Milton Westphal

Etiologic correlates in a study of congenital heart disease in 56,109 births.

Abstract From a prospective study of 56,109 total births some incidence factors and etiologic correlates for congenital heart disease have been identified. The risk of congenital heart disease in infants with Downs syndrome was found to be 1:3, for the offspring of mothers with congenital heart disease 1:20, for the offspring of diabetic mothers 1:39, and for twin infants 1:61. Data from the offspring of mothers with congenital heart disease and from offspring who are twins or siblings of twins suggest that there may be a relatively large element of inheritance in the etiology of pulmonary stenosis. The risk of a great vessel abnormality for offspring of diabetic mothers is reaffirmed. The role of maternal age in the production of congenital heart disease in the offspring is assessed, and several correlates of transposition of the great vessels are identified. Preliminary data are presented on the association of maternal viral infection with congenital heart disease in the offspring.

Changing pattern of neonatal susceptibility to hemophilus influenzae

In a study of neonatal and maternal sera, bactericidal antibody to Hemphilus influenzae B was demonstrated in only 10 per cent of newborn infants (cord blood) and in 25 per cent of mothers. These data represent a reversal of the findings of Fothergill and Wright in 1933, when 90 per cent of the blood from neonates was shown to have bactericidal antibody to this organism. A shift in neonatal susceptibility to H. influenzae is suggssted by these results.

Tissue Culture of Normal and Cystic Fibrosis Sweat Gland Duct Cells I. Alterations in Dome Formation

ABSTRACT: The elucidation of the underlying defect in fluid secretion by cystic fibrosis (CF) sweat glands is hindered by the unavailability of an experimental model for investigating this disease. As a potential model system, a serum-free growth medium was developed that supports the explant growth of epithelial cells from fragments of human skin. Immunohistochemical analysis demonstrated that these epithelial cell outgrowths originated from the duct of the sweat gland. By electron microscopy, the cells were demonstrated to possess keratinocyte-like morphology as noted by the presence of a multilayered outgrowth of cells containing well-defined keratin bundles. Identical outgrowths from skin biopsies of CF patients were compared to normal outgrowths and alterations were noted to occur in dome formation and in the number of intercellular spaces between cells. Doming alterations were also noted to occur in the CF heterozygous state. No differences in cell fine structure or in growth factor requirements for cell proliferation were noted between normal and CF cells. The potential use of this system as a model for CF research is discussed.

Elevated prostaglandin production in culture cells from a patient with fibrodysplasia ossificans progressiva

Prostaglandin E production was measured in cells cultured from both a fibromatoid lesion and a normal area of skin in a patient with fibrodysplasia ossificans progressiva. The synthesis of prostaglandin E-like material (iPGE) was ten- to twenty-fold greater in cells cultured from the patients fibromatoid lesion than in fibroblasts obtained from her normal skin. Addition of indomethacin in vitro resulted in a greater than 95% reduction of iPGE production in both cell cultures. These observations appear to warrant further investigation in additional patients, with this disease.

1112 CRYPTOSPORIDIOSIS: A COMMON CAUSE OF PARASITIC DIARRHEA IN CHILDREN

During an 11 month prospective study of stool samples submitted for ova and parasites, we identified ten cases of cryptosporidiosis in children, five in one family. The diagnosis was made by finding Cryptosporidium oocysts in stool samples which were processed by formalin-ether concentration, examined by direct wet mount and confirmed by modified cold Kinyoun stain. During the study, ten cases of Giardia lamblia were also diagnosed making cryptosporidial infection as common as giardiasis in the pediatric population studied.. One child had coinfection with Giardia and Cryptosporidium.The childrenwith cryptosporidiosis ranged in age from eight months to 5 years and there was an equal number of males and females. The majority of children were in some form of day care program. Family history was positive for diarrheal illness in each case of cryptosporidiosis. Symptoms and signs were variable and included acute and chronic diarrhea, anorexia, vomiting, abdominal pain and weight loss. No child was found to be immunocompromised or immunodeficient.We conclude that cryptosporidiosis is more common in children than previously thought and should be considered in the differential diagnosis of children with diarrhea. Stools examined for ova and parasites should be routinely examined for Cryptosporidium.

