676
Letters to the Editor
which might also adversely affect fetal growth. Unfortunately, the relatively small number of patients whose histories were available for this study made any elaborate stratification of data inappropriate. Furthermore, information on some of the factors he has listed was not consistantly available to us. As noted in the tables in our article, we defined prenatal growth deficiency as a birth length at/or below the third percentile of the expected range, adjusted for sex and gestational age. Although the means of the distributions of birth length were not statistically significantly different for case and control groups, all children identified as having multiple features of the fetal hydantoin syndrome were at/or below the third percentile for the length at the time of birth. These children were judged to show the fetal hydantoin syndrome because of a broad pattern of alterations of growth and morphogenesis. Thus, prenatal growth deficiency was one of the most consistant features found among those children most seriously affected. We wish to re-emphasize that although prenatal growth deficiency is the most consistant single feature of the major known teratogens, in this study we sought a particular pattern of malformations which is characteristic of some infants exposed prenatally to hydantoin anticonvulsants. No one type of abnormality is specific for a particular teratogen. However, most recognized human teratogens produce characteristic patterns of abnormalities which frequently allow for recognition. The fact that a characteristic pattern of malformation, including prenatal growth deficiency, has not been described in infants born to mothers with any of the conditions which Dr. Miller lists, tends to exclude these factors as a primary cause of this syndrome. We would agree, however, that addition of these factors might well offer additional hazards to the fetus of a mother receiving hydantoins. James W. Hanson, M.D. Assistant Professor of Pediatrics Division of Medical Genetics University of Iowa College of Medicine Iowa City, 1A 52242 David 14L Smith, M.D. Professor in Pediatrics Dysmorphology Unit University of Washington School of Medicine Seattle, WA 98195
CIE detection of bacterial antigens in meningitis
The Journal Of Pediatrics April 1977
fluid ( C S F ) / a n d this may also be true for hemophilus capsular antigens? As a result of its small molecular size, the capsular antigen in urine is more difficult to detect by counterimmunoelectrophoresis (CIE) than is the antigen in the CSF or serum. We found that precipitin bands obtained by the reaction of pneumococcal capsular antigen in urine with pneumococcal polyvalent serum often could not be detected until the agarose slides were cooled at 5~ for 2 to 3 hours/ Full development of these reactions usually required 24 hours. If this observation were true for the results reported by Feigin and associates, it would represent a limitation of the CIE test for rapid diagnosis with urinary antigens. (2) Any procedure for concentration of bacterial antigens in urine would seem to carry a risk of producing false positive results in the CIE test. Unless the urine was collected and processed in a controlled way, contaminating organisms might proliferate to high levels; also, individuals with urinary tract infections might have high levels of organisms even in fresh urines. The specificity of CIE in this setting remains to be established. (3) It is difficult to obtain any perspective on the overall diagnostic value of CIE unless the results of CIE are compared with standard (and very simple) procedures such as examination of gram-stained smears of the CSF and the Quellung test. Such evaluation can make clear those instances (which are many in some reports) where C1E is simply an adjunct to diagnosis, as well as those cases where the test has some unique value. This point seems crucial in determining whether CIE is a good enough test to become a standard procedure for determining the etiologic agent in meningitis. J. Donald Coonrod, M.D. Associate Professor of Medicine University of Kentucky School of Medicine Lexington, K Y 40506 REFERENCES 1. Feigin RD, Wong M, Shackelford PG, Stechenberg BW, Dunkle LM, and Kaplan S: Countercurrent immunoelectrophoresis of urine as well as of CSF and blood for diagnosis of bacterial meningitis, J PEDIAXR 89:773, 1976. 2. Coonrod JD: Physical and immunologic properties of pneumococcal capsular polysaccharides produced daring human infection, J Immunol 112:2193, 1974. 3. O'Reilly R J, Anderson P, Ingrain DL, et al: Circulating polyribophosphate in Hemophilus influenzae, Type b meningitis: Correlation with clinical course and antibody response, J Clin Invest 56:1012, 1975. 4. Coonrod JD, and Rytel MW: Detection of type-specific pneunococcal antigens by counterimmunoeleetrophoresis. I. Methodology and immunologic properties of pneumococcal antigens, J Lab Clin Med 81:770, 1973.
