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Chromosomal mosaicism in amniotic fluid cell cultures
Volume 90 Number 3
Letters to the Editor
phosphate insecticides was neither noted in their series nor in their discussion. The organophosphorus insecticides, of which Parathion is the most widely used, act primarily by inhibiting the enzyme cholinesterase which results in an accumulation of acetylcholine. This then causes excessive stimulation of the parasympathetic system, central nervous system effects, and effects at the myoneural junction? The patient will have weakness, abdominal cramps, perspiration, salivation, excessive respiratory tract secretions, and pupillary constriction. In severe cases, respiratory arrest, convulsions, and coma do occur. The insecticides are widely used both in rural farming areas as well as urban areas. Careful history-taking is essential since these agents are absorbed not only orally but by inhalation as well as percutaneously. Furthermore, in addition to the narcotics, this group of drugs also have antidotes that are safe and effective. High doses of Atropine (0.05 mg/kg) are necessary as often as every 20 to 30 minutes to reverse cholinergic effects. Pralidoxime, a cholinesterase reactivator, will reverse the central nervous system as well as the muscular effects of the organophosphates (100 mg/kg).:' In summary, the organophosphate insecticides represent another group of agents that cause coma in children associated with miosis. Recognition of this type of poisoning will allow prompt treatment and hopefully, reversal of the at times very serious symptoms.
RonaM M. Rosengart, M.D. Department of Pediatrics Southern California Permanente Medical Group 1505 N. Edgemont St. Los A ngeles, CA 9002 7 REFERENCES 1. Mitchell A, Lovejoy FH, and Goldman P: Drug ingestions associated with miosis in comatose children, J PEDIATR 89:303, 1976. 2. Zavon N: Poisoning from pesticides: Diagnosis and treatment, Pediatrics 54:332, 1974. 3. Namba T, et al.: Poisoning due to organophosphate insecticides, Am J Med 50:475, 1971.
Reply Dr. Lovejoy expresses appreciation to Dr. Rosengart for this additional information.
Editor
Chromosomal mosaic•m in amniotic fluid cell cultures To the Editor: In a recent letter to THE JOURNAL, Milunsky and Atkins' reviewed the occurrence of chromosomal mosaicism in amniotic
50 1
fluid cell cultures. We here report an additional case of mixoploidy which was the first such observation in cultures derived from over 300 specimens. CASE REPORT A 31-year-old, gravida 4, para 3 patient was referred for prenatal genetic counselling because her third child presented with Down syndrome (trisomy 21). She requested amniocentesis for prenatal chromosomal diagnosis. The procedure was performed at 17 weeks of pregnancy. Family history was otherwise negative. An analysis of 75 metaphases derived from six separate flasks revealed a karyotypic description of 45,X/47,XXX (GiemsaTrypsin G banding). The percentages of 45,X and 47,XXX cell populations were 80 and 20, respectively. The parents were informed of the results. On the basis of the experiences of Milunsky and Atkins 1they were told that a second amniocentesis was not indicated, since it would not eliminate the initial results. The parents elected to terminate the pregnancy at which time amniotic fluid and fetal tissue were obtained. Amniotic fluid cell cultures confirmed our observations given above. Unfortunately the fetal tissue was refractive to cell culture giving to circumstances beyond our control. DISCUSSION We agree with Milunsky and Atkins that the prenatal diagnosis of true mosaicism is difficult. We caution all of our patients that the possibility of mosaicism cannot be eliminated entirely. An additional amniocentesis should not be carried out for the purpose of confirming or excluding initial observations. There are legitimate reasons for repeating an amniocentesis, e.g., Mycoplasma ~ may have contaminated preliminary cultures. Finally, we concur that individual colony or clonal analysis should be the universal method for prenatal chromosomal diagnosis.
