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Biomedical subjects

R M Genta

Publications and source records attributed to R M Genta.

At least 91 records · Page 5Linked to original sources

Recognizing atrophy: another step toward a classification of gastritis.

The Sydney System is a novel classification of gastritis that attempts to incorporate etiologic, topographic, and morphologic criteria into a clinically relevant scheme. In September of 1994, a group of 20 gastric pathologists from various parts of the world gathered in Houston, Texas, U.S.A., to reappraise the Sydney System 4 years after its introduction and to attempt to reach a broad consensus on gastritis. One of the most controversial issues at the Houston Workshop was the concept of atrophy. Several factors converge to foment confusion and disagreement. "Normal" is imprecisely defined; the loss of glands occurs with distinct patterns and has different functional significance in antrum and corpus; inflammatory infiltrate and lymphoid follicles in the lamina propria may alter the architecture of the gastric mucosa, particularly in the antrum, making loss especially arduous to discern from mere displacement; the relationship between atrophy and intestinal metaplasia remains incompletely understood; and finally, and perhaps most important, the topographic patterns of distribution and the genesis and evolution of atrophic gastritis have been among the most divisive predicaments in the tumultuous arena of gastritis. This article explores some of the difficulties surrounding the concept of atrophy, summarizes the resolutions made at the Houston Workshop, and presents a novel approach to the histopathologic evaluation of atrophic gastritis.

Atrophy↗

Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994.

The Sydney System for the classification of gastritis emphasized the importance of combining topographical, morphological, and etiological information into a schema that would help to generate reproducible and clinically useful diagnoses. To reappraise the Sydney System 4 years after its introduction, a group of gastrointestinal pathologists from various parts of the world met in Houston, Texas, in September 1994. The aims of the workshop were (a) to establish an agreed terminology of gastritis; (b) to identify, define, and attempt to resolve some of the problems associated with the Sydney System. This article introduces the Sydney System as it was revised at the Houston Gastritis Workshop and represents the consensus of the participants. Overall, the principles and grading of the Sydney System were only slightly modified, the grading being aided by the provision of a visual analogue scale. The terminology of the final classification has been improved to emphasize the distinction between the atrophic and nonatrophic stomach; the names used for each entity were selected because they are generally acceptable to both pathologists and gastroenterologists. In addition to the main categories and atrophic and nonatrophic gastritis, the special or distinctive forms are described and their respective diagnostic criteria are provided. The article includes practical guidelines for optimal biopsy sampling of the stomach, for the use of the visual analogue scales for grading the histopathologic features, and for the formulation of a comprehensive standardized diagnosis. A glossary of gastritis-related terms as used in this article is provided.

Animals↗

Uncertain clinical significance of duodenal mucosal abnormalities in HIV-infected individuals. Results of a case-control study.

Previous research has described abnormalities of duodenal mucosal morphology in human immunodeficiency virus (HIV)-infected individuals. We wanted to determine the frequency of disturbed villus architecture and investigate its relationship to HIV-related chronic diarrhea. We conducted a case-control study of 120 HIV-infected men, 63 with and 57 without chronic diarrhea. Stools were cultured for bacteria and examined for ova and parasites; esophagogastroduodenoscopy and flexible sigmoidoscopy with mucosal biopsies were performed. Biopsy tissue was examined using light and electron microscopy to detect enteric pathogens and to evaluate mucosal morphology. The mean CD4+ cell count was 143/min3, and enteric pathogens were detected in 56 of 120 men (47%). In approximately half the study sample (57%), duodenal villus architecture was normal; complete villus flattening was not observed. We detected no association between chronic diarrhea and altered villus architecture. Although further study is needed to clarify the pathogenesis of altered duodenal mucosal morphology, our results suggest that the clinical significance of the abnormalities may be small.

Adult↗

Resolution of a metaplastic duodenal polyp after cure of Helicobacter pylori infection.

