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Biomedical subjects

G White

Publications and source records attributed to G White.

At least 91 records · Page 5Linked to original sources
PubMed1995

Non-steroidal anti-inflammatory drugs and hospitalization for acute renal failure.

Non-steroidal anti-inflammatory drugs (NSAIDs) have been implicated in the aetiology of acute renal failure (ARF), but epidemiological studies examining this association have produced disparate results. We conducted a case-control study using a purpose-built record-linkage database for a population of 420,600 patients, resident in Tayside since May 1990. Patients (n = 207) hospitalized with a diagnostic code for ARF between 1990 and 1992 had their diagnosis validated by a renal physician. Six community controls and two hospital controls, matched for age and sex, were generated for each of these cases. Exposure to dispensed oral NSAIDs, topical NSAIDs and aspirin during the 90 days prior to the index date were investigated (recent exposure), as was exposure at any time since January 1989 (previous exposure). The most significant associations were modelled using conditional logistic regression. When community controls were used, recent exposure to NSAIDs and previous exposure to aspirin were independently associated with hospitalization for ARF, with adjusted odds ratios of 2.20 (1.49-3.25) and 2.19 (1.46-3.30), respectively. Only recent exposure to oral NSAIDs was associated when hospital controls were used: 1.84 (1.14-2.93). No significant interactions were present with previous chronic renal failure, other possible causes of ARF or whether the diagnosis was primary or secondary. There is an approximate doubling of the risk of hospitalization for ARF with use of oral NSAIDs.

Acute Kidney Injury↗
PubMed1995

Human alpha and beta subunits contribute to the EC50 for GABA at the GABAA receptor expressed in Xenopus oocytes.

The GABAA receptor/ionophore complex (GABAAR) may be composed of at least alpha, beta, and gamma subunits. Alpha subunits can influence the concentration of GABA at which a half maximal current response is elicited (EC50). There are no data to suggest that beta subunits can also influence this pharmacological property of the GABAAR. We examined the influence of human derived beta and alpha subunits on the EC50 for GABA. Nine different subunit combinations were evaluated: alpha 1, alpha 2, alpha 3 in combination with beta 1 gamma 2, beta 2 gamma 2, and beta 3 gamma 2. cRNA coding for these subunit combinations was injected into Xenopus oocytes that were subsequently recorded from using the two electrode voltage-clamp technique. A two-way analysis of variance showed that both alpha and beta subunits interact to influence the EC50 of GABAARs. The EC50 for alpha 3 changed significantly with beta subunits. The EC50 for alpha 2 was significantly different in beta 3 compared to beta 1 and beta 2 subunits, while the EC50 for alpha 1 was not significantly different between beta subunits. These findings suggests that other pharmacological and physiological properties may also be determined by interactions between alpha and beta subunits.

Animals↗
PubMed1995

Point mutations in the M2 region of the alpha, beta, or gamma subunit of the GABAA channel that abolish block by picrotoxin.

Site-directed mutagenesis and the two-electrode voltage-clamp techniques were used to evaluate the site of action of picrotoxin on rat alpha 1 beta 2 gamma 2 containing GABAA receptors expressed in Xenopus oocytes. Following a sequence comparison between GABAA subunits and the picrotoxin-insensitive glycine beta subunit, the following mutations were made near the center of the M2 region of the alpha 1, beta 2, and gamma 2 GABAA subunits: alpha 1(T261F/T267A), beta 2(T246F/T252A), and gamma 2(T271F/T277A). Wild type (alpha 1 beta 2 gamma 2) GABA channels had an IC50 for picrotoxin of 1.3 +/- O.3 microM. In contrast, alpha 1 beta 2 gamma 2 channels that contained any one of the mutated alpha 1, beta 2, or gamma 2 subunits produced currents that were insensitive to picrotoxin (0.1-100 microM). The single mutant beta 2(T246F), in combination with wild type alpha and gamma subunits, also conferred picrotoxin-insensitivity. In contrast, combinations containing beta 2(T252A) were blocked by picrotoxin with an IC50 of 1.4 +/- 0.4 microM. In some instances, the EC50 to GABA was slightly altered in the mutant receptors; but no change was observed in EC50 or potentiation by the allosteric modulator, alprazolam. The data in this study suggest that picrotoxin's site of action is within the channel pore; however the mechanism by which picrotoxin blocks current remains unknown.

Amino Acid Sequence↗
PubMed1994

A multicenter study of recombinant factor VIII (recombinate): safety, efficacy, and inhibitor risk in previously untreated patients with hemophilia A. The Recombinate Study Group.

