Helicobacter pylori and the etiology of duodenal ulcer: necessary but not sufficient.
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Biomedical subjects
Publications and source records attributed to M Feldman.
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The effects of age on basal, meal-stimulated, and human gastrin-17-stimulated gastric acid secretion rates and serum pepsinogen concentrations were evaluated in 41 healthy men and women. Older subjects (ages 44-71 years; mean, 57 years) had higher mean basal, meal-stimulated, and gastrin-17-stimulated acid secretory rates and basal serum pepsinogen I and II concentrations than younger subjects (ages 23-42 years; mean, 33 years). Age-related differences in acid secretion were especially prominent in men, and age-related differences in serum pepsinogen I and II concentrations were more prominent in women. Higher gastric acid secretion rates in older subjects could not be explained by body size (height, weight, body surface area, or fat-free body mass) or by the higher incidence of infection with Helicobacter pylori. Using a multivariate linear regression model, age had an independent positive effect on acid secretion, and H. pylori infection had an independent negative effect. It was concluded that aging is associated with an increase in gastric acid secretion in humans, especially in men, while infection with H. pylori is associated with lower acid secretion rates.
Secondary bone grafting of residual alveolar clefts has become an integral part of the comprehensive care of children born with facial clefting. Although indications and timing may remain somewhat controversial, bone grafting during the period of mixed dentition has gained widespread acceptance. A number of bone graft sites have been proposed; each has its enthusiastic proponents. We believe that cancellous bone harvested from the ilium provides optimal material to achieve successful alveolar bone grafting. Unfortunately, this site has been associated with significant morbidity, primarily pain, which can prolong a patient's hospitalization. We relate our experience from two centers encompassing 24 patients who underwent percutaneous harvesting of corticocancellous bone grafts from the ilium. With this method we were successful in obtaining adequate quantities of corticocancellous bone with the Craig bone biopsy needle regardless of the cleft size. Each patient was able to ambulate without difficulty within hours of surgery. We are currently performing alveolar bone grafting as an outpatient procedure employing this technique. In addition, we believe this method has particular usefulness in Third World countries.
In conscious, gastric fistula rabbits, gastric acid and pepsin secretion averaged 4.5 +/- 0.1 mmol/h (1.3 mmol.kg-1.h-1) and 4.9 +/- 0.3 IU/h (1.6 IU.kg-1.h-1), respectively; these values represent approximately 40-50% of maximal output. Basal serum gastrin concentrations averaged 24 +/- 4 pg/ml and did not correlate with basal acid secretion. Atropine and vagotomy incompletely inhibited basal acid secretion (by 84 and 50%, respectively) and completely inhibited 2-deoxy-D-glucose-stimulated gastric acid secretion. Atropine and vagotomy similarly inhibited basal pepsin secretion by 50 and 40%, respectively. Ranitidine decreased acid and pepsin secretion, but as with atropine, inhibition was not complete (73 and 37%, respectively). Although omeprazole did not affect pepsin secretion, omeprazole completely inhibited basal acid secretion and elevated postprandial intragastric pH above 5.0. Conscious, gastric fistula rabbits have the highest basal acid and pepsin output among species commonly studied. Both vagal-cholinergic pathways and histamine drive basal acid and pepsin secretion in the rabbit.
We examined the relationship between gastric HCO3- and Na+ secretion under fasting and sham-fed conditions in nine healthy men and also evaluated the effect of the carbonic anhydrase inhibitor acetazolamide on gastric secretion of HCO3- and Na+. Secretion of H+, K+, and Cl- were also measured. Gastric HCO3- secretion rates under fasting and sham-fed conditions closely paralleled Na+ secretion rates. A maximally tolerated intravenous dose (10 mg/kg) of acetazolamide significantly inhibited H+, Cl- and K+ secretion but did not significantly affect Na+ or HCO3- secretion. Thus the gastric mucosa secretes HCO3- and Na+ in parallel in humans both under fasting and sham-fed conditions. Relative to parietal secretion of HCl, nonparietal secretion of HCO3- and Na+ is resistant to carbonic anhydrase inhibition.