Nataline B. Kardon, M.D. Instructor in Pediatrics Cornell University Medical College Division of Genetics North Shore University Hospital Marian Krauss, B.A. Division of Genetics North Shore University Hospital Jessica G. Davis, M.D, Associate Professor Pediatrics Cornell University Medical College Director, Child Development Center Chief Division of Genetics North Shore University Hospital Edmund C. Jenkins, Ph.D. Head of the Cytogenetics Laboratory North Shore University Hospital and New York State Institute for Basic Research in Mental Retardation Staten lsland Child Development Center North Shore University Hospital 300 Community Dr Manhasset, N.Y. 11030
502
Letters to the Editor
REFERENCES 1. Milunsky A, and Atkins L: Prenatal diagnosis of chromosomal mosaicism, J PEDIATR 88:365, 1976. 2. Schneider EL, Stanbridge EJ, Epstein C J. Golbus M. AbboHalbasch G, and Rodgers G: Mycoplasma contamination of cultured amniotic fluid cells: Potential hazard to prenatal chromosomal diagnosis, Science 184:477, 1974.
Acetaminophen and encephalopathy To the Editor: In Dr. Gall and associates' recent article' regarding acute liver disease and encephalopathy mimicking the Reye syndrome, the abnormal liver function studies and abnormal hepatic histopathology he reveals are quite similar to the findings being reported in acute acetaminophen poisoning. ~ The question Dr. Swisher brought up in THE JOURr~AL'S September issue as to the possibility of an "acute toxic encephalopathy" is a real one.:' The potential of an "acute toxic state" is there and investigation is needed. In Dr. Gall's case descriptions there is no mention of the usage of acetaminophen in the treatment of me upper respiratory infection (URI) that preceded each case of liver disease and encephalopathy. In view of the recent theories that viral infections and antihistamines may actually potentiate toxicity of acetaminophen even in therapeutic levels used to treat symptoms of URI-' ' I personally wonder if the classical Reye syndrome, and Reye-like syndromes which we are seeing more and more now in the literature if not directly, are indirectly related to acetaminophen poisoning of some sort. Libeau J. Berthelot, M.D. Captain (MC), USAR 2nd-year resident Fami!F Practice Residency Program Womack Army Hospital Fort Bragg, NC 28307 REFERENCES 1. Gall DG, Cutz E, McClung WH, and Greenberg ML: Acute liver disease and encephalopathy mimicking Reye syndrome, J PED1ATR 87:869, 1975. 2. Romack B, and Mathew H: Acetaminophen poisoning and toxicity, Pediatrics 55:871, 1975. 3. Swisher C: Editorial correspondence, J PEDIATR 89:515, 1976. 4. The Medical Letter on Drugs and Therapeutics, vol. 18, no. 18, (issue 460), August 27, 1976.
Repy To the Editor: In reply to Dr. Berthelot's letter, to the best of our knowledge the three patients described by us with centrilolobular necrosis and encephalopathy did not receive acetaminophen prior to the
The Journal of Pediatrics March 1977
onset of their illness. Because of the concern of a possible association between drug ingestion and Reye syndrome, the parents of these children and their referring physicians were closely questioned about medications received prior to the onset of the disease. All medications ingested prior to their illness are recorded in the case reports. D. Grant Gall, M.D., F.R.C.P.(C) Division of Gastroenterology The Hospital for Sick Children 555 University A re. Toronto, Ont., Canada M5G 1X8
More on "diabetic control ''t. What & it? To the Editor: We are in complete agreement with the article of Malone and coworkers~: urine-reducing sugar and fasting plasma glucose concentrations, considered alone, are not the best criteria to define the degree of diabetic control. The reasons for this are ( I ) glycemia is a flash in the nycthemeral glycemic curve and is not instantaneously reflected by glucosuria, (2) children can be mistaken using the method of detection of glucosuria or in reading the color blocks, ~ and (3) children are not always reliable in noting the results of their daily note book. Nevertheless measurements of glucosuria and glycemia are
Table I. Criteria for diabetic control I. Good diabetic control Reliable daily note book Correct adaptation of insulin doses Existence of hypogtycemic episodes of minor importance No polyuria-polydipsia Glucosuria _<20 gm/l Monthly postprandial glycemia <250 mg/dl Maintenance of normal blood lipids Normal growth I1, Insufficient diabetic control More or less reliable daily note book Adaptation of insulin doses sometimes neglected No hypoglycemia or few serious hypoglycemic episodes Few symptoms of polyuria-polydipsia, with short-lived ketonuria Wide fluctuation of glucosuria (0 to 50 gin/l) Monthly postprandial glycemia often >250 mg/dl Ill. Pdor diabetic control Unreliable daily note book Adaptation of the insulin doses neglected High frequency of symptomatic hypo and/or hyperglycemia Likely ketonuria, but undocumented Admission for failure
Letters to the Editor