Although there have been several reports of hyperplastic gastric polyps associated with persistent Helicobacter pylori gastritis, the association of H. pylori infection with metaplastic polyps in the duodenum has not hitherto been described. After a 52-year-old man had a single episode of hematemesis, endoscopy showed a smooth polyp 1 cm in greatest dimension formed by a proliferation of gastric epithelial cells of fundic and antral type found in the duodenal bulb. The outer surface was entirely covered with a single layer of hyperplastic columnar epithelium with many H. pylori organisms. After administration of metronidazole 500 mg, omeprazole 20 mg for 4 weeks, and clarithromycin 250 mg twice a day for 2 weeks, endoscopy showed a decrease in size of the duodenal polyp. At 12 weeks there was complete regression of the polyp. This report documents a new and unusual finding: resolution of a gastric metaplastic polyp in the duodenum associated with cure of H. pylori.

Anti-Bacterial Agents↗

Metronidazole, ranitidine and clarithromycin combination for treatment of Helicobacter pylori infection (modified Bazzoli's triple therapy).

BACKGROUND: Multi-drug regimens are generally required to reliably cure Helicobacter pylori infection. Metronidazole, clarithromycin and omeprazole has proven to be an effective combination therapy with a cure rate of 90% or greater. METHODS: We evaluated a 14-day combination regimen for H.pylori infection consisting of metronidazole 500 mg b.d., clarithromycin 250 mg b.d. and ranitidine 300 mg b.d. (MRC) instead of omeprazole. Ranitidine alone was continued for an additional 4 weeks. H. pylori status was determined by rapid urease testing, histopathology using the Genta stain, and by culture at entry and 4 weeks after completing antimicrobial therapy. RESULTS: Twenty-seven patients with documented peptic ulcer disease and H. pylori infection were treated. Five had previously failed macrolide-based antimicrobial therapy; none had received metronidazole. All ulcers were healed at week 6 except one patient taking naproxen; his H. pylori infection was cured. Overall, H. pylori infection was cured in 78% (95% CI = 58-91%). In patients with clarithromycin-sensitive isolates, the cure rate was 20 of 23 (87%, 95% C.I. = 66-97%); only one of four patients (25%) with clarithromycin-resistant isolates was cured. In contrast, four of five patients with metronidazole-resistant isolates were cured (80%). In patients with isolates sensitive to both antibiotics, the cure rate was 16 of 18 (89%, 95% C.I. = 65-99%). Mild side effects were reported by 27%, including diarrhoea and altered taste. Compliance averaged 98%. CONCLUSION: These results suggest that the combination of metronidazole, ranitidine and clarithromycin results in high cure rates in patients with clarithromycin-sensitive isolates. Omeprazole may not be required for Bazzoli's triple therapy; and large multicentre comparative trials are indicated.

Adult↗

Twenty-minute fasting version of the US 13C-urea breath test for the diagnosis of H. pylori infection.

BACKGROUND: In large-scale multi-center clinical trials, the US 13C-urea breath test (UBT) has proven to have a sensitivity and specificity of approximately 95%. Ingestion of a meal to delay gastric emptying has advantages of increasing the level of signal as well as prolonging the duration of significantly increased 13C excretion, at the expense of requiring 40 to 60 minutes to complete the test. Our aim was to explore the utility of the 13C-UBT with a total duration of 30 minutes or less. METHODS: After a baseline breath sample was obtained, 125 mg of 13C-urea was given in 100 ml of water, and additional breath samples were taken after 20 and 30 minutes. The results of the UBT were compared to histological assessment, culture, and the rapid urease test. 13C-UBTs were carried out on normal volunteers who underwent gastroscopy during which six mucosal biopsies were taken. Three biopsies were for histological evaluation (Genta stain), two for culture, and one was for agar gel rapid urease testing. The UBT was conducted 2 to 3 days either before or after the endoscopic procedure. RESULTS: The cutoff value for a positive UBT was enrichment of 2.4 delta/1000 (delta over baseline). Of the 66 tests, 51/1000 were Helicobacter pylori-positive. There were no false positive UBTs and only two false negative UBTs at 20 minutes (sensitivity, 96%; specificity, 100%). At 30 minutes, one other UBT was false negative (gray zone of 2.36/1000) (sensitivity, 94%; specificity, 100%). CONCLUSION: These results suggest that omission of the meal and shortening the duration of the US 13C-UBT to 20 minutes still may maintain excellent specificity and sensitivity of the test.

Adult↗

The best gastric site for obtaining a positive rapid ureas test.