T cell lines and clones were derived by coculturing peripheral blood mononuclear cells from young children with newly diagnosed insulin dependent diabetes mellitus (IDDM) with sonicates of HLA-DR haploidentical human islet cells. These cells proliferated in response to human islet cell sonicates but failed to do so when stimulated with sonicates of human exocrine pancreas or thyroid gland. Preparations of islet cells obtained by repeated freezing and thawing also stimulated proliferation of the lines but purified membrane or protein preparations of the islet failed to induce proliferation, suggesting that determinants recognized by T cells were lost on further purification. This method of deriving T cell lines and clones appears to be significantly easier and quicker than non-antigen cloning using anti CD3.
Split-thickness skin grafting of the foot following a burn injury provides excellent coverage to promote early rehabilitation and to facilitate healing. When compared to a more slowly healing, cosmetically unacceptable secondary granulation process, grafting is especially important for the young, active patient for whom hospitalization and immobilization are difficult to maintain. Cosmetic results are also a great concern, especially in the female sector of this age group. The case presentation shows grafting as a successful means of treatment in consideration of these primary goals.
Metastatic clones of murine tumors that manifest impaired expression of class I MHC antigens do not induce an antitumor CTL activity. Transfection of H-2Kb genes into D122 carcinoma and B16 melanoma clones converted these cells to low metastatic immunogenic clones that can be used to protect in vivo against metastases of parental clones. Amplification of the protective effect can be achieved by combination of syngeneic and allogeneic MHC class I genes. Studying the mechanisms involved in MHC class I suppression in tumor cells, we found that changes in H-2 promoter activity were the cause of low expression. Proteins that might be involved were demonstrated by migration retardation methods. The involvement of the fos-jun complex in regulation of MHC expression is discussed.
The Care Windows development project demonstrated the feasibility of an approach designed to add the benefits of an event-driven, graphically-oriented user interface to an existing Medical Information Management System (MIMS) without overstepping economic and logistic constraints. The design solution selected for the Care Windows project incorporates three important design features: (1) the effective de-coupling of severs from requesters, permitting the use of an extensive pre-existing library of MIMS servers, (2) the off-loading of program control functions of the requesters to the workstation processor, reducing the load per transaction on central resources and permitting the use of object-oriented development environments available for microcomputers, (3) the selection of a low end, GUI-capable workstation consisting of a PC-compatible personal computer running Microsoft Windows 3.0, and (4) the development of a highly layered, modular workstation application, permitting the development of interchangeable modules to insure portability and adaptability.
The treatment of cancer through the action of natural host defense mechanisms has been the goal of basic research and medicine. Expanding our understanding of the structure and function of major histocompatibility antigens (MHC) and of their interaction with peptide antigens in T cell immunity, and integrating it with the emerging data on the nature of tumor rejection antigens, may advance our ability to manipulate the immunogenicity of tumors. Downregulation of MHC class I in murine tumors and human tumors and the manipulation of some experimental systems is described.
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Transfection with c-fos genes of cells of a highly metastatic (H-2K- H-2D+) clone, DI22, of the 3LL carcinoma, causes activation of H-2K gene expression. Experiments were carried out to test whether these transfectants exhibit reduced metastatic competence. Studying II mouse c-fos, 6 mouse c-fos and 2 v-fos transfected clones, we observed that clones expressing high steady-state levels of the fos mRNA also expressed elevated levels of H-2K and H-2D mRNA, and high levels of cell-surface H-2K and H-2D glycoproteins. The transfectants were tested for generation of spontaneous metastasis following intra-footpad inoculation of the tumor cells. Clones expressing high levels of fos and of H-2 antigens, particularly those expressing high levels of cell-surface H-2Kb molecules, showed a reduction of their metastatic competence. Statistical analysis revealed that c-fos transfectants are significantly less metastatic than the parental cells. The molecular mechanisms of c-fos activation of H-2 genes is briefly discussed.
Gastric mucosal prostaglandin E2 and F2 alpha content was evaluated in healthy human subjects who received either fish oil or olive oil (control) daily for 3 wk before exposure to aspirin or no aspirin. Two hours after aspirin administration, when mean serum salicylate concentration was approximately 12 mg/dl, gastric mucosal prostaglandin E2 and F2 alpha content was reduced by greater than 95% in the fundus and antrum (p less than 0.001) and there was endoscopic evidence of gastric mucosal damage (erosions, submucosal hemorrhages). Fish oil feeding had no significant effect on mucosal prostaglandin E2 or F2 alpha content or on the damaging effect of aspirin on the stomach, despite the fact that fish oil reduced serum triglyceride concentrations significantly. These studies indicate that the damaging effects of aspirin on the gastric mucosa are not influenced by dietary fish oil.
