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Biomedical subjects

R M Genta

Publications and source records attributed to R M Genta.

At least 127 records · Page 7Linked to original sources
PubMed1993

The role of Microsporidia in the pathogenesis of HIV-related chronic diarrhea.

OBJECTIVE: To determine whether infection with Microsporidia leads to diarrhea in patients with human immunodeficiency virus (HIV) infection. DESIGN: Case-control study. SETTING: Primary care outpatient HIV clinic at a Veterans Affairs medical center. PATIENTS: One hundred six HIV-infected men, 55 with and 51 without chronic diarrhea. MEASUREMENTS: Each patient underwent upper endoscopy and flexible sigmoidoscopy to obtain duodenal, rectal, and sigmoid colonic biopsy specimens. At the time of endoscopy, a fresh stool was obtained for culture, ova and parasite assessment, and Cryptosporidium examination. Biopsy tissue was examined using electron microscopy to detect Microsporidia. RESULTS: The microsporidian parasite Enterocytozoon bieneusi was detected in the duodenal biopsy specimens of 31 of 106 men (29%); 24 of 106 men (23%) had other enteric pathogens. No significant difference was observed in the occurrence of microsporidiosis in patients with (18 of 55 [33%]) and without (13 of 51 [25%]) chronic diarrhea (odds ratio, 1.42; 95% CI, 0.61 to 3.31). A similar nonsignificant difference was observed after controlling for CD4 count and other enteric pathogens (odds ratio, 1.66; 95% CI, 0.68 to 4.06). Among patients with microsporidiosis, no difference was observed in the intensity of infection (defined by the presence of few, moderate, or abundant organisms) among cases and controls (P > 0.2). CONCLUSIONS: This is the first report to document the presence of E. bieneusi in HIV-positive patients without gastrointestinal symptoms. No significant difference was observed in the occurrence of E. bieneusi infection in HIV-infected patients with or without chronic diarrhea. Thus, the association between microsporidiosis and diarrhea, if one exists, may not be as strong as is currently believed.

AIDS-Related Opportunistic Infections↗
PubMed1993

In situ hybridization and immunohistochemical analysis of cytomegalovirus-associated ileal perforation.

A patient with the acquired immunodeficiency syndrome (AIDS) with a cytomegalovirus (CMV) infection localized in the area of an ileal Kaposi sarcoma resulting in perforation is described. Because only one case of such an association of Kaposi sarcoma with CMV leading to perforation has been reported, the presence and distribution of CMV-related nucleic acids and proteins in the affected segment of intestine were evaluated. By using in situ hybridization and immunocytochemical analyses the presence of CMV was shown within epithelial, endothelial, smooth muscle, and inflammatory cells at the site of perforation. This study not only confirmed that CMV can be detected in virtually all components of the intestinal wall despite the absence of distinctive cytomegalic changes, but also generated critical information that illustrates the usefulness of immunohistochemistry and in situ hybridization in elucidating the pathogenesis of CMV-associated lesions. These findings lend further support to the concept that CMV plays a pivotal role in the pathogenesis of intestinal perforation and emphasize the critical importance of in situ hybridization in gaining insight into the mechanisms of CMV-induced injury.

Antigens, Viral↗
PubMed1993

Duodenal morphology and intensity of infection in AIDS-related intestinal cryptosporidiosis.

BACKGROUND: The pathogenesis of intestinal cryptosporidiosis is not known. Previous studies have shown that the intensity of infection varies between patients. The hypothesis of this study is that intestinal injury is related to the intensity of infection. METHODS: The histological abnormalities associated with Cryptosporidium infection were evaluated in duodenal biopsy specimens from 18 patients with acquired immunodeficiency syndrome-associated cryptosporidiosis. The intensity of Cryptosporidium infection was assessed histologically in all patients as the percentage of mucosa covered by organisms and by quantitation of oocyst excretion in the stools of 14 patients. RESULTS: Duodenal biopsy specimens from 13 patients (72%) showed normal villous architecture. In these patients, the inflammatory component of the lamina propria was either normal or moderately increased. This increase consisted mostly of lymphocytes and plasma cells. Five of 18 patients (28%) had flattening of the mucosa associated with a prominent neutrophilic infiltrate. The intensity of infection in patients with villous flattening as measured from biopsy specimens and stool was significantly higher than in those without flattening (92% vs. 12% mucosa occupied with organisms; 738 x 10(3) vs. 199 x 10(3) oocyst/mL stool) (P < 0.004 in both cases). CONCLUSIONS: Most patients with intestinal Cryptosporidium infection had normal duodenal villous architecture. Severe duodenal morphological abnormalities, including flattening of the villi, were associated with high-intensity infections.

