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Biomedical subjects

S D Sharma

Publications and source records attributed to S D Sharma.

At least 127 records · Page 7Linked to original sources

Tourniquet infusion versus hyperthermic perfusion.

The tourniquet infusion method was compared with hyperthermic perfusion in canine limbs by using Adriamycin, actinomycin-D, and melphalan. Tourniquet infusion provided comparable tissue levels with Adriamycin and significantly higher levels with actinomycin-D and melphalan in the treated extremity than hyperthermic perfusion with the same drugs and dosages. Higher systemic leak was observed, more so with melphalan, with the tourniquet infusion method. Tourniquet infusion has caused complete regression of four malignant tumors involving extremities (one malignant melanoma, two Kaposi's sarcomas, one squamous cell carcinoma) and partial greater than 50% regression of nine tumors (three malignant melanomas, three squamous cell carcinomas, one malignant schwannoma, one malignant fibrohistiocytoma, one liposarcoma) followed by excision of residual tumor. Five patients with extremity sarcomas precluding adequate surgical margins were treated preoperatively with the this method. Longer follow-up is needed, as is a larger number of patients for a valid comparison of tourniquet infusion with hyperthermic perfusion.

Aged↗

Hemostasis in experimental pulmonary injury.

Fibrin Seal (consisting of fibrinogen, cold insoluble globulin, factor XIII, antiplasmin, platelet growth factor, thrombin, and calcium chloride), cryoprecipitate, at Avitene were applied to areas of pulmonary wedge resections in dogs and cynomologus monkeys in an attempt to stop bleeding and air leakage. In the control groups, hemorrhage persisted. Comparing the three hemostatic agents used. Avitene was the least effective followed by cryoprecipitate. Fibrin Seal was most effective. In all cases, it eliminated both air leakage and bleeding.

Animals↗

Monoclonal antibodies to stages of Trypanosoma cruzi: characterization and use for antigen detection.

Monoclonal antibodies to the amastigote and epimastigote stages of Trypanosoma cruzi were produced and characterized by immunoglobulin class and subclass. Of the 17 monoclonal antibodies, 14 were of the immunoglobulin M (IgM) class and 2 were of the IgG2 and 1 was of the IgG1 subclass of IgG. Five of the monoclonal antibodies recognized the antigens of amastigotes only, two recognized the antigens of epimastigotes only, and ten recognized an antigen(s) common to both stages of T. cruzi. By using an immunofluorescence test with monoclonal antibodies, it was possible to visually localize amastigote- or epimastigote-specific antigens and the antigens common to both. Antigens specific for epimastigotes were noted on the flagellum or in spots over the entire body of the parasite. The antigens common to both amastigotes and epimastigotes were on one of the extremities of the amastigotes and on the region of the flagellar pouch of the epimastigotes. Four of the monoclonal antibodies were capable of detecting T. cruzi antigen in serum from mice infected with the parasite and in the supernatant of infected cell cultures, suggesting that monoclonal antibodies may be useful for antigen isolation and diagnostic methods.

Animals↗

Studies on platelet aggregation inhibitors in vivo. X. Relationship to thrombolysis.

Human labeled fibrin clots were inserted into femoral veins of stumptailed monkeys (Macaca arctoides). Thrombolysis was slightly increased by treatment with the platelet aggregation inhibitor pentoxifylline. This agent significantly potentiated the thrombolytic effect of urokinase activated human plasminogen. Pentoxifylline was also found to release plasminogen activator activity into the circulation.

Animals↗

Regional chemotherapy via the pulmonary artery for pulmonary metastases.

Regional chemotherapy with Adriamycin via the pulmonary artery produces significantly higher tissue levels in the infused canine lobe than systemic administration. Seven patients with soft tissue sarcomas who had received the maximum dose of Adriamycin and had shown metastatic tumor recurrence to the lungs, received small doses of 10 to 20 mg of Adriamycin in the lobar arteries supplying areas with tumor via a Swan-Ganz catheter, temporarily occluding with its inflated balloon the infused artery. One partial objective regression was noted. A total of 56 injections of Adriamycin was given through individual lobar arteries in the seven patients. This preliminary experience indicates the feasibility and relative safety of the use of the pulmonary artery for regional chemotherapy of pulmonary malignant tumors and suggests further cautious exploration of this method.

Animals↗

Effects of muramyl dipeptide treatment on resistance to infection with Toxoplasma gondii in mice.

Studies were carried out to determine whether treatment of mice with the synthetic adjuvant muramyl dipeptide afforded any resistance to infection with the obligate intracellular protozoan Toxoplasma gondii. Marked resistance to lethal challenge infection was observed in CBA but not C57BL/6 mice pretreated with muramyl dipeptide. In CBA mice, a single muramyl dipeptide treatment administered 14, 7, or 4 days before Toxoplasma challenge did not afford protection, whereas mice treated at -1 day were highly resistant. Additional studies carried out to investigate the mechanisms underlying the enhanced resistance to Toxoplasma in muramyl dipeptide-treated mice failed to reveal either enhanced cytolytic antibodies to the parasite or evidence that peritoneal macrophages from treated mice were activated as determined in vitro by their microbicidal capacity for Toxoplasma or cytotoxic capacity for tumor target cells.

