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Biomedical subjects

R M Ferguson

Publications and source records attributed to R M Ferguson.

214 records · Page 12Linked to original sources
PubMed1976

Differential effects of chlorpromazine on the in vitro generation and effector function of cytotoxic lymphocytes.

Allograft rejection represents a cytotoxic response mediated to a large degree by thymus-derived T lymphocytes (1). The study of such cell-mediated cytotoxic phenomena has been greatly facilitated by the discovery first noted by Hayry and Defendi (2) and Wunderlich and Cany (3), that a natural consequence of allogeneic stimulation in an unidirectional mixed lymphocyte culture (MLC) was the appearance of cytotoxic lymphocytes specific for antigens present on the stimulator cells. Subsequent studies have shown that such in vitro generation of cytotoxic lymphocytes was dependent on the proliferative response in an MLC (4), was genetically determined (5), and possibly required the interaction of several subpopulations of T cells (6). We now report that the surface active agent chlorpromazine: (a) inhibits allogeneic stimulation of the proliferative response in an MLC; (b) inhibits the MLC generation of cytotoxic lymphocytes, (c) has no effect on the recognition, binding, or lysis of target cells by already sensitized lymphocytes; and (d) blocks a postproliferative membrane-mediated event, independent of proliferation, and necessary for the MLC generation of cytotoxic lymphocytes.

Animals↗
PubMed1976

Factors related to success or failure of second renal transplants.

From January 1, 1968 to December 31, 1973, 50 patients received two or more kidney transplants. Patient and graft survival was highly dependent upon the source of the donor and to a lesser extent the functional duration of the first transplant and the elapsed time between first and second graft. Survival (patient and graft) was best in patients receiving two related grafts and worst in patients receiving two sequential cadaver grafts. Intermediate rates of success followed cadaver transplantation after rejection of a related graft. The highest failure rate was encountered when those patients who sustained an early loss of the first cadaver graft received a subsequent cadaver graft within a few months. We recommended removal of the acutely rejected graft and delay prior to retransplantation of patients who rapidly reject cadaver grafts in the face of maximal doses of immunosuppression. A delay will permit recovery from both the immunosuppression and any underlying subclinical infections, and will permit the recognition of anti-HL-A antibodies which may not be manifest soon after rejection. Retransplantation of the patient who is slowly rejecting the first kidney does not require prior removal of the rejected graft or delay in retransplantation.

Adolescent↗
PubMed1976

Seven years' experience with antilymphoblast globulin for renal transplantation from cadaver donors.

Antibody of the IgGab type can be isolated from horses immunized with cultured human lymphoblasts plus complete Freund's adjuvant. The essential steps for the production of a safe, potent anti-human lymphoblast globulin (ALG) are: A) the use of early bleedings after immunization to reduce the titer of antibodies which react with red blood cells and platelets; B) careful absorption with human red blood cell stroma and platelets; C) stabilization with non-crystalline silica dioxide; D) chromatography through QAE sephadex to remove pyrogens, microaggregates and possible inhibitors of ALG activity; E) careful safety testing in animals for toxicity and pyrogenicity; and F) testing in vitro for sterility. Such a purified horse ALG (IgGab) can be administered safely intravenously to patients to supplement a standardized immunosuppressive regimen incorporating azathioprine and prednisone. Under these circumstances, allergic reactions are very rare, antibodies to horse IgG do not develop, skin tests to horse IgG remain negative, and immune elimination of circulating horse IgG from the human circulation cannot be demonstrated. The overall results of ALG patient survival and transplant function after 184 consecutive first cadaver transplants at the University of Minnesota demonstrate a statistically significant improvement in both parameters accompanying increases in ALG dose while rigidly utilizing standardized doses of azathioprine and prednisone. There is a significant reduction in the number of grafts lost to rejection; significant reduction in the number of rejection episodes; significant delay in the onset of rejection episodes; but there is no increase in septic loss of patients or kidneys. These efforts could be seen in the gross data or when subgroups controlling for patient age, tissue typing were analyzed. Excluding patients at high risk did not alter the results. The beneficial effects of ALG were particularly striking in good matches. In the highest doses, ALG may be dangerous for older patients with poor matches who develop an increased incidence of septic loss of kidney and/or life. Thus, ALG appears to be a useful adjunct in the early management of cadaver transplants by reducing the incidence and frequency of rejection episodes. The dose should probably be reduced in the older patients who receive kidneys from badly mismatched donors. One cannot conclude from this study that ALG manufactured in other centers by this or other techniques, will accomplish the same results since the multiplicity of factors involved in the success and failure of transplants must be controlled so that the influence of intravening variables in the assessment of ALG effectiveness can be assessed.

Age Factors↗
PubMed1976

Retrograde perfusion as a method for myocardial revascularization.

