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Biomedical subjects

C E Zimmerman

Publications and source records attributed to C E Zimmerman.

At least 19 recordsLinked to original sources

The use of intermediate and high purity factor VIII products in the treatment of von Willebrand disease.

Since 1985, viral-attenuated blood products have been available for the treatment of patients with hemophilia. Unfortunately, similar viral-attenuated blood products, enriched for von Willebrand factor (vWF), have not been readily available for the treatment of patients with von Willebrand disease (vWD). In the current study, we examined the clinical efficacy and in vivo properties of two viral-attenuated factor VIII products, Koate-HS and Koate-HP, in the treatment of patients with vWD. Twenty-one (21) infusions were evaluated in 17 different vWD patients (4 with type IA; 8 with Type IIA; 1 with Type IID; 4 with type III). Seven (7) patients received Koate-HS and 12 patients received Koate-HP (2 patients received both products; 1 patient was studied three times). Von Willebrand factor antigen, ristocetin cofactor, bleeding time, and the multimeric composition of vWF were determined pre- and post-infusion. Complete or partial correction of prolonged bleeding times was observed in 2 of the 6 patients tested following treatment with Koate-HS and in 7 out of 11 patients tested following treatment with Koate-HP. Surgery was performed on five of these patients, two of whom were treated with Koate-HS and three of whom were treated with Koate-HP. In the surgical patients, clinical hemostasis was achieved regardless of whether the bleeding time was corrected. We conclude that both Koate-HS and Koate-HP can be utilized successfully in the treatment of patients with vWD in spite of the lack of high molecular weight multimers of vWF in these products.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A randomized prospective trial of anti-Tac monoclonal antibody in human renal transplantation.

Patient entry is now complete in a prospective trial of anti-Tac, a murine IgG2a monoclonal antibody directed against the p55 chain of the human IL-2 receptor, for the prevention of renal allograft rejection. Recipients of primary cadaver allografts were randomized to receive either anti-Tac (20 mg q.d. x 10 days beginning POD 1) plus low-dose CsA (4 mg/kg/day), azathioprine (2 mg/kg/day), and prednisone (30 mg q.d.), or conventional triple therapy with CsA (8 mg/kg/day), azathioprine, and prednisone. Forty patients were entered in each group, with current followup from 6 to 26 months. The results show a significant reduction in early rejection episodes in the anti-Tac-treated patients. During the 10-day treatment, 5 of 40 anti-Tac patients had rejection episodes, compared with 21 of 40 control patients (P less than 0.001). Anti-Tac significantly delayed the time to the first rejection (12.5 +/- 6.3 vs. 7.6 +/- 6.7 days) (P less than 0.05). Despite these effects, there were no differences in either actual or actuarial graft or patient survival between the two groups. Pneumonia, primarily CMV, developed in 5 treated and 4 control patients. In patients with functioning grafts mean serum creatinine at 3 months was 1.8 +/- 0.7 in the anti-Tac group and 2.0 +/- 0.8 in the control group (P = NS); at 12 months the values were 2.3 +/- 1.5 and 1.8 +/- 0.5, respectively (P = NS). The peak expression of IL-2 receptors on circulating T-cells was significantly lower in anti-Tac patients (15.1 +/- 3.6%) than in controls (21.9 +/- 4.5%) (P less than 0.05). Seven of 10 patients tested to date developed antimouse immunoglobulin antibodies, with antiidiotype shown in 6. These antibodies do not preclude subsequent treatment with OKT3. Five patients in this and previous anti-Tac protocols have received OKT3 for acute rejection despite known pretreatment antimouse antibodies, with resolution of rejection in all cases.

Adolescent↗

Prophylactic use of monoclonal anti-IL-2 receptor antibody in cadaveric renal transplantation.

In vivo administration of an anti-interleukin-2 (anti-IL-2) receptor monoclonal antibody is a potential new therapy for prevention of allograft rejection of a freshly transplanted organ. Such an approach is more selective than targeting all T cells, or even the CD4 or CD8 major subsets, because only the very recently activated cells should be affected. A clinical trial of anti-Tac monoclonal antibody is in progress in which 20 mg of the immunoglobulin G 2a (lgG2a) antibody is administered intravenously daily for 10 days after cadaveric renal transplantation. Combinations with and without azathioprine, and with varying doses of cyclosporine with prednisone, are being evaluated in a randomized trial. Results to date show a significant immunosuppressive effect of anti-Tac, as measured by a reduced incidence and later onset of acute rejection episodes compared with cyclosporine plus prednisone or cyclosporine plus azathioprine plus prednisone. Removal or cytodestruction of IL-2-receptor positive cells from the peripheral blood does not occur to any major degree, even though serum levels of the antibody are always detectable. In addition, functional studies of MLR, CML, and suppressor cell generation 4 days after cessation of anti-Tac administration show no significant difference between treated and control groups The effect of anti-Tac seems, therefore, to be limited to inhibition of IL-2-mediated T-cell growth during the period of administration, with recovery after a few days' lag period.

Antibodies, Monoclonal↗

Outpatient excision and primary closure of pilonidal cysts and sinuses. Long-term follow-up.

Long-term follow-up data are reported on 52 patients who underwent outpatient excision and primary closure of pilonidal cysts, sinuses, and abscesses while under local anesthesia. The procedure consists of conservative excision of all sinus tracts and cavities plus primary closure with a dead-space-obliterating monofilament suture. Sitting was restricted for 1 to 2 weeks after surgery. Primary healing was obtained in all of the patients, and with follow-up on 84 percent of the patients, no late recurrences have appeared.

Adult↗

Outpatient excision and primary closure of pilonidal cysts and sinuses.

A procedure for outpatient excision and closure of pilonidal cysts and sinuses under local anesthesia is described. The operation is designed to reduce hospital expenses and loss of work time. It utilizes the low tissue friction properties of polypropylene sutures to effect full dead space obliteration and a home care regimen to minimize the incisional tension produced by sitting. Of thirty-two procedures performed, follow-up data were available for twenty-eight, with a mean postoperative time of twenty-four months. Full primary healing was obtained in all cases with a single early wound disruption. There have been no late recurrences.

Adult↗

Quantitative aspects of the metabolic response to pancreatic islet transplantation in rats with severe ketotic diabetes.

Injection of 100-140 mg/Kg of streptozotocin produced severe, ketotic diabetes in 12 pairs of adult rats. Transplantation of intact islets of Langerhans from syngeneic adult donors into a muscle pocket or a pouch created from pancreatic tissue of one animal from each pair eliminated ketonemia in the immediate postoperative period, while ketonemia persisted in the sham-operated controls. Mean survival of transplanted animals was 145 days, versus 70 days for controls. Mean body weight increased and blood sugar decreased in transplanted animals compared with controls; the differences were greatest in those animals which received the largest number of islets per unit body weight. In one animal, all metabolic indices returned to normal for a period of 8 wk following transplantation of 650 islets. After gaining to 300% of initial body weight, diabetes reappeared in this transplanted animal and was again reversed by a second transplantation. The metabolic data indicate that: (1) islet tissue from adult donors survives and functions in severely diabetic, ketotic hosts; and (2) metabolic response to transplantation is a function of the ratio of islet tissue to body mass, a minimum ratio of about 2-3 islets/gm body weight being required to maintain normal homeostasis.

Animals↗