DISEASES OF INFANCY AND CHILDHOOD
Ed Friedlander, M.D., Pathologist
scalpel_blade@yahoo.com

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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.

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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.

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Year II's: I know much of this is repetitious from other lectures and other courses. This creates a dilemma for me -- I don't like repeating material from other courses, and I don't like leaving you with chunks of "objectives" for which there is no handout text. Items with a "#" are those that I believe you already know from this or other courses, or will hear about at length in "Obstetrics" and "Pediatrics", but that you might profitably review at this time.

*  *  * 

      From childhood's hour I have not been
      As others are; I have not seen
      As others saw; I could not bring
      My passion from the common spring.
      From the same source I have not taken
      My sorrow; I could not awaken
      My heart to joy at the same tone,
      And all I loved, I loved alone.
      Thus, in my childhood, at the dawn
      Of a most stormy life, was drawn
      From every spring of good or ill
      The mystery that binds me still...

              -- Edgar Allen Poe, fragment

INTRODUCTION

    EMBRYO: An unborn child / product of conception with child parts for the first eight weeks after the moment of conception

      * Note the misuse of the term "embryonic stem cells" in the current culture-war business. The cells in question are from eight-celled fertilized eggs.

    FETUS: An unborn child / product of conception with child-parts (rather than just placenta), between eight weeks after conception and the moment of live birth ("all-the-way-out with a beating heart" for our lawyer friends).

      * "Partial birth abortion" ("intact dilation and extraction") was a bizarre and repulsive practice brought about itself by strange laws. What was being done was that in an abortion after 21 weeks, the brain was destroyed prior to delivery so as to prevent the unpleasantness of a crying, dying baby. The procedure itself seems to have been based on the curious fact that the law protects the life of a child when, and only when, it is fully delivered. The real purpose is to prevent the birth of profoundly defective children. The obvious alternative is humane, inexpensive care for these children while nature takes its course ("perinatal hospice"; Issues in Law and Medicine 13: 125, 1997) -- which was itself anathema to factions on both the Right and Left.

      Incredibly, "perinatal hospice" is a brand-new idea. Proposed in 2001 (Am. J. Ob. Gyn. 185: 525, 2001), it came into existence in the United States a few years later (J. Repro. Med. 7: 269, 2004) and is now evidently becoming the norm. Note the underlying political change -- the Far Right had the sense to stop demanding that all profoundly defective infants be kept alive at all costs. This is a major and (for me) a welcome shift.

      Although it was (thankfully) rarely practiced, partial-birth abortion became a test-case for abortion opponents. The question went to the Supreme Court: NEJM 344: 152, 2001. The court reaffirmed 5-4 the principle of Roe v. Wade that this isn't the government's business. However, Congress then banned the practice, and the Supreme Court upheld the ban on partial birth abortion / "intact dilation and extraction" in 2007. I suspect that the existence of neonatal hospice had changed the reality, hence the willingness of the Supreme Court to change.

      Since the decision, physicians who do late-term abortions (say, on a profoundly defective, doomed child) inject it with something lethal (digitalis, potassium chloride) beforehand.

    NEONATE: A child in the first four weeks of life after birth.

    INFANT: A child in the first year of life after birth.

    INFANT MORTALITY: For a population, how many of its people per 1000 live births die before their first birthday.

      In the US during the 1990's, it was about 7 out of 1000 babies (CMAJ 163: 497, 2000); today the CIA says 6.3 per 1000. Forty of the world's 222 nations do better than we do. In the mid-1900's, in the "developing world", which was most places, reported infant mortality rates were around 300-400 per 1000. Today there are only 11 nations where it is above 100; Angola is top with 182, and Afghanistan is third with 154 (CIA 2008)

      The scandal of infant mortality in the U.S., especially among poor black people: NEJM 327: 1022, 1992. Ten percent of babies born to black mothers receiving no prenatal care are very-low birth weight (see below). Wall St. J. tells it like it is 1/20/92, quoted in Pediatrics 92: A74, 1993. The racial disparity remains: Am. J. Epidem. 154: 307, 2001.

      Worldwide, reported infant and child mortality figures ("ten million children die each year, almost all of them poor": Lancet 362: 323, 2003) are likely to be much lower than the real numbers, because deaths are not reported. The governments do not care, and do not want the stigma of a high number, since it's obvious that they are not providing the simple interventions that could prevent most of the deaths (Lancet 362: 65, 2003).

      Not surprisingly, child mortality (ages 1-14) dropped tremendously between 1969 and 2000 in the US in all demographic sectors; the authors are dismayed that the gap underclass's figures did not improve porportionately, and that murder remains a terrible problem for underclass children; the overall numbers reminded me that science and social programs ultimately cannot overcome "cultural problems" (Am. J. Pub. Health 97: 1658, 2007).

    PRE-TERM: Born before 37-38 weeks. (Nowadays obstetricians like to try to wait until Baby is 39 weeks old, for the best possible development.) About one birth in ten in the US is preterm. Review Am. Fam. Phys. 57: 2457, 1998; long-term mortality and morbidity to adulthood Lancet 371: 261, 2008)

      The etiology is often obscure. There are many statistical correlations, few "why"'s that make sense...

      • birth defects involving the uterus

      • breaks in the membranes, with possible infection

      • placenta previa or abruption

      • smoking (Am. J. Ob. Gyn. 182: 465, 2000)

      • hypertension (Ob. Gyn. 91: 899, 1998)

      • sex during late pregnancy (??? Ob. Gyn. 97: 273, 2001)

      • bacterial vaginosis (???)

      • poverty (well-established; Br. J. Ob. Gyn. 106 1162, 1999)

      • very young or very old mother

      • Right now, a "usual suspect" is corticotropin releasing hormone ("from stress") causing prostaglandin production that in turn causes the uterus to empty. CRF levels are probably high long before the preterm labor. This makes sense, and might explain why glucocorticoid administration seems to help stop the process. See Am. J. Ob. Gyn. 186: 257, 2002; Science 304: 666, 2004.

        A group of pathologists has finally gotten up a study of placentas from preterm deliveries, and not surprisingly discovered that babies whose placentas display ischemia or infection did worse than babies with "idiopathic preterm labor" (Ob. Gyn. 94: 284, 1999).

      Nowadays a child born at 22 weeks will almost certainly die in the first six months.

      A child born at 23 weeks might survive but will almost certainly be profoundly brain damaged.

      A child born at 25 weeks has about a 3/4 chance of making it to six months and a better-than-half chance of not having gross brain damage on ultrasound (don't believe me, read all about it in NEJM 329: 1597, 1993). Still valid: Lancet 375: 1496, 2010 -- the "continuing ethical and economic debates about provision of neonatal intensive care show no signs of diminishing".

      Even preterm children born later are very likely to have serious disabilities as a result: NEJM 343: 378, 2000. Around 40% of children born 24-28 weeks, and around 30% of children born 29-32 weeks, needed special care by age 5 (Lancet 371: 813, 2008).

      Today's neonatologists are now talking about ethically unjustifiable interventions that maintain life without awareness (we may hope) or any ability to interact with others (obvious). Yet it is still common for children to be kept alive into the teenaged years, often on respirators and requiring round-the-clock nursing, often in status epilepticus. The economics of all of this is complicated, and ideology gets involved. The story of the far-right Baby Jane Doe laws, which were eventually overturned by the Supreme Court, makes disturbing reading. In the US, during most of the 1900's, such a child would impoverish the family, and earn lots of third-party money for the hospital. Nowadays, physicians here and overseas point out that these children consume resources that could go for children with better prognosis (or for profits), and are even making veiled criticisms of parents who demand that such children be kept alive (Lancet 355: 2112, 2000).

    POST-TERM: Both after 42 weeks.

    SMALL FOR GESTATIONAL AGE ("small for dates"): Below 10th percentile on the charts. The child did not grow properly in the uterus, and the organs will have extra problems once the child is born....

      PROBLEMS WITH THE UNBORN CHILD ITSELF

        Chromosomal problems

        Congenital infections ("torch")

          Toxoplasmosis

          Other (syphilis, varicella-zoster, TB, listeria, Chagas disease, a few rare effects of common viruses)

          Rubella

          Cytomegalovirus

          (Herpes, the "H", is usually not an intra-uterine infection)

          (Listeria, which like syphilis passes through the placenta, is less likely to produce actual deformities, though it can be very deadly)

        Other congenital anomalies

        Being conceived by the new reproductive technologies (?? doubles the risk even when you control for twinning ?? NEJM 346: 731, 2002)

      PROBLEMS WITH THE PLACENTA OR UTERUS

        Infarcts

        Tumors

        The thrombophilias (clots in the spiral arteries and between the villi of the placenta): Big news. NEJM 340: 9, 1999.

        Etc., etc.

      PROBLEMS WITH MOTHER

        Cocaine ("crack babies")

        Tobacco

        Opiate abuse

        Alcoholism

        Toxemia and other hypertension

    LARGE FOR GESTATIONAL AGE: Above 90th percentile on the charts. Think of maternal diabetes.

