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Biomedical subjects

W A Walker

Publications and source records attributed to W A Walker.

At least 91 records · Page 5Linked to original sources
PubMed1993

Necrotizing enterocolitis: research agenda for a disease of unknown etiology and pathogenesis.

Necrotizing enterocolitis (NEC) is a significant neonatal public health problem that affects low-birth weight infants in neonatal intensive care units throughout the country. As the survival rate of low-birth weight infants continues to increase and as the number of low-birth weight births remains unchanged, we can anticipate that NEC will continue to be a cause of significant morbidity and mortality in the future. Despite many reports about NEC that describe demographic risk factors and short-term or long-term outcome, there is a paucity of basic science information about neonatal gastrointestinal physiology and pathophysiology in human preterm and even full-term infants. It has become increasingly evident that we need a much better understanding about the developmental aspects of gastrointestinal function in health and disease before we can achieve further advances in our understanding of and thus rational therapy for and prevention of NEC. The purpose of the National Institute of Child Health and Human Development conference "Necrotizing Enterocolitis: Basic Science Approaches to Gut Maturation and Pathogenesis" was to bring together basic science investigators, clinical epidemiologists, and clinical scientists to identify important areas of research that need to be applied to the problem of NEC. The concept of applying the "bench to bedside" type of collaborative research was emphasized and encouraged because many clinical neonatologists may have little scientific interaction with basic scientists. In addition, many basic scientists may be unaware of NEC and the implications for targeted research related to this disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Digestive System↗
PubMed1993

Differential regulation of B7 mRNA in enterocytes and lymphoid cells.

To investigate the molecular details of antigen presentation by cells of lymphoid or epithelial origin, we compared B7 mRNA regulation in intestinal epithelium with that in spleen, since both cell types express class II major histocompatibility complex (MHC) and present antigen. As measured by cDNA amplification using sequence-specific primers, I-A beta mRNA content was found to be similar in mouse full-thickness small intestine, isolated intestinal epithelial cells and spleen. However, in contrast to I-A beta, B7 mRNA intestinal epithelial cell content was markedly lower than in spleen and whole small bowel; cardiac RNA was negative for both sequences. Administration of intraperitoneal interferon-gamma (IFN-gamma) (10(5) U daily for 2 days) to adult mice resulted in an increase in I-A beta mRNA in epithelial cells, but did not alter levels of B7 mRNA. In addition, exposure of the IEC-6 rat cell line to the IFN-gamma resulted in a dose-dependent increase in I-A beta mRNA without altering levels of B7 mRNA. Thus, an apparent dichotomy exists in regulation of B7 and I-A beta gene expression in rodent intestinal epithelial cells. Since maximal T-cell response to splenocytes depends on B7, the absence of B7 mRNA in intestinal epithelium may be a factor in determining why antigen-presenting enterocytes normally do not elicit damaging T-cell proliferative responses.

Animals↗
PubMed1993

Influence of prenatal corticosteroids on bacterial colonization in the newborn rat.

The interactions between bacteria and the host's intestinal barrier appear to be important regulators of bacterial colonization. In this study we investigated the effect of prenatal corticosteroids, known to accelerate the intestinal maturation of newborn rats, on bacterial colonization in the rat pup. Pregnant rats were treated with either cortisone acetate or normal saline on days 18-21 of gestation and were allowed to deliver spontaneously. The pups, after normal delivery, were sacrificed at different times during the first 10 days of life. The entire small intestine was removed, and each lumen was flushed to exclude nonadherent, transient organisms and homogenized. Tenfold dilutions were plated on horse-blood agar (total bacteria) and MacConkey's medium (gram-negatives). Quantitation and bacterial typification was determined after 24 h of incubation at 37 degrees C. Total bacteria and gram-negatives found in association with the mucosa were significantly lower in pups prenatally treated with steroids. These changes were not related to any changes in motility or intraluminal digestion. This suggests that the developmental condition of the host's intestinal barrier may be an important regulator of the bacterial microenvironment of the newborn small intestinal mucosa.

Animals↗
PubMed1993

Immunoglobulin G binding sites on the human foetal intestine: a possible mechanism for the passive transfer of immunity from mother to infant.

In humans, the prenatal transfer of IgG from mother to foetus is facilitated by a receptor for IgG on the placenta. However, amniotic fluid contains IgG of maternal origin, and transfer of swallowed IgG into the circulation from the foetal intestine represents another potential pathway of passive immunization. In this study we assayed for a foetal intestinal IgG receptor to support the hypothesis of this alternate pathway of antibody transfer. Microvillous membrane (MVM) from small bowel of aborted foetuses (18 weeks gestation) were probed with [125I]IgG to detect specific IgG binding sites. Binding was pH dependent and was maximal at pH 6. Competitive inhibition of the binding of [125I]IgG was noted with the addition of increasing amounts of unlabelled IgG. Scatchard analysis showed one binding site with a dissociation constant of 1.58 x 10(-7), similar to that of the IgG receptor described on the suckling rat intestine. The binding of labelled IgG to the human MVM receptor was Fc mediated. These observations provide evidence for an Fc receptor on the human foetal intestine.

Binding Sites↗
PubMed1992

Migration of intravascular balloon after percutaneous embolotherapy of varicocele.

Migration of an intravascular balloon following embolic therapy for varicocele is uncommon. A third case is reported of migration of a left internal spermatic vein embolic balloon to the right lung in an otherwise healthy twenty-five-year-old male who was treated for a symptomatic left varicocele. The patient, a student naval aviator in the jet pilot program, has had his career adversely affected by this complication.

Adult↗
PubMed1992

Expression and developmental regulation of Na+,K+ adenosine triphosphatase in the rat small intestine.