phosphate insecticides was neither noted in their series nor in their discussion. The organophosphorus insecticides, of which Parathion is the most widely used, act primarily by inhibiting the enzyme cholinesterase which results in an accumulation of acetylcholine. This then causes excessive stimulation of the parasympathetic system, central nervous system effects, and effects at the myoneural junction? The patient will have weakness, abdominal cramps, perspiration, salivation, excessive respiratory tract secretions, and pupillary constriction. In severe cases, respiratory arrest, convulsions, and coma do occur. The insecticides are widely used both in rural farming areas as well as urban areas. Careful history-taking is essential since these agents are absorbed not only orally but by inhalation as well as percutaneously. Furthermore, in addition to the narcotics, this group of drugs also have antidotes that are safe and effective. High doses of Atropine (0.05 mg/kg) are necessary as often as every 20 to 30 minutes to reverse cholinergic effects. Pralidoxime, a cholinesterase reactivator, will reverse the central nervous system as well as the muscular effects of the organophosphates (100 mg/kg).:' In summary, the organophosphate insecticides represent another group of agents that cause coma in children associated with miosis. Recognition of this type of poisoning will allow prompt treatment and hopefully, reversal of the at times very serious symptoms.
RonaM M. Rosengart, M.D. Department of Pediatrics Southern California Permanente Medical Group 1505 N. Edgemont St. Los A ngeles, CA 9002 7 REFERENCES 1. Mitchell A, Lovejoy FH, and Goldman P: Drug ingestions associated with miosis in comatose children, J PEDIATR 89:303, 1976. 2. Zavon N: Poisoning from pesticides: Diagnosis and treatment, Pediatrics 54:332, 1974. 3. Namba T, et al.: Poisoning due to organophosphate insecticides, Am J Med 50:475, 1971.
Reply Dr. Lovejoy expresses appreciation to Dr. Rosengart for this additional information.
Editor
Chromosomal mosaic•m in amniotic fluid cell cultures To the Editor: In a recent letter to THE JOURNAL, Milunsky and Atkins' reviewed the occurrence of chromosomal mosaicism in amniotic
50 1
fluid cell cultures. We here report an additional case of mixoploidy which was the first such observation in cultures derived from over 300 specimens. CASE REPORT A 31-year-old, gravida 4, para 3 patient was referred for prenatal genetic counselling because her third child presented with Down syndrome (trisomy 21). She requested amniocentesis for prenatal chromosomal diagnosis. The procedure was performed at 17 weeks of pregnancy. Family history was otherwise negative. An analysis of 75 metaphases derived from six separate flasks revealed a karyotypic description of 45,X/47,XXX (GiemsaTrypsin G banding). The percentages of 45,X and 47,XXX cell populations were 80 and 20, respectively. The parents were informed of the results. On the basis of the experiences of Milunsky and Atkins 1they were told that a second amniocentesis was not indicated, since it would not eliminate the initial results. The parents elected to terminate the pregnancy at which time amniotic fluid and fetal tissue were obtained. Amniotic fluid cell cultures confirmed our observations given above. Unfortunately the fetal tissue was refractive to cell culture giving to circumstances beyond our control. DISCUSSION We agree with Milunsky and Atkins that the prenatal diagnosis of true mosaicism is difficult. We caution all of our patients that the possibility of mosaicism cannot be eliminated entirely. An additional amniocentesis should not be carried out for the purpose of confirming or excluding initial observations. There are legitimate reasons for repeating an amniocentesis, e.g., Mycoplasma ~ may have contaminated preliminary cultures. Finally, we concur that individual colony or clonal analysis should be the universal method for prenatal chromosomal diagnosis.
Nataline B. Kardon, M.D. Instructor in Pediatrics Cornell University Medical College Division of Genetics North Shore University Hospital Marian Krauss, B.A. Division of Genetics North Shore University Hospital Jessica G. Davis, M.D, Associate Professor Pediatrics Cornell University Medical College Director, Child Development Center Chief Division of Genetics North Shore University Hospital Edmund C. Jenkins, Ph.D. Head of the Cytogenetics Laboratory North Shore University Hospital and New York State Institute for Basic Research in Mental Retardation Staten lsland Child Development Center North Shore University Hospital 300 Community Dr Manhasset, N.Y. 11030
502
Letters to the Editor
REFERENCES 1. Milunsky A, and Atkins L: Prenatal diagnosis of chromosomal mosaicism, J PEDIATR 88:365, 1976. 2. Schneider EL, Stanbridge EJ, Epstein C J. Golbus M. AbboHalbasch G, and Rodgers G: Mycoplasma contamination of cultured amniotic fluid cells: Potential hazard to prenatal chromosomal diagnosis, Science 184:477, 1974.