    LOW BIRTH WEIGHT: As it sounds; a mix of "small for gestational age" and "preterm". Caring for tiny babies is expensive, and the outcomes uncertain; statistics are hard to find, but . At school age, surviving low birth-weight children still show signs of damage in all health parameters except happiness (JAMA 267: 2204, 1992; same findings JAMA 289: 3264, 2003; a very long-term Norway shows substantially lower life achievement NEJM 359: 262, 2008; very modest improvements in the US from past eras NEJM 358: 2016, 2008.)

      Low birth weight: <2500 gm

      Very low birth weight: <1500 gm (1.5% of US babies fall in this category)

      Extremely low birth weight: <1000 gm (0.7% of US babies fall in this category)

        Brown U. analyzes the outcomes of extremely low-birth weight babies; basically no child under 500 gm turns out okay, while of the 500-100 gm babies, only 16% turn out "unimpaired" (i.e., see, hear, swallow, and walk normally; 62% of the children were badly disabled or dead: Pediatrics 124: 112, 2009).

      One third of infants that die are very low birth weight infants. Another third are low birth weight infants. The remaining third are of normal weight (NEJM 327: 1022, 1992).

      Although survival of low-birthweight kids has improved tremendously (thanks largely to surfactant administration), there has been no decrease in the numbers of these kids, and it remains closely linked to underclass status (Am. J. Pub. Health 85: 909, 1995). Survivors often need expensive long-term care (lung failure, brain damage).

      Historically, mandating intensive care even for invents with very poor prognosis has been a "social conservative" cause. This changed in the mid-1990's, with even conservative sources now talking freely about "societal concerns about the ethics and justification of intensive care for these infants" (JAMA 281: 799, 1999).

        *The Oregon Plan ranked extraordinary life support for very-low birth-weight Medicaid babies as the second-from-the-bottom on a list of "where does the health care dollar do the most life-enhancing good". Due to right-wing political pressure, the Bush administration decided (1992) that this constituted "discrimination against the handicapped", and the rest is history (Hastings Center Reports 22(6): 21, Nov.-Dec. 1992).

        * For children who do survive... Despite pressure to "do something", it is not at all clear that intensive "interventions to improve cognitive and academic abilities" for these kids do any good at all. See JAMA 277: 126, 1997.

        *You will often hear the claim that "prenatal care prevents low-birth-weight". One group at Ann Arbor studied women in the U.S. (where there's bureaucratic red-tape for a poor pregnant woman to get care) and Canada (where care's basically free and expected.) Poverty (i.e., underclass behaviors), not care, was the overriding risk factor for low-birth-weight (Am. J. Pub. Health 84: 986, 1994); I wish they'd sorted out the pre-term and the small-for-gestational-age kids.

    UTERINE CONSTRAINT to some extent was experienced by most of us beginning around our 35th week of intrauterine life. It's likely to be bad if the uterus is small, bicornuate, or loaded with fibroids, or if we shared quarters with a twin, had oligohydramnios (i.e., too little amnionic fluid, i.e., no kidneys, placental insufficiency, or a slow leak), or if we were positioned badly.

      If we were molded out of shape as a result of uterine constraint, we suffered a DEFORMATION (as opposed to a "malformation", and generally not so ominous; 2% of kids get a significant deformation). Most famous is OLIGOHYDRAMNIOS SEQUENCE, with squashed ("Potter's") face and badly bent limbs, and perhaps hypoplastic lungs.

Fetus papyraceus
Pittsburgh Pathology Cases

Renal tubular dysgenesis
Potter baby
Pittsburgh Pathology Cases

        ARTHROGRYPHOSIS ("joint claws") usually refers to a congenital situation with muscle contractures present at birth, is a relatively common, non-progressive symptom that can result from uterine constraint, CNS disease, or failure of certain muscles to develop.

        A variation on the theme of uterine constraint is the typical deformities (club feet, withered arms, Mobius) caused by uterine contractions in Latin American women who take prostaglandin because abortion is illegal (Lancet 351: 1624, 1998).

Oligohydramnios sequence
WebPath Photo

Oligohydramnios sequence
WebPath Photo

Oligohydramnios with pulmonary hypoplasia
WebPath Photo

Oligohydramnios with pulmonary hypoplasia
WebPath Photo

Meningomyelocele
WebPath Photo

Encephalocele with exencephaly
WebPath Photo

Anencephaly
WebPath Photo

Anencephaly
WebPath Photo

Anencephaly
WebPath Photo

    MALFORMATIONS result from chromosomal problems, genes of large effect, deletions of chunks of a chromosome, polygenic problems, or "just happen". They range from familiar, correctable problems like mild hypospadias to dread, lethal conditions like anencephaly.

      Occasionally the cause is more or less clear; timing is important. Around 3% of kids have a malformation that's at least of serious cosmetic importance (i.e., "a major malformation").

      The syndromes caused by deletions of chunks of chromosome are just now being characterized. Worth remembering: WT-1 complex (* formerly WAGR): Wilms' tumor, aniridia (no iris), growth problems).

      Here's a list of the common congenital malformations and their approximate frequencies:

      • common clubfoot -- 1 in 400 children ("Troy Aikman's disease")

      • patent ductus arteriosus -- 1 in 600 children

      • pyloric stenosis -- 1 in 600 children, more boys

      • ventricular septal defect -- 1 in 1000 children

      • cleft lip (with or without cleft palate) -- 1 in 1000 children

      • meningocele /meningomyelocele -- 1 in 2000 children

      • anencephaly -- 1 in 3000 children

      • atresia of anus or some other portion of the gut -- 1 in 3000 children

    HYDROPS FETALIS is severe edema of the fetus.

      Any cause of neonatal congestive heart failure (i.e., congenital heart disease, other birth defects compromising blood flow) or severe anemia (i.e., high-output CHF -- famous causes include both hemolytic disease of the unborn, the worst thalassemias, and parvovirus B19) can produce severe edema.

    Hydrops fetalis
    Intrauterine death from Rh disease
    KU Collection

    NEONATAL ASPHYXIA is an important cause of death and brain damage in babies.

      Causes:

        Placental problems

          Placenta previa (i.e., a low-slung placenta overlying the os)

          Abruption (i.e., a big bleed between placenta and uterine wall)

        Cord problems

          Compression (around neck, breech delivery, etc., etc.)

        Other (poorly-understood)

          Toxemia

          Prolonged rupture of the membranes

          Chorioamnionitis

          Etc.

      In fatal cases, the pathologist looks for squamous cells in the alveoli, meconium staining of the skin, and hyaline membranes in the alveoli (rather than the terminal bronchioles), as well as evidence of the exact mechanism in the cord, placenta, or dead child.

    BIRTH INJURIES:

      CEPHALHEMATOMA: Hemorrhage under the scalp ("subgaleal hematoma" for pathologists). Trivial; no known risks worth remembering.

      Subgaleal hematoma
      WebPath Photo

      CAPUT SUCCEDANEUM: Edema of the scalp where the head was pressed against the opening cervix. Trivial; no known risks worth remembering.

      INTRACEREBRAL HEMORRHAGES from dural sinuses or brain substance. The most important birth injury. Devastating.

{17430} intracerebral hemorrhage (this was a bleed into the ventricles from the subependymal germinal plate)

      UPPER EXTREMITY INJURIES: Fractured clavicle, brachial plexus injury (Erb's palsy, etc., etc.), fractured humerus

      FACIAL NERVE INJURY: Often from forceps (happened to Silvester Stallone)

      SKULL FRACTURES often result from prolonged labor where there is cephalopelvic disproportion, or from precipitous labor, or from inexpert use of the forceps.

    STILLBIRTH is most common in the poor and middle-income nations, and is much less common in the high-income nations than it was in 1940; in the US, it's most common among the poor and the most common definable cause is infection. (I suspect that the links to smoking and obesity may reflect other lifestyle risks.) Every stillborn should be autopsied and the placenta examined (Lancet 377: 1703, 2011); today we can also do microarray testing in search for known problem genes and at least 8.3% have an identifiable genetic abnormality (NEJM 367: 2185, 2012). * Future pathologists: Here's the progression of "maceration" after intrauterine death.

      Up to eight hours: Red skin only

      Eight hours to two days: Some skin slipping and peeling

      Two to seven days: Extensive skin peeling. There may be red-stained pleural and peritoneal effusions.

      More than seven days: Liver is yellowish; body may be mummified

CHILDHOOD MORTALITY

    In the U.S., around 1 newborn in 60 does not reach age 15. The majority of these are due to birth defects and prematurity. A significant minority (around 1 in 300) will die in an "accident"; the true number of deaths from "SIDS" and child abuse is probably similar (one kid in 6 coming to the emergency room is there because of injuries inflicted by an adult). Cancer kills around 1 child in 2000.

      CHILD ABUSE may be reasonably defined to be harsh treatment of a child sufficient to interfere with the child's functioning.