Vagotomy is known to reduce acid secretion and to increase serum gastrin concentrations. However, there is minimal information on the effect of vagotomy on parietal cell mass or gastrin cell mass. Basal and maximal acid secretions and fasting serum gastrin concentrations were measured in 22 gastric fistula dogs with pyloromyotomy before and up to 56 days following complete bilateral truncal vagotomy (n = 11) or sham vagotomy (n = 11). Dogs underwent total gastrectomy on postoperative days 9 (n = 5 per group) or day 56 (n = 6 per group). Parietal cells were stained with Luxol fast blue and parietal cell mass determined with computer-assisted histomorphometry. Parietal cell mass averaged 10.68 +/- 0.90 billion in control dogs and correlated significantly with maximal acid output (r = 0.76; P less than 0.01). Vagotomy reduced maximal acid output by 40%-50% (P less than 0.001) but had no significant effect on parietal cell mass (8.99 +/- 1.00 billion). Vagotomy increased serum gastrin concentrations significantly, but antral gastrin cell mass in vagotomized dogs (5.66 +/- 1.00 million) was not significantly different than that in control dogs (4.74 +/- 0.50 million). Thus, vagotomy did not lead to parietal cell hypoplasia or gastrin cell hyperplasia despite profound alterations in parietal cell and gastrin cell function.
The effects of a 7.5-day course of orally administered salsalate (3.0 g/day), aspirin (3.9 g/day), or placebo on gastroduodenal mucosal injury, mucosal prostaglandin content, and plasma prostaglandin concentrations in healthy, asymptomatic human volunteers were examined. Mean serum salicylate concentrations after these doses of salsalate and aspirin were nearly identical (approximately 15 mg/dL). When the gastroduodenal mucosa was assessed endoscopically 1 hour after the final dose of medication, there was minimal mucosal injury in placebo-treated or salsalate-treated subjects and considerable injury in the stomach and duodenum of aspirin-treated subjects (P less than 0.001, aspirin vs. salsalate or placebo). In both the stomach and duodenum, aspirin lowered mucosal prostaglandin F2a and E2 content by greater than 90% (P less than 0.001), whereas salsalate produced no significant change. Aspirin also lowered plasma prostaglandin F2a concentrations by 58% +/- 6%, whereas salsalate lowered them by only 11% +/- 9% (P less than 0.001). Thus, the nonacetylated salicylate, salsalate, produced much less gastroduodenal mucosal damage than aspirin at equivalent serum salicylate concentrations, possibly because salsalate did not inhibit mucosal prostaglandin synthesis.
Neonatal sacrococcygeal teratoma (SCT) is a rare and potentially malignant tumor. We report on four cases of neonatal SCT, in which ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) were used preoperatively to accurately establish the extent of the tumor and its relationship to the surrounding anatomic structures. This approach facilitates complete surgical resection and optimal outcome.
Taenia solium cysticercosis is now recognized as a priority in Mexico and a number of other developing countries, both in public health and in economic terms. Recognition of the problem has been greatly aided in recent years by new developments in molecular diagnostics. In this paper data are presented on ELISA for the detection of anti-cysticercus antibodies and of parasite antigens in patients with neurocysticercosis and in cysticercotic pigs. Also, several biological fluids were evaluated: cerebrospinal fluid (CSF), serum and saliva, all of which have proved useful. CSF is, however, the most appropriate for detection of antibodies and antigens in patients and serum in pigs. In addition, saliva may be especially used in epidemiological surveys. The electroimmuno-transfer blot technique (EITB) for antibody detection in patients and pigs has also proved highly sensitive and due to the use of an enriched fraction of glucoproteins, EITB is also highly specific. Cloned cDNA sequences from T. solium are now being assessed as an alternative source of antigens for immunodiagnosis. Two methods for the diagnosis of the adult stage of T. solium are also undergoing standardization. These are an ELISA for the detection of parasite antigens in fecal samples and DNA hybridization techniques for the detection of eggs in stools. Both assays have promising results and should now be assessed in larger numbers of clinical and epidemiological samples.