injury and burn
{07107} electrical trauma
{07109} lightning death
{07504} lightning death
{07183} electrocuted
{07187} electrical injuries
{07480} electrical injuries
{07486} electrical injuries
{07495} electrical injury, where current exited
{11127} electrical injury, where current exited
{07537} lamp-in-the-bathtub homicide

Under given circumstances that surfaced, the results were far less than aesthetically attractive. But with rare serene exceptions, after forty-odd years of experience, it is held that most deaths are without aesthetic attractiveness, regardless of causation.



* Dr. Overman, past medical examiner of Jackson County, shared the following anecdote:

The danger of hypothermia is greatest when the victim is immersed in cold water. This was most strikingly demonstrated when the Titanic struck an iceberg in the North Atlantic. One hour and fifty minutes of the sinking, another ship appeared and picked up the survivors. There were enough life jackets on board for all 2,207 people. 705 people in lifeboats were rescued. All others who were in the water died. Virtually all of them died of hypothermia rather than drowning. At the time of the sinking, the water temperature was approximately 32 degrees F. The Coast Guard estimates that with the water temperature of less than 35 degrees F, the expected survival time immersed in water is less than 45 minutes.

"The Little Match Girl"
Death by hypothermia
/ child exploitation

Cold water

WebPath Photo

{07557} hypothermia


Marks from beating
Note edge contusions
Human Rights Watch

Marks from beating
Note edge contusions
Human Rights Watch

East Timor Human Rights Council Photos
Includes some of the now-famous photos taken by soldiers
and sold (!) to human-rights activists
Not for young or sensitive viewers



    While it is commonplace to dose a part of the body with 4000-5000 rads to kills cancer cells, a total-body dose of radiation will have the following untoward effects.

K192, the WidowMaker
Russian sub K-19, mostly-true story

The worst scandal in American forensic science was the case of Joyce Gilchrist, Oklahoma's forensic chemist, who on the evidence simply fabricated whatever evidence police and prosecutors wanted. Read about her here, here, here, here, and many more. West Virginia's Fred Zain left a similar record of falsified evidence in the 1980's.


{25532} x-ray burn

*  *  * 

Auschwitz Mass grave at Auschwitz

The ballot is stronger than the bullet.

        --Abraham Lincoln 5/19/1855

Who overcomes by force has overcome but half his foe.

        --John Milton, "Paradise Lost"

I am proud of the fact that I never invented weapons to kill.

        --Thomas A. Edison, NYT 6/8/1915

Vietnam War Memorial

Saving Private Ryan I think that people want peace so much that one of these days governments had better get out of the way and let them have it.

        -- Dwight D. Eisenhower, 8/31/1959

If any question why we died,
Tell them, "Because our fathers lied".

        -- Rudyard Kipling

          Formerly England's most popular pro-war poet,
          after the death of his son in World War I

*  *  * 


Violence usually begins with invasion of someone's personal space, respect, or dignity. Everyone feels entitled to these things, whether or not everyone else agrees.

Despite the attention given to RANDOM VIOLENCE, especially in our slums, in recent decades, most homicides are still committed by SOMEONE THE VICTIM KNOWS. The larger story of any homicide or suicide seldom shows the finer side of humankind. Your lecturer is no expert on security or crime prevention, but he's had considerable reading and professional experience relating to homicides.

The following suggestions will not make you immune to becoming a homicide victim, but will greatly reduce your risk of dying at the hand of someone you know:

Huckleberry Finn
Huck Finn

14. Children and teens: If the adults with whom you must live are abusive, pretend you love them anyway until you are able to escape safely. (The murders of non-gang teens, especially girls age 11-14, are typically by a parent "following an argument" -- Arch. Ped. Adol. Med. 157: 355, 2003). Revenge (or forgiveness) can wait -- survive for now, and you'll get your chance. Of course, this also applies in the much-described "intimate partner violence" situation -- today, most victims escape before being murdered thanks to the attention that the syndrome is (rightly) receiving. Nowadays in the US, only about 35% of murders of women are known to be intimate-partner violence (it was once probably much higher); around 6% for men. Worldwide, things are still less encouraging (Lancet 382: 859, 2013) -- for intimate partner homicides, there are six man-kills-woman for every one woman-kills-man. In murder by a present or past intimate partner, the woman's friends and children are likely to be killed as well.