      Everybody knows about the cycle from generation to generation. Of child abuse victims, 1/3 will never abuse their own children, 1/3 will abuse their children with little provocation, and 1/3 may abuse their children when they, themselves, are stressed. It is simplistic to say either "it's willful misbehavior" or "it's society's fault". Am. J. Psych. 150: 1315, 1993.

      There are about 900 child-abuse murders in the US yearly; 65% of the assailants are men, 62% of the assailants are biological parents, and black children are killed at three times the rate of while children (JAMA 282: 463, 1999).

      Here are the twelve most common explanations offered by abusers, as compiled by the late Robert Kirschner MD of Cook County:

      • The child fell from a low height ("killer sofa")
      • The child and fell and the head hit something hard / something hard fell on the child's head.
      • The child was just found dead (when the age / circumstances do not match SIDS)
      • The child was choking so I shook / hit the child.
      • The child suddenly turned blue / stopped breathing so I shook the child.
      • The child suddenly had a seizure.
      • The child just stopped breathing and I did clumsy CPR.
      • The child was injured more than a day before death.
      • I tripped while I was carrying the child.
      • The sibling / dog did it.
      • I left the child in the bathtub for just a moment.
      • The child fell down the stairs.

      What concerns me about this list that it's just possible, in any particular case, that the explanation could be true. This is what makes prosecutions so problematic. Thankfully, there are usually other inconsistencies and/or other evidence of abuse. By contrast, if a decent person / family tells a consistent story that could fit with what you see, probably this IS an accident.

      * Pathologists may estimate the duration of the abuse by studying the thymic cortex ("stress"). See For. Sci. Int. 53: 69, 1992. I've tried this on a couple of my consultation cases and wasn't impressed.

      Even Dr. Plunkett, who's the expert to hire if you are accused of killing a child, agrees that the vast majority of cases that look like homicide are homicide. He's written recently on two cases of resuscitation artifacts where inept pathologists made overcalls (J. For. Sci. 51: 127, 2006 -- rarely CPR ruptures a childs' liver or spleen, good pathologists don't miss obvious asthma, DIC during the agonal hours can bring out apparent bruises).

      Contemporary wars are fought largely by our world's 300,000 child-soldiers (Lancet 363: 861, 2004), who in many cases are kidnapped, brutalized, introduced (often unwillingly) to drugs and rape, and given guns. The children are already bitter over their lives of hunger and menial labor, and are more willing than adults to adopt some stupid ideology or blame their neighbors who look and talk a little different. They are also more willing to take orders than adults, and more willing to throw their lives away. Update JAMA 298: 555, 2007. (This curious study found the worse the PTSD, the less willing the former child soldier is to forgive / reconcile / rejoin society. Which is the cause, and which is the effect?) More on child soldiers: JAMA 292: 553, 2004; Lancet 363: 861, 2004 (pseudo-Christian Ugandan rebels); JAMA 300: 691, 2008 (Nepal's Maoists); eight-session cognitive-behavioral therapy to treat survivors' PTSD JAMA 306: 503, 2011.

    The table in "Big Robbins" lists statistics that may be misleading. Here's what you need to know.

      The major killers of NEONATES AND INFANTS are PREMATURITY and BIRTH DEFECTS. Around 1.3% of US newborns die from these causes. As noted, most of the rest of the "modernized world" (including poverty-ridden Portugal and even Cuba -- CIA 2008) does better than we do, with fewer % underclass and better access to health care.

        As noted above, the causes of premature labor remain elusive, as is the mystery of why it's so much more common in the underclass (NEJM 399: 130, 1998).

        BIRTH DEFECTS cause death in abound 1 in 350 kids during the first year of life (Ob. Gyn. 98: 620, 2001). Numbers from around the world are variable; abortion of defective babies has dropped the overall infant mortality rate in Canada by about 20% (JAMA 287: 1561, 2002).

        In-vitro fertilization / intracytoplasmic sperm injection is reported to double the risk of a major birth defect: NEJM 346: 725, 2002)

        Also worth noting: "Sudden infant death syndrome" kills up to 0.5% of infants during the first year of life; the rate varies tremendously from community to community and from pathologist to pathologist.

        The real prevalence of infanticide is unknown and controversial; at least some are overlooked as "accidents" or "SIDS". The incidence is probably even higher in the Third World (even among "noble savages", and some cultures make no attempt to conceal it, even from the U.S. Left: Science 261: 987, 1993). Killing of little girls in Mainland China ("the people's paradise"): Child. Psych. 23: 53, 1992. At least 1 child in 50,000 in the U.S. is killed or abandonned at birth by their mothers: JAMA 289: 1425, 2003; society is starting to notice and to respond with Safe Haven laws. Abandonment of newborns in ultra-civilized Denmark: Foren. Sci. Med. Path. 7: 4, 317, 2011; 60% of mothers use a plastic bag.

        The perinatal autopsy: JAMA 273: 59, 1995.

      Ages 1-14: "ACCIDENTS" are the leading cause of death, outranking each category of disease by a substantial margin.

        CHILD ABUSE AND NEGLECT (apparently included among "other" in "Big Robbins") is an important killer among children. Again, the true prevalence is unknown and is controversial -- at least some are overlooked ("accidents" or "sudden infant death syndrome").

{39145} sirena ("mermaid baby"; lower extremities are fused)
{09883} sirena
{09888} amnionic band syndrome
{09889} amnionic band syndrome
{18245} omphalocele, failure of abdominal wall to form around umbilical cord

Conjoined "Siamese" twins
WebPath Photo

Conjoined "Siamese" twins
WebPath Photo

Sirena
WebPath Photo

Macerated fetus with phocomelia
WebPath Photo

Amnionic band syndrome
WebPath Photo

Amniotic (amnionic) band syndrome
WebPath Photo

Omphalocele
WebPath Photo

Very large omphalocele
WebPath Photo

Gastroschisis
WebPath Photo

Syndactyly
WebPath Photo

Congenital absence of
the abdominal muscles.
From a Saddam-era Iraqi
propaganda website (!)

Congenital absence of
the abdominal muscles.
From a Saddam-era Iraqi
propaganda website (!)

Ichthyosis "Collodion baby"
From a Saddam-era Iraqi
propaganda website (!)

Syndactyly
From a Saddam-era Iraqi
propaganda website (!)

Hydrocephalus, untreated
From a Saddam-era Iraqi
propaganda website (!)

Severe midline facial defect
From a Saddam-era Iraqi
propaganda website (!)

Sirenomelia
"Seal baby"
Wikimedia Commons

Sporadic phocomelia (?)
From a Saddam-era Iraqi
propaganda website (!)

      Older teens: The classic causes of death...

        Males: (1) ACCIDENTS

            (2) HOMICIDE (this might be first now)

            (3) SUICIDE

        Females: (1) ACCIDENTS

            (2) CANCER

            (3) HOMICIDE (this recently surpassed suicide; you'll find varying statistics)

      Most sources will give you these or similar statistics. Most recent statics: Am. J. For. Med. Path. 29: 208, 2008. During the past quarter-century, the homicide rate for kids increased about 70%; this is almost entirely teens shooting other teens (Pediatrics 97: 791, 1996; JAMA 280: 423, 1998; Acad. Emerg. Med. 4: 248, 1997). This is largely but not entirely among African-Americans and Hispanic Americans; rates have dropped by almost half since the mid-1990's: Prev. Med. 27: 452, 1998. Each year in the US there are about 6500 teen suicides. Suicide remains rampant among American Indian teens (Soc. Sci. Med. 53: 1115, 2001; Lancet 355: 906, 2000; Arch. Ped. Adol. Med. 153: 573, 1999).

Newborn's pneumonia
Premature rupture of membranes
WebPath Photo

IMMATURITY: Please review the section in "Big Robbins" if you are interested in knowing how newborns' tissues differ from other folks'.

    LUNGS:

      20 weeks: The large airways end in blind pouches, never reaching the mesenchyme where alveoli will form. This sets the famous "lower limit" on the age at which a child can survive outside the womb.

      26 weeks: Alveolar type epithelium (type I and II pneumocytes) starts to form

    KIDNEY: Remember you'll see glomeruli still forming under the capsule in a term infant. (Future pathologists: Look closely at this "blastema"; Wilms' tumor will recapitulate it.)

    BRAIN: Very soft in the newborn, but adequate for homeostasis. Preemies have trouble coordinating their autonomic nervous system functions. Even in the term infant, the gyri are still forming, and many centers lack myelin.

      It's very clear nowadays that simply being outside the womb before you should be causes damage to the brain.

      Barring catastrophic ischemia or hemorrhage, the key lesion is loss of oligodendroglia that have not yet myelinated (Arch. Dis. Child. Fetal/Neonatal 93: F153, 2008). No one really understands how this happens.

    LIVER: Getting born jolts the liver into activity after a few days, but during the process, newborns almost all become a bit jaundiced (inadequate glucuronyl transferase at birth). This is worse in smaller babies and especially preemies.

    ADRENAL: Don't expect to see the usual three cortical layers in a newborn. It's mostly the "fetal zone", which involutes during infancy.