Acetylmuramyl-Alanyl-Isoglutamine↗

Development of a refractory stage in a dog model for phenylketonuria.

Dogs were fed a continuous diet of phenylalanine (Phe) daily and para-chloro-phenylalanine (p-CPhe), an inhibitor of phenylalanine hydroxylase (PH-ase) every second day. It was reported that such a diet produces a sustained hyperphenylalanemia in rats. We have found, however, that in dogs an initial rise in circulating Phe is followed, after a period of time, by a return to normal levels in spite of diet maintenance. PH-ase ws measured in liver samples obtained from dogs before the start of the above diet and at the time when Phe levels returned to normal. It was found that the post-feeding liver sample had 57%-100% less activity than the normal sample. Accordingly, decline in Phe levels cannot be attributed to an increase in PH-ase activity. Experiments are being initiated using labelled Phe, to investigate whether chronic feeding of Phe and p-CPhe resulted in an intestinal block to Phe absorption, which may explain our experimental findings.

Animals↗

Generation of alloreactive cytotoxic T lymphocytes: production of T cell and macrophage helper factors in addition to IL 1 and IL 2 by peritoneal cells from mice immunized to Listeria monocytogenes.

We investigate the production and biological activity of soluble helper factors produced by peritoneal T cells and macrophage derived from mice primed in vivo with Listeria monocytogenes. Supernatant fluids from co-cultures of these immune T cells and activated macrophages contained Interleukin 1 (IL 1) and Interleukin 2 (IL 2), and had the ability to assist the generation of cytotoxic T lymphocytes (CTL) from a population of nylon wool nonadherent spleen cells sensitized to allogeneic heat-treated thymocytes. The ability to assist CTL development involved T cell and macrophage factors in addition to IL 1 and IL 2. Immune T cells cultured alone produced a factor, devoid of significant IL 2 activity, that assisted CTL development only if adherent cells were present in the responding population. Activated macrophage produced a 38,000 dalton component, distinct from IL 1 on the basis of m.w., that assisted the development of CTL from nylon wool nonadherent splenic cells. Supernatants fluids from co-cultures of immune T cells and allogeneic, nonactivated macrophage contained a CTL helper factor but did not contain IL 1 or IL 2 activities. In contrast, supernatant fluids from co-cultures of immune T cells and syngeneic, nonactivated macrophage contained all 3 activities. This suggests a genetic restriction for the production of IL 1 and IL 2 that does not restrict the production of a CTL helper factor. These results demonstrate that T cell- and macrophage-derived helper factors distinct from IL 1 and IL 2 participate in the development of CTL.

Animals↗

Role of glutathione in the metabolism-dependent toxicity and chemotherapy of cyclophosphamide.

The role of glutathione in the biological effects of cyclophosphamide (CP) was evaluated by investigating the following: effect of CP on hepatic glutathione levels; relationship between hepatic glutathione depletion (repletion) and the binding of [chloroethyl-3H]CP and [4-14C]CP to hepatic macromolecules; effects of interaction between CP (or acrolein) and diethyl maleate (a classical glutathione depletor), and/or between CP and cysteine on the binding of labeled CP to hepatic macromolecules, on the induction of hematuria, on the content of hepatic cytochrome P-450, on weight gain in rats, on survival in mice, and on the chemotherapeutic efficacy of CP against Walker 256 carcinoma in rats. CP and acrolein produced dose-dependent depletion of hepatic glutathione in mice, whereas phosphoramide mustard was at least one order of magnitude less effective. Acrolein caused death in mice; CP became covalently bound to hepatic macromolecules, prevented weight gain in rats, and produced hematuria and depression of hepatic cytochrome P-450 in vivo. These effects of CP (or acrolein) were enhanced by diethyl maleate but partially blocked by cysteine. On the other hand, reduction in the volume of Walker 256 carcinoma in rats by CP was not antagonized by cysteine. All these investigations point to the following conclusions: (a) acrolein produced during the metabolism of CP binds to proteins and, by doing so may denature these proteins; and (b) acrolein in vivo preferentially reacts with glutathione, and sulfhydryl-containing compounds may protect against acrolein toxicity and at the same time not interfere with the chemotherapeutic activity of CP.

Acrolein↗

Effects of induction of labor on the neurophysiologic functioning of newborn infants.

Neurophysiologic responses of newborn infants delivered after normal onset of labor are compared with those of newborn infants whose mothers had labor induced with oxytocin or prostaglandin F2 alpha. No differences in brain activity or heart rate were detected between groups in terms of frequency of response to auditory, visual, tactile, or olfactory stimulation. Significant differences were found for resting brain activity defined in terms of autoregressive spectral estimates or coefficients. The largest differences were between the groups with normal onset of labor and prostaglandin F2 alpha.

Autonomic Nervous System↗