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Biomedical subjects

R J Hopkins

Publications and source records attributed to R J Hopkins.

At least 19 recordsLinked to original sources

The effect of repellents Ocimum forskolei and deet on the response of Anopheles stephensi to host odours.

The behavioural response of Anopheles stephensi Liston (Diptera: Culicidae) to incubated host odours (from human and goat) and to human odour in combination with a repellent plant, Ocimum forskolei (Labiatae), or deet (N, N, diethyl-toluamide) (20%) was tested in a dual-port olfactometer. An. stephensi was significantly attracted to both host odours compared with air alone, but showed no preference when given a choice between both host odours simultaneously. In choice tests, the addition of deet to human odour did not significantly divert mosquitoes to human odour alone, but did divert them to goat odour. O. forskolei combined with human odour diverted mosquitoes to goat or human odour alone. Combinations of human odour and O. forskolei, and human odour and deet were both as unattractive as air alone, and attracted mosquitoes equally when offered simultaneously. The results indicate that use of O. forskolei as a repellent would be beneficial in reducing vector biting if used in communities in areas with partially zoophilic mosquito species such as An. stephensi, and where animals are present.

Animals↗

Frequency of venous thromboembolism in low to moderate risk long distance air travellers: the New Zealand Air Traveller's Thrombosis (NZATT) study.

BACKGROUND: The frequency and role of risk factors for venous thromboembolism related to air travel is uncertain. We aimed to establish the frequency of this disorder in a group of long distance air travellers and to investigate the role of potential risk factors. METHODS: We designed a prospective study into which we recruited individuals aged between 18 and 70 years, travelling for 4 h or more by aircraft. D-dimer measurement was done before and after travel. Participants with a negative D-dimer (<500 ng/L) before travel were included in the study. Those who became D-dimer positive or developed high clinical probability symptoms during the 3 months after travel were investigated with bilateral compression ultrasonography and CT pulmonary angiography. Suspected clinical and thrombophilic risk factors, and use of prophylactic measures, were assessed. FINDINGS: 1000 individuals were recruited, with 878 meeting inclusion criteria and completing the study. All participants travelled at least 10 h, with a mean total duration of air travel of 39 h (SD 12.5). 112 patients underwent radiological assessment on return. Frequency of venous thromboembolism associated with travel was 1.0% (9/878, 95% CI 0.5-1.9), which included four cases of pulmonary embolism and five of deep venous thrombosis. Six patients with venous thromboembolism had pre-existing clinical risk factors, two had a recognised thrombophilic risk factor, two travelled exclusively in business class, five used aspirin, and four wore compression stockings. INTERPRETATION: Our results suggest an association between multiple long distance air flights and venous thromboembolism, even in individuals at low to moderate risk. The role of traditional risk factors and prophylactic measures in air travel-related venous thromboembolism needs further investigation.

Adolescent↗

In search of the Holy Grail of Heliocobacter pylori remedies.

In this issue, Gisbert et al. (pp. 157-62) present the results of a noncomparative study evaluating a twice daily, 5-day regimen of ranitidine bismuth citrate, amoxicillin, clarithromycin and metronidazole twice daily for Helicobacter pylori cure. This study is one of a few stuides that evaluate a 5-day triple antimicrobial regimen in combination with a antisecretory agent. Although the study design precludes making any definite conclusion, it does encourage additional investigation of these types of regimens. Randomized controlled trials (RCTs) using regimens containing multiple agents should consider both standard-of-care comparator regimens and comparator regimens that will provide a better understanding of why regimens are more effective or better tolerated. The goal of treatment should be to maintain a lower bound 95% confidence interval (CI) of the point estimate of greater than 80% and a 'delta' (lower bound 95% CI of the difference in rates) of less than 10%. All RCTs should conduct susceptibility testing to evaluate the impact of resistance on efficacy and explain eradication failures. Finally, consideration should be given to the inclusion of patients with functional dyspepsia in H. pylori studies evaluating H. pylori cure since patients with peptic ulcer disease are becoming harder to find.

Amoxicillin↗

Helicobacter pylori and early duodenal ulcer status post-treatment: a review.

