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Biomedical subjects

G Neil

Publications and source records attributed to G Neil.

At least 19 recordsLinked to original sources
PubMed2000

Endoscopic biopsy requirements for post-treatment diagnosis of Helicobacter pylori.

BACKGROUND: Data on sensitivities of biopsy tests for Helicobacter pylori diagnosis after modern eradication therapy are limited. We assessed diagnostic yield of endoscopic biopsy tests before and after therapy in 2 U.S. multicenter double-blind trials of 10-day proton pump inhibitor-based triple therapy versus dual antibiotic therapy. METHODS: Three hundred one patients with duodenal ulcer and H pylori infection had endoscopy at baseline and at 8 weeks. Four antral and 3 body biopsies were taken at both endoscopies: 1 antral biopsy for a rapid urease test (CLOtest), 2 antral and 2 body biopsies for histologic examination (Genta stain), and 1 antral and 1 body biopsy for culture. RESULTS: The 2 same-site biopsies (antral or body) for histologic examination were in agreement in 97% of cases before treatment and 100% after triple therapy. Histologic examination of antral biopsies without body biopsies missed H pylori infection in 2% of patients before treatment and 5% after triple therapy. Posttreatment sensitivities for triple therapy were significantly lower than pretreatment sensitivities for all tests (e. g., 18% decrease in sensitivity in antral histology, 22% decrease in antral culture); decreases in sensitivity were greater after triple therapy than after the less effective dual therapy. CLOtest plus histology had a post-treatment sensitivity of 96% in the triple therapy group. CONCLUSIONS: A single antral biopsy for histology provides excellent sensitivity for H pylori in untreated patients, but, after effective therapy, sensitivities of biopsy tests decrease. Use of more than one method of testing may increase diagnostic yield when assessing post-treatment H pylori status with endoscopy, whereas the addition of multiple biopsies for each type of test is of more limited value.

Amoxicillin↗
PubMed1999

Once-daily therapy for H. pylori infection: a randomized comparison of four regimens.

OBJECTIVE: We sought to determine the efficacy and tolerability of novel, once-daily therapies in the treatment of Helicobacter pylori infection. METHODS: One hundred sixty subjects with H. pylori infection documented by endoscopic biopsy or serology plus 13C-urea breath test were randomly assigned to omeprazole 80 mg q.d. and metronidazole extended-release formulation 750 mg q.d. for 10 days (OM); OM plus amoxicillin 1.5 g q.d. for 10 days (OMAm); OM plus azithromycin 500 mg q.d. for 7 days (OMAz); or OM plus clarithromycin 1 g q.d. for 10 days (OMCI). A repeat breath test was done 6 wk after the completion of therapy. Subjects were considered compliant if they took > or = 80% of each study medication as prescribed. RESULTS: Intent-to-treat eradication rates were OM = 8% (95% confidence interval [CI], 2-20%), OMAm = 35% (95% CI, 21-52%), OMAz = 65% (95% CI, 48-79%), and OMCI = 78% (95% CI, 62-89%). Lack of compliance was seen in 5% of subjects given OM, 8% given OMAm, 3% given OMAz, and 15% given OMCI. CONCLUSIONS: This pilot study demonstrated that once-daily triple therapy with high-dose omeprazole, metronidazole extended-release formulation, and clarithromycin achieved an eradication rate approaching 80%. Further study may permit development of optimal once-daily dosing and enhance eradication rates.

Adult↗
PubMed1998

Endometriosis with massive ascites.

We present 4 cases of endometriosis complicated by massive ascites from our institution and a review of 27 cases from the literature. In most of these patients, the presence of ascites with its related symptoms in association with pelvic masses suggested a neoplastic disease. However, a large proportion of these women had also classical manifestations of endometriosis, e.g., dysmenorrhea, cul-de-sac nodularities, and exacerbation of ascites and other symptoms during the menses. The response to hormonal therapy including GnRH agonists was often unsatisfactory. Repeat recurrences and severe complications required multiple laparotomies and thoracotomies for associated pleural and pulmonary involvement.

