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Biomedical subjects

G Foster

Publications and source records attributed to G Foster.

At least 109 records · Page 6Linked to original sources
PubMed1995

Effect of dose adjustment on enalapril-induced cough and the response to inhaled capsaicin.

1. In nine hypertensive patients with enalapril-induced cough the effect of altering the dose of enalapril on subjective cough and the cough response to inhaled capsaicin was examined in a random single-blind balanced cross-over study. They received three doses of enalapril, each for 3 weeks; the dose at entry (mean 10 mg daily); double this dose (mean 20 mg daily); and half this dose (mean 5 mg daily). 2. The cough response to inhaled capsaicin was also measured in two control groups: hypertensive patients on long-term enalapril treatment with no cough (n = 18), and hypertensive patients taking nifedipine (n = 17). 3. In patients with enalapril-induced cough there were significant dose-responses for enalapril as regards severity of cough (P < 0.05) and night time waking by cough (P < 0.05), but not for frequency of cough. Although the cough was less severe (P < 0.02) and caused less night time waking (P < 0.03) on the lowest dose of enalapril (mean 5 mg daily) it did not disappear completely in any patient. 4. The sensitivity to inhaled capsaicin did not differ significantly on the three doses of enalapril. The relative potency of capsaicin on enalapril 20 mg compared with enalapril 5 mg was 1.0 (95% CI 0.4-2.2). The wide confidence limits indicate that an important dose-dependent shift in capsaicin sensitivity is not excluded. 5. The sensitivity to inhaled capsaicin differed significantly between patients with enalapril-induced cough and both control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1995

Cetobacterium ceti gen. nov., sp. nov., a new gram-negative obligate anaerobe from sea mammals.

Phenotypic and phylogenetic studies were performed on a Gram-negative obligately anaerobic rod-shaped bacterium isolated from two sea mammals. 16S rRNA gene sequence analysis demonstrated the bacterium represents a hitherto unknown line of descent peripherally associated to the fusobacteria and low G+C relatives. Based on the result of the phylogenetic analysis and phenotypic criteria, it is proposed that the bacterium should be assigned to a new genus, Cetobacterium ceti gen. nov., sp. nov. The type strain of Cetobacterium ceti sp. nov. is NCFB 3026.

Animals↗
PubMed1995

Novel squalestatins produced by biotransformation.

Microorganisms were screened for the ability to modify the squalene synthase inhibitor squalestatin 1. Biotransformation of 1 by two actinomycetes, S15106 and S15138, yielded three products hydroxylated on the 4,6-dimethyl-oct-2-enoyl side chain either at the 6 position (5) or 7 position (4 two diastereoisomers), and lacking the acetyl ester from the C-1 side chain. Many strains were found to hydrolyse the 4,6-dimethyl-oct-2-enoyl or acetyl esters to yield squalestatins 2 or 3. The 3-methyl ester (6) of 1 was obtained using Fusarium sp. F13945. This fungus also produced a farnesoic acid derivative, possibly in response to inhibition of its squalene synthase by 1. The biotransformation products of 1 all retained potent squalene synthase inhibitory activity.

Actinomycetales↗
PubMed1995

Selecting an appropriate isotopic internal standard for gas chromatography/mass spectrometry analysis of drugs of abuse--pentobarbital example.