BACKGROUND: Data submitted to the FDA were reviewed to analyze the relationship between Helicobacter pylori infection and the incidence of early duodenal ulcers, within 6 weeks, following treatment. MATERIALS AND METHODS: Retrospective analyzes were performed on data from three H. pylori development programs submitted to the FDA: ranitidine-bismuth-citrate (RBC), lansoprazole (L) and omeprazole (O). Efficacy assessments for the RBC, L and O programs were made at end of a 4-week treatment period, 4-6 weeks following the end of a 14-day treatment period, and 4 weeks following the end of a 4-week treatment period, respectively. RESULTS: Overall, there was a 15%, 21% and 23% decrease in the number of patients in the RBC, L and O programs, respectively, with ulcers among H. pylori cleared/eradicated patients post-treatment compared with patients with persistent infection. Among patients who did not have cleared/eradicated H. pylori in the RBC and O programs, where antisecretory agents were continued beyond the antimicrobial treatment period, the number of ulcers was lower in the antisecretory plus antimicrobial subgroups compared with the antimicrobial alone subgroups (37% vs. 46% for RBC and 33% vs. 42% for O). Among patients with cleared/eradicated H. pylori, the number of patients with ulcers in the antimicrobial alone subgroups and antisecretory plus antimicrobial subgroups were similar within each program. Antimicrobials alone had significantly lower rates of ulcers among patients with cleared/eradicated H. pylori as compared with patients without clearance/eradication. CONCLUSIONS: The early incidence of duodenal ulcers is significantly decreased in patients with H. pylori clearance/eradication.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Has the impact of Helicobacter pylori therapy on ulcer recurrence in the United States been overstated? A meta-analysis of rigorously designed trials.

OBJECTIVE: The aim of this study was to assess the effect of H. pylori eradication on ulcer recurrence in North American duodenal ulcer patients by examining only treatment studies that met rigorous methodologic criteria. METHODS: Data sources were computerized bibliographic searches from 1983, review of reference lists, communication with companies that manufacture medications used for H. pylori therapy in the U.S., and H. pylori investigators, review of open presentations to the Food and Drug Administration, and review of abstracts from annual scientific meetings. Criteria for study inclusion were double blind, randomized North American trials of H. pylori therapy for duodenal ulcer, scheduled endoscopic follow-up exams for > or = 6 months, and H. pylori cure documented > or = 4 wk after completion of therapy by at least two endoscopic biopsy tests. Seven relevant trials were identified. Data were abstracted independently and disagreement was resolved by consensus. We obtained missing data and identified erroneous assessments through contact with an author or sponsor of all studies. RESULTS: The common odds ratio for ulcer recurrence was 0.20 (95% CI, 0.13-0.31) and 2.8 patients would need to be successfully treated to prevent one ulcer recurrence at 6 months. The pooled ulcer recurrence rate at 6 months in patients with H. pylori eradication was 20%. CONCLUSION: Results of North American studies of highest methodological quality confirm that H. pylori eradication markedly decreases ulcer recurrence. Nevertheless, 20% of patients in these studies had ulcer recurrence within 6 months, despite successful cure of infection and no reported use of NSAIDs. Non-H. pylori, non-NSAID ulcers may be more common in the U.S. than previously believed.

Double-Blind Method↗

Current FDA-approved treatments for Helicobacter pylori and the FDA approval process.

U.S. Food and Drug Administration (FDA) approval of new drugs expands treatment options and serves as a "safety net" of well-documented efficacy and safety. The information provided in the package insert facilitates physician education and provides some assurance that marketing information is accurate. As of February 1997, three Helicobacter pylori regimes have been FDA-approved for eradication of H. pylori in infected patients with active duodenal ulcers. Regimen 1, omeprazole + clarithromycin (O/C), was supported by two multicenter, controlled studies with a 6-month follow-up. Eradication rates were 74% (n = 53; 95% confidence interval [CI], 62-85) and 64% (n = 61; 95% CI, 52-76). Twenty-five of 26 patients with failed eradication therapy who were taking O/C with clarithromycin-susceptible strains before treatment and who had pretreatment and posttreatment susceptibility tests performed developed clarithromycin resistance after treatment. Regimen 2, ranitidine-bismuth-citrate + clarithromycin, was supported by two multicenter, placebo-controlled studies with a 6-month follow-up. Eradication rates were 84% (n = 19; 95% CI, 60-96) and 73% (n = 22; 95% CI, 50-88). Insufficient pretreatment and posttreatment susceptibility data were collected to assess antimicrobial resistance. Regimen 3, bismuth subsalicylate + metronidazole + tetracycline + an H2-receptor antagonist, was supported by two pivotal literature-based studies. Eradication rates in patients with duodenal ulcer were 82% (n = 51; 95% CI, 70-92) and 77% (n = 39; 95% CI, 61-89), respectively. When extrapolating the results of these three FDA-approved regimens to the clinical setting, particular aspects of the clinical trial should be kept in mind. These include the type of controls, primary end points used, population studied, and number and type of dropouts.