BACKGROUND: Rapid ureas tests (RUTs) provide a simple, sensitive method of detecting Helicobacter pylori infection. OBJECTIVES: Our aim, therefore, was to determine whether the yield of detecting H. pylori infection by RUT varied depending on the site of gastric biopsy. MATERIALS AND METHODS: Gastric biopsies were obtained from 50 patients for RUT by use of hpfast (GI Supply, Camp Hill, PA). Biopsies were taken from the prepyloric greater curve antrum, from the gastric angle, and from the greater curve in mid-corpus. One biopsy specimen was placed in the RUT gel, and the biopsy from the adjacent mucosa was placed in formalin for subsequent histological evaluation by using the Genta stain. RUTs were examined and scored at intervals of 5, 10, 15, 30, and 45 minutes and after 1, 2, 4, and 24 hours. RESULTS: Fifty patients were entered in the rest (150 RUTs), 32 having H. pylori infection. There were no false-positive RUTs (specificity, 100%). The gastric angle site was positive in 100%. The prepyloric site was positive in 87%, and the corpus site was positive in 84.4% (p < .052 for angle or prepyloric antrum versus corpus). The most common pattern was for all to be positive (74%). The median time to positivity was similar with angle and prepyloric sites (37.5 and 60 minutes, respectively, p = not significant) and shorter than the corpus biopsy (180 minutes); (p < .05 for angle or prepyloric antrum versus corpus). CONCLUSION: The maximum probability for detecting H. pylori infection using a RUT is to obtain a biopsy from the gastric angle. To prevent missing a positive result when intestinal metaplasia is present, we recommend that (at a minimum) biopsies be taken from both the angle and the corpus.

Bacterial Proteins↗

Serum CagA antibodies in asymptomatic subjects and patients with peptic ulcer: lack of correlation of IgG antibody in patients with peptic ulcer or asymptomatic Helicobacter pylori gastritis.

AIM/BACKGROUND: Several studies have suggested that Helicobacter pylori which express CagA may be more virulent than those that do not, but limited populations have been studied to date. The aim of this study was to confirm and extend the association of CagA positive H pylori strains in a different geographical area and to a large, well defined patient population. METHOD: A validated ELISA for serum IgG to CagA was used to investigate the prevalence of CagA seropositivity in 100 patients with peptic ulcer compared with 77 with H pylori infection without ulcer disease in a North American population. The extent of antral and corpus inflammation and H pylori density in relation to CagA seropositivity in 40 subjects with H pylori infection were assessed semiquanitatively. All studies were carried out in a coded and blinded manner. RESULTS: The prevalence of serum IgG CagA antibodies was higher in H pylori infected patients with ulcer (59%) compared with healthy H pylori infected volunteers (44%), but the difference was not significant. In contrast, the titre of serum IgG anti-CagA antibodies was higher among the seropositive subjects without ulcer disease, but again the difference was not significant. Comparison of histological features between asymptomatic individuals with H pylori infection in relation to CagA IgG antibody status revealed no differences in infiltration with acute inflammatory cells, H pylori density, or gastritis index. There was no relation evident between the degree of polymorphonuclear cell infiltration and the serum IgG antibody titre to CagA. Mononuclear cell infiltration in the antrum, but not the corpus, was greater in those with CagA IgG compared with those without (median score 5 v 3). CONCLUSIONS: A right association between the presence or titre of serum IgG to CagA and peptic ulcer disease, greater H pylori density or infiltration of the mucosa with acute inflammatory cells could not confirmed in a North American population. Perhaps geographical differences in the prevalence of circulating H pylori strains are responsible for the discrepant results reported.

Antibodies, Bacterial↗

Strongyloides stercoralis: maintenance of exceedingly chronic infections.

Two hypotheses were tested to identify the mechanism(s) by which chronic Strongyloides stercoralis infections are maintained in experimental dogs as a model to explain delayed onset recrudescence in humans. Investigations tested the hypotheses that chronic infections result from 1) periodic reactivation of third-stage larvae from a reservoir of dormant parasites outside the gastrointestinal tract or 2) the periodic rejuvenation of postreproductive female worms remaining from a previous infection, lodged in the mucosal crypts. Populations of parenteral larvae survived in mature experimentally infected female dogs for 66 days; individual worms survived for 88 days, but there was no evidence that these larvae re-established patent, adult worm infections. Late in these infections, female worms were present in greater than predicted numbers with no evidence that autoinfection had occurred, suggesting that some postreproductive worms were long-lived. In separate trials, long-lived spent females were once again capable of producing viable larvae when the host was treated with corticosteroids.

