Gastric mucosal biopsy via a nasogastric tube: a nonendoscopic method for diagnosing fundic and antral mucosal gastritis and Helicobacter pylori infection in man.
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Adult↗
Biomedical subjects
M Feldman
Publications and source records attributed to M Feldman.
Omeprazole prevents indomethacin-induced gastric ulcers in rabbits.
BACKGROUND: The role of gastric acid in the development of non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulcers is unclear. The aim of this study was to determine the effect of the proton pump inhibitor omeprazole on the formation of indomethacin-induced gastric ulcers in a rabbit model. METHODS: Twenty-four rabbits were randomly divided into four groups and treated as follows: vehicle for indomethacin; vehicle for omeprazole; indomethacin (20 mg/kg b.d. subcutaneously for seven doses); and indomethacin plus omeprazole (both at 20 mg/kg b.d. subcutaneously for seven doses). On day 4 (after the seventh injection), rabbits were sacrificed, and gastric mucosal injury and prostaglandin formation were assessed. RESULTS: Subcutaneous administration of 20 mg/kg omeprazole b.d. caused a profound suppression of gastric acidity (i.e. pH above 5.0 continuously). This same dose of omeprazole significantly reduced gastric ulcer formation induced by indomethacin despite significant (> 80%) inhibition of gastric mucosal prostaglandin E2 (PGE2) formation. CONCLUSION: We conclude from these observations that gastric acid plays a critical role in the formation of indomethacin-induced gastric ulcers in rabbits.
Animals↗
Effects of aging and gastritis on gastric acid and pepsin secretion in humans: a prospective study.
BACKGROUND & AIMS: Recent studies suggesting that gastric secretion does not decrease with aging included few elderly individuals and measured only acid secretion. The aims of this study were to measure gastric acid and pepsin output in 206 health Americans (age range, 18-98 years) and to compare secretion rates with gastric histology. METHODS: Immediately after basal and pentagastrin-stimulated acid and pepsin outputs were measured, oxyntic biopsy samples were obtained. RESULTS: Gastric acid and pepsin output rates were similar in young (age range, 18-34 years) and middle-aged (age range, 35-64 years) groups. Stimulated acid output was reduced approximately 30% in the elderly (age range, 65-98 years). However, after adjustment for histology, Helicobacter pylori infection, and other variables, age had no independent effect on acid output. The decline in acid secretion in the elderly was primarily related to a higher prevalence of chronic atrophic gastritis and a lower prevalence of smoking. Pepsin output was reduced by approximately 40% in the elderly. After adjustment for other variables, age remained a robust predictor of reduced pepsin output. CONCLUSION: Although advancing age has no independent effect on gastric acid secretion, it is associated with reduced pepsin output independent of atrophic gastritis, H. pylori infection, and smoking.
Adolescent↗
Role of tyrosine kinases, protein kinase C, and protein kinase A in the regulation of interferon-alpha production induced by herpes simplex virus type 1.
Herpes simplex virus 1 (HSV-1) is able to induce interferon-alpha production by natural IFN-alpha-producing cells. In this study, signal transduction in this process was examined. It was found that sequestering of calcium by EGTA abolished IFN-alpha induction by HSV-infected cells. Stimulation of human PBMC by HSV-1-infected fibroblasts resulted in the production of inositol triphosphate (InsP3) and tyrosine phosphorylation of cellular proteins. The protein kinase C inhibitor, H7, and the tyrosine kinase inhibitor, herbimycin A, were able to suppress IFN-alpha gene expression as determined by IFN bioassay and RT-PCR. An IFN-alpha-specific ELISpot assay revealed that herbimycin A and H7 remarkably decreased the number of IFN-alpha-producing cells. PMA or calcium ionophore A23187 alone did not increase IFN-alpha production. However, PMA in conjugation with ionophores increased IFN-alpha production as early as 2 h. HA1004 and 2',5'-dideoxyadenosine, which are potent inhibitors of PKA pathway, had no effect on IFN-alpha production. In contrast, BrcAMP, a specific PKA activator, inhibited the IFN-alpha secretion and number of IFN-alpha-producing cells and to a lesser extent reduced the level of IFN-alpha mRNA. Our results indicate that protein kinase C, tyrosine kinases, and protein kinase A are involved in the regulation of IFN-alpha production in response to HSV-1.
