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Biomedical subjects

J McRae

Publications and source records attributed to J McRae.

At least 19 recordsLinked to original sources
PubMed1996

Optimum anti-emetic therapy for cisplatin induced emesis over repeat courses: ondansetron plus dexamethasone compared with metoclopramide, dexamethasone plus lorazepam.

BACKGROUND: This study was undertaken to compare the efficacy and tolerability of ondansetron plus dexamethasone (O + D) with metoclopramide plus dexamethasone plus lorazepam (M + D + L) over three consecutive courses of cisplatin chemotherapy. PATIENTS AND METHODS: This was an international, multicentre, double-blind, double-dummy, parallel group study. O+D patients were randomised to receive ondansetron 8 mg intravenously (i.v.) plus dexamethasone 20 mg i.v. prior to cisplatin (50-100 mg/m2) chemotherapy. On the following 4 days they were treated with ondansetron 8 mg bd orally and dexamethasone 4 mg bd orally. M + D + L patients were randomised to receive metoclopramide 3 mg/kg i.v., dexamethasone 20 mg i.v. and lorazepam 1.5 mg/m2 i.v. (max 3 mg) prior to cisplatin chemotherapy and a further dose of metoclopramide 3 mg/kg i.v. approximately 2 hours following the first dose of metoclopramide. Treatment for the following 4 days was metoclopramide 40 mg tds and dexamethasone 4 mg bd orally. Two hundred and thirty-seven patients were recruited into the study (117 patients received O + D and 120 received M + D + L). RESULTS: On the first course chemotherapy, O + D was significantly superior to the M + D + L regimen for complete control of emesis (days 1-5, 54% versus 37%, respectively, P = 0.014). This was maintained over the three treatment cycles; 38% of O + D and 20% of M + D + L patients remained free of emesis (P = 0.003). Maintenance of control of nausea grade as none or mild on days 1-5 over the three courses was significantly better in the O + D group (48%) than in the M + D + L (26%, P = 0.003). The most commonly occurring adverse events in the O + D group were constipation (25%) and headache (19%). In the M + D + L group drowsiness (38% of patients), malaise/fatigue (16% of patients), constipation (13% of patients), anxiety (11% of patients) and dizziness (10% of patients) were the most commonly reported adverse events. Extrapyramidal symptoms were reported by 20% of patients in the M + D + L group. Despite the inclusion of lorazepam, 14% of patients in the M + D + L group were withdrawn from the study due to extrapyramidal symptoms, which in the opinion of the investigators, were probably or almost certainly related to study medication. CONCLUSION: This study show that O + D is significantly more effective and better tolerated than M + D + L for the control of emesis and nausea over a series of three courses of cisplatin chemotherapy.

Adult↗
PubMed1996

A multicentre, double-blind study comparing placebo, ondansetron and ondansetron plus dexamethasone for the control of cisplatin-induced delayed emesis. Ondansetron Delayed Emesis Study Group.