Re ly To the Editor: I would like to make three points concerning the interesting paper on detection of bacterial antigens in the urine in meningitis by Feigin and associates? (1) In pneumococcal infection the capsular antigen that is present in the urine has a much lower molecular size than its counterpart in serum or cerebrospinal
To the Editor: We wish to thank Dr. Coonrod for his observations concerning the use of countercurrent electrophoresis (CIE) of urine in patients with meningitis. Because of the potential problem of
Letters to the Editor
which might also adversely affect fetal growth. Unfortunately, the relatively small number of patients whose histories were available for this study made any elaborate stratification of data inappropriate. Furthermore, information on some of the factors he has listed was not consistantly available to us. As noted in the tables in our article, we defined prenatal growth deficiency as a birth length at/or below the third percentile of the expected range, adjusted for sex and gestational age. Although the means of the distributions of birth length were not statistically significantly different for case and control groups, all children identified as having multiple features of the fetal hydantoin syndrome were at/or below the third percentile for the length at the time of birth. These children were judged to show the fetal hydantoin syndrome because of a broad pattern of alterations of growth and morphogenesis. Thus, prenatal growth deficiency was one of the most consistant features found among those children most seriously affected. We wish to re-emphasize that although prenatal growth deficiency is the most consistant single feature of the major known teratogens, in this study we sought a particular pattern of malformations which is characteristic of some infants exposed prenatally to hydantoin anticonvulsants. No one type of abnormality is specific for a particular teratogen. However, most recognized human teratogens produce characteristic patterns of abnormalities which frequently allow for recognition. The fact that a characteristic pattern of malformation, including prenatal growth deficiency, has not been described in infants born to mothers with any of the conditions which Dr. Miller lists, tends to exclude these factors as a primary cause of this syndrome. We would agree, however, that addition of these factors might well offer additional hazards to the fetus of a mother receiving hydantoins. James W. Hanson, M.D. Assistant Professor of Pediatrics Division of Medical Genetics University of Iowa College of Medicine Iowa City, 1A 52242 David 14L Smith, M.D. Professor in Pediatrics Dysmorphology Unit University of Washington School of Medicine Seattle, WA 98195
CIE detection of bacterial antigens in meningitis
The Journal Of Pediatrics April 1977
fluid ( C S F ) / a n d this may also be true for hemophilus capsular antigens? As a result of its small molecular size, the capsular antigen in urine is more difficult to detect by counterimmunoelectrophoresis (CIE) than is the antigen in the CSF or serum. We found that precipitin bands obtained by the reaction of pneumococcal capsular antigen in urine with pneumococcal polyvalent serum often could not be detected until the agarose slides were cooled at 5~ for 2 to 3 hours/ Full development of these reactions usually required 24 hours. If this observation were true for the results reported by Feigin and associates, it would represent a limitation of the CIE test for rapid diagnosis with urinary antigens. (2) Any procedure for concentration of bacterial antigens in urine would seem to carry a risk of producing false positive results in the CIE test. Unless the urine was collected and processed in a controlled way, contaminating organisms might proliferate to high levels; also, individuals with urinary tract infections might have high levels of organisms even in fresh urines. The specificity of CIE in this setting remains to be established. (3) It is difficult to obtain any perspective on the overall diagnostic value of CIE unless the results of CIE are compared with standard (and very simple) procedures such as examination of gram-stained smears of the CSF and the Quellung test. Such evaluation can make clear those instances (which are many in some reports) where C1E is simply an adjunct to diagnosis, as well as those cases where the test has some unique value. This point seems crucial in determining whether CIE is a good enough test to become a standard procedure for determining the etiologic agent in meningitis. J. Donald Coonrod, M.D. Associate Professor of Medicine University of Kentucky School of Medicine Lexington, K Y 40506 REFERENCES 1. Feigin RD, Wong M, Shackelford PG, Stechenberg BW, Dunkle LM, and Kaplan S: Countercurrent immunoelectrophoresis of urine as well as of CSF and blood for diagnosis of bacterial meningitis, J PEDIAXR 89:773, 1976. 2. Coonrod JD: Physical and immunologic properties of pneumococcal capsular polysaccharides produced daring human infection, J Immunol 112:2193, 1974. 3. O'Reilly R J, Anderson P, Ingrain DL, et al: Circulating polyribophosphate in Hemophilus influenzae, Type b meningitis: Correlation with clinical course and antibody response, J Clin Invest 56:1012, 1975. 4. Coonrod JD, and Rytel MW: Detection of type-specific pneunococcal antigens by counterimmunoeleetrophoresis. I. Methodology and immunologic properties of pneumococcal antigens, J Lab Clin Med 81:770, 1973.
Re ly To the Editor: I would like to make three points concerning the interesting paper on detection of bacterial antigens in the urine in meningitis by Feigin and associates? (1) In pneumococcal infection the capsular antigen that is present in the urine has a much lower molecular size than its counterpart in serum or cerebrospinal
To the Editor: We wish to thank Dr. Coonrod for his observations concerning the use of countercurrent electrophoresis (CIE) of urine in patients with meningitis. Because of the potential problem of