Base Sequence↗
Absence of clinical, virological, and immunological signs of progression in HIV-1-infected patients receiving active anti-interferon-alpha immunization: a 30-month follow-up report.
Twenty-seven HIV-1-infected patients, 16 at early stage of disease and without concomitant antiretroviral therapy and 11 at more advanced stage of disease receiving antiretroviral therapy, have been followed since their enrollment, November 1992 and July 1993, respectively, in phase I/II studies to evaluate safety and immunogenicity of an anti-interferon-alpha (IFN-alpha) vaccine, aimed at modulating the impaired cytokine network in AIDS patients by counteracting IFN-alpha overproduction. We compared clinical, virological, and immunological markers of disease progression, including circulating IFN-alpha levels in a 24- to 30-month follow-up period with those of 62 patients fulfilling the same enrollment criteria and comparable for sex, risk factor, and age, regularly followed at our center. Anti-IFN-alpha immunization consisted of four-six intramuscular injections 1 month apart of a water-in-oil emulsion of 500 micrograms formalin-inactivated recombinant IFN-alpha-2b (iIFN-alpha) followed by intramuscular injections of 250 micrograms iIFN-alpha adsorbed onto calcium phosphate every 3 months. Neither clinical deterioration nor a CD4+ cell count decrease from pretreatment values was observed in IFN-alpha-immunized patients in the follow-up period, whereas clinical and immunological disease progressions were observed among open-comparison patients. Furthermore, statistical analysis showed a strong association between occurrence of clinical manifestations and high circulating IFN-alpha titers, while nonprogression of IFN-alpha-immunized patients was associated with decreased levels of circulating IFN-alpha.
Adolescent↗
Utilization of tests for Lyme disease antibody at a university hospital.
We performed a retrospective study on patients who had a positive screening antibody test result for antibody to Borrelia burgdorferi to determine the clinical indicators used by physicians to order this test. Eighty-two evaluable patients who were screen positive (indirect enzyme-linked immunosorbent assay) between August 1991 and March 1993 were included. Additional tests, isotype-specific capture immunoglobulin enzyme immunoassay and Western blot (immunoblot) analysis (immunoglobulin G), were performed on positive samples. Of 82 patients with a positive screening test result, 54 (66%) had no serologic evidence of Lyme disease on the basis of additional testing (positive predictive value, 34%). Only 28 of 82 patients (34%) had clinical indicators suggestive of Lyme disease. Antibody screening tests may provide misleading information if they are not accompanied by more specific assays. Inappropriate testing of patients without indications of Lyme disease is frequently performed, and the ordering practices of physicians should be reassessed.
Antibodies, Bacterial↗
Laparotomy and proximal gastric vagotomy in Zollinger-Ellison syndrome: results of a 16-year prospective study.
OBJECTIVE: Pharmacological control of gastric acid hypersecretion in the Zollinger-Ellison syndrome has steadily improved, but medical treatment does not address the underlying tumor. The objective of this study was to evaluate the long-term effectiveness of a surgical approach to both tumor and acid hypersecretion in 22 patients with the Zollinger-Ellison syndrome. METHODS: Patients underwent laparotomy to resect tumors, combined with vagotomy to reduce acid secretion, followed by postoperative antisecretory therapy, if necessary. RESULTS: No surgical mortality or serious morbidity occurred. Tumor was found at laparotomy in nine patients (41%) and during long-term follow-up in an additional two patients (9%). Ten-year survival is 81%, with a long-term cure rate of at least 14%. Most patients (86%) have had long-term inhibition of acid secretion. Eight patients have discontinued regular use of acid-inhibiting medications. Patients requiring medication need less of it, and they have an improved acid inhibitory response to medication for up to 16 yr after surgery. CONCLUSION: Cure of the Zollinger-Ellison syndrome is possible in a minority of patients. Acid secretion can be safely reduced in almost all patients with laparotomy/vagotomy, usually allowing discontinuation, or reduced dose, of acid-inhibiting drugs. Long-term survival and quality of life are generally excellent.
