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Clinical facts and curios
Clinical Facts and Curios 1.
Q. What is the “toxic hypoglycemic
syndrome”?
A. The toxic hypoglycemic syndrome (THS) is characterized by the acute onset of profuse vomiting, convulsions, coma, and sometimes death in association with profound hypoglycemia. It is caused by eating aceae. In case you forget, aceae is the national fruit of Jamaica but is also a cause of Jamaican vomiting sickness. By way of explanation, the aceae tree was imported from West Africa to Jamaica in 1778. The tree is now ubiquitous in Jamaica. There, fresh aceae is consumed directly following harvesting or can be obtained in markets when in season. Unripe aceae contains hypoglycin A, a water-soluble liver toxin that induces hypoglycemia by inhibiting gluconeogenesis. If you like aceae and you don’t want to get THS, recognize the potential risk behaviors for aceae food poisoning: (1) selection and cooking of unripe aceae; (2) purchase of tampered, forcibly opened aceae; and (3) reuse of the water in which unripe aceae has been stored. The Jamaican Ministry of Health through public health inspectors monitors aceae fruit that is either freshly sold or canned. Don’t worry about seeing too much of this problem here in the United States since no cases have been reported to date. Fortunately, also no cases of THS are known to have been reported among persons from the United States who have visited Jamaica (MMWR 1992; 4153; Bressler R: N Engl J Med 1976; 295500). 2.
Q. Why is the lowering of blood cholesterol
a good news-bad
news story?
A. Bringing down your cholesterol level is a good news story, obviously from the viewpoint of a lower risk of coronary heart disease. The bad news is that subjects who have a rapid lowering of cholesterol have a significant increase in mortality due to suicides or violence, as demonstrated in a review of six randomized, controlled, primary coronary prevention trials (Muldoon MR: Br Med J 1990; 301:309). Before you assign the purported relationship between-lowering of cholesterol and suicide to something that is a highly qualified candidate for “Ripley’s Believe It Or Not,” recognize that a recent important study verified the effect of lowering cholesterol on brain metabolism. Engelberg (Lancet 1992; 339:727) gave evidence that a lowering of cholesterol lowers brain cell membrane cholesterol as well. This results in a decrease in the number of serotonin receptors in the brain, which may contribute to a decrease in brain serotonin levels. This certainly can affect one’s mood. Is it better to be fat and happy as opposed to trim and in the dumps? You be the judge. 3.
Q. Is it possible
for twins to have two different fathers?
A. Obviously it is possible, but has it happened? Yes. If a woman is polyovulating and has a sexual encounter with more than one man, twins with two different fathers is possible, This phenomenon was described in 1810 (Archer J: Med Re34
Current
Problems
in Pediatrics
/ January
1993
Clinical Facts and Curios
posit 1810; I:31 9) in 1940 (Geyer E: Arch Rassenbiol 1940; 34:226), and most recently in 1992 (Berma RS, et al: Lancer 1992; 339:63). This phenomenon sure makes for some interesting birthday parties. 4.
Q. Do vampire bats still transmit rabies?
A. A little history is in order before answering this question. Fossil evidence indicates the presence of vampire bats in the Americas dating to the late Pleistocene period. Reports of fatal illness in humans and animals bitten by these bats date to the time of the Spanish colonists in 1527. However, the cause was not recognized until 1911 when the death of cattle in Brazil was investigated and Negri bodies were found in the brains of the animals attacked by vampire bats. Even today, from northern Mesico to southern Argentina, the annual losses of cattle from rabies transmitted from vampire bats number in excess of half a million. Human rabies of vampire bat origin was first reported in 1929 when Negri bodies were found in the brains of a cluster of 17 patients in Trinidad. Schoolage children predominated among the cases. Human rabies resulting from vampire bats was also reported every year in Mexico, but the disease was first noted in South America in 1953 when, over a 2-month period, 8 of 43 diamond miners who slept outdoors died of a mysterious illness. The most recent florid outbreak of human rabies is occurring in Peru (Lopez A, et al: Lancet 1992; 339:408). Children between the ages of 5 and 14 are especially most likely to become infected, presumably because they don’t protect themselves with mosquito nets at night as adults do. Rabies from bats in the United States is exceedingly rare but not unheard of. Beware of trips, however, to our neighboring countries to the south. 5.
Q. You are outside, reading this month’s “Clinical Facts and Curios” while on vacation in Hawaii. You recall that there is a risk of ultraviolet injury to the eye, depending on the source of light you are reading by. Is it safe to sit outside and read this page under the conditions described? Would it be safer to be sitting in your study reading by the light of a halogen desk lamp?