In July 1990, the Recombinate Study Group initiated a prospective, open-labeled investigation of recombinant factor VIII (r-FVIII) to assess its safety and efficacy and to characterize the natural history of inhibitor development in previously untreated patients (PUPs) with hemophilia A. All study subjects have severe FVIII deficiency (baseline FVIII level < or = 2% of normal) and no history of blood product exposure before study entry. Following the first r-FVIII infusion, plasma was screened for inhibitors once every 3 months, and plasma recovery of r-FVIII at 30 minutes and 24 hours postinfusion was assayed at least once every 6 months. As of May 1993, 73 of 79 patients originally enrolled in the trial continue to participate. The median number of r-FVIII exposure-days for the 71 subjects who have received at least one r-FVIII infusion is 11. A total of 1,785 infusions have been administered to treat 810 bleeding events. Ninety-two percent of bleeding events responded as anticipated to one or two infusions. Two, nonrecurring, acute adverse reactions occurred coincident with r-FVIII infusion, one of which was unrelated and the other, possibly related to the infusion. Seventeen (23.9%) subjects have developed inhibitors: five with peak titers more than 10 Bethesda units (BU) and 12 with peak titers < or = 10 BU (range, 0.5 to 10). Survival analysis showed that the probability of remaining inhibitor-free in this group of patients with severe hemophilia A is 88.4% after 8, 73.6% after 10, and 61.6% after 25 r-FVIII exposure-days. Inhibitors disappeared in five (29.4%) subjects on retesting 2 to 16 months after the last positive inhibitor assay. r-FVIII is safe and effective in the treatment of hemophilia A-related bleeding. To date, the inhibitor risk associated with its use is comparable to that in patients treated with plasma-derived concentrates. The majority of inhibitors identified are low in titer and do not preclude continued on-demand therapy with r-FVIII.

Antibodies↗
PubMed1994

Patch-clamp recordings from subpopulations of autonomic and afferent neurons identified by axonal tracing techniques.

This study determined whether axonal tracing methods can be used in combination with patch-clamp techniques to examine the electrical properties of identified populations of autonomic and afferent neurons in the adult rat. Fluorescent dyes (Fast Blue, FB and Fluoro-Gold, FG) were injected into the wall of the urinary bladder or colon and into various somatic structures to label postganglionic neurons in the major pelvic ganglia (MPG) as well as visceral and somatic afferent neurons in the lumbosacral dorsal root ganglia (DRG) and trigeminal ganglia (TG). One to 3 weeks after dye injection, neurons were isolated from ganglia by enzymatic dissociation. Following dissociation, single neurons labelled with FB were identified in the three types of ganglion preparations; however FG was only identified consistently in TG neurons. FB was retained in neurons during short-term culture (1-5 days). Following 10 to 20 s exposure to UV light which was required for identification of the cells, whole-cell patch-clamp recordings revealed that the electrophysiological properties of FB-labelled cells did not differ from those of unlabelled cells. However, a more prolonged exposure (1-5 min) of the neurons to UV light produced irreversible damage to the cells which was evident as changes in the action potential, sodium current and resting membrane potential. These results indicate that patch-clamp recording in combination with axonal tracing is a useful approach for studying the electrical properties of identified populations of autonomic and afferent neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1994

Administration of a bolus formulation of baquiloprim and sulphadimidine to calves: plasma concentration--time profiles and efficacy in suppressing experimental pneumonic pasteurellosis.

After administration of a bolus containing 0.8 g baquiloprim and 7.2 g sulphadimidine to six calves, plasma concentrations of these compounds exceeded MICs for Pasteurella haemolytica from about 3 hours to at least 48 hours. Experimental infection of three calves with 2.8 x 10(10) P. haemolytica type A1 organisms by the endobronchial route resulted in extensive pneumonic lesions, and smaller, similar lesions were found post mortem in two other calves which had received the same inoculum. Nine similar calves were also infected in the same manner after dosing six hours previously with a bolus providing doses of 4 mg/kg baquiloprim and 36 mg/kg sulphadimidine. Four of these calves received a second bolus 48 hours later. In contrast to the undosed calves, the treated calves exhibited few symptoms of respiratory disease following infection, and their temperatures remained normal. The mean temperatures of the control calves were significantly elevated for several days after infection. At post mortem examinations 6 days after infection, lung lesions were insignificant in all the dosed calves. P. haemolytica was isolated from the lungs of all 5 control calves but not from any treated animal. The combined dose of 40 mg/kg baquiloprim and sulphadimidine was the minimum recommended for use of the bolus in the field, and the results therefore predict efficacy when used in outbreaks of respiratory infection in calves associated with this organism.