Adult↗
PubMed1998

Accuracy of CLOtest after Helicobacter pylori therapy.

BACKGROUND: The accuracy of rapid urease testing after Helicobacter pylori therapy has not been widely studied and might be diminished because of decreased numbers of organisms. We assessed CLOtest results after therapy in two randomized, double-blind trials. METHODS: A total of 233 patients (in two separate studies) with true-positive baseline CLOtests (by histology or culture) received 2 weeks of omeprazole/amoxicillin, omeprazole, or amoxicillin. In study 1, patients received an additional 2 weeks of omeprazole therapy (20 mg/day) or placebo; no additional therapy was given in study 2. Endoscopy was repeated 4 weeks after completion of therapy in both studies. A diagnosis of cure required at least two negative endoscopic biopsy tests (histology, culture, CLOtest) and no positive tests. RESULTS: After therapy, 178 patients (76%) remained positive for H. pylori by histology and/or culture for both studies combined. Post-therapy CLOtest sensitivity was 86% and specificity was 95%. Sensitivity was poorer in patients after dual therapy than after monotherapy in both study 1 (68% vs. 89%; p = 0.03) and study 2 (75% vs. 94%; p = 0.03). CONCLUSIONS: CLOtest sensitivity after therapy was lower than expected in our large group of patients with baseline true-positive CLOtests. In addition, sensitivity was lower after the use of more effective therapy (i.e., dual therapy as compared with monotherapy). Although most patients with unsuccessful treatment will be identified with the CLOtest alone, a negative result should not be taken as diagnostic of eradication.

Amoxicillin↗
PubMed1998

US double-blind, controlled trials of omeprazole and amoxycillin for treatment of Helicobacter pylori.

BACKGROUND: Widely variable Helicobacter pylori eradication rates have been reported with omeprazole/amoxycillin dual therapy. We present the first US double-blind, controlled trials of this dual therapy. METHODS: Three separate studies were performed: Studies 1 and 2 included patients with an active duodenal ulcer and Study 3 included patients with a documented history of duodenal ulcer. H. pylori eradication regimens in all studies were omeprazole plus amoxycillin vs. omeprazole vs. amoxycillin for 2 weeks. Doses in Study 1 were omeprazole 40 mg b.d. and amoxycillin 500 mg t.d.s., and in Studies 2 and 3 they were omeprazole 20 mg b.d. and amoxycillin 1 g t.d.s. Endoscopic biopsy tests were used for H. pylori diagnosis, and testing for H. pylori eradication was done at least 4 weeks after the completion of therapy. Amoxycillin sensitivities were performed in Study 2. RESULTS: Intention-to-treat (ITT) and per protocol (PP) analyses showed that eradication rates with omeprazole/amoxycillin [ITT: 39%, 40%, 46% (n = 72, 62, 48); PP: 50%, 46%, 54% (n = 54, 52, 37)] were significantly greater than monotherapy with either omeprazole (ITT: 0-4%); PP: 0-5%) or amoxycillin (ITT: 2-5%; PP: 0-11%). No patients taking the dual therapy discontinued therapy due to adverse events. Amoxycillin resistance was not seen at baseline (n = 76) or after amoxycillin therapy (n = 56). CONCLUSIONS: Omeprazole/amoxycillin dual therapy is well tolerated but the eradication rate which can be expected in the USA is at best about 50%.

Administration, Oral↗
PubMed1998

Low rate of emergence of clarithromycin-resistant Helicobacter pylori with amoxycillin co-therapy.

