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Biomedical subjects

D Sampson

Publications and source records attributed to D Sampson.

At least 19 recordsLinked to original sources
PubMed1992

Determination by high-performance liquid chromatography of hydroxyurea in human plasma.

An assay using reversed-phase high-performance liquid chromatography with electrochemical detection was developed to measure hydroxyurea in plasma at concentrations suitable for pharmacokinetic studies. The sample preparation is simple, the analysis rapid and assays can be batched. The between-run precision is excellent (coefficient of variation = 2.8-4.5%) and the limit of detection is 0.02 mmol/l. Preliminary studies have shown that the method is suitable for pharmacokinetic studies.

Chromatography, High Pressure Liquid↗
PubMed1992

Decreased reactivity to sweetness following chronic exposure to mild unpredictable stress or acute administration of pimozide.

Consumption of a palatable wet mash was examined in rats subjected chronically (4-10 weeks) to unpredictable mild stress. Intake of mash containing 0, 10%, or 20% additional sucrose was normal in stressed animals. In control animals, the addition of 30% or 40% sucrose caused a decrease in the quantity of mash consumed, but increased the rate of eating. Both the increase in eating rate and the decrease in intake, at high sucrose concentration, were markedly attenuated in stressed animals (which therefore had higher intakes of very sweet mash and lower rates of eating, relative to control animals). Like chronic mild stress, the dopamine receptor antagonist pimozide (0.2 mg/kg) also increased the intake of a wet mash with 30% added sucrose, while decreasing the rate of consumption. Stressed animals were relatively insensitive to pimozide, though there were significant additive effects on duration of eating (increased) and on postprandial resting (suppressed). The failure of stressed animals to adapt their intake to increases in sweetness, and the similarities between the effects of chronic mild stress and acute pimozide, are compatible with the hypothesis that animals exposed to chronic mild stress are anhedonic.

Animals↗
PubMed1991

Time-, schedule-, and reinforcer-dependent effects of pimozide and amphetamine.

Rats performed on two multiple random-interval schedules, in which sequences of ascending or descending reinforcement densities were balanced between the schedules and between the two halves of the session. Using a standard reinforcer (10% sucrose pellets), pimozide decreased response rates, while amphetamine increased responding. The effects of both drugs were schedule dependent: larger changes were evident in low response rate, reinforcement-lean components than in high response rate, reinforcement-rich components. Both effects were also time dependent, increasing over the course of the session; this casts serious doubt on the applicability of Herrnstein's matching law for studying agents acting on brain dopamine. Increasing the period of food deprivation increased response rates, while withdrawing food deprivation decreased responding. These effects were also schedule dependent, but were time dependent. Substituting 95% sucrose pellets for standard 10% sucrose pellets caused an immediate and sustained decrease in responding, and up to 10% of earned reinforcement was not consumed. Pimozide increased response rates within reinforcement-lean components and reinstated the complete consumption of earned reward typical of standard reinforcement. These apparently paradoxical effects may be consistent with a decrease in the rewarding properties of sucrose pellets. Despite low response rates, amphetamine did not affect responding maintained by 95% sucrose pellets but did further reduce the consumption of earned reward. These results call into question the generality of the rate-dependency principle in the action of psychomotor stimulants.

Amphetamine↗
PubMed1991

Reversal of antidepressant action by dopamine antagonists in an animal model of depression.

Rats subjected chronically (12 weeks) to a variety of mild, unpredictable stressors showed a reduced consumption of sucrose or a sucrose/saccharin mixture in two-bottle consumption tests (sweet solution versus water). The deficit was apparent within 2 weeks of stress; normal behaviour was restored by chronic (7 weeks) treatment with the tricyclic antidepressants desmethylimipramine (DMI) or amitriptyline (AMI). Acute administration of the dopamine D1 receptor antagonist SCH-23390 1 week after withdrawal, or the dopamine D2 receptor antagonist sulpiride 2 weeks after withdrawal, were without effect in vehicle-treated stressed animals, and in non-stressed animals. However, the DA antagonists selectively reversed the improvement of performance in DMI- or AMI-treated stressed animals. This suggests that an increase in functional activity at DA synapses is the mechanism of action of DMI and AMI in this model.

Animals↗
PubMed1990

Dopaminergic mechanism of imipramine action in an animal model of depression.

Rats, subjected chronically (10-12 weeks) to a variety of mild, unpredictable stressors, showed a decrease in their consumption of weak sucrose solutions; normal behavior was restored by chronic (5-9 weeks) treatment with the tricyclic antidepressant imipramine. Acute administration of the dopamine receptor antagonist pimozide or the specific dopamine D2 receptor antagonist raclopride had no effect in nonstressed animals and in vehicle-treated stressed animals, but both drugs selectively reversed the improvement of performance in imipramine-treated stressed animals. The 5HT antagonist metergoline increased sucrose consumption in all groups. The data suggest that the mechanism of action of imipramine in this model is an increase in functional activity at dopamine (DA) synapses.

Animals↗
PubMed1990

A matching law analysis of the effects of dopamine receptor antagonists.

Herrnstein's matching equation was used to analyze drug effects on performance in random interval reinforcement schedules. Pimozide caused effects compatible with both motor and motivational impairments, in a 5-component multiple schedule, a 3-schedule 3-day cycle (ALT-3), and a 2-schedule 2-day cycle (ALT-2). However, at low doses, both sulpiride and SCH-23390, tested in the ALT-3 and ALT-2 procedures, caused effects compatible with selective motivational impairments. In experiments using the non-multiple schedules, motivational effects increased during the course of the experimental session, under all three drugs. The interpretation of "motor" and "motivational" deficits in the ALT-2 procedure was validated by experiments in which the response-force and deprivation level were systematically varied. The results support the view that dopamine may be involved in the maintenance of rewarded behaviour, but not differentially implicate the D1 or the D2 receptor subtype.

