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Biomedical subjects

J A Mannick

Publications and source records attributed to J A Mannick.

36 records · Page 2Linked to original sources

Improved results with femoropopliteal vein grafts for limb salvage.

Over a ten-year period from 1966 to 1975, 154 femoropopliteal vein grafts were performed for limb salvage in 139 patients, including 42 diabetics. The average patient age was 70 years. The one-month operative mortality was 2.9% (four patients). Average preoperative Doppler ankle pressure was 46 mm Hg, with an average ankle-arm systolic blood pressure index (ASPI) of 0.33. The average postoperative Doppler ankle pressure was 96 mm Hg, with an ASPI of 0.76. Five-year vein graft patency was 72%. Poor quality of vein was a statistically significant cause of graft failure (P less than .015). Small saphenous veins of good quality and arm veins gave satisfactory results. Diabetics had a lower, but not statistically significantly decreased, five-year patency. Because of this high success rate and low operative mortality, we recommend an attempt at limb salvage by femoropopliteal vein grafting in patients threatened with limb loss because of atherosclerotic occlusive disease of the femoropopliteal segment.

Aged

Assessment of myocardial performance and optimal volume loading during elective abdominal aortic aneurysm resection.

Myocardial depression has been suggested as a cause of declamping hypotension. To investigate and manage this problem, thermal dilution catheters were placed in 22 elderly, high-risk patients (mean age 71 years) who underwent elective abdominal aortic aneurysm resection. There were no deaths. Myocardial performance curves (MPC) were determined preoperatively, following induction of anesthesia, during aortic clamping, following declamping, and 12 to 48 hours postoperatively. The slope of this curve was taken as an index of myocardial performance. Preoperative cardiac index at a pulmonary artery wedge pressure of 10 mm Hg (CI10) decreased significantly following induction of anesthesia (P less than .002) and persisted during aortic cross-clamping. Following declamping, CI10 rose to preoperative levels. The slope of the MPC followed this same pattern. There was no significant change in blood pressure with the aorta clamped or following declamping. Myocardial performance is depressed following induction of anesthesia but declamping hypotension can be minimized or prevented by optimum volume loading as guided by Starling's myocardial performance curves.

Aged

Association of a circulating immunosuppressive polypeptide with operative and accidental trauma.

The serum from 109 traumatized patients was examined for immunosuppressive activity which might explain diminished host immune responsiveness following operative or accidental injury. Twenty-eight fo 31 (90%) severely tralmatized patients, 25 of 60 (42%) moderately traumatized patients, and 0 of 18 minimally traumatized patients developed serum which suppressed the response of normal human lymphocytes to phytohemagglutinin. The degree and duration of serum immunosuppressive activity paralleled the severity of the clinical course but did not correlate with serum cortisol or barbiturate levels. Suppressive sera were not cytotoxic. The immunosuppressive factor(s) was contained in a low molecular weight (less than 10,000 daltons) peptide fraction and was present in 5--10 times the amount recoverable from normal serum. By size and activity the trauma serum factor resembled immunoregulatory alpha globulin, a naturally-occurring serum inhibitor of T-lymphocyte reactions. Thus, depressed immunoreactivity following trauma may be due in part to high concentrations of an endogenous immunosuppressive polypeptide.

Adolescent

Is axillo-bilateral femoral graft an effective substitute for aortic-bilateral iliac/femoral graft?: an analysis of ten years experience.

During the past ten years, 88 aorto-bilateral iliac/femoral grafts and 56 axillo-bilateral femoral grafts were electively performed for occlusive disease of the abdominal aorta or iliac vessels. The results of this retrospective study indicate that the axillo-bilateral femoral graft, although performed in an older population and more frequently for limb salvage, has a lower operative mortality than does conventional aortic bypass surgery with similar patency (76%) and survival (67%) at five years. However, axillo femoral grafting requires more frequent remedial surgery to obtain long term patency.

Amputation, Surgical

Anti-immunoglobulin as an adjunct in producing long-term antigen-specific allograft survival. Organ localization of immune complexes.

Heterologous anti-immunoglobulin is a potent immunosuppressive agent that prolongs H-2- and H-3-incompatible skin graft survival. In conjunction with antithymocyte serum, anti-immunoglobulin promotes greater graft life than either antiserum used alone, without evidence of toxicity to recipient animals. Combination treatment with anti-immunoglobulin, antithymocyte serum, and donor spleen cells produces long-term allograft survival to the lifetime of the host and can result in antigen-specific immune unresponsiveness of sufficient strength to permit acceptance of a second-set graft. Anti-immunoglobulin complexes formed in treated mice appear to be localized primarily in the lymphatic reticuloendothelial system.