BACKGROUND: Patients with persistent Helicobacter pylori infection following treatment with clarithromycin or omeprazole plus clarithromycin often develop clarithromycin resistance. AIM: To assess pre- and post-treatment antibiotic resistance in three double-blind trials of triple therapy with omeprazole, amoxycillin and clarithromycin. METHODS: Patients with H. pylori and duodenal ulcer (studies 1 and 2) or history of duodenal ulcer (study 3) were randomly assigned to 10 day courses of omeprazole 20 mg b.d., amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (OAC) or placebo, amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (AC). Endoscopy was performed at baseline and 4 weeks after completion of therapy in studies 1 and 2, and at 4-6 weeks after therapy in study 3. At baseline, H. pylori was diagnosed by CLO test with confirmation by histology, or by culture. Eradication was defined as no positive biopsy test and > or = 2 negative tests. Susceptibility testing was performed using the Etest. RESULTS: In the 91 patients with pre-treatment susceptible isolates who had persistent infection after AC, 10 developed resistance, eight had intermediate susceptibility and 73 continued to have clarithromycin-susceptible H. pylori isolates. In the 10 patients with pre-treatment susceptible isolates who had persistent infection after OAC, three developed clarithromycin resistance and seven still had susceptible isolates. CONCLUSIONS: Use of amoxycillin co-therapy results in a low rate of clarithromycin resistance developing in patients with persistent H. pylori infection following therapy with a clarithromycin-containing regimen.

Amoxicillin↗
PubMed1998

Twice-daily, 10-day triple therapy with omeprazole, amoxicillin, and clarithromycin for Helicobacter pylori eradication in duodenal ulcer disease: results of three multicenter, double-blind, United States trials.

OBJECTIVE: We assessed the safety and efficacy of 10-day twice-daily triple therapy for Helicobacter pylori (H. pylori) in three double-blind, controlled trials in patients with duodenal ulcer disease. METHODS: H. pylori-infected patients with one or more duodenal ulcer(s) at endoscopy (studies 1, 2) or with a documented duodenal ulcer history and no duodenal ulcer or erosions at endoscopy (study 3) were randomly assigned to 10-day courses of omeprazole 20 mg b.i.d. plus amoxicillin 1 g b.i.d. plus clarithromycin 500 mg b.i.d. (OAC) or placebo plus amoxicillin 1 g b.i.d. plus clarithromycin 500 mg b.i.d. (AC). In studies 1 and 2, patients received an additional 18 days of omeprazole 20 mg q.d. (OAC group) or placebo (AC group). Endoscopy was repeated 4 wk after therapy in studies 1 and 2 and 4-6 wk after therapy in study 3. At baseline, H. pylori was diagnosed by CLOtest plus histology, or by culture. Eradication was defined as no positive biopsy test and two or more negative tests. Patients were defined as compliant if they took 75% or more of each study drug and missed < or = 3 consecutive days of the 10-day therapy. RESULTS: Intent-to-treat populations of the three studies combined were 241 patients for OAC and 266 for AC. Of all OAC patients combined, 2% stopped study medications due to adverse events, and 93% were compliant. Per-protocol cure rates were 78% to 90% (all studies combined, 84%) for OAC vs 33% to 45% (combined, 39%) for AC (p < 0.001, OAC vs AC); intent-to-treat eradication rates were 69% to 83% (combined, 75%) for OAC vs 32% to 37% (combined, 35%) for AC; (p < 0.001, OAC vs AC). CONCLUSION: Rigorously designed studies indicate that 10 days of twice-daily triple therapy with omeprazole, amoxicillin, and clarithromycin achieves per-protocol eradication rates of approximately 80% to 90% in the U.S.

Aged↗
PubMed1996

Randomized comparison of differing periods of twice-a-day triple therapy for the eradication of Helicobacter pylori.