A. The answer to this question comes from a brief report by Daxecker and colleagues (N Engl J Med 1992; 336:494). As compared with common incandescent light, halogen lamps have the advantage of emitting brillant white light. This advantage is associated with a higher transmission of ultraviolet rays, however. The fact that halogen lamps are more widely used as desk lamps raises a question about the potential risk of keratitis. Daxecker and colleagues, using a highresolution spectrometer, measured the ultraviolet exposure of the cornea under reading conditions with two different types of halogen lamps. The distance from the paper to both the lamp and the eyes was 30 cm. The reflectance of the paper in the ultraviolet range turned out to be approximately 7% and was almost independent of the kind of paper used. To say this differently, whether you are reading “Clinical Facts and Curios” or the Sunday New York Times, you’re going to experience the same risk. The threshold dose for keratitis is known to be 40 J/m2. This dosage is achieved after 10 hours and 55 minutes of reading when a 50-W halogen desk lamp is used. Not to worry, however, since eye injury of this type is not cumulative over time and, fortunately, most of us don’t read for 11 hours continuously. So when do you worry? You worry when you are sitting outside in natural sunlight in June. Daxecker and coworkers showed that the threshold for injury to Current
Problems
in Pediatrics
/ January
1993
35
Clinical Facts and Curios
the eye by ultraviolet light is reached after only 26 minutes of reading in natural sunlight in June at 63 degrees of solar elevation when there are no clouds. To say all this differently, halogen desk lamps are safe. Unless you’re into the “Blues Brothers” you can save your Foster Grants for the beach rather than your off ice.
6.
Q. We all know about jumping jacks. Do you know, however, what a ‘yumping gene” is?
A. The recent description of “jumping genes” in humans represents one of the most significant new insights into disease processes found in recent times. The correct terminology, however, is transposons. Transposons, or transposable genetic elements, are fragments of DNA with an unusual property-they can change their positions within the genome of the organism that carries them. Transposons seem to be ubiquitous in both plants and animals. Until very recently, their relevance to medicine derived chiefly from the fact that antibioticresistance genes in bacteria behave as transposons, capable not only of moving about on the bacterial chromosome but also of transferring to a plasmid (a virus-like DNA cohabitant of the bacterium) and thence to other bacteria. You may recall the linkage of the name transposon to Barbara McClintock, who first described the phenomenon of unstable mutations in the mid-1940s. Barbara persisted with a line of research regarded by many as esoteric (or worse), ultimately being vindicated with an award of the. Nobel Prize in 1983. So what does all this have to do with humans? The first report of a “jumping gene” that produces an identifiable effect in humans was published recently (Dombroski BA, et al: Science 1991; 254:1805). The discovery arose from research on new mutations, that is, on individuals who display all the features of a hereditary disease but have no family history of the condition. The disease in this case was hemophilia A, which lends itself to such studies because it is X-linked and reasonably common, and a substantial proportion of cases are attributable to new mutations. Now that the target gene for hemophilia A, which encodes for the Factor VIII molecule, has been cloned, it has been possible to show that the mutation causing hemophilia in two individuals is due to the insertion within the Factor VIII gene of an extraneous DNA sequence from the individual’s own DNA elsewhere. The interspersed elements are known as LINE-l, a transposon. You’ll be hearing a lot more about transposons and LjNE-1 as a cause of human disease. There are an estimated 100,000 copies of LINE-I in the human genome. The fact that these are able to move about our genes and alter a variety of DNA sequences that are needed to make us all function means that transposons may be a cause of much more than anyone could possibly have imagined. Transposons may well indeed be responsible for a variety of human malignancies Don’t worry that your genes are shuttling about the genome at breakneck speeds. The apparent LINE-l of the newly discovered hemophilia mutation must have been on chromosome 22 for at least 6 million years, since it is present in its native location in chimpanzees and gorillas as well as in humans. Nonetheless, a word to the wise would be to pay attention to further newsbreaks regarding the jumping genes. They are quite important 7.
