Biomedical subjects
Publications and source records attributed to H S Winter.
We report a case of esophageal adenocarcinoma 20 years after esophageal atresia repair. From one case report it is premature to recommend cancer surveillance for all esophageal atresia patients. However, the first survivors are now reaching an age when esophageal cancer related to chronic esophagitis may become more prevalent.
Explore the source record for details and available documents.
A wide range of clinical syndromes exist that are related to adverse reactions to dietary proteins and that affect predominantly the gastrointestinal tract of infants and children. Experimental data suggest a critical role for developmental alterations affecting intestinal permeability and the mucosal immune response that predispose to these conditions. The diagnostic and therapeutic approach to these disorders varies depending on the nature of the presumed offending antigen, the anatomic site affected, the severity of the inflammatory process, and the implications for future dietary and medical management. Ultimately, the proof that a particular dietary antigen is responsible is dependent on observing the response to oral challenge.
Patients who have undergone repair of esophageal atresia and tracehoesophageal fistula as infants have been noted to have residual esophageal dysmotility and pulmonary dysfunction during their childhood years. However, limited information is available about the long-term follow-up of these patients. In this study we performed esophageal and pulmonary function studies on 12 adults who had required surgical repair of these defects in the first week of life. Most patients had symptoms of dysphagia and heartburn at time of evaluation. Pathologic gastroesophageal reflux was documented in 67% of patients and esophagitis was noted in 34%. All patients had esophageal motility abnormalities characterized by low-amplitude nonperistaltic waves throughout most of the esophagus. In addition, although most patients had no respiratory symptoms, mild restrictive lung volumes were noted in many patients. However, airflow obstruction and airway hyperreactivity were not present. These data demonstrate that clinical symptoms and abnormal esophageal manometry and pulmonary function persist well into the third and beginning of the fourth decade after repair of esophageal atresia and tracheoesophageal fistula in infancy.
Nine patients, 6 weeks to 17 years of age with esophageal atresia (EA), developed esophageal strictures and were treated with 26 balloon catheter dilatations over a period of 3 years; 6 are now asymptomatic. Five of the 9 patients had suspected reflux esophagitis, confirmed in 3 by biopsy and treated medically prior to dilatation. Seven of the 9 patients had a primary anastomosis, 1 a gastric tube, and 1 a colonic interposition. Most dilatations in the group of 7 were performed with balloon (B) greater than or equal to the diameter of the distal esophagus (E) (B/E greater than or equal to 1). The 3 residually symptomatic patients include an infant dilated conservatively (B/E less than 1) to facilitate later bouginage, 1 patient with a recurrent stricture after stopping medical therapy and home bouginage, and 1 infant who had a persistent anastomotic stricture, suspected but untreated reflux esophagitis, and a perforation during the second balloon dilatation. Balloon catheter esophageal dilatation, as an alternative to bouginage, is usually a safe and effective procedure when reflux esophagitis is diagnosed and treated prior to dilatation.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In order to define the gastrointestinal manifestations and small intestinal structure and function in a group of infants with chronic nonspecific diarrhea and hypogammaglobulinemia, we retrospectively identified 55 such patients from a population of 518 children evaluated for chronic diarrhea over a 6-year span (10.6%). All patients had IgG levels 2.0 SD or more below the mean values for age. Patients with biochemical evidence of protein loss (enteropathy or nephropathy) were excluded. There was a 50% incidence of small intestinal mucosal injury among these patients, with a spectrum of morphological findings ranging from healing enteritis to severe active enteritis. Carbohydrate malasorption, and infection with Giardia lamblia or Clostridium difficile occurred in 34% and 24% of patients tested, respectively. These structural, functional, and infectious complications were all statistically more common in patients than in a control group of children with chronic diarrhea, normal growth, and normal immunoglobulin levels. This study suggests that immunoglobulin determination, in children who would otherwise carry a diagnosis of chronic nonspecific diarrhea, identifies a group with hypogammaglobulinemia, having an increased incidence of treatable intestinal dysfunction or infection, and a spectrum of small intestinal histologic abnormalities.
Chronic colitis in the cotton-top tamarin (CTT) has been characterized by obtaining distal colonic biopsy specimens, hematocrits, serum albumins, and stools for bacteriologic and parasitic examination in nondebilitated living CTTs. The species specificity of the histologic features of colitis observed in the CTT was assessed by obtaining distal colonic biopsy specimens from 10 animals of other primate species for histologic examination. Histologic evidence of active colitis was found in 50% of adult CTTs but was absent in all non-CTT species studied. Forty-two stool samples obtained from 18 CTTs yielded only one isolate (Campylobacter). In addition to active colitis, CTT rectal mucosa also often had subtle irregularities in mucosal structure that were not present in nonrelated primate species and might represent chronic colitis. Metaplasia was not observed. The therapeutic effects of oral sulfasalazine (50 mg/kg X day) on CTT colitis were assessed in a randomized 10-wk placebo controlled crossover study. This study demonstrated significant improvement in disease activity as judged histologically (p less than 0.05) and significant increases in animal weight (p less than 0.01) and serum albumin (p less than 0.01) during sulfasalazine therapy when compared with saline control. Sulfasalazine therapy can ameliorate the effects of this disease and offers promise in maintaining experimental colonies of this endangered species for future studies.