BACKGROUND: We assessed the efficacy, compliance, and tolerability of the twice-a-day triple therapy, amoxycillin, omeprazole, and clarithromycin, for Helicobacter pylori and studied the effect of treatment duration (7, 10 or 14 days) on these factors. METHODS: One-hundred and fifty subjects with H. pylori infection documented by 13C-urea breath test were randomly assigned to a 7, 10 or 14-day course of amoxycillin 1 g b.d., omeprazole 20 mg b.d. and clarithromycin 500 mg b.d. Subjects returned at the end of therapy for pill count and assessment of side-effects. Subjects returned for a repeat 13C-urea breath test 4 weeks after the end of therapy. RESULTS: Poor compliance (< 80% of medications taken) was seen in 0 subjects at 7 days, 6% at 10 days, and 10% at 14 days (P = 0.03 by chi 2 test for trend; difference for 7 vs. 14 days = 10%; 95% CI, -2% to 18%; P = 0.056). Intention-to-treat eradication rates were 86% at 7 days, 90% at 10 days and 92% at 14 days. Per-protocol eradication rates were 86% at 7 days, 91% at 10 days, and 95% at 14 days (P = 0.11; difference for 7 vs. 14 days = 9%; 95% CI, -2% to 21%; P = 0.17). CONCLUSIONS: One week of twice-a-day amoxycillin, omeprazole and clarithromycin is well tolerated and provides a good rate of H. pylori eradication. Increasing the duration of therapy decreases compliance but has the potential to modestly improve efficacy if the patient takes the full complement of medication.

Adult↗
PubMed1996

Variations in human placental 11 beta-dehydrogenase and 11-oxoreductase activities of 11 beta-hydroxysteroid dehydrogenase enzyme during pregnancy.

Human placental 11 beta-hydroxysteroid dehydrogenase enzyme has an important role in controlling glucocorticoids reaching the fetus. Excess glucocorticoids impair fetal growth. Recent investigations show that the placenta is rich in NAD- and NADP-dependent 11 beta-hydroxysteroid dehydrogenase activity. Elucidation of the activities of both these isoforms is necessary to understand placental glucocorticoid metabolism. Hence we determined both NAD- and NADP-dependent 11 beta-hydroxysteroid dehydrogenase activities throughout pregnancy. 11 beta-dehydrogenase (oxidative) and 11-oxoreductase (reductive) activities of 11 beta-hydroxysteroid dehydrogenase were determined in 16 first-trimester (9-12 weeks) and 14 second-trimester (13-22 weeks) and 17 term (38-42 weeks) placentae. Both NAD- and NADP-dependent activities increased with pregnancy. The second-trimester NAD-dependent activity was higher than the first-trimester activity (p = 0.02). At term this activity was higher than during the second (p = 0.05) and first (p = 0.0002) trimesters. A similar increase was obtained with NADP isoform except that the difference between first and second trimesters was not significantly different at p = 0.05. The NADH-dependent 11-oxoreductase activity was also detected throughout the pregnancy. However, the activity at term was significantly higher than during the second (p = 0.005) and first (p = 0.001) trimesters. This increase may result in a concomitant increase of cortisol reaching fetus, thus helping fetal lung maturation.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

Characterization of the procoagulant-inducing factor derived from the plasma of BXSB mice.

Plasma procoagulant activity inducing factor (PIF) is a spontaneously occurring, potent inducer of macrophage procoagulant activity (PCA) in the male BXSB murine model of systemic lupus erythematosus. The physical characteristics of PCA induction by PIF, aggregated mouse IgG, and lipopolysaccharide (LPS) were compared. Both aggregated IgG and PIF-induced PCA were heat, acid and alkali sensitive. In contrast, LPS-induced PCA was heat resistant and only partially acid and alkali sensitive. Plasma containing PIF was fractionated on Sephacryl S-300. The PIF activity localized to the first protein peak, molecular weight 400,000 to 900,000 daltons. Analysis of peak 1 by an enzyme-linked immunosorbent assay showed the presence of IgM, IgA and IgG. This was confirmed by Western blot analysis using 125I-labelled goat anti-mouse IgM, IgA and IgG probes. The concentration of PIF increased with Sephacryl S-300 chromatography and was reduced by removal of IgG, but not IgA or IgM by affinity chromatography. Peak 1 did not contain DNA as revealed by ethidium bromide staining. Thus, IgG from the plasma of BXSB mice, a strain which develops lupus nephritis, stimulates macrophages to express PCA, accounting for PCA induction in the BXSB model of murine lupus.

Animals↗
PubMed1995

Effect of magnesium on coagulation as measured by thrombelastography.