Animals↗

Low point prevalence of peptic ulcer in normal individuals with Helicobacter pylori infection.

OBJECTIVE: A recent study from Italy reported a high prevalence of ulcer disease in asymptomatic Helicobacter pylori infection. Such results are at variance with previous endoscopy screening studies. Our study was performed to obtain data on ulcer prevalence in normal H. pylori-infected subjects in the United States. METHODS: One hundred and ninety healthy individuals of either gender, over the age of 18, were studied. After completion of a detailed questionnaire and a urea breath test for H. pylori status, endoscopy was performed. Ulcer was defined as a mucosal ulceration > 5 mm in diameter and with apparent depth. RESULTS: There were 108 (57%) women and 82 (43%) men. The mean (+/-SD) age was 38.9 (+/-10.7) yr, range 21-79 yr. Careful history obtained after enrollment revealed presence of dyspeptic symptoms in 35 subjects (18%); the remaining 155 individuals were completely symptom-free. Infection with H. pylori was present in 102 subjects (54%). The infection rate was highest in Hispanics (70%), followed by African-Americans (58%), Caucasians (38%), and Asians (17%). The prevalence increased with age. Only two (1%) of 190 subjects, both with H.pylori infection, had peptic ulcer. In the H. pylori-infected group, the prevalence of peptic ulcer was 2%. CONCLUSION: In the United States, significant unrecognized and asymptomatic gastroduodenal disease is uncommon in H. pylori-infected individuals. These findings do not support the need for a mass screening program for H. pylori infection or for the use of antimicrobial treatment of asymptomatic subjects with this infection.

Adult↗

Noninvasive detection of Helicobacter pylori infection in clinical practice: the 13C urea breath test.

OBJECTIVES: To validate the 13C urea breath test for the detection of Helicobacter pylori infection both before and after treatment. METHODS: 13C urea breath tests with 125-mg and 250-mg doses were carried out on each of 60 infected and 60 noninfected subjects. Results were compared with histological examination of gastric biopsies to establish detection limits. The best cut-off point was used in a clinical trial of the efficacy of the breath test in duodenal ulcer patients before and after antimicrobial therapy. The incremental increase (percentage, delta over baseline in U of delta/mil) in respiratory 13CO2 abundance was associated with histological evidence of H.pylori. Outpatient, tertiary care medical center, and secondary and primary care facilities were included. One hundred twenty healthy asymptomatic subjects and 465 patients with duodenal ulcer disease were studied. The test kit assessed repeatability of breath sample collection and storage and stability of stored samples. Test performance was analyzed by comparison of 125-mg and 250-mg 13C urea with measurements at 30 and 40 min postdose. The test was used to diagnose active H.pylori infection and gauge success of antimicrobial therapy. RESULTS: The test kit results were highly reproducible. The cut-off values were higher with 250-mg compared with 125-mg doses of 13C urea and 40 min compared with 30 min. Using a 125-mg 13C urea and test detection limit of 2.4% at 30 min, the accuracy was 94.8 (95% confidence interval = 92-97%) before antimicrobial therapy and 95.4% (95% confidence interval = 91-98%) after. An increase of 2.4% in the abundance of breath 13CO2 measured 30 min after a 125-mg dose of 13C urea reliably indicated the presence of active H.pylori infection either before or after antimicrobial therapy. The 13C urea breath test provides a simple and reliable and noninvasive method of assessing H.pylori status.

Anti-Bacterial Agents↗

p53 protein accumulation in tumors of the ampulla of Vater.