Animals

Immunosuppressive activity of IRA on the plaque-forming response to SRBC in vitro: reversal with educated cells.

The alpha-globulin-rich fraction of Cohn Fraction IV, designated IRA, suppresses the in vitro antibody response to sheep red blood cells (SRBC) without cytotoxicity. IRA was effective if added before or up to 24 hr after antigen exposure. The suppression could be reversed after 24-hr treatment by washing the cells two to three times; after 48 hr of IRA treatment, however, suppression could only be partially reversed. The addition of a population of thymus-derived cells educated to the antigen SRBC could effectively reverse the IRA-induced inhibition of antibody production, whereas BSA-educated T cells could not.

Alpha-Globulins

Suppression of tumor-specific cell-mediated cytotoxicity by immunoregulatory alpha-globulin and by immunoregulatory alpha-globulin-like peptides from cancer patients.

The suppression of tumor-specific cell-mediated cytotoxicity by human immunoregulatory alpha-globulin (IRA), by a peptide fraction derived from IRA, and by IRA-like peptides from the serum of cancer patients was studied in a syngeneic murine tumor-host system. Splenic lymphocytes from tumor-immunized mice were cytotoxic specific tumor cells in vitro as measured by the [125]-iododeoxyuridine release microcytotoxicity assay. However, this effect was significantly depressed if 1.25 to 5 mg of IRA per ml were added to the cultures. Pooled lyophilized normal human serum protein was inactive. IRA peptide and IRA-like peptide fractions from cancer patients were also highly suppressive of cell-mediated cytotoxicity at much lower concentrations (0.05 to 0.5 mg/ml). Control human serum peptide, which failed to inhibit the induction of hemolytic plaque-forming cells in sheep erythrocyte-injected mice, had no effect on cell-mediated cytotoxicity. IRA and IRA-like peptide fractions were not cytotoxic to the effector lymphocytes or to the target cells at the concentrations used.

Alpha-Globulins

The specificity of concomitant tumor immunity at large tumor volumes.

Two antigenically distinct fibrosarcomas, designated BP-8 and BP-9, induced in syngeneic C3H/HeN mice by 3,4-benzo(a)pyrene were used to study tumor-specific immunity, concomitant tumor immunity and the effect of large tumor volumes on the loss of immunological reactivity. Two groups of mice were immunized to the BP-8 tumor by amputation of growing BP-8 isografts. One group was rechallenged with the BP-8 cells, and tumor growth was not noted. Both groups of mice then received an inoculum of BP-9 cells that grew to palpable tumors to the same extent as in control mice. BP-8-immunized mice bearing progressively larger PB-9 tumors were sacrified at varying intervals after the BP-9 isograft. Tumor weight was recorded as a percentage of total body weight and viable spleen cells from these animals were tested in vitro for cytotoxicity against BP-8 and BP-9 cells in the [125I]iododeoxyuridine microcytotoxicity assay. Spleen cells from untreated mice were used as controls. The mice with growing BP-9 tumors developed an immune reaction against the tumor antigens which increased with time from initial tumor isograft and with increasing tumor size up to a definite but variable limit. Cytotoxicity to BP-9 cells rose from 18% when the BP-9 tumor was not palpable to a maximum of 77% when the tumor represented 5 to 10% of the total body weight. Cytotoxicity to BP-9 fell progressively as tumor size exceeded 15% of the total body weight and approached the 10% background cytotoxicity of control lymphocytes to BP-9 cells, when the tumor weight achieved 25% of the animal's weight. Conversely, cytotoxicity of lymphocytes against the BP-8 tumor did not vary significantly and remained about 41 to 44% over the same interval even while specific reactivity to BP-9 cells significantly decreased. In addition, with time, lymphocyte-mediated cytotoxicity to the BP-8 tumor increased from 41 to 70% if the BP-8-immunized mice had been rechallenged with antigenically identical BP-8 cells prior to the BP-9 isograft. These data suggest that loss of immunoreactivity at large tumor volumes is tumor and, presumably, antigen specific. No evidence of a generalized immune paralysis was demonstrated, since the mice always maintained immunity to the BP-8 tumor despite progressive and lethal growth of the antigenically distinct BP-9 tumor.

Animals