VARIABILITY IN RESPONSE TO LEAD EXPOSURE: DEMONSTRATION OF A GENETIC INFLUENCE

Examination of dose-response factors in childhood lead exposure has generally been concerned with environmental and physiological studies. We have studied eight monozygotic and seven dizygotic twin pairs as a means of demonstrating a genetic influence in lead handling and toxicity. Lead exposure and toxicity were assessed by determinations of whole blood lead, (B.L.) hematocrit, erythrocyte porphyrins, (E.P.) and delta-aminolevulinic acid dehydratase activity,(ALA-d). The intraclass correlation coefficients suggest that, in general, monozygotic twins respond more similarly than do dizygotic twins, in all parameters. The difference in correlation coefficients are significant at the p<05 and p<.01 level for E.P. and B.L. respectively, when tested by Fishers Z transformation.Since each twin pair was exposed, in utero and throughout life, to a similar environment, the variation appears to suggest a genetically determined difference in the dizygotic twins as compared to the genetically identical monozygotic twins. These data suggest the need for further evaluation of the genetic determinants of lead metabolism.

ELECTROPHYSIOLOGIC MEASUREMENTS OF RECTAI|[period]| MUCOSA IN CYSTIC FIBROSIS - ABNORMAL RESPONSE TO AMILORIDE

The negative potential difference (PD) between rectal mucosa and subcutaneous (SC) space is mainly due to transmucosal sodium transport from the lumen. In order to examine the electrolyte transport defect in Cystic Fibrosis (CF) we measured change in rectal PD in response to normal saline, 10-4M amiloride, 10-4M furosemide and 0.102 M Na2SO4 applied topically. Seven CF Patients and seven Controls were in Na balance on diets containing 120 mleq Na per day. We perfused the rectum through a double lumen, double balloon catheter.Mean Negative PD between Rectal Mucosa and SC SpaceDuring amiloride perfusion CF patients had a significantly smaller negative rectal-SC PD than normal controls. Thus, amiloride blocked rectal Na transport more completely in CF than in normals. Rectal PDs during perfusion with normal saline and with furosemide and Na2SO4, both CF blockers, were similar for CF and normals. These data are compatible with defective facilitation of sodium transport in CF or with the presence in the normal of a non-amiloride sensative Na+ transport mechanism which is absent in CF.

GLYCOPROTEINS OF HUMAN JEJUNAL CELLS: LOCATION, MATURAT10NAL CHANGES AND INDIVIDUAL VARIATION

A battery of 12 lectins conjugated to horseradish peroxidase was used to characterize secretory and cell surface glycoproteins (GP) in secretions from small bowel biopsies of 9 children. The glycoproteins found differed from site to site, among individuals at a given site and from crypt to villar tip. In goblet cells stored secretions showed individual variation in intensity of staining and increasing fucose content from crypt to villus. Terminal N-acetylglucosamine was seen in the Golgi cisternae but not in stored secretion, suggesting capping of this sugar by other residues during GP biosynthesis. Terminal α-N-acetylgalactosamine was present in Golgi cisternae of all and in the stored secretion of two-thirds of the specimens. Immature cryptal columnar cells had fucose-rich GP presumably in secretory granules. Mature villar cells did not. Columnar cells showed mannose-rich GP, presumably lysosomal enzymes, in apical punctate bodies. In some specimens the basolateral plasmalemma of columnar cells stained selectively for fucose and β-galactose. Brush border staining generally paralleled that of goblet cell secretions with similar maturational changes. Staining for terminal galactose highlighted cells, presumably leukocytes, infiltrating the epithelium and lamina propria. The diversity and variability of the GP in human jejunal mucosa suggest a relationship between specific chemical structures and biologic function at the cytologic loci.

1357 MATERNAL RISK FACTORS IN VERY LOW BIRTHWEIGHT INFANTS

Newborns weighing under 1500 gm defy the ministrations of perinatologists and contribute heavily to the nations high perinatal mortality rate, yet, maternal risk factors for the birth of such infants have not been analyzed separately. To determine whether maternal factors associated with the delivery of very low birth-weight infants (VLBW) under 1500 gm are different from those associated with low birthweight infants (LBW) of 1500 to 2500 gm, prenatal data on 11,114 deliveries were evaluated. The sample included 435 VLBW infants. Maternal race, age, height, weight, gravidity, parity, past pregnancy performance and present pregnancy complications were analyzed using chi-square. Factors related to an increased incidence of VLBW but not of LBW infants were: 1) maternal age ≤ 15 years, ≥ 36 years, 2) gravidity over 8, 3) previous abortions, 4) previous fetal deaths, and 5) hypertensive vascular disease/essential hypertension. Race (black) and low prepregnancy weight were not related to VLBW but were associated with an increase in LBW. The finding that low prepregnancy weight is not related to VLBW implys that limited paturient mass is not a factor in supporting a fetus up to 1500 grams. The other positive findings suggest that suboptimal reproductive capacity and preexisting hypertension predispose to the birth of a VLBW rather than an LBW infant. These results contradict the concept of a uniform set of predisposing factors for the birth of all infants weighing ≤ 2500 gm.