36
Current
Q. An obstetrician friend of yours calls you to ask for a consultation. He has just done an ultrasonic examination on a young pregnant woman at 18 weeks’ gestation. There appears to be a marked increase in echogenicity within the fetal
Problems
in Pediatrics
I January
1993
Clinical Facts and Curios
abdomen, suggestive ther steps to follow. Your suggestions?
of a meconium
ileus. He seeks your advice on what fur-
A. Your best advice probably would be to first determine whether there is amniotic fluid evidence of a fetal gastrointestinal (GI) obstruction. Secondly, if such a process is present, you would recommend studies to determine the cause of the obstructive process. Fetal GI obstruction can be determined by enzyme activity analysis of amniotic fluid. Enzymes such as y-glutamyl transpeptidase, leucine aminopeptidase, and alkaline phosphatase are passed within fetal stool into the amniotic fluid. With GI obstruction, levels of these enzymes, whose normal ranges in amniotic fluid are well known, will be diminished in quantity. Cystic fibrosis is obviously the classic disease that produces fetal GI obstruction. Hirschsprung’s disease rarely affects fetuses. In the case of the obstetrician above, you would probably have recommended that AF508 or other cystic fibrosis DNA mutations be analyzed in the parents and possibly in the fetus. In fact, these studies were done in the pregnancy described and the results were negative. The parents of the fetus decided to abort and at postmortem examination, it was determined that the fetus was infected with cytomegalovirus. The cytomegalovirus caused the marked intestinal dysmotility by infecting myenteric plexus neurons, as was demonstrated at autopsy. The description of pseudo-meconium ileus due to cytomegalovirus infection was made by investigators in Paris (Dechelotge PJ, et al: Pediatr Pathol 1992; 12:73). Indeed, three cases of prenatal diagnosis of cytomegalovirus infection, made by ultrasound detection of pseudo-meconium ileus, were described in this French report. A similar pattern of intestinal obstruction in the newborn was noted in an infant with congenital syphilis (Siplojich BL, et al: J Pediatr Surg 1988; 9:810). The next time you run across the problem of prepartum meconium ileus, think of the possibility of psuedo-meconium ileus and don’t just do tests for the possibility of cystic fibrosis; think also of cytomegalovirus and perhaps even syphilis. 8.
Q. You care for a child with juvenile rheumatoid arthritis. You find that the child’s grandmother has been recommending a folk remedy to the child’s parents in order to treat the arthritis. The parents ask you whether badger grease would be helpful.
A. Don’t assign the grandmother
to the loony bin too quickly. Indeed, badger grease has been a folklore cure for rheumatism for many years, both in this country and in Europe. Purely by coincidence, in a study of autoimmune disease in badgers, it was found that badger fat has a much higher than expected level of corticosteroids (Gallagher J, et al: Vet Ret 1979; 105:456). Badgers, particularly old badgers, are becoming quite the fad in terms of medical studies, particularly when it comes to aging. One fourth of autopsies in old badgers have revealed atherosclerosis, virtually identical to that seen in humans (Laplaud PM: Atherosclerosis 1986; 61:43). If you discarded the pharmacologic prowess of the grandmother described above, it is you who are the old badger. Me/es me/es, the badger, has a lot to teach us all. 9.
Q. A good friend of yours, a retired dentist, seeks your advice. He has just had a computed tomography (CT) scan of the chest, performed because of an ab-
Current Problems in Pediatrics / January 1993
37
Clinical Facts and Curios
normal appearance on chest x-ray film suggestive of a pleural mass. Indeed, the CT scan appears to show a chest wall tumor with a pleural effusion. Your friend wants some reassurance that this is not a serious problem. Can such reassurance be given?
A. No. If you suspect a relationship between a chest wall tumor and the prior occupation, that of dentistry, you are correct. In this country, prior to 1976, dentists were occupationally exposed to asbestos as part of their dental practice. The asbestos was in paper used to line casting rings and crucibles and was supplied on large dry rolls. The liners were used to cast dentures. Even though a dentist may never have practiced a form of dentistry in which dentures were produced, virtually all dental undergraduates during their dental school training were required to cast a minimum number of sets of dentures. Thus, most dentists over the age of 45 have had some degree of exposure (Council on Dental Therapeutics: J Am Dent Assoc 1976; 92:777). In. case you think the circumstances described are more theoretic than real, a 60-year-old retired dentist recently presented with a recurrent left pleural effusion. Malignant cells highly suggestive of mesothelioma were seen in the pleural aspirate. At the time of biopsy a diagnosis of malignant mesothelioma was made. The patient died after 10 months (Reid AS, et al: Lancet 1991; 2:696). The only good news in any of this story is that the potential danger to dental personnel was realized some time ago and such products were no longer accepted in this country after 1976. Additional good news is that there is no known danger to any patients who received care prior to this time. 10.
Q. What /-/o//ywood actor died of a malignant mesothelioma?
A. Steve McQueen. 11.
Q. An 8-year-o/d boy is referred by a family practitioner to your practice for evaluation of anemia. The boy had been in his usual state of good health until 10 days previous/y when he developed varicella. The chickenpox peaked at 7 days from the onset of infection. The patient had begun to fee/ much better until approximately 3 days ago when he began to look pale and yellow to his parents. A hematocrit performed by the family practitioner showed a value of 19%. The family practitioner reported that the patient’s urine was brown-tinged and contained 4+ protein and hemoglobin. A serum lactate dehydrogenase value was 1,430 unitsll and the bilirubin level was 7.1 mgldL. * What further studies would you perform?