GALACTOSEMIA

    Three autosomal recessive inborn errors of metabolism, of variable severity. Both feature elevated blood galactose. These are often confused, and tend to get missed during classical pathology courses, and are discussed here.

    The not-so-bad kind of galactosemia is usually caused by lack of galactokinase. Kids get cataracts only (probably from galactitol (dulcitol), by analogy with the sorbitol cataract of the diabetic).

{18241} galactosemia cataract

    The bad kind of galactosemia is usually caused by galactose-1-phosphate uridyl transferase deficiency. Probably it's galactitol (dulcitol) that causes the cerebral edema and brain damage (J. Ped. 138: 260, 2001).

      Fortunately this is rare (maybe 1 in 40,000 kids), and all 50 states screen newborns.

      The classic story is a child is born normal, is fed milk, and fails to thrive. Jaundice, diarrhea, vomiting, and sleepiness develop. They are followed by enlargement of the liver and spleen, failure of the liver (biopsy shows fatty change, cholestasis with the liver cells arranged around bile plugs like flower petals, and eventually cirrhosis) and by the development of cataracts. Finally somebody notices that "Clinitest" shows "sugar in the urine", but "the dipstick" doesn't.

      In the past, we've probably overtreated this disease by restricting fruits and vegetables with mere traces of galactose (Arch. Dis. Child. 89: 1034, 2004).

{20137} liver in galactosemia, architecture isn't normal

      Eventually, there is multi-system failure. The proximal tubular cells fail ("Fanconi syndrome", with aminoaciduria), and the leukocytes fail to control bacteria, with gram-negative sepsis a common mechanism of death. In adults who survived galactosemia, the ovaries tend to have atrophied.

      Affected kids are taken off milk, with improvement in their labs and liver histology, and arrest of the disease. There is not, unfortunately, reversal of the brain damage that has already occurred.

      The allele itself seems to have at least as much to do with the severity of the long-term brain damage as does the effort made to keep the disease under control after diagnosis. See Arch. Dis. Child. 83: 248, 2000.

      * Distinctive for survivors is "verbal dyspraxia", i.e., the inability to coordinate the elements of speech ("nose" may be pronounced "zone", "music" may become "mukis", and words are scrambled). Read about it in Pediatrics 88: 346, 1991.

CYSTIC FIBROSIS ("CF", "mucoviscidosis"; Lancet 373: 1891, 2009)

    This common mostly-white-peoples' genetic disease (1/2500 births) is caused by homozygous lack of a membrane component essential to proper chloride / bicarbonate transport across membranes of the mucus-producing exocrine glands and eccrine sweat glands in response to cAMP.

      The disease is named for changes in the pancreas and mucous salivary glands, which have their ducts plugged by viscous mucus. "Cysts" form behind the plugs, and "fibrosis" ensues after years of obstruction.

      Heterozygotes have minimal symptoms (i.e., they are a bit more wheezy than normals, on the average; see Thorax 42: 120, 1987), and it's been known for years that they enjoy a relative resistance to chloride-secreting gram-negative intestinal infections, allowing natural selection for the gene. And surprise! CFTR is the typhoid bug receptor, homozygotes are completely immune, heterozygotes much protected Nat. Med. 4: 663, 1998). The disease is rare in black or oriental children.

    The locus for the disease (chromosome 7q), its normal product, and their place in biology were discovered in the late 1980's by Francis Collins and his team (Science 245: 1059, 1066 & 1073, 1989; Thorax 45: 46, 1990; Science 256: 774, 1992).

      In health, increasing cAMP levels open ("activate") the apical chloride channels in the airway epithelium. This causes chloride to flow out, and water follows. In cystic fibrosis, cAMP fails to activate the chloride channels.

      The gene product is the transmembrane regulator of the passage of ions through the chloride channel, and expression of the good gene (but not the bad alleles) cures cystic fibrosis at the cellular level (Nature 347: 358, 1990).

        In fact, expression of the gene opens chloride channels, even in recombinant, non-epithelial cells (Nature 352: 628, 1991).

        The healthy gene is named "CFTR" (cystic fibrosis transmembrane regulator). Its expression in tissues: Nature 353: 434, 1991. Exactly where it sits in relation to the rest of the chloride pumping apparatus is still unclear (Proc. Nat. Acad. Sci. 88: 5277, 1991).

          * Other functions are being discovered (i.e., it plays a role in exocytosis: Science 256: 444 & 530, 1992).

          * Rare CF-phenotype patients have normal CFTR: NEJM 347: 405, 2002.

      Studying the gene has confirmed clinicians' impression that mild forms of cystic fibrosis caused by one or two "mild" alleles are common (NEJM 323: 1685, 1990; "why" Nature 362: 160, 1993). Interestingly, some male heterozygotes and some men with only mild mutations are healthy except for absent vas deferens (JAMA 267: 1794, 1992).

        * Could Chopin's illness have been a milder allele of cystic fibrosis (Med. J. Aust. 147: 586, 1987)? Your lecturer finds this persuasive. In his era, those with the full-blown illness did not reach adulthood.

      * The CF recombinant mouse: Nature 359: 211, 1992; Lancet 340: 702, 1992.

        The mouse did not get lung disease, but a newer mouse does: Nat. Med. 10: 453 & 487, 2004.

        *  Interestingly, in the new model, it's accumulation of ceramide (!) in the respiratory tract that seems to cause much of the damage. Watch for new therapies based on this (Nat. Med. 14: 382, 2008; Am. J. Resp. Crit. Care Med. 182: 369, 2010).

        Pig model: Am. J. Path. 176: 1377, 2010.

    The clinical syndrome is complex and reflects the underlying pathophysiology.

      The sweat glands perform normally, but chloride is not reabsorbed through the sweat ducts. Hence, these children's sweat is excessively salty. This forms the basis for the old midwives observation that "a baby that tastes salty when you kiss it will die in the first year", and the modern-day "sweat test".

        *Allele with lung disease but a normal sweat test: NEJM 331: 974, 1994.

      In the bronchial epithelium, the defective chloride pump fails to excrete water into the bronchial lumens. The lumens become plugged by super-thick mucus, and lung infections (Staph. aureus, Pseudomonas aeruginosa, and Berkholderia species (formerly Pseudomonas cepacia / "mucoid pseudomonas) occur again and again, with pneumonias, lung abscesses, bronchiectasis (i.e., chronic, never-healing ulcers of the airways that increase dead space), etc. Death comes through respiratory failure from scarring, an intractable infection, pneumothorax, or massive hemoptysis.

        The pseudomonads in an individual patient seem to evolve over the years, with changing patterns of virulence over the years (Am. J. Resp. Crit. Care Med. 180: 138, 2009).

        * Berkholderia is handled by normal people's lungs using CFTR, which apparently causes it to enter the epithelial cells and get destroyed, something of a surprise, and unusual for a bacterium (Proc. Nat. Acad. Sci. 94: 12088, 1997).

        Obviously the damage to the airways is mediated by inflammation. Update on the cell and molecular biology: Chest 133: 489, 2008.

      Newly recognized as a pathogen in cystic fibrosis, perhaps almost as important as Burkholderia, is Pseudallescheria boydii (Arch. Path. Lab. Med. 130: 1843, 2006.)

      Even in the absence of infection, the airways of patients with cystic fibrosis remodel. The walls thicken, and in particular there is a proliferation (though not differentiation) of mucous glands 174: 1018, 2006). This is the focus of much work, with a resurgence in interest in biopsy work (Chest 131: 1710, 2007). "Cystic fibrosis as a mucosal immunodeficiency syndrome" Nat. Med. 18: 509, 2012.

{11075} cystic fibrosis, lung (see the pus / mucus)
{10139} cystic fibrosis
{20076} cystic fibrosis, lung
{20077} cystic fibrosis, lung (see the mucus plugs)
{26249} cystic fibrosis, lung
{41466} cystic fibrosis, x-ray

Adult cystic fibrosis
Mucus and muciphages
KCUMB Team

Adult cystic fibrosis
Bronchiectasis
KCUMB Team

Cystic fibrosis
Bronchiectasis
KU Collection

Adult cystic fibrosis
Neutrophils and DNA
KCUMB Team

Adult cystic fibrosis
Mucus in bronchus
KCUMB Team

Adult cystic fibrosis
Survived into her 60's
KCUMB Team

      In the pancreatic ductal epithelium, chloride secretion also fails (* Ignore "Big Robbins" on bicarbonate), pancreatic ducts become plugged, and the pancreas undergoes atrophy. Malabsorption and vitamin deficiencies (notably vitamin A and K deficiencies) result.

        Some alleles are harder on the pancreas than on the lung; why this should be is not clear (NEJM 323: 1685, 1990; Lancet 336: 1081, 1990). Others seem to spare the pancreas and intestine: Am. J. Hum. Genet. 51: 245, 1992.

        Secondary diabetes from destruction of the islets occurs in a few percent of these patients (update J. Ped. 142: 97, 2003); when it happens, it is ominous (J. Ped. 152: 540, 2008).