BACKGROUND: The purpose of this study was to investigate the efficacy and safety of oral ondansetron, given alone or in combination with dexamethasone in the control of cisplatin-induced delayed emesis. PATIENTS AND METHODS: This was an international, multicentre, double-blind, randomised, placebo-controlled, parallel group study. A total of 640 chemotherapy-naïve patients received ondansetron 8 mg i.v. and dexamethasone 20 mg i.v. for the control of acute emesis prior to cisplatin (> or = 70 mg/m2) on day 1. Patients who were not rescued or withdrawn on day 1 were to be randomised 24 hours after the start of cisplatin administration to one of four groups; group I placebo oral (p.o.), twice daily (bd) on days 2-6 (n = 125); group II ondansetron (8 mg p.o. bd) on days 2/3 followed by placebo (p.o. bd) on days 4-6 (n = 199); group III ondansetron (8 mg p.o. bd) on days 2-6 (n = 214); group IV ondansetron (8 mg p.o. bd) plus dexamethasone (4 mg p.o. bd) on days 2-6 (n = 66). RESULTS: On day 1, 81% of patients had complete control of acute emesis, with 68% having no emesis and no nausea. Over days 2/3 and over days 2-6, significantly more patients receiving ondansetron plus dexamethasone (group IV) reported no emesis and no nausea (49% and 45%, respectively) compared to ondansetron alone (32% and 27%, respectively) or placebo (group I; 33% and 27%, respectively; P < 0.05 for all pairwise comparisons). There were no significant differences in the control of emesis over days 2/3, where 61% of patients had complete emetic control (0 emetic episodes) with ondansetron plus dexamethasone (group IV), 54% with ondansetron (groups II + III) and 49% with placebo (group I). In the distribution of nausea grades, ondansetron plus dexamethasone (group IV) was significantly superior to ondansetron (groups II + III); P = 0.037) and placebo (group I; P = 0.013) over days 2/3. Over days 2-6 there were no significant differences in the control of emesis, however a comparison of the distribution of nausea grades over days 2-6 showed ondansetron plus dexamethasone (group IV) to be significantly superior to ondansetron (group III; P = 0.043) and placebo (group I; P = 0.024). All treatments were well tolerated and no unexpected drug-related adverse events were reported. There were no differences in the overall incidence of adverse events between the active treatment groups or placebo. Constipation and headache, recognised side effects of 5-HT3 receptor antagonists, were the most commonly reported adverse events with the incidence of constipation with ondansetron alone (group III) being significantly greater than with over days 2-6 (14% vs. 6%; P = 0.030). CONCLUSION: In contrast to some previous investigations, in this study, ondansetron alone appears to have a minor role in the control of cisplatin-induced delayed emesis and nausea. In conclusion, the combination of oral ondansetron plus dexamethasone is superior to ondansetron and to placebo.

Adult↗
PubMed1993

Immunohistological detection of C5b-9 complement complexes in normal and pathological human livers.

The immunohistological localization of components and neoantigens of the C5b-9 human terminal complement complex was studied in 30 human liver biopsies. C5b-9, apparently in the soluble SC5b-9 form, was invariably detected in normal liver capsule and normal portal tract connective tissue. In livers with fibrosis and or cirrhosis, the pathological connective tissue contained variable amounts of SC5b-9 which was distributed in a similar way to that seen in normal livers. There was no significant C5b-9 deposition outside of the portal tract and capsule in any of the liver biopsies. In particular, in pathological livers, there was no deposition in relation to cellular infiltrates or areas of hepatic necrosis. These data support the concept that C5b-9 is a common component of connective tissue but do not indicate that C5b-9 mediated pathways are involved in the pathogenesis of hepatic injury.

Clusterin↗
PubMed1990

What happens to patients after five years of intensive case management stops?

Seventy-two patients who received five years of intensive case management services were transferred into mainstream community mental health center services with a much higher patient-to-staff ratio. At the end of a two-year follow-up, 91 percent of the patients were still receiving treatment. Compared with the previous five years, hospitalizations during the follow-up period increased, but not significantly so. Contacts with mainstream CMHC services increased significantly. Overall costs in constant 1979 dollars showed a nonsignificant decrease, dropping by about $1,500 per patient per year. The staff time and resources gained by the programmatic changes were used to treat a larger number of chronic patients seeking services.

Adult↗
PubMed1989

Outcomes of five years of continuous intensive case management.

Five years of intensive case management and specialized alternatives to hospitalization were provided to 72 young recidivistic, treatment-resistant, chronically thought-disordered patients. Compared with a two-year prestudy baseline, patients' days in the hospital during the five years were reduced by 75 percent, but this reduction was offset by a 193 percent increase in structured residential care days in the community. Patients' level of functioning as rated by the Global Assessment Scale and other measures remained essentially the same over the five years. However, use of emergency services and after-hours on-call services decreased steadily throughout the study. Comprehensive cost-analysis revealed that savings in hospital costs were offset by increased costs of community care. The authors conclude that this treatment approach effectively stabilized the treatment-resistant patients in the community but did not reduce net costs in constant dollars.