A. If you answered a Coombs’ test, you would have been correct. The child represents the fifth reported case of autoimmune hemolytic anemia following the onset of chickenpox (Friedman HD, et al: J C/in Pathol 1992; 27:92). The antibody in question turned out to be a cold agglutinin of the IgM class. Recognize that most infection-associated cold agglutinin disease is transient The association with certain infectious agents is particularly strong and these tend to elicit cold agglutinins with regular specificity. Mycoplasma pneumoniae is the most commonly associated infectious agent. Epstein-Barr viral disease is probably next highest in line to cause this problem. Although less common, cold agglutinin disease has been observed in a variety of other viral, bacterial, and protozoa1 diseases. 12. 38
Current
Q. Does crying exacerbate
Problems
in Pediatrics
G/ reflux in infants?
I January
1993
Clinical Facts and Curios
A. Crying does not exacerbate
GI reflux in infants. Susan R. Orenstein, at the University of Pittsburgh, has dispelled this myth (J Pediatr Gastroenterol Nutr 1992; 14:34). Orenstein examined the behavior and intraluminal esophageal pH in a large group of infants. She examined the frequency of esophageal reflux episodes per hour of time spent crying, per hour of time awake without crying, and per hour of time asleep. The findings showed that sleeping decreased reflux frequency and that contrary to expectation, crying appeared to decrease, rather than increase both reflux frequency episodes per hour awake and total duration of reflux episodes. Another old wives’ tale bites the dust. Infants with GI reflux can cry their hearts out without fear that they are burping themselves too much.
13.
Q. How good are mothers at recalling their infant’s birth weight?
A. Some years ago, and somewhat more recently as well, it was suggested that maternal recall of birth weight was not particularly accurate, especially under certain circumstances (Gayle HD, et al: Public Health Rep 1988; 103:143; Hoekelman RA, et al: C/in Pediatr 1976; 15261). Among factors thought to impair the accuracy of maternal recall are maternal age less than 18 years, low birth weight, multiparity, and black or nonwhite racial origin. Are such factors truly related to the inability of mothers to recall birth weight? No. Wilcox and coworkers (C/in Pediatr 1991; 30509) examined a number of variables to evaluate the impact of each of these on the accuracy of maternal recall of an infant’s birth weight. This study was performed in the pediatric clinics of Grady Memorial Hospital in Atlanta. Over 96% of mothers said they could recall the birth weight of their child. Among those who said they could give an answer, 95.2% were able to correctly categorize their infants as either being of normal birth weight or of low birth weight. Approximately 80% of mothers were correct within 200 g of the exact weight. Maternal age at birth of the index child, parity at time of birth of the index child, years since birth of the index child, neonatal health problems, and maternal racial origin had no influence on the ability of these mothers to accurately recall their infant’s birth weight. It seems likely that the accuracy of maternal birth weight recall may be more closely related to the accuracy and diligence with which health care personnel obtain and report the information to a new mother during the neonatal stay than it is to anything else. Hats off to the newborn team in the delivery room at Grady Memorial Hospital! 14.
Q. If you’re going to be bitten by a ratt/esnake, ten the most?
where don’t you want to be bit-
A. There are probably many parts of your body that you would like to see protected from rattlesnakes but the one part of your body that you should be worried about most is your finger. Finger bites result in the greatest functional longterm disability as a sequela of rattlesnake bites. This is because digit bites have the highest proclivity for the development of a compartment syndrome resulting in neurologic impairment. If you want to read more about rattlesnake bites, including a variety of very good recommendations with respect to treatments, read the excellent review of this topic by Downey and coauthors (J Trauma 1991; 31: 1380). 15.
Q. HOW good is the pig as a broker of food? Current
Problems
in Pediatrics
/ January
1993
39
Clinical Facts and Curios
A. This question was answered in an editorial that appeared some 75 years ago in Lancet (editorial comment: Lancet 1917; 1:221). In case you haven’t gotten the drift of the question, the issue relates to whether it is more efficient to feed food to a pig and then eat the pig, or eat the food directly. The latter, in fact, is more efficient. Only some 25% of the protein and some 45% of the total energy of food supplied to a pig is ultimately recoverable as pork or bacon. To say this differently, the pig is an expensive broker, keeping 55%. Needless to say, a pig could be brought up on usury charges.