Adolescent↗
Racial differences in gastric function among African Americans and Caucasian Americans: secretion, serum gastrin, and histology.
We measured gastric juice fluid output, acidity, tonic strength (osmolality), and pepsin concentrations basally and after the injection of pentagastrin in 120 healthy African Americans and 60 Caucasian Americans of similar age and gender. Sera for basal gastrin concentration and IgG for antibody to Helicobacter pylori (Hp) organisms also were obtained, as were gastric body mucosal biopsies to ascertain the presence or absence of Hp or gastritis. Gastric juice hydrogen ion concentrations and osmolality were significantly lower in African Americans than in Caucasians. At the same time, African Americans had significantly higher gastric juice fluid outputs than did Caucasians. From measurements of gastric juice fluid output, acidity, and osmolality, we used a previously validated method for calculating gastric HCO3- and H+ secretion, as well as nonparietal and parietal fluid secretion. Gastric HCO3 secretion and nonparietal fluid were significantly higher in African Americans, while H+, parietal fluid, and pepsin secretion rates were nearly identical in the two racial groups. Basal serum gastrin concentrations and antibody titers to Hp also were significantly higher in African Americans (p < .001). Mucosal biopsies demonstrated a much higher prevalence of Hp infection and chronic active superficial gastritis in African Americans than Caucasians (p < .001). When only Hp-negative subjects were considered, racial differences in gastric secretion and basal serum gastrin concentration were still present. The mechanism or mechanisms causing higher gastric bicarbonate and nonparietal fluid secretion and for higher serum gastrin concentrations in African Americans remains to be elucidated.
Adult↗
Combined vaccination with major histocompatibility class I and interleukin 2 gene-transduced melanoma cells synergizes the cure of postsurgical established lung metastases.
We have analyzed and compared in detail the malignant phenotypes of, the immune mechanisms induced by, and the immunotherapeutic potentials of B16-F10.9 melanoma cells manipulated by gene transfer to express syngeneic H-2Kb molecules or to secrete the cytokines interleukin 2 (IL-2) or IL-6. Local tumor growth in the footpad of transduced cells is mainly retarded by expression of H-2Kb and IL-2 genes and less by expression of IL-6. Mice given injections intrafootpad of tumorigenic doses of transduced clones manifested significantly reduced postsurgical spontaneous metastasis. After i.v. inoculation, mice given injections of F10.9-Kb expressors did not develop experimental lung metastases; mice given injections of F10.9-IL-6 secretors developed reduced metastatic loads; whereas mice given injections of F10.9-IL-2 secretors developed high loads of lung metastases. On the basis of injections into nude mice, in vivo depletions of CD4+, CD8+, and NK1.1+ cells, and in vitro CTL and natural killer (NK) assays, we show that all F10.9-modified cells induce CD8+ tumor-specific CTL activity and that F10.9-IL-2 secretors also induce nonspecific NK/lymphokine-activated killer cell activity. Vaccinations with F10.9-modified cells were capable of significantly reducing metastatic spread from small established F10.9 footpad tumors. However, in mice carrying preestablished lung metastases, a highly therapeutic effect was achieved only when H-2Kb expressors and IL-2 secretors were combined in vaccination, whereas individual vaccines or other combinations had marginal effects. This higher efficiency of the combined vaccine is due to the combined effect of efficient CTL induction and NK/lymphokine-activated killer cell activity as concluded from depletion of CD8+ and NK1.1 cells during immunotherapy. Thus, the cure of established metastasis can be achieved by the synergistic effects of vaccination with class I and IL-2-transduced tumor cells.
