Biomedical subjects
Publications and source records attributed to F R Sinatra.
The diagnosis of optic nerve hypoplasia and hypopituitarism must be entertained in infants who present for evaluation of cholestatic jaundice, particularly if there is associated hypoglycaemia and wandering nystagmus. Although the hepatic dysfunction seems to resolve, the long term prognosis of liver disease in optic nerve hypoplasia remains unknown.
The potential cholestatic effect of amino acids and metabolites of tryptophan were evaluated by use of seven daily intraperitoneal injections to suckling and weanling rat pups. Of the amino acids present in parenteral nutrition solutions, only tryptophan (given at a dose of 4 mM/kg) produced a significant (p less than 0.01) elevation of serum cholylglycine (12.8 +/- 1.0 microM/liter) as determined by radioimmunoassay, compared to 4.9 +/- 0.4 microM/liter in saline-treated control animals. Total serum conjugates of cholic acid, as determined by radioimmunoassay, were similarly elevated, as was serum alanine aminotransferase. Tryptophan injection resulted in elevated cholylglycine concentrations only at doses of 3 mM/kg/day or higher. Animals more than 2 weeks old did not demonstrate elevation of serum cholylglycine. Injection of light-exposed tryptophan in suckling animals caused a greater elevation of cholylglycine (39.0 +/- 8.6 microM/liter) than freshly prepared tryptophan solutions (p less than 0.005). Tryptophan and its spontaneous degradation products could contribute to the cholestatic liver changes observed during parenteral nutrition therapy.
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Five full term infants with necrotizing enterocolitis, confirmed histologically, presented in the first five days of life. All passed grossly bloody stools and three mucosal casts. Severe perinatal asphyxia with accompanying secondary hyperammonemia was present in all, and abnormal liver function studies were present in three. An awareness of the clinical characteristics of these infants may lead to their early identification and conservative management.
Fecal alpha 1-antitrypsin excretion, a noninvasive indicator of protein-losing enteropathy, was correlated with clinical disease activity in pediatric patients with Crohn's disease. Disease activity was defined as the sum of 11 abnormal clinical parameters which were adapted from previously published disease activity scoring methods. Each patient was also given a subjective clinical rating when evaluated. In addition, four different devised disease activity scoring methods were correlated retrospectively with subjective clinical ratings for hospitalized patients. A total of 125 random fecal alpha 1-antitrypsin determinations were performed on 22 patients. Ninety-six percent of clinically active episodes of Crohn's disease were associated with elevated fetal alpha 1-antitrypsin (p less than 0.001). The degree of elevation was found not to correlate directly with the severity of assessed disease activity or site of intestinal involvement. A direct linear relationship was demonstrated between 23 paired random fecal alpha 1-antitrypsin and intestinal alpha 1-antitrypsin clearance assays (r = 0.93). There was a high, and remarkably similar, degree of correlation with each of the four different derived activity scoring methods and simple subjective ratings (r = 0.89-0.93). We conclude that: (a) fecal alpha 1-antitrypsin excretion may be helpful in assessing the presence or absence of Crohn's disease activity by providing an objective and specific indicator of intestinal damage; and (b) it appears that a simple subjective rating score is as clinically useful as other previously devised activity indices.
In 11 patients with childhood amebiasis, only two had dysentery. Additional clinical findings included hematochezia without diarrhea (four patients), dysentery with appendicitis (one patient), exacerbation of ulcerative colitis (two patients), and disseminated infantile amebiasis (two patients). All patients with hematochezia examined by proctosigmoidoscopy had colitis. The diagnosis of amebiasis was confirmed by microscopic examination of fresh stool specimens, pathologic findings, and/or serologic titers. Amebiasis should be considered in the differential diagnosis of infants and children with hematochezia or hepatomegaly, especially in endemic areas.