40
Current
Problems
in Pediatrics
/ January
1993
Q. What is the “toxic hypoglycemic
syndrome”?
A. The toxic hypoglycemic syndrome (THS) is characterized by the acute onset of profuse vomiting, convulsions, coma, and sometimes death in association with profound hypoglycemia. It is caused by eating aceae. In case you forget, aceae is the national fruit of Jamaica but is also a cause of Jamaican vomiting sickness. By way of explanation, the aceae tree was imported from West Africa to Jamaica in 1778. The tree is now ubiquitous in Jamaica. There, fresh aceae is consumed directly following harvesting or can be obtained in markets when in season. Unripe aceae contains hypoglycin A, a water-soluble liver toxin that induces hypoglycemia by inhibiting gluconeogenesis. If you like aceae and you don’t want to get THS, recognize the potential risk behaviors for aceae food poisoning: (1) selection and cooking of unripe aceae; (2) purchase of tampered, forcibly opened aceae; and (3) reuse of the water in which unripe aceae has been stored. The Jamaican Ministry of Health through public health inspectors monitors aceae fruit that is either freshly sold or canned. Don’t worry about seeing too much of this problem here in the United States since no cases have been reported to date. Fortunately, also no cases of THS are known to have been reported among persons from the United States who have visited Jamaica (MMWR 1992; 4153; Bressler R: N Engl J Med 1976; 295500). 2.
Q. Why is the lowering of blood cholesterol
a good news-bad
news story?
A. Bringing down your cholesterol level is a good news story, obviously from the viewpoint of a lower risk of coronary heart disease. The bad news is that subjects who have a rapid lowering of cholesterol have a significant increase in mortality due to suicides or violence, as demonstrated in a review of six randomized, controlled, primary coronary prevention trials (Muldoon MR: Br Med J 1990; 301:309). Before you assign the purported relationship between-lowering of cholesterol and suicide to something that is a highly qualified candidate for “Ripley’s Believe It Or Not,” recognize that a recent important study verified the effect of lowering cholesterol on brain metabolism. Engelberg (Lancet 1992; 339:727) gave evidence that a lowering of cholesterol lowers brain cell membrane cholesterol as well. This results in a decrease in the number of serotonin receptors in the brain, which may contribute to a decrease in brain serotonin levels. This certainly can affect one’s mood. Is it better to be fat and happy as opposed to trim and in the dumps? You be the judge. 3.
Q. Is it possible
for twins to have two different fathers?
A. Obviously it is possible, but has it happened? Yes. If a woman is polyovulating and has a sexual encounter with more than one man, twins with two different fathers is possible, This phenomenon was described in 1810 (Archer J: Med Re34
Current
Problems
in Pediatrics
/ January
1993
Clinical Facts and Curios
posit 1810; I:31 9) in 1940 (Geyer E: Arch Rassenbiol 1940; 34:226), and most recently in 1992 (Berma RS, et al: Lancer 1992; 339:63). This phenomenon sure makes for some interesting birthday parties. 4.
Q. Do vampire bats still transmit rabies?
A. A little history is in order before answering this question. Fossil evidence indicates the presence of vampire bats in the Americas dating to the late Pleistocene period. Reports of fatal illness in humans and animals bitten by these bats date to the time of the Spanish colonists in 1527. However, the cause was not recognized until 1911 when the death of cattle in Brazil was investigated and Negri bodies were found in the brains of the animals attacked by vampire bats. Even today, from northern Mesico to southern Argentina, the annual losses of cattle from rabies transmitted from vampire bats number in excess of half a million. Human rabies of vampire bat origin was first reported in 1929 when Negri bodies were found in the brains of a cluster of 17 patients in Trinidad. Schoolage children predominated among the cases. Human rabies resulting from vampire bats was also reported every year in Mexico, but the disease was first noted in South America in 1953 when, over a 2-month period, 8 of 43 diamond miners who slept outdoors died of a mysterious illness. The most recent florid outbreak of human rabies is occurring in Peru (Lopez A, et al: Lancet 1992; 339:408). Children between the ages of 5 and 14 are especially most likely to become infected, presumably because they don’t protect themselves with mosquito nets at night as adults do. Rabies from bats in the United States is exceedingly rare but not unheard of. Beware of trips, however, to our neighboring countries to the south. 5.
Q. You are outside, reading this month’s “Clinical Facts and Curios” while on vacation in Hawaii. You recall that there is a risk of ultraviolet injury to the eye, depending on the source of light you are reading by. Is it safe to sit outside and read this page under the conditions described? Would it be safer to be sitting in your study reading by the light of a halogen desk lamp?