AIDS-Related Opportunistic Infections↗
PubMed1993

Gastric lymphoid follicles in Helicobacter pylori infection: frequency, distribution, and response to triple therapy.

To determine the prevalence and distribution of gastric lymphoid follicles in patients with Helicobacter pylori infection, to evaluate their relationship with gastroduodenal pathology, and to assess their evolution after eradication of H pylori, mapped gastric biopsy specimens were obtained from 20 H pylori-negative normal volunteers, 25 asymptomatic volunteers with H pylori infection and no ulcer disease, 21 duodenal ulcer patients, and 16 patients with gastric ulcer. Nine infected subjects were treated by triple therapy, and biopsy specimens were obtained at 1, 4, and 12 months posttreatment. Lymphoid follicles were counted and other histologic features were scored semiquantitatively. None of the noninfected subjects had lymphoid follicles. All subjects with H pylori had follicles, which were more numerous in the antrum than in the corpus (P < .001) and on the lesser rather than on the greater curvature (P = .003). Ulcer patients had greater numbers of follicles than asymptomatic infected volunteers (P < .05). There was no relationship between number or distribution of follicles and patients' age, sex, or other mucosal inflammatory responses (except for numbers of lymphocytes: r = .785, P < .001), intensity of H pylori infection, or intestinal metaplasia. Eradication of H pylori resulted in a slow decrease (but not in the disappearance) of lymphoid follicles in all patients. Our results indicate that the careful examination of multiple specimens will reveal lymphoid follicles in the gastric mucosa of all patients with H pylori infection. The normal stomach does not contain mucosa-associated lymphoid tissue, and this study supports the concept that H pylori may be a precursor in the development of primary gastric lymphomas.

Adult↗
PubMed1993

Diarrhea in helminthic infections.

Enteric helminths are among the most prevalent parasites of humankind, yet only scanty information exists about their effects on the gastrointestinal tract of their hosts. Specifically, there is little agreement on which worms definitely cause diarrhea. The available evidence suggests that five helminthic parasites are associated with human diarrheal disease: Trichinella spiralis (early phases of infection), Trichuris trichiura, Strongyloides stercoralis, Capillaria philippinensis, and Schistosoma (particularly Schistosoma mansoni). All these parasites have an invasive phase during which adult worms, their eggs, or their larvae establish intimate contact with the host's intestinal mucosa and elicit strong local inflammatory responses resulting in various structural and functional alterations of the gut. In contrast, strictly intraluminal worms do not seem to interfere with their hosts' intestinal structure and function to a degree sufficient to cause diarrhea.

Animals↗
PubMed1993

Intensity of infection in AIDS-associated cryptosporidiosis.

A fluorescent monoclonal anti-Cryptosporidium antibody was used to count the oocysts in stools of 12 AIDS patients with chronic cryptosporidiosis. Oocyst excretion was present throughout the day in all 12 patients. Stool-to-stool variation in oocyst concentration was within one order of magnitude. Small variations were also found in daily mean oocyst concentration and total daily oocyst excretion in 3 patients who had multiple 24-h stool collections. However, there was a large patient-to-patient variation in mean oocyst concentration (from < 5.0 x 10(3) to 9.2 x 10(5) oocysts/mL) and 24-h total oocyst excretion (from < 6.0 x 10(6) to 1.2 x 10(9) oocysts/day). There was a significant correlation between oocyst excretion and numbers of Cryptosporidium organisms seen on small bowel biopsy. Oocyst excretion was reduced in 4 patients treated with paromomycin, but diarrhea improved only in the 2 patients with high initial oocyst excretion.

AIDS-Related Opportunistic Infections↗
PubMed1993

Enterovesical fistula due to non-Hodgkin lymphoma in AIDS.

Enterovesical fistula associated with lymphoma is exceedingly rare. We report three patients with the acquired immunodeficiency syndrome who presented with fecaluria and pneumaturia. Non-Hodgkin lymphomas involving the intestine and the urinary bladder creating an enterovesical fistula were found at surgery in two patients and at autopsy in the third. Extranodal lymphomas are becoming more common in AIDS patients, so that the possibility of lymphoma should be considered in the differential diagnosis of enterovesical fistulas in these patients.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Short report: a non-metronidazole triple therapy for eradication of Helicobacter pylori infection--tetracycline, amoxicillin, bismuth.