Anti-Bacterial Agents↗

Relationship between Helicobacter pylori eradication and reduced duodenal and gastric ulcer recurrence: a review.

BACKGROUND & AIMS: The aim of this study was to determine whether the current literature supports the use of Helicobacter pylori cure as the primary efficacy end point in peptic ulcer clinical trials. This could potentially reduce the complexity of future trials. METHODS: Published articles containing information on both H. pylori eradication and ulcer recurrence were searched with MEDLINE. Abstracts were found by reviewing references from both primary and review articles. RESULTS: Fourteen duodenal ulcer and five gastric ulcer studies satisfied requisite inclusion criteria. Ulcer recurrence was significantly less common among H. pylori-cured patients vs. noncured patients (6% vs. 67% for patients with duodenal ulcers; 4% vs. 59% for patients with gastric ulcers). For H. pylori-cured patients, duodenal ulcer recurrence was higher in studies using two endoscopic tests compared with three tests (9% vs. 3%) and higher in abstracts compared with published articles (14% vs. 4%). Timing of H. pylori eradication (4 weeks vs. < / = 12 weeks) and ulcer recurrence assessment (6 months vs. < / = 12 months) was not significantly related to duodenal ulcer recurrence. CONCLUSIONS: The current literature strongly suggests that H. pylori eradication 4 weeks after therapy should be used as the primary efficacy end point for reduced gastric and duodenal ulcer recurrence for the purpose of clinical trial design.

Clinical Trials as Topic↗

Loss of Helicobacter pylori hemagglutination with serial laboratory passage and correlation of hemagglutination with gastric epithelial cell adherence.

Adherence of Helicobacter pylori to gastric epithelial cells is thought to be important in the pathogenesis of infection and may be essential to maintain lifelong colonization. However, the factors responsible for adherence to gastric epithelial cells in vivo have not been characterized, and the significance of adherence to standard epithelial cell lines is unclear. Hemagglutination is also thought to be important in H. pylori adherence. However, no studies have clearly linked H. pylori hemagglutination or adherence to cultured epithelial cells to primary gastric epithelial cell adherence. Furthermore, it is not clear whether laboratory strains which have undergone multiple passages lose potential colonization factors. In this study, we examined the effect of serial laboratory passage on hemagglutination and correlated the hemagglutination characteristics of H. pylori strains to primary gastric cell adherence. Variable expression of hemagglutination was seen with serial laboratory passage of 15 strains. After 100 serial laboratory passages, all strains had lost hemagglutination activity. Hemagglutination was seen in association with adherence to primary gastric cells in vitro isolated from 2 patients. An association with ultrastructural intimate adherence was seen with HEp-2 cells, but not with gastric adenocarcinoma cells. Ultrastructural adherence was seen in corresponding antral biopsies of patients whose strains were hemagglutination positive, but hemagglutination was not associated with gastric inflammation. These data indicate that H. pylori hemagglutination is lost with serial passage and that hemagglutination may play a role in the attachment of H. pylori to gastric epithelial cells, but the role of adherence to chronic gastric inflammation is unclear.

Adenocarcinoma↗

Helicobacter pylori: the missing link in perspective.

Helicobacter pylori, an organism responsible for a common human infection, may act as a cofactor to produce gastrointestinal disease in a significant minority. The exact mechanisms of transmission are still unclear, but likely involve direct person-to-person spread and fecal-oral or waterborne/environmental transmission. Infection is a necessary condition for the development of duodenal ulcers and chronic nonspecific gastritis. It also likely contributes to the development of gastric ulcers, and the intestinal-type gastric carcinoma, but further studies are needed to confirm these hypotheses. Multiple effective treatment regimens currently exists. We recommend using bismuth, metronidazole, and tetracycline as the initial regimen of choice. Unfortunately, the relative importance of bacterial virulence factors is still unclear when compared with host susceptibility factors, and much knowledge needs to be gained about pathogenesis before vaccine development can proceed.

Gastrointestinal Diseases↗

Cerebral mucormycosis associated with intravenous drug use: three case reports and review.

We describe three cases of cerebral mucormycosis in intravenous drug users and review 22 previously reported cases. Involvement of the basal ganglia was demonstrated in all but two cases. Seven of the 10 patients tested for antibodies to the human immunodeficiency virus (HIV) were seronegative. Eight of the 25 patients survived and were discharged from the hospital; for 7 of 10 patients, cultures of brain lesions yielded Rhizopus arrhizus. The radiographic findings varied, and in most cases, no or minimal contrast enhancement was seen in the initial computed tomography scans. Although uncommon, the diagnosis of cerebral mucormycosis should be considered when basal ganglia lesions are present in an intravenous drug user, regardless of previous exposure to HIV.