Administration, Oral↗
PubMed1994

Treatment of complex abdominal aortic aneurysms by a combination of endoluminal and extraluminal aortofemoral grafts.

PURPOSE: The purpose of this study was to test the hypothesis that abdominal aortic aneurysms (AAA) whose morphology makes them unsuited for repair with an endoluminal tube graft can be treated by a combination of a transluminally placed aortofemoral graft and a femorofemoral crossover graft. In addition the technique involves either ligation or balloon occlusion of the contralateral common iliac and internal iliac arteries in such a manner that excludes the AAA from the circulation. METHODS: We report the use of this technique in three male patients with 6.4 to 7.0 cm diameter AAA. Two had renal impairment and cardiac function too poor to permit open repair, and the third had an unfavorable abdomen caused by previous surgery and the presence of a permanent colostomy. Each patient had an individually tailored Dacron tube graft constructed on the basis of preoperative arteriograms and computed tomography scans. The grafts were delivered transluminally into the aorta through a sheath in the iliac arteries and anchored proximally with a stainless steel stent under radiographic control. The grafts were then anastomosed distally to the femoral artery. RESULTS: Recovery was complicated by a midgraft stenosis corrected by percutaneous balloon dilation in one patient, an episode of pulmonary edema in the second and an unexplained pyrexia in the third. Follow-up with duplex scanning confirmed normal flow through the grafts and the presence of thrombus between the prosthetic graft and the aneurysmal sac. CONCLUSIONS: We conclude that transluminal placement of an aortofemoral graft combined with a femorofemoral crossover graft is feasible in patients who are unsuited to repair with an endoluminal tube graft. The outcome with this technique is not known and requires further careful evaluation.

Aged↗
PubMed1994

The effect of exercise episode duration on blood pressure.

OBJECTIVE: To investigate the effect on blood pressure for 10-min compared with 40-min episodes of physical activity for 4 days. DESIGN AND METHODS: The design used a randomized crossover trial of two exercise episode durations, involving 17 subjects, which were performed in a university setting. The intervention was exercise on a stationary bicycle for four consecutive days, at 50% of maximal oxygen uptake (determined by heart rate), for episode durations of 10 or 40 min. A rest period of 10 days followed before exercise for the alternative duration was performed. The main outcome measure was blinded assessment of blood pressure 24 h after the last exercise episode. RESULTS: Significant reductions were found in systolic and diastolic blood pressure after 4 days of 40 min but not after 4 days of 10 min stationary cycling. The reduction in blood pressure was significant for both systolic and diastolic blood pressure for 4 days of 40 min of exercise episodes. CONCLUSION: Exercise of moderate intensity on a stationary bicycle for 10 min for 4 days is not effective in lowering blood pressure in comparison with the same exercise for 40 min for 4 days. The experimental design employed in the present study has potential for monitoring the effects of exercise on blood pressure.

Blood Pressure↗
PubMed1994

The Saskatchewan Clinical Stroke Prevention Project: design.

The Saskatchewan Clinical Stroke Prevention Project aims to examine the process and impact of incorporating enhanced stroke prevention into the routine clinical practice of family physicians. Twenty-four physicians in three practices in Saskatchewan are participating in a staged series of educational interventions over two years to enhance their management of smoking, transient ischemic attack/stroke, atrial fibrillation and hypertension. The components of each intervention include a seminar, printed materials, a one-to-one case discussion or "academic detailing," a self-documented chart audit and changes to the office system. Patients for whom this intervention is targeted are those 55 to 75 years of age presenting for a periodic health examination with one or more of the four main risk factors for stroke. Intervention will consist of counselling on relevant risk factors by the doctor and nurse teams, supported by appropriate patient education materials. Patient follow-up will be carried out according to clinical indications and will be done at least 3, 6, 12 and 24 months after entry into the study. Evaluation comprises measures of the process of implementing change in preventive practice as well as of the impact of such change. The former includes semi-structured interviews and focus groups with physicians, support staff and patients. The latter includes an assessment of knowledge, attitudes and charted practice before and after intervention.

Adult↗
PubMed1994

Educational contracts in family medicine residency training.

An educational contract for family medicine residency training and evaluation addresses many of the difficulties and challenges of current postgraduate medical education. This article identifies important principles for developing a contractual approach; describes the contract used in one program and its implementation; and discusses its theory, advantages, and limitations.

Clinical Competence↗
PubMed1993

Love sick.

Explore the source record for details and available documents.

Ethics, Medical↗
PubMed1993

Baquiloprim, a new antifolate antibacterial: in vitro activity and pharmacokinetic properties in cattle.