BACKGROUND: Accurate preoperative diagnosis of tumors of the ampulla of Vater is difficult because ampullary biopsies have a high false-negative rate. Recently, it has been suggested that p53 mutations in tumors of the ampulla of Vater are associated with the transformation of adenomas and low grade carcinomas to high grade carcinomas. The purpose of this study was to determine the extent of p53 protein accumulation in tumors of the ampulla of Vater, and to determine whether p53 accumulation can be detected in false-negative biopsies. METHODS: Using a monoclonal anti-p53 antibody, sections of 4 normal ampullas, 5 adenomas, 17 carcinomas, and 9 initial biopsies of 9 of the tumors of the ampulla of Vater that had no morphologic evidence of carcinoma were immunostained. RESULTS: None of the 4 normal ampullas (0%), 2 of 5 adenomas (40%), and 16 of 17 carcinomas (94%) were positive for p53. This p53 positivity was present through all stages of ampullary carcinoma. Of the nine initial biopsies negative for carcinoma, seven were positive for p53 and, of these, six (86%) were found to be carcinomas upon resection. CONCLUSIONS: 1) The molecular events leading to p53 accumulation in tumors of the ampulla of Vater occur early in the neoplastic process. 2) Tumors of the ampulla of Vater with biopsies negative for malignancy but positive for p53 are very likely to be carcinomas.

Adenoma↗

Determination of Helicobacter pylori status by reverse transcription-polymerase chain reaction. Comparison with urea breath test.

We previously reported the development and the possible application of reverse transcription-polymerase chain reaction (RT-PCR) assay for the detection of H. pylori in gastric mucosal biopsy specimens. In this communication, the application of this assay was assessed by comparing its results from 79 gastric biopsy specimens obtained from 68 patients with the more traditional [13C]urea breath test. When the amplified products were examined, the specificity and sensitivity of this RT-PCR assay were 100% and 47% on agarose gels and 80% and 91% by Southern hybridization, respectively. The specificity and sensitivity of urea breath test were 91% and 96% and were generally superior to RT-PCR (negative predictive value of 94% for UBT and 59-76% for RT-PCR). Although our RT-PCR results compare favorably with other PCR assays applied to gastric biopsy specimens for the detection of H. pylori, the use of this method did not add significantly to currently available noninvasive diagnostic methods.

Adult↗

Intestinal function and injury in acquired immunodeficiency syndrome-related cryptosporidiosis.

BACKGROUND/AIMS: The pathogenesis of the diarrhea in acquired immunodeficiency syndrome (AIDS)-related cryptosporidiosis is not known. The hypothesis of this study was that the intestinal dysfunction and injury are related to the number of organisms infecting the intestinal mucosa. The aim of this study was to study the influence of intensity of infection on intestinal function and injury in AIDS-related cryptosporidiosis. METHODS: In 16 patients with AIDS with intestinal Cryptosporidium infection, the intensity of infection was quantified by counting the total number of fecal oocysts excreted in 24 hours and by determining the percent of duodenal epithelium covered by organisms. Intestinal function was assessed by vitamin B12 absorption and serum D-xylose test. Intestinal injury was assessed by morphology of duodenal mucosa, differential urinary excretion of lactulose and mannitol, and fecal alpha 1-antitrypsin clearance. Measurements were repeated after treatment with paromomycin. RESULTS: Vitamin B12 and D-xylose absorption negatively correlated with intensity of infection. Villus atrophy occurred only in patients with oocyst excretion of > 10(8) oocyst/24 hours. Lactulose/mannitol urinary excretion ratio showed a positive correlation with intensity of infection. Intestinal function and injury improved in patients whose oocyst counts were reduced by treatment with paromomycin. CONCLUSIONS: Cryptosporidium infection in patients with AIDS causes malabsorption and intestinal injury in proportion to the number of organisms infecting the intestine.

AIDS-Related Opportunistic Infections↗

Observations on the pathological spectrum and clinical course of microsporidiosis in men infected with the human immunodeficiency virus: follow-up study.