Adolescent↗
PubMed1988

Thromboxane biosynthesis and platelet function in type I diabetes mellitus.

It has been speculated that platelet activation may contribute to the evolution of vascular complications in patients with Type I diabetes mellitus. To address this hypothesis, we measured the plasma and urinary metabolites of thromboxane, presumably of platelet origin, and of prostacyclin, derived from endothelial cells, in addition to more conventional indexes of platelet function. Urinary excretion of the metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha did not differ between diabetics with or without retinopathy and nondiabetic controls. Furthermore, measurement of platelet granule constituents, the aggregation responses to ADP or arachidonic acid, and levels of serum thromboxane B2 failed to discriminate between the groups. The institution of tight diabetic control with multiple daily injections of insulin failed to alter either urinary metabolite excretion or plasma levels of 11-dehydro-thromboxane B2. Conversely, insulin-induced hypoglycemia failed to alter the concentrations of plasma or urinary thromboxane metabolites in nondiabetic volunteers, despite a mean 60-fold increase in plasma epinephrine. These studies suggest that platelet activation does not precede the development of microvascular complications in patients with Type I diabetes who lack clinical evidence of macrovascular disease and have normal renal function. Furthermore, it is unlikely that platelet activation due to intermittent hypoglycemia contributes to the reportedly accelerated development of retinopathy in such patients, when they are subject to tight diabetic control.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

A ten-year study of civil commitments in Washington State.

A ten-year longitudinal study of all civil commitments was conducted in a mid-sized county in Washington State, beginning with the 1974 effective date of a more stringent commitment law and encompassing the introduction of more lenient criteria five years later. A major finding was the increase in the number of 72-hour detentions and 14-day commitments that preceded by one year the passage of the broader criteria. The number of detentions continued to rise throughout the study period, while 14-day and 90-day commitments rose but less sharply. Data on repeated detentions showed that 21 percent of the patients were detained more than once. This group of recidivists accounted for 45 percent of the total number of detentions.

Commitment of Persons with Psychiatric Disorders↗
PubMed1986

Caffeine ingestion and isokinetic strength.

The purpose of this study was to investigate the effects of caffeine on maximum voluntary contractions of the dominant knee extension and flexion muscles in 12 male intercollegiate track sprinters. Caffeine (5 mg.kg-1) and placebo (225 mg methylcellulose) gelatin capsules were administered orally in randomly assigned order. Muscle function was measured isokinetically by a Cybex II dynamometer interfaced with a data reduction computer. Six repetitions maximum of the extensors and flexors were performed at three sequential ordered speeds (30 degrees, 150 degrees and 300 degrees s-1) with a one-minute rest between varying velocities. Peake torque and power were than assessed after treatment conditions, as well as a fatigue index calculated from a series of 60 repetitions maximum ato 150 degrees s-1. Results of the 2 X 3 ANOVA and paired t-test indicated no difference in measures of peak torque and power at the varying contracting velocities and fatigue index after caffeine ingestion. These findings indicate the ingestion of caffeine in a small dose exerts no ergogenic effect on muscle function under anaerobic conditions.

Administration, Oral↗
PubMed1983

Interorgan relationships of alanine and glutamine during fasting in the conscious dog.