There are social networks of violent people ("the knife and gun club") -- people who are socially networked with people with a history of violence are much more likely to be murdered (the African-American experience Am. J. Pub. Health 104: 143, 2014). Sociobiology in action: Living with a step-parent is the most powerful risk factor for child abuse yet identified. See Science 261: 987, 1993. A child in Canada is sixty times more likely to be murdered by a step-parent than by a parent: Sci. Am. 273(4): 174, Oct. 1995. Readers will not be surprised that in the US, infanticide is far more common if Mom is less than 17: NEJM 339: 1211, 1998. The mentally ill are much more likely that healthier folks to be murdered: BMJ 346: f557, 2013 (substance abusers ~9x, personality disorder without substance abuse ~3x, schizophrenia without substance abuse ~2x, etc.; this is not surprising.)

* Child-kills-parent: rare. Usually Dad is murdered, usually for being a control freak.

* In the townships of "the new South Africa", a child is almost as likely to be killed in cold blood (often shot to death, something that almost never happens in the U.S.) as he/she is to die in an accident (Am. J. For. Med. Path. 24: 141, 2003).

NOTE: Alcohol is a factor in a majority of homicides. Certain men, under the influence of alcohol, are prone to fire their handguns at other people for no reason. Even when there is some motive, a majority of murderers have alcohol on board at the time of the crime, and a majority of victims have alcohol on board.

NOTE: When there is a motive for murder, other than disputes among drug-culture types, sex is almost always involved, and usually somebody has insulted the murderer's pride in this particular area. The most classic of all non-underworld, non-underclass homicides is the man who kills the woman who left him.

* NOTE: There are around 20,000 murders yearly in the US (J. For. Sci. 42: 279, 1997). The one situation in which no doubts that the death penalty is a deterrent is to prevent the murder of a witness -- if someone has already committed a heinous crime, they have no reason not to kill the principal witness against them unless the threat of the death penalty hangs over them. "If a man kills one person, he's a criminal. If a man kills 100,000 people, he's a hero." Whether the violence is individual or institutionalized, violent people will surprise you by their selective delicacy of conscience. They may be crusaders for good causes and pillars of the local place of worship, exhibit extreme tenderness toward children, the sick, the elderly, and so forth. Hitler and Ted Bundy embraced vegetarianism, because they professed to abhor harming innocent creatures. Hitler was opposed to using animals for medical research. Lancet reports that since 1973, 139 people on American death rows have been exonerated after an average of 9.8 years in prison (Lancet 375: 1516, 2010). This doesn't surprise me.

* NOTE: Criminality has no easy explanation. The classic parents of a criminal (an alcoholic bully father, a hysterical pill-popping mother) are folks whom you'll meet soon enough, but many criminals come from "nice homes", and most brothers of hardened career criminals have no criminal records themselves. For decades, the social psychologists have insisted that "violent criminals suffer from low self-esteem", and based "treatments" on this ideology. A review team found that there was never been any empirical evidence that this is true. Having known a few, I tend to agree with the team that they are mostly big-ego types who have decided they are special, above the law (Sci. Am. 284(4): 96, 2001). Other "enlightened" explanations for criminality just don't fit the facts either: Poverty isn't the explanation, since self-reports of misbehavior correlate very little with class. Most poor folk are decent, law-abiding people who hate the criminals among whom they must live. Despite much effort, nobody's been able to demonstrate that police and courts treat blacks and whites differently if they've done the same bad things. Injustice isn't the explanation, since police, victims, and criminals all agree about what's right and wrong and what should be done with wrongdoers. A few traits of career criminals are well-known: (1) they socialized poorly as kids; (2) they were poorly supervised by their parents; (3) they are sensation-seekers and continually seek new excitement; (4) by any reasonable definition, they are racists; (5) they drink alcohol; (6) they have never been seriously interested in serious religion; (7) they suffer less from a bad conscience than do the rest of us. I would have added (8) they are demanding of everyone except themselves; career criminals are the worst crybabies. Most criminals learn early to cite past wrongs (personal, ancestral) to gain sympathy and special privileges. There's a review in Nature 368, 111, 1994. There's a adoption study that concluded that childhood misbehavior was mostly caused by the environment, but found that your number of adult convictions correlated better with convictions of your biological parents rather than your adoptive parents (!!; Lancet 345: 466, 1995; has a list of candidate genes). Studying behavioral genetics has been a problem historically. When Brunner's disease (mutant monoamine oxidase A producing mild mental retardation and outbursts of senseless violence) was described (Science 262: 578, 1993), the discovers were smeared by media for political incorrectness. This seems to have stopped.

