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Biomedical subjects

H S Winter

Publications and source records attributed to H S Winter.

At least 37 records · Page 2Linked to original sources
PubMed1992

Pancreatitis in pediatric human immunodeficiency virus infection.

Because pancreatitis has been reported frequently in adults with human immunodeficiency virus infection, we sought to determine the incidence of pancreatitis in children with acquired immunodeficiency syndrome by reviewing all records of children with AIDS, their serum amylase and lipase levels, and the factors associated with pancreatitis through a case-control analysis. During a 6-year period pancreatitis developed in 9 (17%) of 53 pediatric patients with AIDS. Six children had vertical transmission of infection and three patients had acquired HIV infection through contaminated blood products. Pancreatitis developed at a median age of 5.2 years (range 1.2 to 20 years). All patients had vomiting and abdominal pain. When the patients were first seen, lipase values were elevated more than amylase values (p = 0.028). Amylase and lipase levels declined at comparable rates. In the case-control analysis, pentamidine isethionate was significantly associated with pancreatitis (p = 0.02); the risk was greater in patients who received pentamidine isethionate and had absolute CD4 T-lymphocyte counts less than 100 cells/mm3 (p = 0.001). Infections associated with the onset of pancreatitis included cytomegalovirus (4), Cryptosporidium (1), Pneumocystis carinii pneumonia (3), and Mycobacterium avium intracellulare (1). Coinfection with cytomegalovirus was associated with a protracted course in four children. Ultrasonographic examination demonstrated biliary ductal dilatation 6 months after the onset of pancreatitis in one child. Seven children have died at a mean of 8 months after the initial onset of pancreatitis; the one living child has survived 5 months from the onset of pancreatitis. We conclude that pancreatitis is common in pediatric patients with AIDS and may be related to pentamidine isethionate exposure, especially when absolute CD4 T-lymphocyte counts are less than 100 cells/mm3. Serum amylase levels do not always accurately predict the onset of pancreatitis; serum lipase levels should be measured in children with symptoms. The onset of pancreatitis in an HIV-infected child is a poor prognostic indicator.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Efficacy of domperidone in infants and children with gastroesophageal reflux.

This study sought to define the therapeutic efficacy of domperidone in infants and children with gastroesophageal reflux. A double-blind, placebo-controlled trial was performed in seventeen children (ages 5 months to 11.3 years) with moderate to severe gastroesophageal reflux who had not responded to standard nonpharmacological therapy. Subjective and objective measures (weight gain, esophageal pH probe study, radionuclide gastric emptying scan) of gastroesophageal reflux were evaluated. Therapy with domperidone for 4 weeks was effective only in reducing the total number of reflux episodes in the two-hour postprandial period (p less than 0.01); however, it did not result in symptomatic improvement or significant improvement in other measures of gastroesophageal reflux or gastric emptying. After therapy for 8 weeks symptomatic improvement was reported in some patients who had denied improvement after 4 weeks of therapy, suggesting that more than 4 weeks of therapy may be required for some patients to obtain a clinical response. Mild self-limited diarrhea was reported by six patients (four domperidone, two placebo). We conclude that domperidone is tolerated by most infants and children with gastroesophageal reflux; however, 4 weeks of therapy was only minimally effective in producing objective improvement of gastroesophageal reflux and did not result in symptomatic improvement. Further studies of longer duration are needed to resolve the question raised by this study: that domperidone may be beneficial for patients with gastroesophageal reflux when given for more than four weeks.

Child↗
PubMed1992

Carnitine deficiency: a possible cause of gastrointestinal dysmotility.

An infant with delayed development and peripheral myopathy, nourished on a soy-based liquid diet deficient in carnitine, had gastrointestinal dysmotility manifested by postprandial vomiting, oral drooling, delayed gastric emptying and infrequent bowel movements. Oesophageal manometry showed a reduced lower oesophageal sphincter pressure for age with abnormal distal motility. Serum carnitine concentration was 9.9 mumol l-1. After dietary supplementation of carnitine the gastrointestinal symptoms resolved, oesophageal manometry returned to normal, and serum carnitine increased to 37.2 mumol l-1. Dietary carnitine deficiency in infancy may be a cause of smooth muscle dysmotility of the gastrointestinal tract.

Bottle Feeding↗
PubMed1991

Human intestine matures as nude mouse xenograft.

This report describes a novel system for the study of the development and function of human intestine. Human fetal bowel transplanted into a subcutaneous tunnel on the back of athymic nude (nu/nu) mice develops a new microcirculation within 4 weeks. Tissues undergo morphological development, become similar to adult human bowel tissue, and may survive for 6 months after transplantation. Monoclonal antibody immunoperoxidase staining shows that the epithelial and some endothelial elements are of human phenotype, but the circulating blood cells and migrating mucosal lymphocytes are of mouse origin.