{08854} cystic fibrosis, pancreas
{08855} cystic fibrosis, pancreas

      Those salivary glands that produce mucus (i.e., all but the parotid) may show some degree of plugging and atrophy, and the saliva of cystic fibrosis patients is more salty than healthy people.

      The intestinal crypts also secrete a certain amount of chloride (Gastroenterology 101: 1012, 1991). Babies may have bowel obstruction due to thick mucus ("meconium ileus", etc.; affects around 5-10% of these babies); the lack of pancreatic enzymes in the gut doesn't help either.

{20078} meconium ileus, gross
{20079} meconium ileus, cross-section
{20080} meconium ileus, microscopic

Meconium ileus
WebPath Photo

Meconium ileus with peritonitis
WebPath Photo

      Despite references in pathology books to cystic fibrosis as an important cause of cirrhosis, only around 5% of patients suffer this complication (Arch. Dis. Child. 66: 698, 1991; update Arch. Dis. Child. 81: 129, 1999) and rarely die of it. The cause, of course, is plugging of the bile ducts.

        There's a locus for risk of serious liver disease at -- of all places -- the alpha-1 antitrypsin, with the Z allele conferring the risk (JAMA 302: 1076, 2009)

    Cystic fibrosis is a particularly cruel disease, causing the lingering deaths of teenagers and young adults.

      In the old days, these children all died in infancy. Today, the life expectancy of a cystic fibrosis patient is around 25 years, but there are many variables. Pancreatic enzymes can be replaced, lung infections treated, and meconium ileus treated.

      Thanks both to better care and increased recognition of milder cases, around half of cystic fibrosis patients nowadays are over age 18 (JAMA 298: 1787, 2007).

      Almost all cystic fibrosis patients eventually suffer from recurrent lung infections with cumulative scarring. The typical patients spends two weeks in the hospital several times per year. Teens with cystic fibrosis become familiar friends, hold "prom" on the wards, etc., etc.

      Males with the disease are usually infertile ("plugged vas" is the old story; while the vas is typically absent in a man with CF, it's now clear that CFTR plays a role in spermatogenesis; see Nature 353: 434, 1991). Females have diminished fertility; CFTR is expressed in the uterine epithelium.

      Today, various screening protocols are worked out, involving immunoreactive trypsinogen in a blood spot taken on day 4-5 of life, coupled with gene analysis (Br. Med. J. 302: 1237, 1991).

    A number of novel treatments for cystic fibrosis are in use or on the horizon.

      Recombinant human DNAse I unclogs secretions nicely (JAMA 267: 1947, 1992; NEJM 326: 812, 1992; marketed in 1993 as "Pulmozyme"). You will appreciate on histology how much DNA is present in the plugs, and how the tangled threads must contribute to their viscosity.

      * Ivacaftor, which miraculously relieves the disease in the 4% of patients with the G551D mutation, may be a promise of more to come (Lancet 379: 1475, 2012).

      * The common-sense idea of inhaling mannitol, which absorbs water by osmosis into the plugs: (Chest 133: 1388, 2008). The common-sense remedy of inhaling hypertonic saline seems to be another big help (NEJM 354: 229, 2006). A variety of medicines, including iboprofen and azithromycin, have been used empirically as modulators of inflammation.

      Lung transplantation became part of the treatment of cystic fibrosis in the mid-1980's (Thorax 46: 213, 1991; J. Thoracic Cardiovasc. Surg. 101: 633, 1991); 5-year survival was around 50% during the 1990's. Obviously, this is simply changing one hard-to-manage illness (cystic fibrosis) into another (transplant recipient who must be immunosuppressed and still has cystic fibrosis everywhere else), and a big dose of reality was delivered by NEJM 357: 2143, 2007 -- the numbers don't really show improved survival.

      In March 1993, a mouse was reported cured of cystic fibrosis by gene therapy (Nature 362: 25, 1993; unborn mouse Lancet 349: 619, 1997).

      Various trials of gene therapy of cystic fibrosis is underway, using retroviruses to place the functional gene into the respiratory epithelium. Results in 2004 were encouraging, though one needed to have the vector given by aerosol frequently (Chest 125: 509, 2004). Keep your fingers crossed.

      * Trying to get the good CFTR gene into the lungs without using a retroviral vector: Lancet 353: 947, 1999.

    Antenatal diagnosis of cystic fibrosis is now available.

      In people of northern European ancestry, the allele delta-F508 (which lacks three base pairs) is the most common variant. (Milder alleles were soon discovered: Lancet 337: 631, 1991). CFTR made by this gene is not taken to the plasma membrane (Nature 358: 709 & 761, 1992). Of course, it can be detected using the polymerase chain reaction or other techniques. Prenatal detection of delta-508 was announced in 1990 (NEJM 322: 291, 1990). Of course, many more alleles have been identified and become available.

      We can now detect most heterozygotes. Despite lots of early nay-sayers, mass-screening is now a reality among the Ashkenazi in the US (long-accustomed to screening for Tay-Sachs and Gaucher's): Arch. Int. Med. 158: 77, 1998. Finding one case costs $11,000 dollars (Lancet 356: 789, 2000). The lifetime cost "to society" is $800,000 (JAMA 279: 1068, 1998), and the respiratory care alone costs around $40,000 per year, with deoxyribonuclease actually bringing costs down (Ann. Pharm. 34: 304, 2000).

      * The case against screening: JAMA 263: 2777, 1990. This is still a good read. The author of this fascinating article points out the massive ignorance of grammar-school math and science among parents and clinicians. Remember this, whether or not you agree with the author's rejection of screening for CF.

      Only around 20% of parents of young children with cystic fibrosis say they would abort a second child with the disease (Am. J. Pub. Health. 81: 992, 1991; of course, they haven't seen what it will do to their kid yet). Pre-implantation testing of test-tube babies for CF: NEJM 327: 905, 1992. The awful human impact of cystic fibrosis: "Shattered Dreams", Discover, July 1988.

      * Although most people with chronic nasal sinus trouble have normal CFTR genes, mutated CFTR is much over-represented among them, making their sinus disease a forme fruste of cystic fibrosis (JAMA 284: 1814, 2000). Watch for more on this.

CHILDHOOD TUMORS

    Children get different cancers from adults.

    Basic cancer biology successfully predicts that cancers would be much less common early in life, when there's been less time to accumulate mutations. However, it's hard to explain why any cancers would be more common in children than in adults.

    The explanation must be that these cancers arise from cell types that adults have lost. And again, this fits with what you can see for yourself. Wilms' tumor arises from blastema, and neuroblastoma from neuroblasts, both of which you can easily find and see to be dividing in a healthy baby. Both cell types lose their mitotic potential and vanish soon after birth.

    We know this is true of neuroblastomas, which often "mature" into benign masses of nerve-like tissue. Probably the high curability of Wilms' tumor and acute leukemia in the young also results from the last few cells losing their mitotic potential (and/or undergoing apoptosis) just as if they'd never turned malignant. Remember we now cure around 77% of cancers in children under age 15 (NEJM 351: 145, 2004).

    However, we haven't yet identified the genes to explain this. Stay tuned.

    Here are the tumors worth remembering at different ages:

      Age 0-4

      • acute lymphoblastic leukemia

      • retinoblastoma

      • neuroblastoma ("often present at birth")

      • Wilm's tumor ("seldom present at birth")

      • hepatoblastoma

      • embryonal rhabdomyosarcoma

      Age 5-9

      • acute lymphoblastic leukemia

      • retinoblastoma

      • Ewing's sarcoma

      • medulloblastoma and juvenile pilocytic astrocytoma (infratentorial)

      Age 10-14

      • Hodgkin's disease

      • osteosarcoma

      • alveolar rhabdomyosarcoma

      • papillary carcinoma of the thyroid

{08455} sacrococcygeal teratoma

Nasopharyngeal teratoma
WebPath Photo

*  *  * 

When young lips have drunk deep of the bitter waters of hate, suspicion and despair, all the love in the world will not wholly take away that knowledge.

      -- Rudyard Kipling, "Baa Baa Black Sheep" 1888

Joany Phony [Joan Baez]: Oh, look at all those poor orphans! I'm going to stop right here and donate ten thousand dollars!
Li'l Abner: In money?
Joany Phony: No, in protest songs!

      -- Al Capp, "Li'l Abner", 1967

* Politicians will interfere with your ability to be a good doctor for children. This is as true in the United States as anywhere -- in fact, the UK's venerable Lancet (perhaps not altogether fairly) wrote about the Bush administration's weird handling of child health as if we were a third-world kleptocracy (Lancet 369: 799, 2007).

Children do not vote. When politicians and ideology get involved, children are almost always big-time losers. I would like to cite five examples. You can add others.

