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Biomedical subjects

V Farewell

Publications and source records attributed to V Farewell.

31 records · Page 2Linked to original sources
PubMed1988

Pathogenesis of hypotension in septic shock: correlation of circulating phospholipase A2 levels with circulatory collapse.

Circulating phospholipase A2 (PLA2) has been recognized as a mediator of circulatory collapse in experimental endotoxic shock. To assess the role of serum PLA2 in septic shock in man, we determined serum PLA2 profiles in a prospective study in 12 patients with septic shock. During the hypotensive phase of sepsis, serum PLA2 levels were consistently elevated as high as 33,428 U/ml (normal range 115 +/- 12 [SE]; n = 101). In all 12 patients, PLA2 levels correlated directly with the magnitude and duration of circulatory collapse (p less than .001), with a progressive fall of serum PLA2 levels during convalescence. In contrast, serum PLA2 levels in patients with cardiogenic shock secondary to myocardial infarction remained low. In pancreatitis, PLA2 levels paralleled fluctuations of serum amylase and lipase, whereas in septic shock without pancreatic involvement, PLA2 changes were discordant with changes in pancreatic enzymes. As well, septic shock serum PLA2 failed to crossreact by radioimmunoassay with antiserum against human pancreatic PLA2. These data are consistent with an extrapancreatic source of intravascular PLA2 release during sepsis. Since endogenous serum PLA2 levels correlate directly with the magnitude of hypotension in both experimental endotoxic shock and clinical septic shock, and since parenteral administration of purified exogenous PLA2 reproduces hypotension in experimental models, we conclude that high levels of intravascular PLA2 may contribute similarly to the circulatory collapse in septic shock in man.

Adult↗
PubMed1988

Concordance of endogenous cortisol and phospholipase A2 levels in gram-negative septic shock: a prospective study.

Lipocortins, a group of corticosteroid-induced phospholipase-inhibitory proteins, are thought to play a prominent role in the mediation of the anti-inflammatory effects of steroids. The synthesis and release of these proteins may represent a major endogenous mechanism of regulation of extracellular phospholipase A2 (PLA2) activity. Because soluble PLA2 activity has been associated with circulatory collapse in hyperphospholipasemic conditions, such as septic shock and pancreatitis, we examined the relationship between circulating PLA2 activity and adrenocortical function. In a prospective study of 10 episodes of septic shock, serum PLA2 and cortisol levels correlated significantly in all survivors (p less than 0.0001), whereas such a correlation was absent in all nonsurvivors (p less than 0.07). No significant correlation of cortisol and adrenocorticotropic hormone (ACTH), or PLA2 and ACTH, was found in any patient, suggesting that the stimulus for cortisol release arises from outside the hypothalamic-pituitary axis. These data suggest that, in human beings, the regulation of soluble PLA2 activity may be mediated by adrenocortical hormones, perhaps through the intermediary action of lipocortins.

Adrenocorticotropic Hormone↗
PubMed1988

Early function as the principal correlate of graft survival. A multivariate analysis of 200 cadaveric renal transplants treated with a protocol incorporating antilymphocyte globulin and cyclosporine.

We examined the factors determining graft survival in 200 consecutive cadaveric renal transplants managed on a quadruple-therapy protocol: Minnesota antilymphoblast globulin, cyclosporine, azathioprine, and low-dose prednisone. Perioperative central venous pressure monitoring and volume expansion were emphasized. To avoid CsA nephrotoxicity in the early posttransplant period, patients were treated with ALG until renal function was established (a mean of 7 days). Therapeutic CsA levels were achieved before ALG was discontinued. Azathioprine was used to supplement CsA in patients with nephrotoxicity or rejection. Twelve-month graft survival was 85% (first transplants 86%, retransplants 79%), with patient survival of 95%. ALG was not associated with excessive clinical cytomegalovirus infections, which occurred in 5% of patients, or with malignancy. When 3 technical failures were excluded, an analysis of numerous factors in the pretransplant and peritransplant period revealed that the strongest correlate of one-year graft survival was early renal function. Grafts with delayed function (DF) had 75% survival, compared with 91% for grafts with good early function (EF). A multivariate analysis confirmed this association: the relative risk of graft loss was increased 2.86 times for DF compared with EF. The mechanism of the deleterious effect of DF was apparently multifactorial: the DF group, by definition, contained all the kidneys that never functioned, but some risk also persisted in kidneys that achieved function. One reason for this may be that DF kidneys that achieved function had higher mean serum creatinine values at 1 month: elevated serum creatinine values at 1 month were strongly associated with increased risk of graft loss regardless of initial function. There was also a higher number of rejection episodes diagnosed in the DF group. These observations suggest that early renal function is a major determinant of graft outcome and should be a target for efforts to further improve renal graft survival.

Antilymphocyte Serum↗
PubMed1986

Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia.

We treated 93 patients who had acute nonlymphoblastic leukemia in the first remission or chronic myelocytic leukemia in the chronic phase (median age, 30 years) with high-dose cyclophosphamide and fractionated total-body irradiation, followed by infusion of marrow from an HLA-identical sibling. To evaluate postgrafting prophylaxis for graft versus host disease, we studied these patients in a sequential, prospective, randomized trial that compared the effect of a combination of methotrexate and cyclosporine (n = 43) with that of cyclosporine alone (n = 50). All patients had evidence of sustained engraftment. A significant reduction in the cumulative incidence of grades II to IV acute graft versus host disease was observed in the patients who received both methotrexate and cyclosporine (33 percent), as compared with those who were given cyclosporine alone (54 percent) (P = 0.014). Seven patients who received cyclosporine alone acquired grade IV acute graft versus host disease, as compared with none who received both methotrexate and cyclosporine. Thirty-five of the 43 patients given both methotrexate and cyclosporine and 31 of the 50 patients given cyclosporine are alive as of this writing, at 4 months to 2 years (median, 15 months); the actuarial survival rates in the two groups at 1.5 years were 80 percent and 55 percent, respectively (P = 0.042). We conclude that the combination of methotrexate and cyclosporine is superior to cyclosporine alone in the prevention of acute graft versus host disease after marrow transplantation for leukemia, and that this therapy may have a beneficial effect on long-term survival.