Many disorders are capable of producing cholestasis in infancy. Primary hepatobiliary diseases and systemic infectious, toxic, and metabolic insults may present clinically as conjugated hyperbilirubinemia. A careful, organized diagnostic evaluation allows early identification of potentially treatable lesions. Recent success in the surgical management of biliary atresia, previously a uniformly fatal disorder, has emphasized the need for early diagnosis. Medical management of the complications of chronic cholestasis remains a major challenge. Liver transplantation currently offers the only chance for long-term survival for infants with progressive cirrhosis.
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Three infants born to mothers who were hepatitis B surface antigen (HBsAg) positive and had antibody to hepatitis Be antigen (anti-HBe), developed acute icteric hepatitis B within three months of birth. All three infants clinically recovered and developed circulating anti-HBs. Contrary to previous studies, these three cases indicate that mother-infant transmission of the hepatitis B virus (HBV) does occur in infants born to HBsAg-positive, HBe-Ag-negative carrier mothers, and these infants may develop severe acute icteric hepatitis. Therefore, immunoprophylaxis in such newborns may be indicated.
Four children experienced kwashiorkor six weeks to six months following the introduction of a low-protein, high-fat, nondairy creamer into their diets. In all cases, the milk substitute eventually became their sole nutritional source and resulted in hypoproteinemia, edema, and hepatic abnormalities. All patients had been given the milk substitute in an attempt to control suspected milk protein sensitivity. Only one of the four patients was subsequently shown to have cow's milk sensitivity. All had complete resolution of symptoms within six weeks following institution of a nutritionally adequate diet.
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Random fecal alpha-1-antitrypsin concentration was measured in children with various gastrointestinal diseases and in normal subjects. One hundred fifteen subjects were evaluated: controls (39); chronic inflammatory bowel disease (20); chronic diarrhea (18); acute gastroenteritis (17); allergic gastroenteropathy (5); chronic pancreatic exocrine insufficiency (4); acute gastrointestinal bleeding (4); nonspecific colitis (4); celiac disease (3); and intestinal lymphangiectasia (1). Mean fecal-alpha-1-antitrypsin for the controls was 0.98 mg/g lyophilized stool. All children with celiac disease, allergic gastroenteropathy, lymphangiectasia, nonspecific colitis, acute gastrointestinal bleeding, and 19 of 20 patients with active chronic inflammatory bowel disease had fecal alpha-1-antitrypsin concentrations greater than 2.6 mg/g stool (mean of the controls + 2 SD). These disorders have all been previously documented to cause protein-losing enteropathy by 51Cr-labeled albumin excretion tests. The other study patients had normal fecal alpha-1-antitrypsin excretion when compared with controls. Serial fecal antitrypsin concentrations paralleled disease activity and clinical response to therapy. The results suggest that random fecal antitrypsin concentration is a valuable screening test for mucosal disorders associated with abnormal transmucosal serum protein loss.
Of 33 children with various cholestatic syndromes who were studies with sonography, 19 also had 131I rose bengal scintigraphy, and 12 also had 99mTc sulfur colloid scintigraphy. Patients were categorized into intra- or extrahepatic etiologies for their cholestasis. Of 19 children in the extrahepatic category, 17 had abnormal sonographic studies; two with biliary atresia appeared normal. All 14 patients in the intrahepatic category had normal sonographic studies. Rose bengal was most useful when demonstrating biliary patency. Some cases of biliary atresia with normal sonography and lack of rose bengal excretion into the intestinal tract could not be separated from cases of neonatal hepatitis using a similar combination of studies. Radiocolloid studies were less valuable than other examinations except when demonstrating diffuse hepatic reticuloendothelial dysfunction as found in two cases of congenital syphilitic hepatitis.