Animals↗
PubMed1991

Lymphocytes bearing the gamma delta T-cell receptor in normal human intestine and celiac disease.

Monoclonal antibodies to T-cell receptors were used to investigate the prevalence of the two distinct T-cell subpopulations (TCR alpha beta+ and TCR gamma delta+ cells) in the intestinal mucosa of children with celiac disease (gluten-sensitive enteropathy) as compared with normal intestinal mucosa. TCR gamma delta+ cells were rarely identified in the epithelium of human fetal or normal postnatal intestine and few were present in the lamina propria, whereas the number of distribution of TCR alpha beta+ cells closely resembled that of CD3+ cells. Compared with normal intestine, a significant increase in the number of CD3+, CD8+, TCR alpha beta+, and TCR gamma delta+ intraepithelial lymphocytes was present in celiac disease. Although the mucosal TCR gamma delta+ cells were less numerous than TCR alpha beta+ cells in celiac disease, there was a marked increase in the number of TCR gamma delta+ cells as compared with controls. The ligand recognized by the gamma delta T-cell receptor and the function of these cells have not been determined; however, these findings suggest a possible role for TCR gamma delta+ lymphocytes in mucosal immune responses and tissue injury as seen in celiac disease.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

Autoimmune enteropathy and nephropathy with circulating anti-epithelial cell antibodies.

We describe a child with circulating anti-epithelial cell antibodies, autoimmune enteropathy with intestinal villous atrophy, and membranous glomerulonephritis. The patient had persistent diarrhea at 6 months of age, and a small bowel biopsy showed active enteritis, villous atrophy, and crypt hyperplasia. When the patient was, 10 months of age, nephrotic syndrome developed because of membranous glomerulonephritis. Results of tests for circulating immune complexes were negative. Indirect immunofluorescence studies revealed a circulating antibody directed against renal epithelial cells. Circulating antibodies directed against normal small intestine epithelial cells were also detected by the immunoperoxidase technique. Western blot and immunoprecipitation identified a 55-kd antigen, in both small bowel and kidney, that reacted with an antibody in the patient's serum. High-dose prednisone therapy induced a clinical remission, resolution of the small bowel injury, and diminished serum anti-epithelial cell antibodies; after dose reduction, clinical relapse occurred with villous atrophy and reappearance of anti-epithelial cell antibodies. When the patient was 45 months of age, persistent diarrhea recurred despite intravenous administration of corticosteroids, cyclosporine, and total parenteral nutrition. Autoantibodies to a 55-kd epithelial cell protein are temporally related to the development of enteropathy and nephropathy. Study of similar patients is needed to determine the role of such antibodies in this disorder.

Atrophy↗
PubMed1991

Cloning of a human homeobox gene that resembles a diverged Drosophila homeobox gene and is expressed in activated lymphocytes.

A new homeobox gene, HB24, has been isolated from a human B-lymphocyte cDNA library. Northern blot analysis of polyadenylated RNA purified from activated human B cells revealed a single mRNA transcript of approximately 2.3 kb. Two cDNA clones were sequenced and provided 2,250 nucleotides (nt) of DNA sequence information. There is a single methionine codon-initiated open reading frame of 1,458 nt in frame with a homeobox and a CAX repeat, and the open reading frame is predicted to encode a protein of 51,659 daltons. When the homeodomain from HB24 was compared to known mammalian and Drosophila homeodomains it was found to be only moderately conserved, but when it was compared to a highly diverged Drosophila homeodomain, H2.0, it was found to be 80% identical. The HB24 mRNA was absent or present at low levels in normal B and T lymphocytes; however, with the appropriate activation signal HB24 mRNA was induced within several hours even in the presence of cycloheximide. Characterization of HB24 expression in lymphoid and select developing tissues was performed by in situ hybridization. Positive hybridization was found in thymus, tonsil, bone marrow, developing vessels, and in fetal brain. HB24 is likely to have an important role in lymphocytes as well as in certain developing tissues.

Amino Acid Sequence↗
PubMed1991

Immunology of inflammatory bowel disease: summary of the proceedings of the Subcommittee on Immunosuppressive Use in IBD.

As outlined, scanty data exist with regard to immunologic therapy in children with IBD despite the fact that the pediatric population affords a unique opportunity for clinical evaluation. Children are less affected by modifying conditions such as smoking, alcohol ingestion, and the long-term use of medications, and because of their specific needs for ponderal and linear growth, children might benefit most from immunological therapy that has been proven to be steroid sparing. Therefore, clinical trials to evaluate the efficacy of 6-MP and/or azathioprine in growing children with Crohn's disease would appear to provide a fruitful avenue for collaborative research. Efforts to organize a multicenter evaluation of these agents have been initiated. The studies are crucial in evaluating the efficacy and safety of immunosuppressive therapy in the pediatric population with IBD.