A. The answer to this question comes from a brief report by Daxecker and colleagues (N Engl J Med 1992; 336:494). As compared with common incandescent light, halogen lamps have the advantage of emitting brillant white light. This advantage is associated with a higher transmission of ultraviolet rays, however. The fact that halogen lamps are more widely used as desk lamps raises a question about the potential risk of keratitis. Daxecker and colleagues, using a highresolution spectrometer, measured the ultraviolet exposure of the cornea under reading conditions with two different types of halogen lamps. The distance from the paper to both the lamp and the eyes was 30 cm. The reflectance of the paper in the ultraviolet range turned out to be approximately 7% and was almost independent of the kind of paper used. To say this differently, whether you are reading “Clinical Facts and Curios” or the Sunday New York Times, you’re going to experience the same risk. The threshold dose for keratitis is known to be 40 J/m2. This dosage is achieved after 10 hours and 55 minutes of reading when a 50-W halogen desk lamp is used. Not to worry, however, since eye injury of this type is not cumulative over time and, fortunately, most of us don’t read for 11 hours continuously. So when do you worry? You worry when you are sitting outside in natural sunlight in June. Daxecker and coworkers showed that the threshold for injury to Current
Problems
in Pediatrics
/ January
1993
35
Clinical Facts and Curios
the eye by ultraviolet light is reached after only 26 minutes of reading in natural sunlight in June at 63 degrees of solar elevation when there are no clouds. To say all this differently, halogen desk lamps are safe. Unless you’re into the “Blues Brothers” you can save your Foster Grants for the beach rather than your off ice.
6.
Q. We all know about jumping jacks. Do you know, however, what a ‘yumping gene” is?
A. The recent description of “jumping genes” in humans represents one of the most significant new insights into disease processes found in recent times. The correct terminology, however, is transposons. Transposons, or transposable genetic elements, are fragments of DNA with an unusual property-they can change their positions within the genome of the organism that carries them. Transposons seem to be ubiquitous in both plants and animals. Until very recently, their relevance to medicine derived chiefly from the fact that antibioticresistance genes in bacteria behave as transposons, capable not only of moving about on the bacterial chromosome but also of transferring to a plasmid (a virus-like DNA cohabitant of the bacterium) and thence to other bacteria. You may recall the linkage of the name transposon to Barbara McClintock, who first described the phenomenon of unstable mutations in the mid-1940s. Barbara persisted with a line of research regarded by many as esoteric (or worse), ultimately being vindicated with an award of the. Nobel Prize in 1983. So what does all this have to do with humans? The first report of a “jumping gene” that produces an identifiable effect in humans was published recently (Dombroski BA, et al: Science 1991; 254:1805). The discovery arose from research on new mutations, that is, on individuals who display all the features of a hereditary disease but have no family history of the condition. The disease in this case was hemophilia A, which lends itself to such studies because it is X-linked and reasonably common, and a substantial proportion of cases are attributable to new mutations. Now that the target gene for hemophilia A, which encodes for the Factor VIII molecule, has been cloned, it has been possible to show that the mutation causing hemophilia in two individuals is due to the insertion within the Factor VIII gene of an extraneous DNA sequence from the individual’s own DNA elsewhere. The interspersed elements are known as LINE-l, a transposon. You’ll be hearing a lot more about transposons and LjNE-1 as a cause of human disease. There are an estimated 100,000 copies of LINE-I in the human genome. The fact that these are able to move about our genes and alter a variety of DNA sequences that are needed to make us all function means that transposons may be a cause of much more than anyone could possibly have imagined. Transposons may well indeed be responsible for a variety of human malignancies Don’t worry that your genes are shuttling about the genome at breakneck speeds. The apparent LINE-l of the newly discovered hemophilia mutation must have been on chromosome 22 for at least 6 million years, since it is present in its native location in chimpanzees and gorillas as well as in humans. Nonetheless, a word to the wise would be to pay attention to further newsbreaks regarding the jumping genes. They are quite important 7.