Internal standards are commonly used for the quantitative determination of drugs of abuse and their metabolites (drug/metabolite) in biological fluids and tissues by the selective ion monitoring (SIM) gas chromatography/mass spectrometry (GC/MS) procedure. Analogs of drugs/metabolites that are labeled with three or more deuterium atoms (isotopic analog) at appropriate positions are considered to be the most effective internal standards for these applications. Before a specific deuterated analog can be adopted as an internal standard in a GC/MS assay, the mass spectrum of the compound or its derivative must be evaluated along with the corresponding spectrum from the parent drug/metabolite. There should be an adequate number of sufficiently high-mass ions (typically three for the drug/metabolite and two for the isotopic analog) that can be attributed to each analyte, and these ions should be sufficiently free of interference from the other analyte of the pair (cross-contribution). Interferences may be caused by the presence of an isotopic impurity in the deuterated analog (extrinsic factor) or may be due to the ion fragmentation characteristics of the compound (intrinsic factor). The extrinsic factor may be corrected by the manufacturer with different synthetic methods and purification procedures, while the intrinsic factor may be partially or wholly corrected through the use of different chemical derivatives (sample preparation stage) or different ionization (GC/MS assay stage) procedures. In this study, pentobarbital/d5-pentobarbital is used as the exemplar analyte/deuterated analog pair to illustrate the ion selection and evaluation procedures. Full-scan mass spectra were employed for preliminary ion selection. SIM data were then used to calculate the extent, if any, of cross-contributions.(ABSTRACT TRUNCATED AT 250 WORDS)

Gas Chromatography-Mass Spectrometry↗
PubMed1995

Comparison of the accuracy of impedance plethysmography and compression ultrasonography in outpatients with clinically suspected deep vein thrombosis. A two centre paired-design prospective trial.

Impedance plethysmography (IPG) and compression ultrasonography (CUS) have been reported to be highly accurate for the diagnosis of deep vein thrombosis (DVT) in symptomatic patients. In many centres CUS has become the method of choice. However, direct comparisons of the accuracy of IPG to CUS have not been performed. To determine the test of choice we performed a two centre prospective comparison of IPG and CUS, with venography, and determined how the size and distribution of thrombi influenced the accuracy of each test. 495 symptomatic outpatients with suspected DVT had evaluable venograms. The prevalence of DVT was 27% (130/495), 84% (109) of which were proximal. The sensitivity of IPG and CUS for proximal vein thrombosis was 77% and 90% respectively (p = .002). The specificity of IPG was 93% whereas the specificity of CUS was 98% (p = 0.04). There were significant differences in accuracy between the two centres as a consequence of differences in the size and location of thrombi The majority of proximal thrombi not detected by IPG and CUS involved less than 5 cm of the distal half of the popliteal vein and most of these thrombi occurred in one centre. Exclusion of these thrombi from the analysis increases the sensitivity of CUS to 99% (86/87) and IPG to 91% (72/79), for proximal thrombi (P = .019). The positive predictive value of CUS was strongly influenced by the number of abnormal venous segments (three sites were examined); 100% (80/80) if two or three sites were abnormal, but only 68% if a single site was involved. We conclude that: 1) CUS is more accurate than the IPG for the diagnosis of DVT in symptomatic outpatients, and this relationship holds true regardless of the size or location of the DVT, 2) the sensitivities of IPG and CUS are much lower for small proximal DVT, and 3) confirmatory venography is warranted if the abnormality with CUS is limited to one venous segment.

Ambulatory Care↗
PubMed1994

Ipsilateral breast tumor recurrence postlumpectomy is predictive of subsequent mortality: results from a randomized trial. Investigators of the Ontario Clinical Oncology Group.

PURPOSE: To determine whether ipsilateral breast tumor recurrence (IBTR) postlumpectomy was independently predictive of distant relapse and mortality in women with node negative breast cancer. METHODS AND MATERIALS: A randomized trial was conducted in Ontario between 1984 and 1989, in which 837 women with node negative disease who had undergone lumpectomy and axillary dissection were randomized to either postoperative radiation (40 Gy in 16 fractions to the whole breast, followed by a boost of 12.5 Gy in five fractions to the primary site), or no further treatment. A Cox proportional hazards regression analysis was performed for the endpoints mortality and distant relapse using the fixed covariates, treatment, age, tumor size, estrogen receptor status, progesterone receptor status, and nuclear grade; and the time dependent variable IBTR. RESULTS: The analysis was based on 799 patients for which all fixed covariate data was available. Median follow-up was 66 months. The cumulative rate of IBTR at 5 years was significantly greater for the no treatment group compared to the radiation group; 30% vs. 8% respectively (p < 0.0001). No difference was detected in overall survival between the treatment groups (p = 0.45). Significant independent predictors for mortality were nuclear grade, high vs. medium or low (relative risk (RR) = 2.28, p = 0.0001); and tumor size > or = 2 cm. vs. < 2 cm. (RR = 1.64, p = 0.01). In addition, IBTR predicted increased mortality (RR = 2.18, p < 0.0006). Similar results were observed for distant relapse. An IBTR within 1 year of surgery was associated with a higher risk of distant relapse and mortality. CONCLUSION: Local breast recurrence following lumpectomy is associated with an increased risk of distant relapse and death.