Magnesium has long been assumed to have anticoagulant properties, but the effect has been poorly quantified. The thrombelastograph (TEG) was used to evaluate the effect of magnesium using blood from volunteers. Magnesium sulphate was added to one blood sample and another sample was used as a control. Both samples were tested simultaneously and the results evaluated against the magnesium concentration measured in each sample. At serum magnesium concentrations < 3 mmol litre-1, there were no significant effects of magnesium. With increasing magnesium concentrations there was a statistically significant but small prolongation of the r time, k time and r + k time. Maximum amplitude was affected only at magnesium concentrations > 7 mmol litre-1. Magnesium has only minimal effects on coagulation which are unlikely to be clinically important.

Blood Coagulation↗
PubMed1995

Limited efficacy of omeprazole-based dual and triple therapy for Helicobacter pylori: a randomized trial employing "optimal" dosing.

OBJECTIVES: To evaluate the efficacy and side effects of dual omeprazole/amoxicillin therapy for Helicobacter pylori given in "optimal" fashion (omeprazole twice a 3 g of amoxicillin daily, drugs started concurrently, 2 wk of therapy) and to assess the utility of adding a second antibiotic, tetracyline. METHODS: Sixty healthy volunteers with H. pylori infection documented by 13C-urea breath test were randomly assigned to receive 2 wk of therapy with either 1) omeprazole 20 mg b.i.d. and amoxicillin 1 g t.i.d. (OA), or 2) OA plus tetracycline 500 mg t.i.d. (OAT). Patients returned after 2 wk for pill count and clinical assessment, and 13C-urea breath test was repeated 4 wk after the end of therapy. RESULTS: H. pylori was eradicated in 15 (50%) of 30 patients receiving OA therapy and in nine (30%) of 30 given OAT (p = 0.19). Side effects occurred in five (17%) patients in the OA group [two (7%) discontinued therapy due to side effects] and eight (27%) of the OAT group [three (10%) stopped therapy due to side effects]. Good compliance (> 80% of prescribed study drugs taken) was seen in 87% of each group, and eradication rates were 54% and 35% among patients with good compliance in the OA and OAT groups (p = 0.26). CONCLUSIONS: Dual therapy with omeprazole and amoxicillin, when given in "optimal" fashion, had limited efficacy, with an eradication rate of 50%. The addition of tetracycline to the dual therapy did not improve the rate of cure. Because virtually all of our subjects were from minority groups, with over three-fourths Hispanic, we speculate that differences in H. pylori strains or host factors may explain, at least in part, the discrepancy between our results and those in Northern European populations.

Adult↗
PubMed1994

Sera from habitual aborters induce monocyte procoagulant activity: a lymphocyte-dependent event.

Placental thrombosis is a prominent feature in patients with unexplained recurrent fetal loss. To determine whether induction of monocyte procoagulant activity might be a relevant mechanism for unexplained recurrent fetal loss, peripheral blood mononuclear cells isolated from normal healthy controls were cocultured with (a) sera from normal healthy controls (n = 16), (b) sera from habitual aborters (n = 41), and (c) lipopolysaccharide as a positive control. Sera from three patients were fractionated on Sephracryl S-300 and the inducing molecule(s) characterized. Sera from normal healthy controls failed to induce procoagulant activity above basal levels of 21 +/- 4.6 mU/10(5) peripheral blood mononuclear cells. Of the sera from 41 habitual aborters examined 26 (63%) induced procoagulant to a mean value of 410 +/- 48 mU/10(5) peripheral blood mononuclear cells (P < 0.01). Sera from 15 patients failed to augment procoagulant activity. The induction of procoagulant activity was maximal after 6 hr of incubation and was lymphocyte dependent. Fractionation of serum from the three patients on Sepharcryl S300 revealed the procoagulant activity (PCA)-inducing factor(s) to have a molecular weight of between 300,000 and 800,000 Da. The serum factor was found to be heat, alkaline, and acid sensitive. Both anti-IgM and anti-IgA immunoabsorbents reduced the PCA-inducing factor. We conclude that IgM and IgA from some patients with unexplained recurrent fetal loss are capable of inducing procoagulant activity and could contribute to the development of placental microthrombi and infarction, prominent features of this syndrome.