This study was designed to assess the interorgan relationships of glutamine and alanine in the conscious, overnight fasted dog, and to determine changes which occur with progressive fasting. Dogs were fasted for 18 hr (n = 6), 48 hr (n = 6), and 96 hr (n = 6) prior to the study. Catheters had been previously implanted in the femoral artery, renal vein, portal vein, and hepatic vein, and were used for blood sampling at 30-min intervals during the 3-hr experimental period. Hepatic and renal blood flows were determined by indocyanine green and para-aminohippuric acid (PAH) extraction methods, respectively. Balance data (micromoles/kilogram/minute) were estimated by multiplying the appropriate arteriovenous concentration differences by blood flows. Hepatic uptake of glutamine decreased 50% after a 48-hr fast, and by 96 hr, the liver became a net producer of glutamine. Gut utilization remained constant throughout fasting. The kidney's utilization gradually increased with fasting. The hepatic extraction of alanine fell with fasting, declining to 40% of its original uptake at 96 hr. The gut's production of alanine fell during the first 48 hr of fasting, but remained stable thereafter. The kidney's production of alanine increased throughout the period of starvation. The arterial concentration of glutamine rose with fasting, while that of alanine fell even with a 48 hr fast. The liver, by becoming a net producer of glutamine, and the kidney, by increasing its production of alanine, decrease demands for peripheral release of these two amino acids, and thus may have protein-sparing actions during fasting.

Alanine↗
PubMed1983

The effect of acute and chronic glucocorticoid excess on leucine kinetics and protein turnover in vivo.

The present studies were undertaken to assess the effects of excess cortisol on amino acid exchange in the conscious dog. Three groups of 18-hr fasted dogs with catheters chronically implanted in the femoral artery were studied: Group I (n = 6) received saline; Groups II and III (n = 5, each) received ACTH intravenously (1 U/min) for 7 hr; in addition, Group III received ACTH, 500 U/day intramuscularly for 4 days. Leucine rates of appearance (Ra) and clearance were measured using a constant infusion of L-4,5-[3H]leucine. ACTH treatment resulted in a 9-fold increase in plasma cortisol in Groups II and III (from 2 +/- 1 to 18 +/- 1 and 17 +/- 2 micrograms/dl, in II and III, respectively P less than 0.001), with no effect on either plasma insulin or glucagon. Plasma leucine (mmole/liter) increased from 118 +/- 6 (I) to 153 +/- 6 (II, P less than 0.005) to 275 +/- 35 (III, P less than 0.001). Leucine Ra (micromoles/kilogram/minute) did not change in II, but rose by 39% (P less than 0.005) in III. Clearance (milliliters/kilogram/minute) dropped from 25 +/- 2 (I) to 18 +/- 2 (II, P less than 0.005), to 15 +/- 2 (III, P less than 0.001). It is concluded that acute elevations of cortisol increased plasma leucine only by inhibiting its rate of disposal, whereas chronic elevations had a dual effect; they inhibited leucine disposal and increased its entry into the plasma compartment, suggesting an inhibition of protein synthesis and stimulation of protein breakdown.

Adrenocortical Hyperfunction↗
PubMed1977

Applications of ventilation lung imaging with 81mKrypton.

A method for the evaluation of regional lung ventilation using 81mKr eluted from a rubidium generator is described. The tracer distribution at equilibrium is a function of regional ventilation, not of volumes. The study can be performed on a wide range of patients, including unconscious and mechanically ventilated patients, and can be performed immediately following or concurrently with a perfusion study. Thus, precisely comparable ventilation and perfusion images can be obtained.

Humans↗
PubMed1976

Location of aldosterone-producing adenomas with 131I-19-iodocholesterol.

We used 131I-19-iodocholesterol as an adrenal-imaging agent in 27 hypertensive patients who had biochemical evidence of abnormalities in the renin-angiotensin-aldosterone system. In 10 of 12 patients in whom the biochemical findings suggested the presence of an aldosterone-producing adenoma the adrenal uptake was asymmetric. The adenoma was subsequently confirmed in all eight patients in this group who underwent operation. In contrast, the adrenal uptake was asymmetric in only one of 13 patients with biochemical evidence of iodopathic hyperaldosteronism or low-renin essential hypertension. Two patients with adrenal carcinoma causing primary aldosteronism did not concentrate the isotope in their tumors. When metabolic studies suggest an aldosterone-producing adenoma, adrenal imaging with 131I-19-iodocholesterol may locate the tumor before operation.

Adenoma↗