* Easy, wrong answers: If "violence in the movies and on TV" is a major factor in our epidermic of violence (as suggested in JAMA 267: 3059, 1994), why is the murder rate 10 x lower in Canada, where they watch the same shoot-'em-ups? See Lancet 365: 702, 2005 (if there's a causal link, it's weak and hard to study); J. Ped. 154: 759, 2009 -- concludes violence in the media does not produce increased aggression. And if handguns are the problem, why is the murder rate similar in non-inner-city Canada (where murderers use knives and bludgeons) and non-inner-city areas our own states that adjoin Canada (where gun ownership is much higher, and the murderers use guns; see Am. J. Epidem. 134: 1245, 1991)? More on international comparisons: JAMA 263: 3292, 1990. In some US elementary and high schools, most of the students are armed with guns simply for self-protection, yet there are surprisingly few shootings, and the kids are far safer in school then outside. Although there is much less legal gun ownership in Sweden, there are still plenty of mass-shootings: AJFMP 19: 34, 1998. Murder rates per 100000 people per year worldwide: South Africa 75.3 (Am. J. For. Med. Path. 24: 141, 2003), Philippines 38, Lesotho 36, Jamaica 18, US 8, France 4, Britain 1.3, Ireland 0.5. Obviously there's something more than "guns cause murders". A Jamaican pathologist's perspective: Br. Med. J. 335: 1097, 2007. More easy explanations that aren't true... The familiar right-wing claim that more people have died violently since the 1859 publication of "The Origin of Species", and the familiar left-wing claim that "science leads to a devaluing of human life", both ignore the fact that the world is more densely populated today thanks to science (public health, fertilizer); nevertheless, Tamurlane probably killed as many people as Hitler did in his own era. The familiar right-wing claim that child abuse is a new phenomenon caused in particular by the decline in "family values" ignores the fact that physicians simply denied, ignored, or covered it up during the "good old days" before the 1960's. Reading about how we "discovered" why some babies have multiple fractures of different ages is chilling. Society calls for radical changes in the wake of shooting sprees (by loonies whose neighbors knew something was badly wrong, by high-school kids who were teased and ridiculed for years by their "well-adjusted" peers, and so forth). But at the same time, society goes gah-gah when honest scientists try to look at the impact of genes or brain chemistry on bad behavior, or when people talk about putting obviously dangerous, mentally-ill people in long-term institutional care. On average, 20% of welfare schizophrenics will commit a violent act and/or threaten someone with a lethal weapon during a six-month period (Arch. Gen. Psych. 63: 490, 2006; Am. J. Psych. 163: 1404, 2006), and for those who are rampaging around and having delusions of persecution, the risk is much higher; all that American society is able to do at present is either think of ways to keep particular individuals in jail, or leverage their welfare checks, which (2006) has the lawyers in an uproar. Diagnosed bipolars are also more than twice as likely as normal folks to be violent (Arch. Gen. Psych. 67: 931, 2010). Again, there are no easy answers.

* To compound the mystery... During the early 1990's, the rates for murder, assault, robbery, and burglary all dropped precipitously in the US. The causes remain obscure (Sci. Am. 290(2): 82, Feb. 2004). The epidemic of murder among black and hispanic men ages 14-24 peaked around 1991 (5x above the usual norms, 1 in 20 ended up being murdered by a peer in some communities) and is dropping, perhaps because crack use is being replaced by marijuana use, and marijuana dealers are a non-violent bunch (uh...?) Booming economy (timing's off)? Roe v. Wade causing fewer unwanted neglected children (timing's off)? More cops (NYC experience)? Concealed-carry (maybe)? More prisons with the bad people off the streets (uh, this isn't the "politically correct" answer, but it's the one I find easiest to believe)? Crime prevention as a public health measure is reviewed in Britain's Lancet 358: 1717, 2001; it holds America's ugliest statistics up for examination, and points what has worked and what hasn't; its explanation for the drop in our murder rate is the policy by the police to focus their attention ("by the book" or not) on the really bad people and the really bad places. The statistics (a 1% increase in prison population reduces murder by 1% and violent crime by about 2%) seem to confirm the common-sense idea that keeping bad people off the streets until middle-age settles them down is also helpful. Simply increasing the numbers of officers is supposedly less helpful, and the "zero-tolerance" nonsense (i.e., busting kids for having nailclippers or an aspirin) does no good.