1. "The War on Poverty!" In the early 1960's and the decades before, only 10% of children in the U.S. were born out of wedlock. These children were typically put up for adoption, and since 10% of couples are infertile, this worked out nicely. Thanks largely to "compassionate social policies" that make it far more lucrative and immediately-gratifying for girls to have babies than to go to school, get jobs, or get married, one third of U.S. children were born out of wedlock from the mid-60's through the early 90's. Dad had a strong disincentive to stay around, since Mom got more money if he disappeared. At the crack houses, "mothers' day" meant the day the welfare checks came. By the mid-1990's, even the Far Left had to agree that the status quo wasn't the best we could be doing for our children, and the rest is now history. I noted with pleasure in mid-1999 that with the loss of government incentives to have children out of wedlock, the illegitimacy rate had dropped spectacularly, and the US teen pregnancy rate was suddenly lower than it had been in a century. It's hard not to see this as cause-and-effect. The numbers (though not the "why"'s): National Vital Statistics Reports 48: 1, 2000.

2. Pious-rightwing "get tough on crime" politics: As a volunteer in criminal justice in Tennessee in the mid-1980's, I learned that there was (of course) no money for child protective services, but that there was plenty of money to protect society from "dangerous kids". The system would take a kid in an abusive or neglectful home situation, find him guilty of something, and put him in reform school. This also seemed to be the rule nationwide, particularly for black youngsters (Am. J. Orthopsych. 61: 578, 1991). I cannot think that the long-term results of this policy are salutary.

3. Intellectual-leftwing "multiculturalism and diversity" politics: In 1972, the social workers framed a major policy document stating that allowing white families to adopt a black child was "a form of genocide". The result was many white families eager but unable to adopt a black child, and around 50,000 black children at a time chronically institutionalized, almost all of whom could easily have been placed if legal barriers to timely transracial adoption had not existed. When the debate was re-opened in the early 1990's, the black community was divided. Rev. Jesse Jackson and others argued that it was more important for every child to have a stable, loving home. Other leaders and organizations (including, regrettably, Ben Chevis's N.A.A.C.P) argued that it was more important that every child grow up sharing not only minority group identity, but especially minority group resentments and hostilities. I am not making this up. See, for starters, K.C. star op-ed 1/2/94. For a scathing critique of the "mental health" pseudo-expertise at the heart of this fiasco, see Bull. Am. Acad. Psych. Law. 19: 339, 1991. See also Child Welfare 70: 477, 1991, Am. J. Orthopsychiatry 67: 568, 1997 (the kids do great), and the references in Am. J. O., above. The Multi-Ethnic Placement Act (1996 thanks Bill) prevent federally-funded organizations from interfering with transracial adoptions and foster-care, but it was widely ignored, with social workers writing no-data articles about how bad it is (for example, Social Work 43: 104, 1998). Only in the early 2000's did academia start coming out strongly in favor of "humanitarian values" (their word) and enforcing the 1996 law: "We need to instill respect for all minority cultures while also incorpo rating them into the larger culture that oneday will appreciate the values of tolerance and diversity (J. Am. Acad. Psych. Law 34: 303, 315 & 321, 2006 -- from Yale Med, Harvard Med and Vermont med schools respectively -- none noted for conservatism). I say that mainstream society already for the most part respects its minorities and their special contributions and experiences; you may disagree.

4. In modern warfare, it is commonplace for governments to deliberately put their own children where they are most likely to be killed. This is of course done to obtain media coverage and sympathy, in the hopes that "compassionate peace-loving peoples around the world" will let the tyrants get their own way. Every informed person is aware of this, and I have always been surprised that neither "liberals" nor "conservatives" raise much fuss over it. The Viet Cong practice of placing anti-aircraft guns atop schools and hospitals was succeeded by Saddam Hussein's use of "human shields" during the first bombing of Baghdad. More recent examples come from the Middle East and Sri Lanka.

5. Here's a tale from Brown, your lecturer's alma mater, where the students were and maybe still are overdosed on "cultural relativism":

In the past year, [child abuse survivor and ethics professor Richard Cheit] has often wondered whether he can go on teaching ethics. "They're such moral relativists", he says of his students. "In the midst of this whole thing, one of my seniors asked, 'Aren't these moral taboos just cultural constructions? Isn't incest bad just because we think it is?'" (U.S. News Nov 29, 1993, p. 63).

6. This could not happen, or even be considered, in the United States (in fact, I didn't see it in the papers), but in 2008, the Australian government declared a state of emergency and turned the reservations for its "indiginous peoples" into police states because of rampant child abuse and rampant sexual assault. The description in Lancet 371: 108, 2008 also talks bluntly about "the tedium of life on welfare in tiny, remote communities, and the resultant diabetes, hypertension, cardiac disease, and mental illness."

* Being a sick kid in the U.S. is always difficult. The worst part, for many of them, is the isolation from peers. Being a healthy school kid in the U.S. isn't always easy, either. Before you decide that a kid with school phobia is "a victim of secret sexual abuse" or has "attention deficit disorder" or whatever's the current fad in psychiatry, remember that today's schools are full of gangs, guns (in some communities, kids reportedly have to carry them just to travel safely to and from school; guns in the schools Arch. Ped. Adol. Med. 151: 360 & 555, 1997, Arch. Ped. Adol. Med. 153: 21, 1999, just before Columbine), bullies (suddenly discovered as a problem: Br. Med. J. 310: 274, 1995; Child Abuse & Negl. 22: 705, 1998; J. Child Psych. 39: 533, 1998; JAMA 285: 2094, 2001; Br. Med. J. 323: 480, 2001; Arch. Ped. Adol. Med. 161: 78, 2007 (systematic review of how schools can and cannot stop it -- kids who are crippled or otherwise different are singled out for torment), and a percentage of moronic-cruel teachers. Yes, getting bullied (or having fun being a bully) can and does cripple people emotionally and socially in the short-term (Pediatrics 118: 130, 2006) and evidently for the rest of their lives (Arch. Gen. Psych. 63: 1035, 2006). Bullied kids are much more likely to self-harm as teens -- but the ones who do are much more likely to also be physically (not just verbally) abused by the adults in their lives (go figure -- BMJ 344: e2683, 2012; article concludes that since it's impossible to stop bullying by peers or abuse by parents, the psychiatrists are working on ways to help these kids "cope more appropriately with their distress"). Violent deaths at school: JAMA 275: 1729, 1996. The most celebrated school shootings were by boys who had been ridiculed and bullied viciously (Sci. Am. Sept. 1998). Weakling Michael Carneal, who opened fire on a "prayer fellowship" in Kentucky, had been ridiculed, bullied and threatened by members of the group (though he did not shoot his chief tormentors); one "Christian" responded to the boy's cry for help a few days earlier by threatening to beat him up: US News Dec. 15, 1997; the facts are still being challenged. If you have ever gone hungry because your lunch money was stolen, or had your homework or art project maliciously destroyed, or been unable to use the bathroom because you would get roughed up, you can perhaps understand. The Left ("Let's spend a lot of somebody else's money for a course in conflict resolution!" "Differences must be tolerated and encouraged!" "Schools should be a place where values are clarified!"), despite their general interest in finding "victims", have always ignored the bullies. (There is zero evidence that "teaching conflict resolution", the 1990's fad, was anything but a cruel sham: Sci. Am. Sept. 1998). The Right ("D.A.R.E."; "I don't think they should teach ANY science until college"; "Schools should be a place where family values are taught") have always ignored the bullies. Doc: Pre-teen won't tell why he's afraid? Ask about shyness in the group shower. Public schools have long been dominated by politics and ideology, so that today, especially in poor communities, teachers have no incentive to teach well, and students have no (or negative) incentive to learn well. In the inner cities especially, longstanding attitudes about education have reduced the schools to mere day-care centers. Of course, this feeds into the cycle of non-achievement and hopelessness that shouldn't be part of any kid's life, but is. Sooner or later, somebody needs to claim "victim" status on a talk show or a sentencing hearing "because I was never forced to do homework as a kid, and now I'm stupid." In the area of science education alone, the impacts of both far-Right and far-Left have made the United States the laughing-stock of the world scientific and educational community. Today, there's even a bureaucratic procedure whenever a student bored into fidgeting because of hours of passive and rote learning gets "recommended for Ritalin therapy" by a teacher. (Ritalin, i.e., methylphenidate, is now known to work in the same way on anybody, whether or not they "have A.D.D."; it enables anybody to stay focused on a boring task, and present estimates are than 10% of U.S. grade-school boys are on the stuff: Br. Med. J. 312: 657, 1996.) I was in grammar school in the 1950s, and I remember left-handed kids being punished for writing with their left hands. That's how stupid and cruel it gets. Since then, I've watched most-if-not-all of our young people's problems blamed (more or less successively) on the international communist conspiracy, teaching evolution, non-conformity, food additives, "elitism", dyslexia and "minimal brain dysfunction", refined sugar, "secular humanism", attention-deficit disorder, all-pervasive-yet-imperceptible vicious racism, cow's milk, multicultural insensitivity, grading students instead of "focusing on building their self-esteem", not teaching radical Afrocentrism, multiple chemical sensitivities, and secret-forgotten sexual abuse. Simplistic (when not totally wrong), and proposed/attempted solutions (which are always part of somebody's political-economic agenda) are just as dumb. The 1990's mandate to remove asbestos from school buildings is now universally recognized as having been a colossal waste of money. And I think most educators today will tell you that today's entitlements for children with special needs have grown far in excess of what is reasonable, and interfere seriously with teaching reading, writing, and arithmetic to the healthy children. Read at your leisure about the "Individuals with Disabilities Education Act" of 1975, a strange federal law that mandates that even profoundly-handicapped children get priority in education, using your money that Congress promised but never appropriated. It became a bureaucratic nightmare for everyone involved, and some states simply stopped complying. "No Child Left Behind" mandated states show improved results from special education programs, without specifying how. From the mid-1980's to the mid-1990's, there was a monumentally stupid fad to ban (not just de-emphasize) the study of phonics and teach reading by word-recognition only (i.e., kids aren't allowed to sound-out words, but must guess what they are from context. This was a repeat of the "Why Johnny Can't Read" fiasco of the 1950's. It was a dumbing-down abuse of the "Whole Language" model, it clearly explains the sharp rise in U.S. illiteracy in the past ten years, and it finally was banned in California in early 1997; California was the center of the no-phonics fad, and the good citizens of the state were dismayed when it resulted in their children's reading scores plummeting to second-to-the-bottom in the US. I predicted the disaster in 1985. In 1998, after Congressional hearings, even the National Research Council (Feds) came out with a statement that kids learn best if they learn phonics too. During the stupid fad, savvy parents bought phonics packages for home-teaching. The fiasco in retrospect: Sci. Am. 286(3): 84, 2002. "Bilingual education", long a cornerstone of education in communities with many Hispanic members, is recognized today as having been another disaster. After "Saving Private Ryan", two different teens on two different occasions asked me, "Why were we never taught in school about D-day or what the second world war was fought about?" If it got covered at all, it's not sticking. The perennial desire is for "the schools to teach values", which, if they're not taught in the home and backed up by tough-love discipline, get nothing but lip service (and after-hours ridicule) from savvy children. As a country in which only 17% of us grown-ups say grace with our families at meals, only 33% show up at weekly services, but 80% of us want our children to be taught to pray the classroom, I'd say that we grown-ups are getting what we deserve when 12-year-old kids rob us at gunpoint. You may disagree. As a physician, you are educated to recognize bad science and emotionally-based foolishness. You may wish to take an interest in your local public schools.