Animals↗
Interleukin-6: effects on tumor models in mice and on the cellular regulation of transcription factor IRF-1.
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Animals↗
Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes.
Plasmodium falciparum-infected human erythrocytes evade host immunity by expression of a cell-surface variant antigen and receptors for adherence to endothelial cells. These properties have been ascribed to P. falciparum erythrocyte membrane protein 1 (PfEMP1), an antigenically diverse malarial protein of 200-350 kDa on the surface of parasitized erythrocytes (PEs). We describe the cloning of two related PfEMP1 genes from the Malayan Camp (MC) parasite strain. Antibodies generated against recombinant protein fragments of the genes were specific for MC strain PfEMP1 protein. These antibodies reacted only with the surface of MC strain PEs and blocked adherence of these cells to CD36 but without effect on adherence to thrombospondin. Multiple forms of the PfEMP1 gene are apparent in MC parasites. The molecular basis for antigenic variation in malaria and adherence of infected erythrocytes to host cells can now be pursued.
Amino Acid Sequence↗
Relationships between the acidity and osmolality of popular beverages and reported postprandial heartburn.
BACKGROUND/AIMS: Although many beverages produce heartburn, the relationship between the acidity and osmolality of beverages and heartburn is unclear. The aim of this study was to relate the acidity and osmolality of beverages with their ability to cause heartburn. METHODS: We measured pH, total titratable acidity, and osmolality of 38 beverages in vitro and then correlated acidity and osmolality with the amount of heartburn reported by questionnaire in 394 people with heartburn. RESULTS: Among 17 citrus drinks and juices, titratable acidity correlated with reported heartburn scores (r = 0.65; P = 0.004). Soft drinks had the lowest pH readings of any beverages studied, and decreasing pH among soft drinks was correlated with reported heartburn scores (r = 0.82; P < 0.001). Alcoholic beverages (wines and beer), coffee, and (to a lesser extent) tea were associated with significant amounts of reported heartburn when compared with water. Milk was also associated with a modest amount of reported heartburn that was related to its fat content. Osmolality of beverages was unrelated to reported heartburn. CONCLUSIONS: High titratable acidity of citrus drinks and juices and low pH of soft drinks are associated with more reported heartburn. Our findings provide a foundation for dietary advice in patients with heartburn and reflux esophagitis.
Acids↗
From Aristotle, through Spemann, to tumor immunology: a personal experience.
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Animals↗
Regression of established murine carcinoma metastases following vaccination with tumour-associated antigen peptides.
The cure of micrometastases following surgery is the major goal of cancer immunotherapy. We have recently isolated tumour-associated antigen (TAA) peptides, MUT 1 and MUT 2, derived from a mutated connexin 37 gap-junction protein, from the malignant 3LL-D122 murine lung carcinoma. We now report that synthetic MUT 1 or MUT 2 induces effective antitumour cytoxic T lymphocytes. Peptide vaccines protect mice from spontaneous metastases of 3LL-D122 tumours. Moreover, peptide vaccines reduce metastatic loads in mice carrying pre-established micrometastases. Tumour-specific immunity was primarily mediated by CD8+ T cells. This is the first evidence that peptide therapy may be effective in treatment of residual tumours and provides a rationale for the development of peptide vaccines as a modality for cancer therapy.
Animals↗
Suppression of acid secretion in peptic ulcer disease.