36
Current
Q. An obstetrician friend of yours calls you to ask for a consultation. He has just done an ultrasonic examination on a young pregnant woman at 18 weeks’ gestation. There appears to be a marked increase in echogenicity within the fetal
Problems
in Pediatrics
I January
1993
Clinical Facts and Curios
abdomen, suggestive ther steps to follow. Your suggestions?
of a meconium
ileus. He seeks your advice on what fur-
A. Your best advice probably would be to first determine whether there is amniotic fluid evidence of a fetal gastrointestinal (GI) obstruction. Secondly, if such a process is present, you would recommend studies to determine the cause of the obstructive process. Fetal GI obstruction can be determined by enzyme activity analysis of amniotic fluid. Enzymes such as y-glutamyl transpeptidase, leucine aminopeptidase, and alkaline phosphatase are passed within fetal stool into the amniotic fluid. With GI obstruction, levels of these enzymes, whose normal ranges in amniotic fluid are well known, will be diminished in quantity. Cystic fibrosis is obviously the classic disease that produces fetal GI obstruction. Hirschsprung’s disease rarely affects fetuses. In the case of the obstetrician above, you would probably have recommended that AF508 or other cystic fibrosis DNA mutations be analyzed in the parents and possibly in the fetus. In fact, these studies were done in the pregnancy described and the results were negative. The parents of the fetus decided to abort and at postmortem examination, it was determined that the fetus was infected with cytomegalovirus. The cytomegalovirus caused the marked intestinal dysmotility by infecting myenteric plexus neurons, as was demonstrated at autopsy. The description of pseudo-meconium ileus due to cytomegalovirus infection was made by investigators in Paris (Dechelotge PJ, et al: Pediatr Pathol 1992; 12:73). Indeed, three cases of prenatal diagnosis of cytomegalovirus infection, made by ultrasound detection of pseudo-meconium ileus, were described in this French report. A similar pattern of intestinal obstruction in the newborn was noted in an infant with congenital syphilis (Siplojich BL, et al: J Pediatr Surg 1988; 9:810). The next time you run across the problem of prepartum meconium ileus, think of the possibility of psuedo-meconium ileus and don’t just do tests for the possibility of cystic fibrosis; think also of cytomegalovirus and perhaps even syphilis. 8.
Q. You care for a child with juvenile rheumatoid arthritis. You find that the child’s grandmother has been recommending a folk remedy to the child’s parents in order to treat the arthritis. The parents ask you whether badger grease would be helpful.
A. Don’t assign the grandmother
to the loony bin too quickly. Indeed, badger grease has been a folklore cure for rheumatism for many years, both in this country and in Europe. Purely by coincidence, in a study of autoimmune disease in badgers, it was found that badger fat has a much higher than expected level of corticosteroids (Gallagher J, et al: Vet Ret 1979; 105:456). Badgers, particularly old badgers, are becoming quite the fad in terms of medical studies, particularly when it comes to aging. One fourth of autopsies in old badgers have revealed atherosclerosis, virtually identical to that seen in humans (Laplaud PM: Atherosclerosis 1986; 61:43). If you discarded the pharmacologic prowess of the grandmother described above, it is you who are the old badger. Me/es me/es, the badger, has a lot to teach us all. 9.
Q. A good friend of yours, a retired dentist, seeks your advice. He has just had a computed tomography (CT) scan of the chest, performed because of an ab-
Current Problems in Pediatrics / January 1993
37
Clinical Facts and Curios
normal appearance on chest x-ray film suggestive of a pleural mass. Indeed, the CT scan appears to show a chest wall tumor with a pleural effusion. Your friend wants some reassurance that this is not a serious problem. Can such reassurance be given?
A. No. If you suspect a relationship between a chest wall tumor and the prior occupation, that of dentistry, you are correct. In this country, prior to 1976, dentists were occupationally exposed to asbestos as part of their dental practice. The asbestos was in paper used to line casting rings and crucibles and was supplied on large dry rolls. The liners were used to cast dentures. Even though a dentist may never have practiced a form of dentistry in which dentures were produced, virtually all dental undergraduates during their dental school training were required to cast a minimum number of sets of dentures. Thus, most dentists over the age of 45 have had some degree of exposure (Council on Dental Therapeutics: J Am Dent Assoc 1976; 92:777). In. case you think the circumstances described are more theoretic than real, a 60-year-old retired dentist recently presented with a recurrent left pleural effusion. Malignant cells highly suggestive of mesothelioma were seen in the pleural aspirate. At the time of biopsy a diagnosis of malignant mesothelioma was made. The patient died after 10 months (Reid AS, et al: Lancet 1991; 2:696). The only good news in any of this story is that the potential danger to dental personnel was realized some time ago and such products were no longer accepted in this country after 1976. Additional good news is that there is no known danger to any patients who received care prior to this time. 10.
Q. What /-/o//ywood actor died of a malignant mesothelioma?
A. Steve McQueen. 11.
Q. An 8-year-o/d boy is referred by a family practitioner to your practice for evaluation of anemia. The boy had been in his usual state of good health until 10 days previous/y when he developed varicella. The chickenpox peaked at 7 days from the onset of infection. The patient had begun to fee/ much better until approximately 3 days ago when he began to look pale and yellow to his parents. A hematocrit performed by the family practitioner showed a value of 19%. The family practitioner reported that the patient’s urine was brown-tinged and contained 4+ protein and hemoglobin. A serum lactate dehydrogenase value was 1,430 unitsll and the bilirubin level was 7.1 mgldL. * What further studies would you perform?