A new class of hepatobiliary imaging agents has become available--the N-substituted iminodiacetic acids. After intravenous administration, these compounds are quickly extracted by the hepatocytes and rapidly excreted into the biliary tree. By using a 99mTc label, sufficient activity may be given to allow excellent gamma-camera imaging, 99mTc-labeled p-isopropylacetanilido-iminodiacetic acid (PIPIDA) has been used in the evaluation of infants with biliary excretion disorders, including two infants with neonatal hepatitis, three with intrahepatic cholestatic jaundice, and 10 with biliary atresia. Follow-up evaluation of surgically created portoenterostomies has been performed as well. In comparison with the previously available agent (131I rose bengal), the marked reduction in radiation to the liver alone should predicate the use of 99mTc PIPIDA. In addition, the speed of handling of this agent by the liver and the vastly improved imaging statistics make 99mTc PIPIDA a desirable agent for the evaluation of biliary excretion disorders in infancy.
Twelve infants with severe perinatal asphyxia were found to have elevated blood ammonia levels (302 to 960 microgram/100 ml). In the seven survivors, hyperammonemia was associated with CNS irritability, hyperthermia, hypertension, and wide neonatal heart rate oscillations. Follow-up examinations revealed severe neurologic dysfunction in five of seven infants. CNS depression, hyperthermia, hypertension, and a nonreactive, fixed heart rate characterized the infants that died. These findings suggest a clinical entity secondary to perinatal asphyxia whose signs and symptoms may be related to hyperammonemia.
The prevalence of primary adult lactose malabsorption and the pattern of milk use were studied among 109 Indians from various tribes of the American Great Basin and Southwest. Included were 100 persons who reported being full-blooded Indians as well as three with Mexican admixture and 6 with some European ancestry. Lactose malabsorption was found in 92% of the full-blooded Indians but in only 50% Indians who acknowledged European admixture. These results agree with those of studies of native Americans done elsewhere which show very high prevalences of such lactose malabsorption among adults reported as fullblooded and lower prevalences among individuals with admitted European ancestors. The suggestion made is that in pre-Colombian times, before interbreeding with Europeans began on any scale, such lactose malabsorption may have been nearly universal among native American adults. Most of the Indians studied consumed abundant milk since childhood but were nevertheless predominantly malabsorbers as adults. This argues against the induction hypothesis advanced by some to explain the striking ethnic differences that occur around the world in primary adult lactose malabsorption.
The intractable diarrhoea syndrome of infancy continues to be a major diagnostic and therapeutic challenge to the paediatrician and paediatric gastroenterologist. A carefully organized, staged approach to diagnosis will provide the best method of identifying those infants in whom a specific aetiology exists and for whom specific therapy is often available. Regardless of aetiology, however, the early use of appropriate nutritional support will not only reduce morbidity and mortality in these infants, but will prevent the development of many of the secondary consequences of malnutrition. The physician must compulsively pay attention to the details of daily management and provide an organized approach to diagnosis and treatment in order to improve the outcome of infants with intractable diarrhoea.
Lactose loading tests and other means were used to determine the pattern of primary "adult" lactose malabsorption (LM) and milk use among 171 subjects, including 122 children and 49 adults, almost all of them Pima Indians of Arizona. LM develops at quite young ages in full-blooded Pima children: already in the 3- to 4-year age group, 40% had LM. Of 62 full-blooded Indians (greater than or equal to 4 years of age), 59 (95%) had LM. Of 41 Indians (greater than or equal to 4 years) who were of mixed Indian-northern European ancestry, however, only 25 (61%) had LM, and, among them, prevalence of LM correlated with degree of northern European admixture. Whereas only 21% of Pima lactose absorbers reported symptoms after the loading test, 72% of malabsorbers did so, with older malabsorbers more likely to experience symptoms. In their everyday lives, only 23% of malabsorbers recognized symptoms brought on by milk consumption, but the percentage of malabsorbers making such an association increased with age. Nevertheless the Pima, adults as well as children, continue to drink reasonable quantities of milk. Family pedigrees are consistent with the hypothesis that adult lactose absorption is inherited as an autosomal dominant trait. Over-all results of this study, moreover, support the geographic hypothesis advanced to explain ethnic or racial differences in prevalence of LM, rather than the induction hypothesis.