Aminosalicylic Acids↗
PubMed1991

Malnutrition and carbohydrate malabsorption in children with vertically transmitted human immunodeficiency virus 1 infection.

The nutritional needs of children with human immunodeficiency virus infection are poorly understood. Twenty-eight children with vertically transmitted human immunodeficiency virus infection were evaluated for carbohydrate malabsorption using lactose hydrogen breath tests and d-xylose absorption studies. Lactose malabsorption was a common finding in human immunodeficiency virus-infected children and occurred in 8 of 20 patients who had no identifiable enteric pathogen. Lactose malabsorption occurred at an earlier age in human immunodeficiency virus-infected children than in an age-matched group of 45 symptomatic control children (P = 0.02). However, lactose malabsorption was not associated with higher rates of diarrhea or growth failure. Abnormalities in d-xylose absorption were not significantly associated with either diarrhea or growth failure. However, 39% of d-xylose studies (9 of 23) showed abnormal results and were significantly associated with enteric infections (P = 0.004). Abnormalities in small-bowel morphology were found in 4 of 9 children with growth failure, 3 of whom had an enteric infection and low d-xylose absorption. Lactose hydrogen breath testing and d-xylose testing showed carbohydrate malabsorption in 61% of children (17 of 28). This study demonstrates that human immunodeficiency virus-infected children are at risk for malabsorptive disorders, which are not always related to clinical symptoms. We speculate that human immunodeficiency virus may be directly involved in the development of lactose malabsorption. Carbohydrate malabsorption in human immunodeficiency virus-infected children may not be the only factor responsible for growth failure.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Azathioprine in the treatment of children with inflammatory bowel disease.

During a 6-year period, we treated 21 patients with azathioprine, 2 mg/kg/day, as an adjunct to their customary regimen. Nine patients had ulcerative colitis and 12 patients had Crohn disease; the patients' ages ranged from 3 to 17 years. The median duration of disease before the start of azathioprine therapy was 2 years, and median follow-up was 2 years. Sixteen patients seemed to respond to azathioprine therapy: six patients in each disease group had complete responses and four patients (one with ulcerative colitis and three with Crohn disease) had partial responses. Two patients with ulcerative colitis and three patients with Crohn disease did not respond. The median time until patients responded was less than 3 months for patients with ulcerative colitis and 4 months for those with Crohn disease. Reduction of corticosteroid dose was possible for all patients who responded to azathioprine therapy. Only minimal side effects were attributable to the drug. We conclude that azathioprine is an effective adjunctive agent for the treatment of inflammatory bowel disease in childhood, but because questions remain regarding its long-term safety, its use should be reserved for children with refractory disease or severe and unacceptable side effects of corticosteroids.

Administration, Oral↗
PubMed1990

The distribution of T and B lymphocyte populations and MHC class II expression in human fetal and postnatal intestine.

The development of the intestinal mucosal immune barrier is an important protective adaptation for postnatal life. The distribution and phenotype of T and B lymphocytes in human fetal intestine and lymphoid tissues have been characterized and compared to the distribution and phenotype of lymphocytes in postnatal intestine. The characterization of lymphocyte phenotype and MHC class II antigen distribution was done using MAb and an avidin-biotin complex immunohistochemical staining technique. Intraepithelial lymphocytes were occasionally present in fetal intestine and were primarily CD3+, CD8+. T lymphocytes were readily identified in the lamina propria of fetal intestine, but most were clustered in lymphoid aggregates. Cells identified by anti-IgA1 and anti-IgA2 were the most numerous cells of B cell lineage in the lamina propria of postnatal intestine, whereas IgM+ and IgD+ lymphocytes predominated in fetal tissues. However, IgA-bearing cells were identified in lymphoid aggregates of the intestine or spleen of some fetuses. This finding suggests that B lymphocytes can undergo Ig switching in utero. Additionally, fetal intestinal epithelial cells did not express MHC class II antigens, unlike some postnatal intestinal tissues. It is possible that postnatal events such as antigen exposure may be important for the induction of these class II antigens on intestinal epithelial cells.

B-Lymphocytes↗
PubMed1990

Allergy-related proctocolitis in infants: diagnostic usefulness of rectal biopsy.

To evaluate the diagnostic utility of rectal mucosal biopsies in infants with proctocolitis, we compared the clinical and histologic features of an allergy-related group (N = 36) with those of normal (N = 12) and inflammatory (N = 8) controls. Clinical features were nondiscriminatory among the three groups of patients, except for an increased absolute peripheral eosinophil count in the allergic group. Similarly, morphologic evidence of proctitis (cryptitis and crypt abscesses) and small or moderate numbers of eosinophils (less than or equal to 60 per ten high power fields) in the lamina propria of the biopsies did not discriminate among the three groups. However, large numbers of eosinophils (greater than 60 per ten high power fields) and eosinophils located in the muscularis mucosae or as the predominant cell in crypt abscesses were significantly associated with allergy-related disease. No histologic features of chronic colitis were noted in the allergy-related group. Thus, in tandem with the remainder of the clinical data, rectal mucosal biopsy is a useful adjunct in the diagnosis of allergic proctocolitis.