A. If you answered a Coombs’ test, you would have been correct. The child represents the fifth reported case of autoimmune hemolytic anemia following the onset of chickenpox (Friedman HD, et al: J C/in Pathol 1992; 27:92). The antibody in question turned out to be a cold agglutinin of the IgM class. Recognize that most infection-associated cold agglutinin disease is transient The association with certain infectious agents is particularly strong and these tend to elicit cold agglutinins with regular specificity. Mycoplasma pneumoniae is the most commonly associated infectious agent. Epstein-Barr viral disease is probably next highest in line to cause this problem. Although less common, cold agglutinin disease has been observed in a variety of other viral, bacterial, and protozoa1 diseases. 12. 38
Current
Q. Does crying exacerbate
Problems
in Pediatrics
G/ reflux in infants?
I January
1993
Clinical Facts and Curios
A. Crying does not exacerbate
GI reflux in infants. Susan R. Orenstein, at the University of Pittsburgh, has dispelled this myth (J Pediatr Gastroenterol Nutr 1992; 14:34). Orenstein examined the behavior and intraluminal esophageal pH in a large group of infants. She examined the frequency of esophageal reflux episodes per hour of time spent crying, per hour of time awake without crying, and per hour of time asleep. The findings showed that sleeping decreased reflux frequency and that contrary to expectation, crying appeared to decrease, rather than increase both reflux frequency episodes per hour awake and total duration of reflux episodes. Another old wives’ tale bites the dust. Infants with GI reflux can cry their hearts out without fear that they are burping themselves too much.
13.
Q. How good are mothers at recalling their infant’s birth weight?
A. Some years ago, and somewhat more recently as well, it was suggested that maternal recall of birth weight was not particularly accurate, especially under certain circumstances (Gayle HD, et al: Public Health Rep 1988; 103:143; Hoekelman RA, et al: C/in Pediatr 1976; 15261). Among factors thought to impair the accuracy of maternal recall are maternal age less than 18 years, low birth weight, multiparity, and black or nonwhite racial origin. Are such factors truly related to the inability of mothers to recall birth weight? No. Wilcox and coworkers (C/in Pediatr 1991; 30509) examined a number of variables to evaluate the impact of each of these on the accuracy of maternal recall of an infant’s birth weight. This study was performed in the pediatric clinics of Grady Memorial Hospital in Atlanta. Over 96% of mothers said they could recall the birth weight of their child. Among those who said they could give an answer, 95.2% were able to correctly categorize their infants as either being of normal birth weight or of low birth weight. Approximately 80% of mothers were correct within 200 g of the exact weight. Maternal age at birth of the index child, parity at time of birth of the index child, years since birth of the index child, neonatal health problems, and maternal racial origin had no influence on the ability of these mothers to accurately recall their infant’s birth weight. It seems likely that the accuracy of maternal birth weight recall may be more closely related to the accuracy and diligence with which health care personnel obtain and report the information to a new mother during the neonatal stay than it is to anything else. Hats off to the newborn team in the delivery room at Grady Memorial Hospital! 14.
Q. If you’re going to be bitten by a ratt/esnake, ten the most?
where don’t you want to be bit-
A. There are probably many parts of your body that you would like to see protected from rattlesnakes but the one part of your body that you should be worried about most is your finger. Finger bites result in the greatest functional longterm disability as a sequela of rattlesnake bites. This is because digit bites have the highest proclivity for the development of a compartment syndrome resulting in neurologic impairment. If you want to read more about rattlesnake bites, including a variety of very good recommendations with respect to treatments, read the excellent review of this topic by Downey and coauthors (J Trauma 1991; 31: 1380). 15.
Q. HOW good is the pig as a broker of food? Current
Problems
in Pediatrics
/ January
1993
39
Clinical Facts and Curios
A. This question was answered in an editorial that appeared some 75 years ago in Lancet (editorial comment: Lancet 1917; 1:221). In case you haven’t gotten the drift of the question, the issue relates to whether it is more efficient to feed food to a pig and then eat the pig, or eat the food directly. The latter, in fact, is more efficient. Only some 25% of the protein and some 45% of the total energy of food supplied to a pig is ultimately recoverable as pork or bacon. To say this differently, the pig is an expensive broker, keeping 55%. Needless to say, a pig could be brought up on usury charges.
40
Current
Problems
in Pediatrics
/ January
1993