Animals↗
PubMed1979

Posttransplant hypersplenism.

Posttransplant hypersplenism, manifested by leukopenia and azathioprine intolerance, can be diagnosed with a high degree of accuracy and promptly reversed by emergency splenectomy. Functioning cadaver kidney homograft survival rates in patients undergoing posttransplant splenectomy are equal to that of patients undergoing pretransplant splenectomy and are statistically superior (p less than 0.01) to recipients who have never had their spleens removed. However, mortality (21%) for posttransplant splenectomy is excessively high when compared to our mortality (1.3%) for pretransplant splenectomy.

Azathioprine↗
PubMed1978

Flow and function in machine-preserved kidneys.

One hundred machine-preserved cadaver kidneys were transplanted irrespective of their flow rates on the preservation machine. Twenty-five per cent had flows of below 100 ml/min and 11 per cent had flows of below 80 ml/min. There was no correlation between the flow rate and function at 1, 3 or 12 months. There was no difference in the flow rate between those kidneys which functioned immediately and those which never functioned. A fall in flow rate was associated with acute tubular necrosis of longer duration but eventual function was not impaired. There was a higher incidence of early aggressive rejection in kidneys which functioned immediately. Preservation failure per se is a rare cause of primary non-function. Adherence to a policy of ignoring the flow characteristics of machine-preserved kidneys could make up to 25 per cent more kidneys available for transplantation.

Cadaver↗
PubMed1978

Studies on levamisole, a potentially useful drug in the treatment of Behçet's syndrome.

The anthelmintic drug, levamisole, was shown to amplify the response of human peripheral blood lymphocytes to vegetable mitogens. A similar enhancement of blast formation in the mixed lymphocyte culture was also demonstrated. High concentrations of the drug led to depression of both of these responses. These observations led to studies in a rat breast cancer model in which immunopotentiation was demonstrated in vivo, and this effect was associated with tumor regression. As in the human in vitro studies, high doses of the drug were not associated with augmentation of the immune response and in this circumstance no inhibition of tumor growth was observed. Assuming that potentiation of immune responsiveness is of benefit to patients suffering from Behçet's syndrome, the development of clinical trials employing levamisole appears justified, as long as the drug dosage is carefully monitored.

Animals↗
PubMed1978

Randomized steroid therapy of human kidney transplant rejection.

This randomized, double-blind study failed to show any therapeutic benefit of a 30-mg/kg bolus over a 3-mg/kg bolus of methylprednisolone for the treatment of acute kidney transplant rejection. Since there was a slight associated increase in infections and septic mortality, routine use of high-dose methylprednisolone bolus therapy is not recommended or justified.

Double-Blind Method↗
PubMed1978

Immunopotentiation and tumor inhibition with levamisole.

The immunopotentiating drug, levamisole, was found to augment human lymphocyte responses to vegetable mitogens in vitro. However, the effect was dose-dependent and at high concentrations suppression rather than augmentation of the immune response was observed. In view of the potential widespread use of the drug in the treatment of human cancer, a study was undertaken in rats bearing breast cancer to determine whether a similar dose-response effect would be observed in terms of tumor growth. Tumor inhibition was found to be dose-dependent, and at high doses tumor inhibition did not occur while at lower doses the growth of the cancer was inhibited. The rate of tumor growth correlated well with the responses of splenic lymphocytes to vegetable mitogens. In a later study, it was not possible to show that levamisole had any effect in boosting immune responses of patients undergoing surgery. It is concluded that levamisole is capable of increasing immune responses in man in vitro, and that the drug is able to inhibit the growth of breast cancer in the rat. However, these effects are dose-dependent, and clinical trials of the use of levamisole in patients with cancer should include careful immune monitoring to be sure that augmentation rather than suppression of the immune response is being achieved.

Animals↗
PubMed1977

High dose (bolus) intravenous methylprednisolone at the time of kidney homotransplantation.

A completely randomized double-blind study of bolus methylprednisolone versus dextrose in water, administered at the time of human kidney transplantation, has failed to demonstrate any beneficial effect of the steroid therapy. No differences were observed in the number of complete, irreversible graft rejections, the number of acute rejection episodes, or the number of postoperative steroid boluses administered in the treated or the control groups. Similarly, there were no differences in the mean serum creatinines at 30, 60, 90 days post-transplantation. There was a slight increase in mortality and incidence of complications in the group of patients receiving an intravenous bolus of methylprednisolone at the time of transplantation as compared to controls. The failure to demonstrate any beneficial effect and the slight increased mortality and morbidity associated with the bolus methylprednisolone dosage makes this therapy unjustifiable.

Clinical Trials as Topic↗
PubMed1977

Prevention of transplant renal artery stenosis.

Transplant renal artery stenosis occurred in 17 of 142 consecutive transplants (12 percent). All stenoses were in the renal artery distal to the anastomosis and two separate forms are recognized: angulation and segmental stenosis. Successful surgical correction in 12 of 17 patients relieved the hypertension and resulted in improved renal function. No patients receiving dipyridamole, a drug which inhibits platelet aggregation and intravascular fibrin deposition, developed segmental renal artery stenosis. No other factors could be identified which were important in either causing or preventing renal artery stenosis. Since intrarenal vascular changes are an integral aspect of rejection, the protection afforded by dipyridamole against segmental renal artery stenosis indicates that segmental stenosis is probably a manifestation of rejection.

Cadaver↗