The Na+,K(+)-ATPase ion pump plays a critical role in fluid and electrolyte physiology of the small intestine. Here we show that, of the three known alpha isotypes (alpha 1, alpha 2, and alpha 3) of the sodium pump found in the rat, only alpha 1 is expressed in the small intestine. The expression of this isotype, considered at the level of mRNA, is under developmental control, with the adult intestine exhibiting approximately a threefold increase in alpha 1 message over the neonate. Cortisone treatment of the neonate results in near-adult levels of alpha 1 mRNA expression. An increase in the abundance of alpha 1 isotype parallels the changes in its mRNA expression. beta subunit mRNA is expressed coordinately with the alpha 1 subunit mRNA. A four- to five-fold rise in the Na+,K(+)-ATPase activity is also developmentally induced.

Age Factors↗
PubMed1992

Diminished Clostridium difficile toxin A sensitivity in newborn rabbit ileum is associated with decreased toxin A receptor.

Human infants are relatively resistant to Clostridium difficile-associated diarrhea and colitis compared to adults. In that toxin A is the major cause of intestinal damage with this organism, we compared toxin A receptor binding and biological effects in newborn vs adult rabbit ileum. Purified toxin A (M(r) 308 kD) was labeled with tritium or biotin with full retention of biologic activity. Appearance of specific toxin A brush border (BB) binding was strongly age dependent with minimal [3H]toxin A specific binding at 2 and 5 d of life, followed by gradual increase in binding to reach adult levels at 90 d. Absence of toxin A binding sites in newborn and presence in adult rabbits was confirmed by immunohistochemical studies using biotinylated toxin A. Toxin A (50 ng to 20 micrograms/ml) inhibited protein synthesis in 90-d-old rabbit ileal loops in a dose-dependent fashion. In contrast, inhibition of protein synthesis in 5-d-old rabbit ileum occurred only at the highest toxin A doses (5 and 20 micrograms/ml) and at all doses tested was significantly less than the adult rabbit ileum. In addition, toxin A (5 micrograms/ml) caused severe mucosal damage in adult rabbit ileal explants but had no discernable morphologic effect on 5-d-old rabbit intestine. Our data indicate that newborn rabbit intestine lacks BB receptors for toxin A. The absence of the high-affinity BB receptor for toxin A in the newborn period may explain lack of biologic responsiveness to purified toxin, and the absence of disease in human infants infected with this pathogen.

Age Factors↗
PubMed1992

The mucosal barrier, IgE-mediated gastrointestinal events, and eosinophilic gastroenteritis.

The "mucosal barrier" plays an important role in regulating immune responses in the gastrointestinal tract. Although the precise mechanisms controlling mucosal immune responses have not been defined, when an abnormal response such as IgE production is initiated, a variety of complex and incompletely understood pathophysiologic events occur and can result in gastrointestinal pathology. This article attempts to present the complexity of such abnormal responses. Although more questions have emerged than were answered, in recent years our knowledge of the pathophysiology of IgE-mediated events in the gastrointestinal tract has advanced significantly. Our understanding of the pathophysiology of these events will ultimately allow the development of more directed and effective therapeutic interventions for allergic gastrointestinal diseases. In addition, through further clinical and basic research, we should begin to unravel the more enigmatic conditions affecting the gastrointestinal tract, such as EG.

Acute Disease↗
PubMed1991

Delayed chest wall pain due to sternal wire sutures.

This report describes 18 patients with disabling chest wall pain due to one or more sternal wire sutures. The pain occurred from 2 to 84 months after a median sternotomy. The pain was described either as sharp and stabbing or as a deep-seated ache. The involved wires had an exaggerated fibrous tissue reaction surrounding the twisted portion. The adjacent noninvolved wires had minimal reaction. In the last 7 patients, serial sections of the fibrous tissue revealed entrapment of one or more sensory nerve fibers. In 6 of the 7 electrical potentials were measured and found to be elevated, indicating wire damage during twisting. Ferroxyl tests confirmed the collection of iron ions at this anodic point as a result of corrosion. Removal of the involved wires and the fibrous tissue surrounding this anodic point relieved the symptoms of pain and tenderness resulting from entrapped sensory nerves.

Bone Wires↗
PubMed1991

Primary Aspergillus osteomyelitis of the sternum.

We report 2 cases of primary sternal osteomyelitis caused by Aspergillus; previously reported cases have been complications of sternotomy. Both patients were healthy young men with recent intravenous drug abuse. No other focus or predisposing factors were found. Both were treated with partial sternectomy and chondrectomy; 1 received long-term amphotericin B therapy. Both are doing well 2 1/2 years after operation. Drug usage, acquired immunodeficiency syndrome, and medical immunosuppression may lead to other cases.

Adult↗
PubMed1991

Thermally induced pulpalgia in endodontically treated teeth.

Two cases of thermally induced pulpalgia in teeth previously endodontically treated are presented. Reproduction of the patient's chief complaint was the key to identifying the teeth involved. In both cases, the pulpalgia was stimulated by heat. After locating and treating an unfilled canal, the teeth have remained asymptomatic. Possible explanations for this occurrence are discussed.

Adult↗
PubMed1991

Rapid development of vitamin K deficiency in an adolescent boy receiving total parenteral nutrition following bone marrow transplantation.

In this case report the development of a vitamin K deficiency in a neutropenic adolescent receiving parenteral nutrition following bone marrow transplantation is described. The parenteral nutrition solution did not provide vitamin K and the patient had been receiving oral antibiotics prior to and during use of the intravenous feeding. Oral intake was minimal. Standard adult oral and intravenous multivitamin preparations for use in individuals older than 11 years do not routinely contain this vitamin. The function of vitamin K and causes for development of a deficiency are reviewed. Recommended intakes and guidelines for supplementation are also discussed.

Adolescent↗