Too many textbooks and discussions leave students free to make up their minds about things.

              -- Mel Gabler, Texas "conservative" textbook critic

* Regrettably, concern with child abuse (sexual and otherwise) has become the preoccupation of the lunatic fringes (right, left), tending to discredit others who want to do something about this very serious problem. When we come to CNS, we'll discuss the "hypnotically-enhanced memories" fiasco of the 1988-1995 era, in which amateur and pseudo-professional psychotherapists convinced troubled people that their fathers or some other man had molested them bizarrely over many years, and hundreds of families were broken up, lives were ruined, men were sent to prison, and so forth. However, if an activist wants to "find" horrid, weird, secret abuse in a day care center, hypnosis isn't even required. Kids are extremely suggestible, and even "experts" are notoriously unable to agree as to whether a child's story of common-style sexual mistreatment is credible, and what's the future risk (i.e., it ain't a science, folks; Bull. Am. Acad. Psych. Law. 218: 281, 1993). In the contemporary witch-hunt, once one student makes one accusation, some community nut (on the lunatic fringe of the "Christian right", "New Age", "child protective advocacy", "feminist", and/or "recovery" movements) takes up the cause, the rest of the kids are told they are "in denial", and they get grilled repeatedly for months by "therapists" and prosecutors until they "remember". As any doctor knows, the best way to get the truth during an interview is to ask open-ended questions; activist "therapists" typically do just the opposite. Eventually, preposterous, constantly-changing stories emerge ("He slaughtered a giraffe in the kindergarten room" is typical), innocent people are put on trial, lives are ruined, and so forth (New Yorker 10/3/94). There have been over one hundred such trials, almost all of them extremely long and expensive. The prosecutors (who aren't always stupid) may realize it's all rubbish, but must continue the prosecutions for political reasons. The "therapists" always say "Believe the children! Believe the children! You are victimizing them again if you don't believe them!", never explaining why they don't believe the children originally when they say nothing happened. At least one acquitted defendant was murdered afterwards by a vigilante. The same kind of thing happened at the Salem Witch trials of 1692, where 20 people were put to death (19 hanged, one tortured to death) on the testimony of a group of children, ages 5-12. Case law, which is very sane, deals only with procedural stuff, and leaves the decision about the child's testamentary capacity to the judge (Supreme Court White vs. Illinois 1992, Coy vs. Iowa 1988). Children have enough problems with gangs, drugs, crime, and honest-to-goodness abuse (i.e., almost always in the home). We ought to stop coercing them into making up stories of abuse.

* "Family values!" is a positive-inferential term that means many things to many people. As politicians (liberal, conservative) make political capital by decrying Joe Camel and dirty pictures on the internet ("Protect our children! Protect our children!"), around two million kids silently leave home for the streets, or otherwise become homeless, each year (see, for example, Pub. Health. Rep. 108: 150, 1993). On any night, there are at least 100,000 kids living on the streets, separated from their families. Some are "runaways". Many are "throwaways". Most are something-in-between. Almost all are escaping intolerable family living situations (Hosp. Comm. Psych. 43: 155, 1992). Most support themselves on the "street economy" (MMWR 42: 873, Nov. 19, 1993) by panhandling, petty crime, the drug trade, and/or prostitution. (I use the "politically-incorrect" term without apology to the Left. The term "commercial sex work" implies a certain dignity and work-satisfaction that child prostitution doesn't possess. Child prostitution around the world: Lancet 359: 1417, 2002. A large minority of runaways, male and female, turn to prostitution; of course the "academic" literature refers to these kids as "sexually delinquent".) The Right talks about "protecting the family and the authority of parents" and offer no humane solutions whatsoever. (I note with hope the new emphasis of the conservative "Promise Keepers" on not being physically or verbally abusive with your family, while at the same time demanding decent behavior. Newt's orphanages sounded like the best idea so far to me -- ask me why, if you want.) The Left will usually suggest trendy-lucrative "drug, alcohol, and AIDS counseling" and some also offer their brand of political indoctrination. Actual effective help for these kids (who are mostly mistrustful, recalcitrant, and lacking in useful skills) comes from apolitical private individuals and agencies and mainstream religious organizations. There's plenty written about these kids; if you're going to do primary care and/or care about children, spend a few hours at a big medical school library and read up on the problem like I did. Runaways-throwaways tend to come from violent, abusive families in which kids are offered little opportunity for autonomy or individuation (gee whiz, Adolescence 28: 867, 1993). Adolescents are every bit as likely to be beaten by their parents as are younger kids; not surprisingly, these kids are mostly not paragons of virtue and social responsibility, and interestingly, people at protective services are likely to say that getting beaten is the teen's own fault (JAMA 270: 1850, 1993). It is impossible to please an abuser, since their behavior results from their own internal problems. Until the partner / kid figures this out, life is horrible and the guilt gets internalized. Abusers typically say, "We / my partner / you spoiled the child." Examined in the cold light of reason, the decision by many girls to run away seems to be itself the result of clear thought and reflection: Adolescence 27: 387, 1992 (i.e., neither the far-Left nor the far-Right, despite all their talking, are willing to actually do anything to protect her from incest or whatever). Suspect incest when a parent (usually the father) is "overprotective" of a child, severely restricting outside activities; often these abusers are big on "family values" and right-wing anti-everything "spirituality". Not surprisingly, street teens are typically unable to read ("thank you, Today's Educational Establishment"), and those who can aren't much inclined to read things, in particular pamphlets on AIDS prevention (Pub. Health Rep., above, gee whiz Uncle Sam.) Government AIDS education projects for street kids seem like a total flop to this reviewer: MMWR 42: 873, 1993 for the statistics; Pub. Heath Rep. above agrees (gee whiz). An elaborate program based on "educational theory" intended to prevent kids from taking sexual risk was a total flop: Br. Med. J. 324: 1430, 2002; so was a massive intervention to educate girls not to get pregnant: Br. Med. J. 324: 1426, 2002 The current ideology in the child-protection business is "Don't break up the biological family; give everybody lots of counseling instead". ("Elisa Izquierdo syndrome"). That means more money for trendoid-counselors and of course less money spent overall; does it work well? Of course not. Adults who beat up children are not reasonable people interested in benefiting from psychotherapy. Children know it's a sham and become bitter. Some workers in the trenches, where it really matters, testify that the current system simply isn't reaching kids in need or doing what it's supposed to do: J. Adol. Health 12: 555 & 576, 1991. There is, of course, no real access to health care for runaway kids, for example, if they're HIV-positive (J. Adol. Health. 12: 504, 1991). One statistic I could not find is how many "sexually delinquent" street boys were thrown out of their homes for "being gay" in the first place (pseudo-conservatism strikes again! -- this is NOT what "family values" means to most of us), but this fiasco is extremely common (J. Adol. Health 12: 515, 1991; homosexual orientation is almost never a deliberate choice, a fact which is ignored by right-wing adults trying to make political capital at these kids' expense. A teenaged boy who believes he is gay often has a choice, particularly in a "conservative moral home", of being ridiculed and beaten regularly by his parents (J. Consult. Clin. Psych. 62: 261, 1994) and suiciding or running away: JAMA 275: 1354, 1996.) It is extremely difficult to provide effective social services for these kids, since they are pawns in the culture war (left vs. right: Child Welfare 73: 291, 1994; Child Welfare 85: 361, 2006); there are only a few programs ("transitional living" to get one's life together and one's skills up: Child Welfare 85: 385, 2006). Fewer than half of adolescent male prostitutes have had normal sex with a woman (J. Adol. 14: 229, 1991). The pop wisdom that being molested sexually typically has major long-term pervasive adverse consequences is now being challenged (Psych. Bull. 124: 22, 1998) -- when the impact of a crazy home is controlled for, the effect of sexual abuse largely disappears. (This is the famous article that the US Congress unanimously "condemned"; common-sense told me the authors went too far in their rhetoric, even if their data is okay.) This is not to say that sexual contact between adults and children isn't wrong or that it should be treated lightly. It is also part of our world. According to the British, three-and-a-half million "sex tourists" go to the poor nations each year with the specific intent of having sex with children (Lancet 363: 542, 2004 -- Spain cracks down....) We'll briefly review childhood sexual abuse under "CNS", when we talk about the "repressed memories" fiasco of 1988-1995. Reading on victims and perpetrators of the real thing: Br. J. Psych. 169: 408, 1996. Sexual behavior in children includes a considerable amount of exploring, and not everybody agrees about how much of this is wholesome (Child Abuse & Neglect 22: 289, 1998). The current definition of "sexual abuse" seems to include simply getting flashed once, or shown dirty pictures once, or even showing it to an older kid who asked (Br. Med. J. 312: 1326, 1996); under these definitions, 10% of boys are sexually abused and 33% of girls are sexually abused, and these numbers seem to hold up internationally. (The horrendous adult misbehavior that most of us think of when we hear the words "sexual abuse" is far, far less common, thankfully.) Kids running away from insufferable homes are, of course, nothing new. If you haven't read "Huckleberry Finn" or the novels of Charles Dickens, do so sometime. In the poor nations, children are simply left even in the most atrocious situations (J. Urol. 160: 1116, 1999, young boys are returned to families that just cut their penises off); otherwise they would starve. In 2003 (Lancet 361: 1196, 2003) Brazil suddenly discovered that its huge number of homeless kids include child prostitutes and promised they will all stop being prostitutes by 2004. It didn't happen.