Acute Disease↗
PubMed1986

Marrow transplantation for severe aplastic anemia: methotrexate alone compared with a combination of methotrexate and cyclosporine for prevention of acute graft-versus-host disease.

Forty-six patients with severe aplastic anemia (median age, 23 years) were treated with high-dose cyclophosphamide followed by infusion of marrow from an HLA-identical family member. To evaluate postgrafting prophylaxis for graft-v-host disease (GVHD), they were entered into a prospective randomized trial comparing the effect of a combination of methotrexate and cyclosporine (n = 22) to that of methotrexate alone (n = 24). Forty-four of the forty-six patients had evidence of sustained marrow engraftment. Only one patient in each of the two study groups showed graft rejection. A significant reduction in the cumulative incidence of grades II to IV acute GVHD was seen in patients given methotrexate/cyclosporine (18%) compared with those given methotrexate alone (53%) (P = .012). In three patients given methotrexate alone, grade III developed, and in six, grade IV acute GVHD developed, compared with none given methotrexate/cyclosporine. Eighteen of the 22 patients given methotrexate/cyclosporine and 15 of the 24 given methotrexate alone are alive between 5.5 and 44.5 months (median, 18 months), with actuarial survival rates at 2 years of 82% and 60%, respectively (P = .062). The incidence of fatal infections was higher in patients given methotrexate alone, whereas there are as yet no significant differences in the incidence of chronic GVHD. We conclude that methotrexate/cyclosporine treatment resulted in a significant decrease in the incidence and severity of acute GVHD in patients who received transplants for severe aplastic anemia and thus an improvement in survival.

Acute Disease↗
PubMed1985

Cybex evaluation of the relationship between anterior and posterior compartment lower leg muscles.

Twenty adult males were tested with the Cybex II isokinetic dynamometer, comparing in each leg the torque produced by the anterior and posterior muscle compartments. Significant torque is produced by the gastroc soleus muscle group, even when the knee is bent 90 degrees. There is a significant increase in anterior compartment dorsiflexion torque produced with the knee in extension as compared to flexion. There is no difference in right or left handedness in comparing the results of torque generation in the lower extremity. On the average, dorsiflexion torque is approximately one-third of plantarflexion torque at slow speeds and half that of plantarflexion at fast speeds.

Adult↗
PubMed1982

Analysis of late infections after human bone marrow transplantation: role of genotypic nonidentity between marrow donor and recipient and of nonspecific suppressor cells in patients with chronic graft-versus-host disease.

Infections occurring 6 mo or later after bone marrow transplantation for severe aplastic anemia or hematologic malignancy were analyzed in 98 long-term survivors. Varicella-zoster (VZ) infections were analyzed separately from all other infections. The factor predisposing most strongly to late VZ infection was genotypic nonidentity for HLA between marrow donor and recipient. There was a suggestion that chronic graft-versus-host disease (GVHD) associated with the presence of nonspecific suppressor cells also predisposed to late VZ infection, while age less than 10 yr was protective against such infections. Chronic GVHD predisposed to late non-VZ infections, but this was not increased by the presence of nonspecific suppressor cells. HLA nonidentify between patient and marrow donor further increased the risk of late non-VZ infections over and above that due to the presence of chronic GVHD. Receipt of a syngeneic transplant appeared protective for late non-VZ infections. These findings suggest that full genotypic identity for HLA between donor and recipient may be required for optimal immune reconstitution after marrow transplantation and may denote a possible biologic role for nonspecific suppressor T cells in humans.

Acute Disease↗
PubMed1981

The treatment of Wilms' tumor: results of the Second National Wilms' Tumor Study.

One-hundred-eighty-eight children up to 16 years of age were randomized in the second National Wilms' Tumor Study (NWTS) with tumors that were confined to the kidney and that had been totally excised (Group I). Most fared well whether treated for six or for 15 months with both actinomycin D (AMD) and vincristine (VCR). No postoperative radiation therapy (RT) was given. The two-year relapse-free survival (RFS) and two-year survival rates were 88 and 95%, respectively. Two-hundred-sixty-eight randomized patients with more advanced local lesions (Groups II and III) and 57 with distant metastases (Group IV) had postoperative RT and were scheduled for 15 months treatment with either AMD and VCR (Reg. C) or AMD plus VCR plus Adriamycin (Reg. D). The 77% two-year RFS rate for Reg. D was significantly different from the 63% with Reg. C. As in the first NWTS, patients with tumors of unfavorable histology (UH) had a significantly worse prognosis than those with favorable histology (FH), as did those with positive nodes. Survival rates at two years were 54% for UH vs. 90% for FH, and 54% vs. 82% for those with and without lymph node involvement.

Adolescent↗
PubMedDate not supplied

The relationship of upper extremity strength to throwing speed.

Cybex II Isokinetic Dynamometer (Lumex Corp. Ronkonkoma, NY) tests for the upper extremity strength of eight professional baseball players, together with radar gun measurements of their individual throwing speeds, were subjected to statistical analysis. Results of simple and multiple regression analysis showed a relationship between the strength of the elbow extension and wrist extension movements and throwing speed.

Arm↗