Acetaminophen and encephalopathy To the Editor: In Dr. Gall and associates' recent article' regarding acute liver disease and encephalopathy mimicking the Reye syndrome, the abnormal liver function studies and abnormal hepatic histopathology he reveals are quite similar to the findings being reported in acute acetaminophen poisoning. ~ The question Dr. Swisher brought up in THE JOURr~AL'S September issue as to the possibility of an "acute toxic encephalopathy" is a real one.:' The potential of an "acute toxic state" is there and investigation is needed. In Dr. Gall's case descriptions there is no mention of the usage of acetaminophen in the treatment of me upper respiratory infection (URI) that preceded each case of liver disease and encephalopathy. In view of the recent theories that viral infections and antihistamines may actually potentiate toxicity of acetaminophen even in therapeutic levels used to treat symptoms of URI-' ' I personally wonder if the classical Reye syndrome, and Reye-like syndromes which we are seeing more and more now in the literature if not directly, are indirectly related to acetaminophen poisoning of some sort. Libeau J. Berthelot, M.D. Captain (MC), USAR 2nd-year resident Fami!F Practice Residency Program Womack Army Hospital Fort Bragg, NC 28307 REFERENCES 1. Gall DG, Cutz E, McClung WH, and Greenberg ML: Acute liver disease and encephalopathy mimicking Reye syndrome, J PED1ATR 87:869, 1975. 2. Romack B, and Mathew H: Acetaminophen poisoning and toxicity, Pediatrics 55:871, 1975. 3. Swisher C: Editorial correspondence, J PEDIATR 89:515, 1976. 4. The Medical Letter on Drugs and Therapeutics, vol. 18, no. 18, (issue 460), August 27, 1976.
Repy To the Editor: In reply to Dr. Berthelot's letter, to the best of our knowledge the three patients described by us with centrilolobular necrosis and encephalopathy did not receive acetaminophen prior to the
The Journal of Pediatrics March 1977
onset of their illness. Because of the concern of a possible association between drug ingestion and Reye syndrome, the parents of these children and their referring physicians were closely questioned about medications received prior to the onset of the disease. All medications ingested prior to their illness are recorded in the case reports. D. Grant Gall, M.D., F.R.C.P.(C) Division of Gastroenterology The Hospital for Sick Children 555 University A re. Toronto, Ont., Canada M5G 1X8
More on "diabetic control ''t. What & it? To the Editor: We are in complete agreement with the article of Malone and coworkers~: urine-reducing sugar and fasting plasma glucose concentrations, considered alone, are not the best criteria to define the degree of diabetic control. The reasons for this are ( I ) glycemia is a flash in the nycthemeral glycemic curve and is not instantaneously reflected by glucosuria, (2) children can be mistaken using the method of detection of glucosuria or in reading the color blocks, ~ and (3) children are not always reliable in noting the results of their daily note book. Nevertheless measurements of glucosuria and glycemia are
Table I. Criteria for diabetic control I. Good diabetic control Reliable daily note book Correct adaptation of insulin doses Existence of hypogtycemic episodes of minor importance No polyuria-polydipsia Glucosuria _<20 gm/l Monthly postprandial glycemia <250 mg/dl Maintenance of normal blood lipids Normal growth I1, Insufficient diabetic control More or less reliable daily note book Adaptation of insulin doses sometimes neglected No hypoglycemia or few serious hypoglycemic episodes Few symptoms of polyuria-polydipsia, with short-lived ketonuria Wide fluctuation of glucosuria (0 to 50 gin/l) Monthly postprandial glycemia often >250 mg/dl Ill. Pdor diabetic control Unreliable daily note book Adaptation of the insulin doses neglected High frequency of symptomatic hypo and/or hyperglycemia Likely ketonuria, but undocumented Admission for failure