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Biomedical subjects

D Sampson

Publications and source records attributed to D Sampson.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1977

Dose dependence of immunopotentiation and tumor regression induced by levamisole.

Breast cancer was induced in female Sprague-Dawley rats by 7,12-dimethylbenz(a)anthracene. Once tumors had become established, they were treated with varying doses of the immunopotentiating drug, levamisole. Tumor growth was measured in the various dosage groups, and at 6 months after tumor induction the animals were sacrificed. Their immunological competence at this time was measured by the mitogen responses of splenic lymphocytes. Untreated animals with breast cancer were found to be immunosuppressed compared to normal animals. The drug levamisole resulted in immunopotentiation, but at high doses it was immunosuppressive. Tumor regression was observed at doses that resulted in immunopotentiation, but not at high doses. There was a significant correlation between immune competence and tumor regression. It is concluded that levamisole can cause regression of breast cancer in the rat but that this effect is critically dependent on the dose of the drug; these observations confirm previous studies carried out on human cells in vitro. It is recommended that high doses of the drug be avoided in human clinical trials and that the patients who receive this drug should have their immune responses carefully monitored.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1976

Suppressor activity of the human spleen and thymus.

Both the spleen and thymus of man contain a population of cells which can suppress the mixed lymphocyte reaction. Splenic cells suppress the MLC 58 +/- 4.8 percent, and the thymus is able to suppress the MLC 90 +/- 2.6 percent. However, splenic cells require stimulation by vegetable mitogens before suppressor activity can be observed, and the thymus displays spontaneous suppressor activity without prior stimulation. The suppressor effect is linearly related to the log of the cell dose (r = 0.8, p less than 0.01), and at low doses the suppressor cells stimulate rather than inhibit the MLC. The cells are exquisitely sensitive to immunosuppressive drugs, and blood levels encountered in clinical organ transplantation abrogate their suppressive activity. The suppressive activity of the cells is nonspecific, and they are able to inhibit the MLC between individuals totally unrelated to the spleen or thymus donor. Since these cells likely play a role in the development of tolerance, further characterization of their properties is required.

Histocompatibility Testing↗
PubMed1976

The effect of levamisole on cell-mediated immunity and suppressor cell function.

The immunopotentiating drug, levamisole, was found to augment human lymphocyte responses to allogeneic cells and plant mitogens in vitro. The effect was critically dose dependent and, at high doses, suppression rather than augmentation of the immune response was observed. Our hypothesis that augmentation of immune responses by the drug is due to the selective impairment of immunoregulatory suppressor activity was tested in a model using human splenic and thymic suppressor cells. Contrary to expectation, the drug was found to be capable of augmenting suppressor activity rather than abolishing it. It is concluded that levamisole is a nonspecific stimulator of lymphocyte function, irrespective of the role played by these cells in the human response.

Dose-Response Relationship, Drug↗
PubMed1976

Immunological responses in identical twins with renal transplants from a common donor.

Two identical twins suffering from end stage renal failure due to chronic pyelonephritis received cadaver renal allografts from one donor. Immune status was measured in both by in vitro responses to vegetable mitogens and by reactivity in mixed lymphocyte culture with a random volunteer. Both patients underwent rejection episodes at different times; these were of differing severity. Reactivity to PHA and in MLC was minimal during rejection and increased following recovery in spite of continued high levels of immunosuppression. In contrast, reactivity to pokeweed mitogen and concanavalin A increased at the time of rejection and fell with recovery. The changes seen in the twins, while qualitatively similar, differed in magnitude and timing. It is concluded that environmental factors as well as histocompatibility play a part in influencing immune responsiveness, and that studies of immune responsiveness should be interpreted with caution in the management of renal allograft recipients.

Diseases in Twins↗