* The sleepwalking defense after a violent crime: Nobody knows. See Am. J. Psych. 161: 1149, 2004.

* You heard it here first. Today's polygraph testing is considered by some to be reasonably useful especially for criminal investigations (JAMA 256: 1172, 1986 -- also deplores using it as the sole basis for screening your employees for crooks to fire), or as a parlor trick, mere salesmanship-and-subscience (NEJM 327: 122, 1992, Lancet 360: 1261, 2002, The fact that a bunch of Castro's people all beat the polygraph to go to work for the CIA some years back, tells something.) It is impossible to do really controlled studies, but my impression after 20 years hanging around criminal justice is that a polygraph operator with integrity and skill can usually give an accurate reading, and that not all operators possess skill-plus-integrity. The Japanese experimented with brain wave patterns that indicate whether a suspect recognizes, or does not recognize, a crime scene. Sounds interesting. For. Sci. Int. 51: 95, 1991. Brain mapping for deception and truth telling: Radiology 238: 679, 2006. More generally, your lecturer has fair confidence in the criminal justice system's ability to discriminate guilt from innocence, usually, with the unique exception of men falsely accused of sex crimes. This is what the inmates themselves told me in the 1980's, and my own experiences and reading bear this out. In today's political climate, an innocent man must often plea-bargain and even serve prison time (Science 256: 301, 1992; KC Star March 13, 1993; remember also Potiphar's wife Genesis 39:7-20). This has now become a public scandal, as happened with the "false memories" fiasco of the early 1990's and the ultra-bizarre, no-physical-evidence child-molestation witch-hunts ("Believe the children!") of the past 40 years. In the meantime, men, you must "love defensively", and you shouldn't even talk at all to a woman unless you know she isn't crazy. Of course, women have always known not to talk to a man until she knows he isn't crazy, because there is still plenty of real violence and abuse.

A man always finds it hard to realize that he may have finally lost a woman's love, however badly he may have treated her.

        "Sherlock Holmes", "The Musgrave Ritual"

Punch and Judy

* Punch-and-Judy have been considered funny, but domestic violence isn't. Wife-beating (and girlfriend-beating, and of course child abuse) continues epidemic despite the fact that it's receiving much more attention lately (as it should). About 1.5 million women in the US experience "intimate partner violence" each year (JAMA 288: 589, 2002; this is still too many though it may be fewer than you've been told). Around 10% of emergency room visits by adult women result from their getting beaten in an ongoing man-beating-woman situation (JAMA 1995; discusses the error in Am. J. Psych. 151: 630, 1994 by militant feminists who claimed the number was 35%). He is often an alcoholic bully or junkie with scrambled brains, but the stereotype doesn't always hold. Psychiatrists talk about insecurity as the basis for the habitual wife-bearer's part (gee whiz), and so forth. A small minority are sociopaths, i.e., charming, personable men who are incapable of acting from moral principles. While they were dating, she liked his aggressive, assertive style. Now she's sorry, but where would she go? Plus, she likes it when he apologizes and makes up each time (even after she has him arrested). If she is a nagger, things become even worse. When a man kills a woman, it's likely that this stuff has been going on beforehand. Both partners usually have lousy overall living skills, though sometimes the woman is well-educated and/or hard-working and just has poor people-skills. Because of politics, if she beats him, or both beat each other, or if he even grabs her arms to keep her from hitting or scratching him, the system still focuses on him as the problem. With the focus on "keeping the family together to keep Mom off welfare", the problem will get worse. Some of these people may be educable, for their sake and for the kids'. In the meantime, your first concern as a physician is the physical safety of the woman and children. Exactly what to do to help in the long-term is much tougher to know; getting women to shelters and to advocacy seems to help, nobody really seems to have anything that helps the men be better husbands / boyfriends, and there are risks of causing reprisals (JAMA 289: 589 & 601, 2003).

* Whether it's abuse of a child or a romantic partner, the behaviors of the abuser are pretty much stereotyped, and you will come to recognize the constellation.