During examination of the half-lives in cattle of a series of 5-substituted diaminobenzyl-pyrimidines, it was found that replacement of the phenyl ring of trimethoprim (TMP) by bicyclic structures, particularly a quinolyl group, led to increases in half-life. The presence of a dimethylamino group on the quinolyl ring of the compound baquiloprim (BQP) conferred a half-life of about 10 hours. In contrast to TMP (half-life about one hour), BQP was well absorbed from the gastrointestinal tract in all ages of cattle, plasma concentrations reaching a plateau on the day after dosing followed by a slow decline. BQP showed the same high broad spectrum antibacterial activity as TMP, with marked synergy with sulphonamides. Its differential binding of the dihydrofolate reductases of Escherichia coli and rat liver predicted a margin of safety similar to that of TMP. The results of efficacy studies in mice in comparison with TMP showed that the longer half-life of BQP was associated with greater efficacy, and therapeutic properties superior to those of TMP in cattle were therefore predicted for BQP.

Administration, Oral↗
PubMed1993

Isolated limb perfusion with urokinase for acute ischemia.

PURPOSE: Isolated limb perfusion with urokinase was used to salvage an acutely ischemic lower limb. METHODS: Isolated limb perfusion with urokinase over a 90-minute period was used in the treatment of a 69-year-old female patient with acute ischemia of the left leg after thrombosis of a femoral artery bypass graft. Previous balloon embolectomy and heparin therapy had failed. The flow rate was able to be increased progressively without rise in the line pressure during the course of the perfusion, indicating an increase in capacity of the peripheral arterial bed. Fibrinogen and plasminogen levels in the isolated circulation remained low throughout the perfusion. The concentration of cross-linked fibrin degradation particles (d. dimer) rose progressively in the isolated circulation but remained at normal levels in the systemic circulation during perfusion. RESULTS: Completion angiography demonstrated clearance of thrombus in the popliteal artery and appearance of arteries not seen on preperfusion films. Clinical improvement paralleled the angiographic appearances, with restoration of limb viability. CONCLUSION: We concluded that isolated limb perfusion with use of urokinase is safe and worthy of further investigation.

Acute Disease↗
PubMed1993

Mammographically detected breast cancer: location in women under 50 years old.

The mammograms of 86 women under the age of 50 years with mammographically detected cancers were reviewed. Sixty-three of these cancers (73%) were found at the periphery of the breast as defined by a zone 1 cm wide beneath the subcutaneous fat or anterior to the retromammary fat. This finding is likely due to the geometric configuration of the breast. If the breast is hemispheric, then more than 50% of the volume of breast tissue lies within this zone in a large percentage of women. Furthermore, the contrasting adjacent fat likely improves the ability to perceive an abnormality. Interaction of the terminal ducts with chemicals contained within or produced by the fat is a much less likely reason for the high percentage of cancers in this zone. Radiologists should be aware of this phenomenon and pay particular attention to this zone.

Adipose Tissue↗
PubMed1993

Open dose-finding study of a new potent and selective nonsteroidal aromatase inhibitor, CGS 20 267, in healthy male subjects.

The aim of this open, dose-finding study was to evaluate the effects of single dose CGS 20 267, a new oral nonsteroidal aromatase inhibitor, on the inhibition of estrogen production and also on the production of adrenal and testicular steroids in healthy male subjects. Nine dose levels ranging from 0.02-30 mg and placebo were tested, each dose being given to 3 subjects only. A total of 18 subjects were included; 12 of them received 2 single administration, the remaining 6 were exposed only once to one of the 2 highest dose levels. A reduction in serum estrogen levels when compared to baseline was already observed after 2 h, reaching maximum suppression between 10 and 48 h after administration. After 24 h, a suppression of estrone levels by 60-85% from baseline was achieved with all tested doses. A reduction in estradiol levels by about 30% from baseline was observed at the lowest dose (0.02 mg). This reduction was further enhanced dose dependently to a maximum of about 90% from baseline at 24 h after administration of the highest dose (30 mg). With the higher doses (10 and 30 mg), estrogen suppression was maintained up to 3 days. A dose-dependent increase of testosterone, LH, and FSH was observed and was most pronounced in the 10- and 30-mg dose groups, which can be considered as a consequence of the long-lasting aromatase inhibition achieved with these high doses. No effect on serum cortisol and aldosterone levels was observed up to the highest dose. No clinically relevant changes were observed in blood chemistry and hematology tests. The systemic and subjective tolerability of CGS 20 267 was good at all doses. This study has shown that CGS 20 267 is a well tolerated, potent, selective, and long-acting inhibitor of the aromatase enzyme after single administration.

Administration, Oral↗