The purposes of this research were to determine whether microsporidian infection is accompanied by structural alterations of the duodenal mucosa and to characterize the clinical and morphological evolution of intestinal microsporidiosis. In a previous systematic electron microscopic evaluation of mucosal biopsy specimens from patients with human immunodeficiency virus infection, we detected Enterocytozoon bieneusi in the duodenal tissue of 31 men. This report concerns a follow-up study of these 31 men, who underwent repeated clinical and laboratory evaluations, including repeated duodenal biopsies. Eighteen men had chronic diarrhea at enrollment and 13 had no diarrhea. The CD4+ cell counts (per mm3) ranged from 10 to 660 and were normal for three men. E. bieneusi infection was accompanied by a wide spectrum of histopathology of duodenal tissue; over a mean follow-up of 15 months, no consistent change in duodenal mucosal morphology was observed, and diarrhea did not invariably develop. These observations indicate that diarrhea and severe villus injury do not invariably accompany infection. Further studies are needed to determine the relationship between E. bieneusi infection and clinical illness.

AIDS-Related Opportunistic Infections↗

HEp-2 cell-adherent Escherichia coli in patients with human immunodeficiency virus-associated diarrhea.

Diarrhea occurs commonly in African human immunodeficiency virus (HIV) infections. A case-control (HIV-positive vs. -negative) study of adults with diarrhea was done in Lusaka, Zambia, to determine the prevalence of intestinal infection by HEp-2 cell-adherent Escherichia coli. Adherent E. coli were more common in HIV-positive patients with acute diarrhea than among HIV-negative controls (60% vs. 33%) and were found significantly more often in HIV-positive patients with chronic diarrhea than among HIV-negative controls with chronic diarrhea (79% vs. 17%, P < .002). Adherent strains were found significantly more often among HIV-positive patients (69%) than in 22 asymptomatic subjects (36%, P < .02). The HEp-2 cell adherence of the E. coli strains did not show a common pattern. Adherent bacteria were also observed in colonic biopsies from 32% of Zambians with chronic diarrhea who underwent endoscopy. Adherent E. coli may be an important cause of HIV-associated diarrhea in Zambia.

Acute Disease↗

Metronidazole, omeprazole and clarithromycin: an effective combination therapy for Helicobacter pylori infection.

BACKGROUND: Successful treatment of Helicobacter pylori infection results in cure of peptic ulcer disease. Multi-drug regimens are needed to cure this infection. We studied the effectiveness and side effect profile of two antibiotics active against Helicobacter pylori, metronidazole and clarithromycin, combined with omeprazole. METHODS: We evaluated a combination therapy for H. pylori infection consisting of metronidazole (500 mg b.d.), omeprazole (20 mg b.d.), and clarithromycin (250 mg b.d.) for 2 weeks, followed by ranitidine 300 mg daily for 4 weeks. RESULTS: Thirty-three patients with documented H. pylori infection were studied. Twenty had previously failed antimicrobial therapy, including one with metronidazole-based triple therapy and eight with macrolide-based therapy (five with clarithromycin-based therapy), and 11 with amoxycillin, tetracycline, and bismuth. H. pylori status was determined by histopathology using the Genta stain and by culture. H. pylori status was determined at entry and 4 weeks after completing antimicrobial therapy. The H. pylori infection was cured in 88% (95% CI = 72%-96%) including 90% of those who had failed previous anti-H. pylori therapies. Mild side effects were reported by 18%. CONCLUSION: We conclude that the combination of metronidazole, omeprazole and clarithromycin is an effective treatment for H. pylori infection.

Adult↗

Helicobacter pylori, duodenal ulcer, gastric cancer: tunnel vision or blinders?

The focus of this paper is on the relationship between Helicobacter pylori gastritis and gastric cancer, one of the most compelling issues after the recent decision of the IARC (International Agency for Research on Cancer) to categorize H. pylori as a carcinogen. Our aim is to identify areas where additional work is not needed and suggest new directions of inquiry. We review what has been accomplished with the advantage of hindsight. Our review of the data regarding current putative virulence factors found that disease and outcome specificity were lacking. The same can be said of the data regarding low gastric juice ascorbate or increased mucosal cell turnover in H. pylori gastritis. We conclude that, while it is certainly possible that some of the factors discovered to date may initiate or mediate certain pathogenetic aspects of H. pylori-related disease, none of them can be seriously proposed as the factor responsible for either gastric cancer or duodenal ulcer. Finally, we identified research areas that might lead to disease-specific associations as well as areas where helicobacters may be used as models for other diseases. We propose that it is time to pause, reflect on what has been done, and focus more sharply on the questions that remain unanswered.

Duodenal Ulcer↗