Abortion, Habitual↗
PubMed1994

Spinal anaesthesia but not general anaesthesia enhances neutrophil biocidal activity in hip arthroplasty patients.

The purpose of this study was to compare neutrophil cidal activity during general or spinal anaesthesia. Assays were performed on neutrophils extracted from the blood of patients after surgery had been under way for one hour. First, the ability of the neutrophils to kill a standard laboratory strain of S. aureus was examined. Neutrophils extracted from the blood during surgery in the spinal anaesthetic group and incubated with the staphylococci for one hour killed twice as many bacteria than those from two groups of patients that received halothane or isoflurane general anaesthesia (P < 0.05). This effect persisted, to a lesser extent, in the spinal group neutrophils after two hours of incubation with the bacteria. Second, neutrophils from patients under the same conditions of surgery and anaesthesia were tested to examine the effect of the different anaesthetic techniques on neutrophil biocidal mechanisms. Neutrophils extracted during surgery in the spinal group released more superoxide in response to phorbol-12-myristate-13-acetate (PMA) than those from both groups of patients that received general anaesthesia (P < 0.05). It is concluded that there is an increased state of reactivity of the neutrophil cell membrane NADPH oxidase system in patients receiving spinal anaesthesia than in patients receiving general anaesthesia.

Adult↗
PubMed1991

Monoclonal antibody analysis of a unique macrophage procoagulant activity induced by murine hepatitis virus strain 3 infection.

A panel of 24 IgG2ak monoclonal antibodies was produced against murine hepatitis virus strain 3 (MHV-3)-induced procoagulant activity (PCA) from murine macrophages. The antibodies were specific and did not react in an enzyme-linked immunosorbent assay with purified MHV-3; lipopolysaccharide-induced PCA; crude mouse, human, or rabbit tissue factor, or unstimulated murine macrophages. Sixteen of 24 monoclonal antibodies inhibited functional PCA expression in a one-stage clotting assay. More detailed studies on one monoclonal antibody, 3D4.3, demonstrated that it inhibited prothrombin cleavage at concentrations of greater than or equal to 0.1 microgram/ml, and by Western blot this antibody reacted with proteins of a molecular mass of 140, 74, and 70 kDa on nonreduced gels and 74 and 70 kDa on reduced gels distinct from tissue factor known to have a molecular mass of 47 kDa. Induction of PCA was dependent on both host RNA and protein synthesis. Immunofluorescence studies showed specific binding to MHV-3-stimulated PCA-positive macrophage membranes. Both numbers of positive macrophages and intensity of staining correlated with multiplicity of infection. These monoclonal antibodies will be useful in isolation and characterization of the unique viral-induced PCA as well as in determining its biologic role in MHV infection and other diseases in which the prothrombinase has been implicated.

Animals↗
PubMed1991

Intracast pressure measurements in Colles' fractures.

Intracast pressures were recorded in conventional plaster-of-Paris below-elbow casts and compared with a new prefabricated brace for the functional treatment of Colles' fractures. Interface pressures were consistently higher in the brace than in the conventional plaster cast throughout the treatment period, and demonstrated more specific loading to the fracture site.

Adolescent↗
PubMed1991

Effect of high-fat and low-fiber meals on the cell proliferation activity of colorectal mucosa.

Normal healthy volunteers (n = 43) were divided into four groups that received diets providing low or high levels of dietary fat (33 or 96 g/day) and low or high levels of dietary fiber (6 and 41 g/day) for a period of five days. Proliferation was assessed with tritiated thymidine labeling of three rectal biopsies. After five days on the prescribed diets, the average thymidine labeling index (LI) of the group on the high fat-low fiber diet was only 25% higher than the average LI of the group on the low fat-high fiber diet, a difference that is not statistically significant. We conclude that a short-term increase in dietary fat and decrease in dietary fiber does not result in a large increase in cell proliferation rate.

Adult↗