* Nowadays, "Huckleberry Finn syndrome" refers to a person of substantial natural abilities but little direction or ambition, supposedly as a result of neglectful or abusive parents. The theme of the novel is that a child from a trash background is nevertheless wiser and morally superior to the "sivilized" folks who even he feels are his betters.

* Loathsome teenage ideas (racism of all varieties, silly-disgusting occultism, right-wing and left-wing demagoguery, proud do-nothing bitterness and bad-mouthed entitlement, live-fast-die-young, amoral pseudo-mysticism, and glorification of weird sex, death, and violence; have you visited your local music store lately?) are supposed to provide a focus for peer groups that are "a substitute for caring parents and other figures that these youngsters can look up to..." and so forth. They also deal directly and explicitly (though I'd say badly and foolishly) with issues that parents have learned not to speak about. I believe this is substantially correct [abstract 92376240; from Germany, where they talk more bluntly, I guess]. Kentucky teen vampire cult: Child Psych. Hum. Dev. 29: 209, 1999. Kids who commit genuine hate crimes don't belong to grown-up hate groups (Am. J. Psych. 160: 979, 2003).

* The neuropathology of attention deficit disorder, in which the kid can't concentrate or focus, is being worked out; the current work focuses on the caudate and its frontal lobe connections, which have to do with the ability to pay attention (Am. J. Psych. 151: 1791, 1994). It appears to be autosomal dominant with variable penetrance. One locus might be the dopamine transport gene DAT1 (Am. J. Hum. Genet. 56: 993, 1995); dopamine transport is inhibited by methylphenidate and amphetamine, which help attention deficit disorder. This writer believes this is a real entity (you can tell, because the kid can't focus on play: Br. Med. J. 311: 72, 1995), amenable to therapy with sympathomimetics (or try the few-foods approach: Arch. Dis. Child. 69: 564, 1993; JAMA 293: 1871, 1995). The writer also wonders what ever happened to kids who are disruptive simply because they are undisciplined, or unproductive because they lack guidance (no $ in diagnosing this, I guess, and somebody might get offended and boohoo to the judge). Tartrazine yellow, long considered an exacerbating factor by mothers and the tabloid press, might really make these kids worse: J. Ped. 125: 691, 1995. Before you diagnose "attention deficit disorder", I trust you'll rule out hearing problems, vision problems, lead poisoning, a chaotic home, and lack of discipline. Good luck. Likewise, by the mid-1990's, learning disability were diagnosed in 3 million U.S. kids, typically on the basis of academic performance staying below measured IQ. The kids then get special treatment. This writer believes learning disabilities are real, but wonders what happened to kids who are lazy, unmotivated, or unsupervised by their parents. Such kids, if they exist (ha ha) would meet the above criteria for "learning disabled", but there is no $ in diagnosing this, I guess, and somebody might get offended and boohoo to the judge. Even Science 267: 1896, 1995 is with your writer on this; in the years that followed, the literature started getting more sensible, and limiting the term "learning disability" to what we used to call "mental retardation" (Lancet 362: 811, 2003), affecting 1.5-2% of the population. We'll cover pervasive developmental defect ("autism", "Rain Man") under "CNS"; it's entirely a wiring problem and anyone who tells you otherwise is ignorant.

* As a family physician, you should see a teen who wishes to be seen without the parents' knowledge. Don't expect to get paid, Doc. Further, you're damned-if-you-do, damned-if-you-don't because of confidentiality issues (Curr. Op. Ped. 5: 395, 1993). Of course, if there's an anti-abortion tell-the-parents snitch-law in your state, and this applies to the teen's problem, you need to let the teen know. Your lecturer, who objects to abortion under most circumstances (and who recognizes and respects the fact that many people disagree with him), would take the anti-abortion militants more seriously if they also wanted to make contraception more available to teens -- some girls, especially in very bad neighborhoods, truly have no choice. Approach to the kid who is supposedly sexually abused: South. Med. J. 87: 1242, 1994.

* Shakespeare's "Romeo and Juliet" may have been spoiled for you as required reading in high school, and/or by parodies of the balcony scene and/or a bad (left-wing, right-wing) college "Western Civ" course. Think: The play's about godawful teenaged murder-suicide. (Juliet is 14, Romeo 16.) Shakespeare's plot-source was a warning to teenagers to obey their parents. The themes of the play, which were pretty-much new with Shakespeare and very radical in his time, are (1) young people ought to be allowed to marry for love, not just whoever their parents choose for them; (2) young people's tragedies likely result from their parents' stupidity and meanness; (3) love matures people, and gives dignity, meaning, and beauty even in the worst of circumstances. By the way, did you notice that Papa Capulet is an old guy ("past [his] dancing days", thirty years since he was "in a mask"), but Mama Capulet is was pregnant with Juliet at age 13. In other words, she was the old lecher's forced child-bride and she is setting up the same thing for Juliet. Forced marriage is still common (and an extremely common cause for a young girl's suicide) in much of our world. Did you notice that the Capulets are not terribly surprised to find Juliet dead on her wedding day? The fact that forced marriage is illegal in the United States and England may be due, at least in part, to the fact that we listened when Shakespeare showed us who we are. Dicksee, Romeo and Juliet

* "Coraline" is a novel that was extremely popular with teens, and eventually made into a graphic novel and a movie (2009). The theme explains its popularity. "If you're too busy to nurture and guide your child, somebody else will. And it will probably be the wrong somebody."

* Final note, citing what is (after "I have a right to...") probably our era's most popular slogan: I am glad that many people champion what they perceive to be good causes, though none of us agree with all of these. However... When someone championing a cause or philosophy tells you that "A society is to be judged by how it cares for its most helpless members" (meaning, depending on the speaker, irreversible coma patients, people who caught the very bad sexually transmitted disease, unwanted fetuses, fetuses with Duchenne's muscular dystrophy, people with end-stage multiple sclerosis seeking Dr. Kevorkian's services, babies born without a forebrain, the non-compliant mentally ill on the streets, alcoholic bullies, heroin addicts, spotted owls, albino lab rats, beef cattle, unwanted puppies, frozen blastulas, cold-blooded lying murderers on death row, etc., etc., etc.), find out whether the speaker has ever done anything for the healthy, neglected and mistreated kids in his or her own town.

You can lead a kid to knowledge but you can't make him think.

      -- Robert Heinlein, "Starship Troopers"

BIBLIOGRAPHY / FURTHER READING

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