Triple therapies using bismuth, metronidazole and tetracycline or amoxicillin were the first truly successful anti-H. pylori therapies. Metronidazole resistance has become an increasing problem that has severely limited the usefulness of the original triple therapy. Resistance to tetracycline or amoxicillin has not been reported and both are effective against H. pylori. We therefore tested a new triple therapy consisting of 500 mg tetracycline, 500 mg amoxicillin, and 2 tablets of bismuth subsalicylate each administered four times daily (with meals and at bedtime) for 14 days during treatment with ranitidine 300 mg daily. H. pylori eradication was defined as no evidence of H. pylori one or more months after stopping therapy. H. pylori status was evaluated by a combination of urea breath test and histology. Sixteen patients with H. pylori infection and active peptic ulcers were enrolled. The new triple therapy was successful in only 7 individuals (43%). Metronidazole appears to be critical for the effectiveness of the original triple therapy. An alternative to metronidazole will be required for a new successful triple therapy.

Adult↗
PubMed1993

Detection of Helicobacter pylori in dental plaque by reverse transcription-polymerase chain reaction.

To investigate whether the oral cavity is a potential reservoir and possible sanctuary for Helicobacter pylori, supragingival and subgingival plaques were analyzed by a Helicobacter genus-specific reverse transcriptase-polymerase chain reaction based on the sequence data of H. pylori 16S rRNA. The amplified 500-bp DNA fragment was identified by ethidium bromide staining after agarose gel electrophoresis and by Southern hybridization. Twenty-five dyspeptic patients were studied. Histologic examination of gastric biopsy specimens revealed that 18 had H. pylori gastritis and 7 did not. For seven of the 18 (38.8%) patients with proven H. pylori gastritis, H. pylori was also identified in their dental plaque. None of the patients without H. pylori gastritis had H. pylori in their dental plaque. The detection of H. pylori in dental plaque suggests that this H. pylori colonization is not restricted to the gastric mucosa and that this ecological niche may serve as a possible sanctuary which may be responsible for reinoculation of the stomach after topical anti-H. pylori therapies such as bismuth.

Adult↗
PubMed1993

Helicobacter pylori infection and exaggerated gastrin release. Effects of inflammation and progastrin processing.

Helicobacter pylori infection is associated with exaggerated gastrin release. We investigated whether this abnormality was due to the bacteria or the immune response. Fasting and meal-stimulated 'total' and amidated gastrin were measured in 10 H. pylori-infected volunteers before eradication therapy, after 2 and 14 days of therapy, and 4 weeks after completion of therapy. The exaggerated meal-stimulated gastrin concentration remained unchanged after 2 days of therapy, although the polymorphonuclear cell infiltrate and H. pylori bacteria were no longer evident. The expected fall in gastrin concentration after 14 days of therapy was associated with a reduction in the density of mucosal mononuclear cells, suggesting exaggerated gastrin release was related to chronic inflammation or to H. pylori or its products. The effect of H. pylori on normal progastrin processing was also assessed; 2 control groups were included: 10 H. pylori-uninfected volunteers and 13 patients with H. pylori peptic ulcers. There was a significant difference in the proportion of circulating gastrins that were biologically active amidated gastrins between ulcer patients and uninfected controls (56.7 +/- 4% versus 33.8 +/- 4%, p < 0.001). The proportion of amidated to total gastrins did not increase after successful eradication.

Adult↗
PubMed1993

Intestinal metaplasia, not atrophy or achlorhydria, creates a hostile environment for Helicobacter pylori.

A 54-year-old man with dyspepsia, Helicobacter pylori-associated chronic active atrophic gastritis without intestinal metaplasia, and hyperplastic gastric polyps was followed up for 1 year after H. pylori eradication with sequential endoscopic gastric mucosal mapping and gastric function tests. Eradication of H. pylori by triple therapy resulted in the histologic resolution of gastritis. However, the patient's condition, gastric function, and morphology of the polyps were not affected. This case illustrates that: a) in the absence of intestinal metaplasia, H. pylori can infect the stomach with gastric atrophy; b) the absence of acid does not preclude H. pylori infection; c) advanced atrophic gastritis may be an irreversible condition; and (d) the neutrophilic infiltrate in hyperplastic polyps is independent of the presence of H. pylori.

Achlorhydria↗
PubMed1993

Southern-blot analysis and simultaneous in situ detection of hepatitis B virus-associated DNA and antigens in patients with end-stage liver disease.