Retroperfusion of the superficial coronary venous system was studied in 44 canine fibrillating in vivo, normothermic preparations, with exclusion of the systemic circulation using cardiopulmonary bypass techniques in order to assess its value as a method of myocardial revascularization. Perfusion of either the isolated aortic arch via a brachiocephalic cannula or of the coronary sinus through the free end of a vein anastomosed to the atrial rim of the sinus was performed for 1 h at 100 cm3/min in groups II-IV following 30 min of anoxia. Oxygen uptake, vascular resistance, venous outflow and venous enzyme levels (CPK, GDH) were studied. Group I controls (antegrade perfusion, no anoxia) showed continued aerobic metabolism in contrast to group II (antegrade perfusion) and III (retrograde perfusion) which displayed negative lactate balance. Oxygen consumption was greater in group III than II (p less than 0.01) with a higher oxygen extraction in III (p less than 0.005). Group IV, which was given intravenously 30 mg/kg methylprednisolone prior to anoxia and then retroperfused, showed continued aerobic metabolism with low GDH venous levels and adequate oxygen consumption. Three dogs were then subjected to aortoatrial rim coronary sinus vein grafts with ligation of the left common coronary artery at its bifurcation with distal left circumflex and anterior descending artery-internal mammary vein anastomoses for venous drainage. The right coronary artery was left intact. Arterial inflow into the coronary sinus was associated with a left ventricular pressure of 70-80 mm Hg for up to 1.5 h while regular sinus rhythm was maintained. We conclude that retroperfusion of the coronary sinus represents a surgically feasible technique for providing oxygen delivery to the ischemic myocardium.

Animals↗
PubMed1976

Inhibition of mitogen-induced lymphocyte transformation by local anesthetics.

Chlorpromazine (CPZ) and lidocaine were added to cultures of mouse spleen cells stimulated by concanvalin A (Con A), phytohemagglutinin (PHA), pokeweed mitogen (PWM) and lipopolysaccharide (LPS). Concentrations of CPZ greater than 5 x 10(-6)M and concentrations of lidocaine greater than 2 x 10(-3)M totally inhibited the mitogenic responses to all four mitogens. Minimal inhibitory concentrations of neither drug interferred with cell viability as determined by trypan blue uptake or 51Cr release. The effects were totally reversed by the removal of the drugs from the culture. Addition of the drug at intervals after mitogen exposure demonstrated that the inhibited event occurred relatively soon after exposure to the mitogen. For example, the addition of lidocaine or CPZ more than 24 hr after Con A stimulation had no effect on tritiated thymidine incorporation. Elevated concentrations of cyclic AMP, cyclic GMP (or their derivatives) or calciunown membrane active actions of these drugs and the rapid reversibility of the effect strongly support the idea that the local anesthetics act on the surface membrane of lymphocytes. Binding of radiolabeled Con A or LPS to lymphocyte membranes in the presence of lidocaine or CPZ was not inhibited. The possibility exists that CPZ and lidocaine disorganized cell membranes so as to interfere with the surface membrane elaboration or action of a second messenger, or interfere with cell-cell interactions.

Animals↗
PubMedDate not supplied

Analysis of retinoid-mediated immunosuppression in vivo. Effects of Ro23-6457 on cellular alloimmune responses.

We have investigated the immunosuppressive effects of a synthetic retinoid, Ro23-6457, on the in vivo development of cellular alloimmunity. We initially observed that treatment of C57B1/6 mice with 10 mg/kg/day Ro23-6457 drug could prolong the survival of DBA/2 cardiac allografts, thus verifying its immunosuppressive potential in murine experimental models. We next used the sponge matrix model of allograft rejection and limiting dilution analysis (LDA) of cytotoxic T lymphocyte (CTL) frequency to dissect this phenomenon further. In this experimental system we observed the following effects of Ro23-6457: (1) dose-dependent decrease in the number of LDA-detectable, donor-reactive CTL accumulating in sponge matrix allografts; (2) failure to interfere with in vitro assays of cellular alloimmunity, including LDA; and (3) antigen non-specific depression of LDA-detectable CTL in lymph nodes, spleen and especially in peripheral blood. For peripheral blood CTL, the drug eliminated LDA-detectable CTL, an effect that was reversible and could not be attributed to the activation of suppressor cells. Since Ro23-6457 has little effect on the number of peripheral blood Thy1.2+ cells, it appears that this drug does not physically eliminate CTL, but makes them temporarily hyporesponsive to antigen stimulation, and thus undetectable in functional assays like LDA.

Animals↗
PubMedDate not supplied

Corynebacterium equi: a review of 12 cases of human infection.

Corynebacterium equi, an aerobic, variably acid-fast, gram-positive "diphtheroid," is an unusual cause of pulmonary infection in immunosuppressed patients. Initially, infection with C. equi may be mistaken for a mycobacterial infection. Two cases in a two-year period were observed and compared with the 10 cases previously reported in the literature. All but one patient had pulmonary involvement, and the presentation of all other patients was typically insidious, with fatigue, fever, and nonproductive cough. Chest roentgenograms showed cavitary lesions in seven of 11 patients. Four of 12 patients had associated bacteremias, and three of 12 had subcutaneous abscesses or lymphadenitis. One of our patients developed multiple brain abscesses. Overall mortality was 25%. The organism is susceptible to vancomycin, erythromycin, aminoglycosides, and chloramphenicol. Optimal duration of antibiotic therapy and the proper role of surgery in treatment is uncertain, but relapses have been common and many weeks of antibiotic therapy have generally been required for cure.

Abscess↗
PubMedDate not supplied

Variant angina: a nursing approach.

Variant angina presents as an atypical form of angina caused by coronary artery spasm. Due to the sudden disruption of blood and oxygen supply to the myocardium, a number of severe hemodynamic changes may occur, including life-threatening dysrhythmias, and left ventricular dysfunction. Rapid intervention can alleviate the symptoms caused by the arterial spasm and prevent catastrophic results. The critical care nurse plays a vital role in the diagnosis of variant angina and rapid treatment of the patient.

Adult↗