Breast Neoplasms↗
PubMed1994

Determinants of the demographic impact of HIV-1 in sub-Saharan Africa: the effect of a shorter mean adult incubation period on trends in orphanhood.

Recent evidence suggests that the adult HIV-1 incubation period may be shorter in some sub-Saharan African populations than in Western populations. In this article we use mathematical-model-based simulations to show that, other things being equal, a shorter incubation period can result in smaller but more pronounced HIV-1 epidemics and faster, more acute, changes in demographic features, such as adult mortality, orphanhood and population structure. Empirical studies of orphanhood reveal similar patterns to those found in the simulations, but suggest that migration patterns and structural factors can give rise to greater concentrations of orphans in areas of relatively low HIV-1 prevalence.

Adolescent↗
PubMed1994

Influenza A outbreak in a nursing home: the value of early diagnosis and the use of amantadine hydrochloride.

An outbreak of respiratory tract infection due to influenza A virus occurred in February 1994 among residents of an 88-bed long term care facility in Toronto, Ontario. Eighteen confirmed and four probable cases of influenza were identified for an attack rate of 25%. Seventy-one per cent of the residents were known to have been immunized with trivalent influenza vaccine, but vaccine efficacy was determined to be only 32%. Influenza A viral antigen was rapidly detected by immunofluorescence microscopy of nasopharyngeal swabs, and amantadine hydrochloride was started in 76 residents within 48 h of recognizing the outbreak. Only two of the residents (3%) at risk became ill more than 48 h after amantadine was started. Amantadine was discontinued in four residents (5%) because of adverse effects (agitation, confusion, unsteady gait). In conclusion, rapid identification of the outbreak and prompt administration of amantadine hydrochloride prophylactically appears to be safe and effective in preventing further spread of influenza A.

Amantadine↗
PubMed1994

Improved gas chromatography/mass spectrometry analysis of barbiturates in urine using centrifuge-based solid-phase extraction, methylation, with d5-pentobarbital as internal standard.

Effective solid-phase extraction, derivatization, and GC/MS procedures are developed for the simultaneous determinations of butalbital, amobarbital, pentobarbital, and secobarbital, using a deuterated pentobarbital (d5-pentobarbital) as the internal standard. Buffered (pH 7) urine samples were extracted with Bond Elute Certify II cartridge. Iodomethane/tetramethylammonium hydroxide in dimethylsulfoxide was used for methylation, while a HP 5970 MSD equipped with a 13 m J & W DB-5 column (5% phenyl polysiloxane phase) and the Thru-Put Target software package were used for GC/MS analysis and data processing. This protocol was found to be superior, in both chromatographic performance characteristics and quantitation results, over a liquid-liquid extraction procedure without derivatization using hexobarbital as the internal standard. Extraction recoveries observed from control samples containing four barbiturates range from 80% to 90%. Good one-point calibration data are obtained for all four barbiturates in the 50 to 3200 ng/mL range. Interestingly, the one-point calibration data for pentobarbital are inferior to the other three barbiturates--due to interference from the internal standard (d5-pentobarbital). The calibration data of pentobarbital are best described by a hyperbolic curve regression model. Precision data (% CV) for GC/MS analysis, over-all procedure, and day-to-day performance are approximately 2.0%, 6.0%, and 8.0%, respectively. With the use of a 2 mL sample size, the attainable detection limit is approximately 20 ng/mL.