To gain new insights into the pathogenesis of hepatitis B virus-induced chronic liver disease, we have used nonisotopic in situ detection methods for the simultaneous analysis of hepatitis B virus DNA and antigens at the single-cell level. Paraffin-embedded liver specimens from 23 cirrhotic patients (12 HBsAg positive and 11 HBsAg negative) who underwent liver transplantation were evaluated by in situ hybridization with a digoxigenin-labeled DNA probe and digoxigenin detection system and by immunohistochemistry with an enhanced biotin-streptavidin technique. DNAs extracted from liver and serum specimens were analyzed by Southern- and slot-blot hybridization, respectively. Using the in situ techniques, we detected hepatitis B virus-specific DNA and antigens in 11 of 12 HBsAg-positive patients and in none of the 11 HBsAg-negative individuals. Replicative intermediates of hepatitis B virus DNA were detected by Southern-blot analysis in the same 11 HBsAg-positive patients, 6 of whom had no serological markers of hepatitis B virus replication. Therefore a good correlation was found between the results obtained by the in situ and Southern-blot hybridization analyses of tissue specimens. However, a lack of correlation was found between serum- and tissue-associated markers of viral replication. In addition, the simultaneous in situ detection analyses revealed that some hepatocytes containing high levels of viral DNA were devoid of detectable HBcAg, suggesting a mechanism by which the virus may escape immunological surveillance.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Southern↗
PubMed1993

Clarithromycin as monotherapy for eradication of Helicobacter pylori: a randomized, double-blind trial.

UNLABELLED: Current regimens to eradicate Helicobacter pylori usually consist of metronidazole plus a bismuth compound, as well as a third agent such as tetracycline. Such regimens are not ideal because organisms may be metronidazole-resistant, side-effects occur, and compliance is often poor. This randomized, double-blind study was designed to assess the ability of clarithromycin, a new macrolide antimicrobial, as monotherapy to eradicate H. pylori. Thirty-seven healthy volunteers who were H. pylori positive by 13C-urea breath test plus histology and/or culture completed 14 days of oral therapy with clarithromycin in one of three dosages. Eradication, defined as all three tests negative at 4-6 wk after the end of therapy, was achieved in 2/13 (15%) with clarithromycin 500 mg bid, 4/11 (36%) with 1000 mg bid, and 7/13 (54%) with 500 mg qid. Isolates of H. pylori were resistant to clarithromycin prior to therapy in 12% of subjects, and became resistant during therapy in 21% of subjects. Taste perversion, the most common side effect, resulted in one subject terminating therapy. CONCLUSIONS: Whereas clarithromycin is a promising antimicrobial in the eradication of H. pylori, it is not sufficient to be used as monotherapy.

Adult↗
PubMed1993

Changes in the gastric mucosa following eradication of Helicobacter pylori.

Although most studies reporting on the examination of Helicobacter pylori infection have focused on the clearance of the bacteria and the rapid disappearance of the neutrophil infiltrates, the evolution of inflammatory and architectural changes in the antral and corporal mucosa following the eradication of H. pylori has not been addressed systematically. This study examines in detail the histopathologic appearance of the antral and corporal mucosa in a group of patients infected with H. pylori and follows the spectrum of morphologic changes in each of them after the eradication of the infection. At least 11 biopsies ("gastric mapping") were obtained from the antrum and body of each of 15 patients with H. pylori. Complete mapping was then repeated 1, 4, and 10 to 12 mo after the eradication of H. pylori by a course of "triple therapy." Each biopsy was assessed in a semi-quantitative fashion for presence of H. pylori, neutrophils, eosinophils, lymphocytes, lymphoid follicles, and intestinal metaplasia. Other features (integrity of surface epithelium, architecture, fibrosis) were evaluated descriptively. Results were compared with those obtained from a control group of 16 uninfected, healthy adult volunteers. H. pylori infection was eradicated in 11 subjects. The disappearance of neutrophils and the normalization of the surface epithelium closely paralleled that of H. pylori. Persistence of even small numbers of neutrophils was a predictor of relapse. Eosinophils and lymphocytes decreased slowly and did not return to normal levels within 1 yr. Lymphoid follicles decreased very slowly in all patients but were still present in all gastric locations at one year after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Gastric mucosal hydrophobicity and Helicobacter pylori: response to antimicrobial therapy.