Heterogeneity of colonic mucin glycoprotein was examined in rectal mucosal biopsy specimens from a variety of primate species (Saguinus oedipus, n = 18; Macaca mulatta, n = 2; Macaca fascicularis, n = 2; Aotus trivirgatus, n = 2; Saimiri sciureus, n = 2; and Callithrix jacchus, n = 2). After initial separation of radiolabeled mucin and nonmucin glycoproteins solubilized from mucosal biopsy specimens, at least five labeled mucin components were found in monkey rectal mucosa in contrast to the six mucin fractions observed in the human colon. Although primates consistently lacked the earliest eluting component present in human colonic mucin, other mucin components cochromatographed with comparable fractions previously identified in human colonic biopsy specimens. The relative proportions of each fraction were consistent throughout all species except the cotton-top tamarin (S. oedipus), an animal that develops a chronic colitis. The cotton-top tamarin was found to have a markedly reduced amount of one mucin component (IV) in a manner analogous to the reduction in a human mucin fraction previously noted in patients with ulcerative colitis. Sequential evaluation of mucin profiles in cotton-top tamarins (n = 12) treated with sulfasalazine (50 mg/kg X day) or placebo in a 10-wk double-blind crossover study demonstrated the persistence of the selective reduction in tamarin species IV unrelated to disease activity. In contrast, the relative amount of tamarin mucin III was greater in association with increased disease activity than that observed in association with reduced disease activity (46% +/- 11% total mucin vs. 19% +/- 7% total mucin posttreatment).
Explore the source record for details and available documents.
Prolonged elevation of the serum transaminase concentration in an asymptomatic child is usually thought to be secondary to liver disease. Four children with unexplained persistent elevation of serum transaminase concentration were referred to a pediatric gastroenterologist for studies of liver disease. Subsequent evaluation disclosed abnormal muscle biopsy findings in all four patients. This experience suggests that an appropriate workup for occult myopathy is indicated in such patients before invasive diagnostic procedures for evaluation of liver disease are undertaken.
A 20-yr-old man developed recurrent respiratory symptoms and left lower lobe pneumonia 14 yr after long-segment colonic interposition for corrosive esophageal injury. A fistula, from a redundant supradiaphragmatic pouch of colon to a subsegmental bronchus of the lower lobe of the left lung, was discovered and treated successfully with surgical resection. This previously unreported complication, therefore, should be considered in patients who develop respiratory symptoms after coloesophageal interposition.
In hereditary tyrosinemia, an autosomal recessive disorder of infants, it has been postulated that hepatic toxicity arising from defective degradation of tyrosine accounts for the severe liver disease that is a feature of this condition. We measured the concentration of alpha-fetoprotein, a marker for liver disease, and of amino acid in cord blood from three infants with hereditary tyrosinemia and found that the concentration of alpha-fetoprotein was greatly increased at birth, whereas the level of tyrosine was normal or not specifically elevated, and that hypertyrosinemia developed only postnatally. These results indicate that liver disease is prenatal in hereditary tyrosinemia and that therapy aimed at reduction of the elevated tyrosine level is unlikely to be of fundamental value.
Controversy exists regarding the value of gross mucosal changes of the esophagus at the time of endoscopy in predicting histologic esophagitis. Accordingly, we reviewed the records of 279 pediatric patients who underwent both an upper endoscopy and simultaneous grasp esophageal biopsy. Of those patients with no gross mucosal abnormalities, 30% had evidence of esophagitis on biopsy. Similarly, there was a poor association between the presence of endoscopic findings and histologic esophagitis. We conclude that gross esophageal mucosal changes are poor predictors of histologic esophagitis and that endoscopic evaluation alone is inadequate for children and adolescents in whom esophagitis is suspected. Esophageal biopsies should be obtained in all such patients, even when no gross mucosal abnormalities are found.
Lymphokine production by newborn lymphocytes was assessed by measuring migration inhibition factor (MIF) and leukocyte inhibition factor (LIF) of isolated mononuclear cells from cord blood, 1-7-days-old newborns, and adult controls. Ficoll-Hypaque separated mononuclear cells were stimulated with phytohemagglutinin (PHA) or allogeneic lymphocytes in a mixed leukocyte culture (MLC), and the supernatants were harvested at optimal times for lymphokine assays. Thymidine incorporation into DNA was also assayed to calculate a proliferative index. MIF was assessed by the inhibition of adult mononuclear phagocyte cell migration under agarose; LIF was assessed by polymorphonuclear cell migration under agarose. Although the proliferative responses of cord and newborn cells are equivalent or greater than those of adult controls, the PHA-induced MIF production in cord blood and newborn lymphocytes was only 46% and 12.5% respectively of mean adult levels; MLC-induced MIF production was 44% and 7%, respectively of mean adult levels. PHA-induced LIF production in cord blood was 27% of adult levels. These differences are only appreciated if dilutions of the supernatants are assayed. Simultaneous assay of MIF and LIF production in dilution of supernatants from adult lymphocytes showed higher LIF activity, whereas in cord lymphocytes MIF activity was greater than LIF activity. This further emphasizes the non-identity of MIF and LIF. These results indicate another abnormality of T cellular immunity in newborns not detected by T-cell enumeration or proliferative responses and parallels other defects in specialized T cell function such as cytotoxicity and immune interferon production.
The evaluation of mucosal cellular immune function in the gastrointestinal tract has focused on properties of lymphocytes. We describe methods for use in guinea pig and human tissue that will now permit the maintenance and in vitro study of intestinal macrophages. This study characterizes the resident gastrointestinal macrophage population in the two species and shows that morphologic and ultra-structural characteristics are similar to macrophages from other tissues. Histochemically, the cells are esterase positive and peroxidase negative. They possess surface receptors for immunoglobulin G and complement, and are phagocytic via the Fc receptor.