AIDS-Related Opportunistic Infections↗

Seroprevalence of Helicobacter pylori in Chile: vegetables may serve as one route of transmission.

Helicobacter pylori infection is very common in Chilean adults, but the age-related prevalence, risk factors for infection, and mode of transmission in Chilean children are unknown. An ELISA was used to test for H. pylori antibodies in 1815 Chileans < 35 years of age. Seropositivity was > 60% in lower socioeconomic groups. H. pylori seropositivity correlated with increased age, low socioeconomic status, and consumption of uncooked vegetables by use of a logistic regression analysis. Risk factors that reached marginal significance were consumption of uncooked shell-fish, female sex, and residence in Santiago. Although multiple modes of transmission for H. pylori undoubtedly exist, prior studies have suggested that contamination of irrigation water by raw sewage (and the subsequent contamination of vegetables that are eaten uncooked) is a key factor in the transmission of enteric pathogens in Chile; H. pylori may be transmitted by a similar route.

Adolescent↗

Serologic response to Helicobacter pylori among children and teenagers in northern Chile.

The serologic response to Helicobacter pylori was determined in 388 children and teenagers living in Iquique, Chile by using an IgG enzyme-linked immunosorbent assay. Serum antibody levels, as measured by optical density, correlated strongly with age. Increases in the mean antibody level were seen primarily after age five, with rates of seropositivity increasing to > or = 70% among teenagers. The reasons for this age-related pattern of acquisition of infection remain to be determined.

Adolescent↗

Seropositivity to Helicobacter pylori: lack of association with length of hospitalization.

To examine the possibility of nosocomial spread of Helicobacter pylori, a serosurvey (n = 238) was conducted at Perry Point Department of Veterans Affairs Medical Center, an institution providing both acute and chronic care. We hypothesized that if significant nosocomial transmission was occurring, seropositivity (as measured by enzyme-linked immunosorbent assay [ELISA]) would correlate with length of stay in the facility. Whether treated as a continuous or dichotomous variable, the ELISA results did not correlate significantly with length of stay even after adjustments were made for age, race, antibiotic use, gastrointestinal instrumentation, and diagnoses by using multiple-regression models. Age was found to be a significant risk factor for a higher ELISA optical density value. A history of chronic obstructive pulmonary disease was significantly protective among internal medicine ward patients in adjusted analysis; black race was a significant risk factor among psychiatry ward patients. Our results confirm the association of H. pylori infection with age but provide no indication that extended hospitalization is a risk factor for infection.

Adult↗

Stability of morphine sulfate in Cormed III (Kalex) intravenous bags.

The stability of various concentrations of morphine sulfate solution stored in Cormed III (Kalex) i.v. bags at two temperatures was investigated. Solutions of morphine sulfate 0.5, 15, 30, and 60 mg/mL were prepared under a horizontal-laminar-airflow hood with 0.9% sodium chloride solution and placed into 100-mL Kalex bags. Two bags were prepared for each concentration; one was stored at 5 degrees C and the other at 37 degrees C. Samples were analyzed in triplicate by high-performance liquid chromatography on days 0, 2, 5, 9, and 14. All morphine sulfate solutions were stable for 14 days at 37 degrees C, and the 0.5-, 15-, and 30-mg/mL solutions were stable for 14 days at 5 degrees C. However, the 60-mg/mL solution stored at 5 degrees C was found to contain 57% of the actual initial concentration on day 9 and 51% on day 14; the decrease coincided with the appearance of a white precipitate. Beginning on day 5, all the solutions displayed a light brown color that darkened as the study proceeded. This qualitative change was not associated with any change in morphine concentration. Solutions of morphine sulfate 0.5 to 60 mg/mL stored at 5 or 37 degrees C were stable for 14 days in Kalex bags, except for 60-mg/mL solutions stored at 5 degrees C for nine days or longer.

Chromatography, High Pressure Liquid↗

Seroprevalence of Helicobacter pylori in Seventh-Day Adventists and other groups in Maryland. Lack of association with diet.

To evaluate the possible role of diet in the transmission of Helicobacter pylori, we compared H pylori seroprevalence among Seventh-Day Adventists (who are vegetarian and abstain from alcohol, caffeine, and meat; n = 94) and two non-Seventh-Day Adventist control groups (n = 168). With the use of an enzyme-linked immunosorbent assay H pylori antigen prepared in a French pressure cell, we found no difference in seroprevalence among these groups; however, seropositivity strongly correlated with age and black race.

Adult↗