The hydrophobic properties of the gastric mucosa are reduced by NSAIDs and by Helicobacter pylori infection. Our investigation was to determine whether this abnormality was due to the bacteria or to the inflammatory response. Contact angle measurements were made on gastric antral and corpus biopsies taken from 10 H. pylori-infected volunteers before eradication therapy, after 2 and 14 days of therapy, and 4 weeks after therapy. The contact angle improved steadily and statistically throughout the 2 weeks of therapy (for day 0, 3, 14, respectively) antral mucosa 54.2 +/- 2, 59.3 +/- 2, and 63.2 +/- 2; corpus mucosa 55 +/- 1, 57.8 +/- 3, and 66.6 +/- 1. After 2 days of therapy, H. pylori bacteria were no longer evident, and yet the contact angle continued to improve, suggesting that bacteria and bacterial products (e.g., lipases) may not be critical factors. H. pylori was eradicated in five and failed in five. One month after ending therapy, the contact angles of those with recrudescence of infection and those with eradication were similar and higher (p < 0.05) than before therapy (antrum: 69.8 +/- 1 vs. 71.1 +/- 2, corpus: 66.4 +/- 4 vs. 70.8 +/- 2) (p > 0.25 for both). We conclude that gastric surface hydrophobicity abnormalities do not appear to be directly related to the presence of H. pylori organisms or the histologic features of acute inflammation, but are responsive to antimicrobial therapy.

Adult↗
PubMed1993

Frequency of positive tests for cytomegalovirus in AIDS patients: endoscopic lesions compared with normal mucosa.

Ten patients with the acquired immunodeficiency syndrome and an endoscopic erosive/ulcerative lesion in esophagus (4), stomach (3), or colon (3) were prospectively studied with multiple biopsies (244 biopsies from 33 sites) to determine: 1) the frequency of positive tests for cytomegalovirus (CMV) in the lesions versus normal mucosa, 2) the influence of number of biopsies on the rate of positivity. As seen on histology, five out of 10 lesions had cytomegalic cells, but only six of 45 (13%) of the biopsies taken from lesions that were positive showed the diagnostic changes. Immunoperoxidase was positive in two of the lesions with cytomegalic cells, but the positive staining occurred in only three of 35 (9%) biopsies from the histologically positive lesions. Culture was positive in one of 10 lesions, and the rate of positivity did not depend on number of cultures sent or number of biopsies per culture. Polymerase chain reaction was positive in six of 10 lesions, including all lesions positive by either histology (5), immunoperoxidase stain (2), or culture (1). The frequency of a biopsy being positive for CMV in normal mucosa was found to be 4%, 0%, 17%, and 28% by histology, immunoperoxidase stain, culture, and polymerase chain reaction, respectively. In AIDS patients at high risk for CMV, histologic evidence of CMV infection is uncommon in normal mucosa but is frequent in suspicious lesions. However, the frequency of diagnostic histology is highly dependent on the number of biopsies taken and the diligence of the pathologist. Polymerase chain reaction has the potential to become a rapid test to rule out CMV infection in gastrointestinal tissue.

AIDS-Related Opportunistic Infections↗
PubMed1992

Factors influencing the eradication of Helicobacter pylori with triple therapy.

Helicobacter pylori infection has been associated with gastritis, duodenal ulcer, gastric ulcer, and the epidemic form of gastric carcinoma. Eradication of H. pylori infection has proven to be difficult. Recently, combinations of antimicrobial drugs have been shown to eradicate greater than 50% of infections; however, the results have proven variable, and the factors influencing effectiveness of therapy are unclear. In the present study, the effectiveness of a triple therapy for eradication of H. pylori infection was evaluated. Triple therapy consisted of 2 g tetracycline, 750 mg metronidazole, and five or eight tablets of bismuth subsalicylate daily in 93 patients (70 with duodenal ulcer, 17 with gastric ulcer, and 6 with simple H. pylori gastritis). Combinations of a sensitive urea breath test, serology, culture, and histology were used to confirm the presence of infection, eradication, or relapse. Eradication was defined as inability to show H. pylori greater than or equal to 1 month after ending therapy. The overall eradication rate was 87%. The factors evaluated for their effect on predicting eradication included age, gender, type of disease, duration of therapy, amount of bismuth subsalicylate [five or eight Pepto-Bismol tablets daily (Procter & Gamble, Cincinnati, OH)], and compliance with the prescribed medications. Stepwise regression showed that compliance was the most important factor predicting success; the success rate was 96% for patients who took greater than 60% of the prescribed medications and 69% for patients who took less. For those taking greater than 60% of the prescribed therapy, the eradication rates were similar (a) for patients receiving therapy for 14 days or when tetracycline and bismuth subsalicylate were taken for an additional 14 days; (b) for patients with duodenal ulcer, gastric ulcer, and simple H. pylori gastritis; and (c) whether five or eight bismuth subsalicylate tablets were taken. It is concluded that triple therapy is effective for eradication of H. pylori and that future studies need to take compliance into account for comparisons between regimens.

Adult↗