Until recently, suppression of gastric acid secretion in patients with peptic ulcer was empirical and of unproven value. Anticholinergic drugs had only modest inhibitory effects on acid secretion, many side effects, and uncertain efficacy. Controlled trials using antacids demonstrated the value of reducing gastric acidity for healing duodenal ulcer. The discovery of histamine-2 (H2) receptor antagonists in the 1970s and the introduction of H+,K(+)-ATPase inhibitors in the 1980s made reduction of acid secretion the first-choice modality for healing and preventing recurrences of duodenal and gastric ulcers. The demonstration in the late 1980s and early 1990s that Helicobacter pylori (Hp) was a major risk factor for duodenal and gastric ulcer recurrences suggested that peptic ulcer could be cured by eradicating this organism from the stomach. However, antibiotic eradication of Hp can be difficult, often requiring simultaneous administration of a drug that suppresses acid secretion. Therefore, H2 and proton pump inhibitors continue to play a role in the management of duodenal and gastric ulcers associated with Hp and also play a primary role in the therapy of other acid-related disorders, such as gastroesophageal reflux diseases, stress ulcers, ulcers associated with nonsteroidal anti-inflammatory drugs, and gastrinoma (Zollinger-Ellison syndrome) and other acid hypersecretory states.
Antacids↗
The incidence of birthmarks in Israeli neonates.
BACKGROUND: Several studies have documented cutaneous findings in neonates of various racial groups. Our purpose was to determine the frequency of birthmarks in Israeli neonates of Jewish and Arabic origin. METHODS: A cohort of 1672 newborn infants under 96 hours of age were examined for the presence of birthmarks. Of these 841 (50.3%) were Jewish and 831 (49.7%) were Arab. The Jewish group was further subdivided into various ethnic groups according to parental ancestry. RESULTS: Melanocytic brown lesions (Mongolian spots, congenital nevi, and café-au-lait spots), were more common in Arab infants. The vast majority of Jewish infants with Mongolian spots were of Asian or African ancestry. On the other hand, congenital melanocytic nevi were found only in Jewish infants of European ancestry. Vascular lesions (salmon patch and port-wine stain) in Arab neonates exhibited a female preponderance. CONCLUSIONS: Our data suggest that the prevalence of birthmarks in Israeli neonates is similar to the prevalence reported by others in white neonates.
Africa↗
Depression in male and female patients undergoing cardiac surgery.
The present longitudinal study was designed to determine the prevalence of depression in male and female patients undergoing cardiac surgery, and to examine what factors are associated with depression before and after surgery. One day prior to surgery (T1), and one day prior to discharge from the hospital (T2), 141 patients completed a psychometric test battery including the Center for Epidemiological Studies Depression Scale (CES-D), the State-Trait Anxiety Inventory (STAI), and the Perceived Social Support Scale (PSSS). Data were also collected on 13 physiological measures. Forty-seven per cent of patients were depressed (defined as a score of 16 or above on the CES-D) at T1. Scores on the CES-D significantly increased from T1 (M = 15) to T2 (M = 20), with 61 per cent of patients classified as depressed at T2. Factors associated with depression at T1 were female gender, higher state anxiety, and less social support. Depressed patients at T2 were characterized by higher scores on the STAI at T2 and higher scores on the CES-D at T1. The prevalence of depression in cardiac surgery patients, particularly women, may be underrecognized and warrants increased attention.
Adult↗
Emergency department utilization in a large pediatric group practice.
The effect of a triage and care system, which employs continued patient education, alternatives to emergency department (ED) care for nonemergent problems, and close cooperation between ED staff and the primary care physician on inappropriate ED use, was analyzed for three groups of patients: (a) Medicaid patients, all of whom had unrestricted access to the ED; (b) group A patients who required prior physician approval and copayments for all ED services; and (c) patients enrolled in group B who were responsible for copayments only and did not require prior physician approval for ED use. Two hundred ninety-nine (299) charts were prospectively reviewed for age, payer status, date, time of visit, diagnosis, outcome of visit, and severity of illness. Medicaid patients utilized the ED much more than expected, compared to either group A or B patients (P < 0.001). Expected rates of utilization were based upon that particular group's representation in a medical associate's patient panel, which was based upon patient billing data. Medicaid patients were significantly younger than group A or B patients (P < 0.001) and had lower severity scores (P = 0.04). Our triage and care system failed to alter patterns of ED utilization for Medicaid patients.
Age Factors↗