Biopsy↗
PubMed1989

The alpha 1-antitrypsin gene is expressed in a human intestinal epithelial cell line.

alpha 1-Antitrypsin (alpha 1-AT) is considered a typical plasma protein and a prototype of the serine proteinase inhibitor (serpin) family. It is synthesized in hepatocytes and, to a lesser extent, in macrophages. In this study we show that the alpha 1-AT gene is also expressed in human intestine and in a human colonic epithelial tumor cell line, Caco2. A single 1.6-kilobase alpha 1-AT-specific mRNA is present in jejunum and in Caco2 cells. It is identical in apparent size to that present in human hepatoma HepG2 cells but slightly smaller than that present in human macrophages, cells in which an alternative upstream transcriptional start site is used. Synthesis and secretion of alpha 1-AT in Caco2 cells is similar to that in HepG2 cells. It is synthesized as an approximately 52-kDa precursor polypeptide, converted to its mature, fully glycosylated 55-kDa form intracellularly, and the native protein is secreted with a half-time of 37 min. Functionally active alpha 1-AT is secreted into the basolateral and apical (luminal) fluid in pulse-chase labeling experiments of Caco2 cells cultured in polarized orientation on collagen-coated nitrocellulose membranes. Expression of alpha 1-AT in Caco2 enterocytes is not affected by soluble factors that regulate expression of alpha 1-AT in macrophages and hepatocytes. However, expression of alpha 1-AT increases markedly in Caco2 cells as they differentiate into enteric villous-type cells.

Adenocarcinoma↗
PubMed1989

Expression of immune sensitization to epithelial cell-associated components in the cotton-top tamarin: a model of chronic ulcerative colitis.

Chronic colitis is present in up to 50% of adult cotton-top tamarins, but the etiology is unknown. To explore one putative immunopathogenic pathway for the chronic colitis, we determined whether immune sensitization to macromolecules associated with mucosal epithelium of intestine (designated ECAC) had occurred in this primate species. Specifically, we sought to define (a) whether antigenic determinants associated with ECAC are present on tamarin gut epithelium in vivo; (b) if immunoglobulin, capable of binding ECAC, is detectable in tamarin serum; (c) whether the presence of ECAC-specific immunoglobulin is positively correlated with age of the animal or the severity of the colitis, or both; and (d) the number of glycoprotein fractions composing ECAC (denoted as P1 through P4) that are reactive with tamarin immunoglobulin. Expression of ECAC was found by immunofluorescence using characterized oligo-specific or monoclonal antibody: tamarin intestinal epithelium--but not lamina propria, muscularis mucosae, subserosa, or glycocalyx--demonstrated determinants of the ECAC antigen system. Furthermore, coded sera from 10 tamarins with biopsy-proven inflammation involving colonic intestinal mucosa and in which disease activity was moderate to severe showed ECAC-specific cytotoxicity of 3.6% +/- 1.6%. Test values for 9 of 10 of those animals were above the upper limit of normal for the assay (2.1%), and exceeded the level of lysis found with serum from histologically normal tamarins less than 2 yr old (less than 0.3%). When the data were reanalyzed by age of the animal, the incidence of ECAC-specific cytotoxicity correlated with age greater than 2 yr (r = 0.86, p less than 0.001). Epithelial cell-associated component-specific serum binding was confirmed by a second methodology (enzyme-linked immunosorbent assay), where the A405 for tamarins with lesions of moderate-severe grade (0.35 +/- 0.26) clearly exceeded that for young tamarins who were histologically normal (0.02 +/- 0.039) (p less than 0.05). Most of the reactivity was directed toward the P1 fraction of ECAC. Thus, immune sensitization to a fraction of macromolecules associated with colonic epithelium has been found in the cotton-top tamarin, analogous to findings in humans with chronic inflammatory bowel disease.

Animals↗
PubMed1989

Surgical treatment of pancreas divisum causing pancreatitis in children.

Although controversial, pancreas divisum has been implicated as a cause of acute pancreatitis when there is stenosis of the accessory papilla that drains the duct of Santorini. Over the past 5 years, four children with pancreas divisum and recurrent pancreatitis were successfully treated surgically. The diagnosis was made by endoscopic retrograde cholangiopancreatography (ERCP) in each case. Surgical treatment included sphincteroplasty to the accessory papilla to improve drainage of the duct of Santorini, opening the ampulla of Vater to expose the ostium of the duct of Wirsung to enlarge it, and cholecystectomy.

Acute Disease↗