Amobarbital↗
PubMed1991

Effect of sulindac on the cough reflex of healthy subjects.

The effects of a single dose of sulindac 200 mg and placebo on the capsaicin-induced cough reflex were studied in a two-phase double-blind crossover study in 18 healthy subjects. Sulindac increased the threshold for capsaicin cough response significantly, but did not alter D5, peak response, or the total cough response when compared with placebo values.

Adult↗
PubMed1991

Prevalence of persistent cough during long-term enalapril treatment: controlled study versus nifedipine.

The prevalence and severity of cough during long-term enalapril treatment were examined by comparing a cohort of 136 hypertensive patients who started treatment with enalapril with consecutive age and sex-matched patients who commenced nifedipine therapy during the same period. Cough and other symptoms were assessed by a questionnaire designed to avoid bias towards reporting cough. After a mean of 27 months' treatment patients on enalapril had an excess of persistent cough (16 per cent, 95 per cent CI 7-25, p less than 0.01), voice change (14 per cent, 95 per cent CI 2-27, p less than 0.05) and sore throat (10 per cent, 95 per cent CI -0.1 to 20.3 per cent, p less than 0.01) when compared to nifedipine-treated patients. The cough was usually dry, moderate or severe, paroxysmal, and troublesome at night. Cough tended to be more common in women (23 per cent vs. 7.2 per cent), non-smokers, and at higher doses of enalapril, but was not related to age, duration of treatment, or chronic respiratory disease. Dry cough commonly persists as a troublesome side-effect during long-term enalapril treatment, and is often associated with voice change and sore throat.

Cough↗
PubMed1990

Three-generation reproduction study with dioctyl sodium sulfosuccinate in rats.

Groups of 30 male and 30 female rats (F0) were fed diets containing 0, 0.1, 0.5, or 1.0% dioctyl sodium sulfosuccinate (DSS) for 10 and 2 weeks, respectively. The F0 animals were then mated to produce an F1 litter. Groups of 30 male and 30 female F1 animals were fed the same dose levels for at least 10 weeks postweaning, and the breeding program was repeated to produce F2 animals. F3 animals were produced from F2 animals by the same procedure. The study was terminated with the F3 weanlings. Test diets were fed continuously throughout the study. All F0, F1, and F2 adults and F3 weanlings (one/sex/litter) were necropsied and given a macroscopic examination. There were no effects on reproductive function for parental animals of either sex during any of the three generations in this study. At the highest dose level (1.0% DSS), body weights were lower than those of controls during the premating phase for males in all three generations and for F1 and F2 females. Body weights for F1 and F2 males and females in the 0.5% dose group were also low during the premating phase. Pup weights on Lactation Day 0 were significantly lower than those of controls only for the high-dose group during the third generation. However, lower pup weight gains in the mid- and high-dose groups resulted in significantly lower pup weights on Day 21 for all three generations. Perinatal pup survival across three generations ranged from 96 to 100% for the control and treated groups. Pup survival ranged from 95 to 100% for controls, from 98 to 100% for low- and mid-dose groups, and from 91 to 99% for the high-dose group. There were no treatment-related mortality and antemortem or macroscopic observations. In summary, DSS administered in the diet to three successive generations of rats at levels of 0.5 and 1.0% caused a reduction in body weights for parental males in all generations and for F1 and F2 females. Pup weights at the 0.5 and 1.0% dose levels were also lower than those of the control in all three generations. However, the reduced body weights did not interfere with development of normal reproductive performance. DSS at levels up to 1.0% had no effects on the reproductive function of either sex in any generation and produced no treatment-related antemortem or macroscopic observations.

Animals↗