The common denominator, of course, is that THE ABUSER FEELS ENTITLED TO LOVE, and has such poor living skills that he or she cannot get it any other way. Public discussions usually ignore this obvious fact, but understanding it may help you, the physician, help people make sense out of the vicious cycle. The crew at Galveston has finally gotten up evidence to show that, yes, beating a pregnant woman can give her preterm labor and chorioamnionitis (Am. J. Ob. Gyn. 170: 1760, 1994).


Suicide is a permanent solution to a temporary problem.

Here's a list of principal reasons people take their own lives. This pathologist's impression is that this is approximately the sequence from most-common toward least-common. It is not exclusive, but covers the large majority of cases. This list is among the greatest of all monuments to human stupidity and cruelty, typically by those surrounding the ultimate victim (there are exceptions).

      1. Failed relationship... (any age, either sex)

      2. Organic mood disorders... (young and middle-aged adults)

      3. Financial disaster... (adult men -- the Swedish experience during the recession Am. J. Pub. Health 103: 1031, 2013). The most malignant cause is problem gambling.

      4. Chronic poor health... (teens and adults, either sex; suicide in older folks is very often triggered by impending nursing home placement)

      5. Abuse (physical or verbal) by a parent... (older children, teens)

        * Turkish pathologists complain that teens are too sensitive when a 13 year old boy hangs himself after his parents slaughter and try to force him to eat his pet: J. For. Leg. Med. 18: 299, 2011.

      6. Fear of being a homosexual... (teens and up, mostly men; see Am. J. Pub. Health 92: 1338, 2002; nowadays it's most likely to happen if the person has been ridiculed / bullied by parents or at school or work: Am. J. Pub. Health 103: 70, 2013)

      7. Bad body image... (teens, younger adults)

      8. Schizophrenia... (teens and adults, either sex)

      9. Being arrested (trigger for suicide in high-achievers in difficult situations)

NOTE: Alcohol is a contributing factor to the crisis that precipitates the suicide in at least 1/3 of cases, probably more.

NOTE: Illegal drug use will exacerbate any of the above problems.

NOTE: The large majority of suicides have had no contact with mental health services, even though they are widely available and the easier and more convenient they are to access, the lower the suicide rate (Lancet 379: 981, 2012).

NOTE: In the developed world, the suicide rate among young men (ages 15-34) has been dropping dramatically since about 1993 (BMJ 336: 515 & 800, 2008; others). Your lecturer believes that this is because of the internet, where people can find friends, support, opportunities, and accurate information. The deadliest warning sign -- withdrawal from friends -- keeps the support system from functioning unless the friends are VERY alert. The availability of good antidepressant medications, and the hope they offer, probably contributes as well.

Reactive depression usually results from being dumped or being trapped; both are more depressing than the death of a loved one (Arch. Gen. Psych. 60: 789, 2003). In "conservative traditional societies", it is commonplace for a teenaged girl to commit suicide after being forcibly "married" to a man she hates (Am. J. For. Med. Path. 24: 214, 2003.)

You will accomplish nothing with the suicidal patient by simply listening sympathetically. Help them solve their current life problems, and learn problem-solving skills. Help them monitor their thoughts -- your feelings about your situation are perhaps valid, but you are not helpless, you do not need to be unlovable, you can tolerate distress even though it goes deep and is physical. Look at what you have done RIGHT so far, the progress you've made, and can you think of any advantages of being alive over being dead.

You can find something better than death everywhere.
        -- The Bremen Town Musicians

* Shakespeare's Hamlet in the soliloquy is asking "Is life worth living?" He calls death "the undiscovered country" from which "no traveler returns" despite (according to Shakespeare's sources) having recently talked with a ghost. This is probably intentional. Despite the trappings of supernaturalist religion, Hamlet could be any post-Age-of-Faith person considering suicide.

NOTE: AMONG PHYSICALLY-HEALTHY YOUNG PEOPLE WHO ATTEMPTED SUICIDE, FAILED, AND GOT APPROPRIATE FOLLOW-UP CARE, 99% ARE PLEASED, ONE YEAR LATER, THAT THEY FAILED. In the vast majority of cases, the situations that precipitate suicide of a person in decent physical health are temporary. For a more recent, pretty-much equally optimistic study from Vanderbilt, see J. Traum. 33: 457, 1992; in addition to the familiar truisms, intervening in crazy family situations seems to be critical.

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