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Biomedical subjects

J C Fish

Publications and source records attributed to J C Fish.

At least 37 records · Page 2Linked to original sources
PubMed1987

An in vitro model for analyzing the nephrotoxicity of cyclosporine and preservation injury.

Renal damage caused by cyclosporine (CsA) has been documented. Clinical experiences have shown preservation injury further potentiates CsA nephrotoxicity. This study examined the mechanism of nephrotoxicity defined by changes in protein synthesis, DNA synthesis, and ornithine decarboxylase activity in an in vitro model. Initial results showed that CsA inhibited dog kidney epithelium cell (MDCK) replication at a dose of 200 ng after 24 hr (P less than .01) and 100 ng after 48 hr (P less than .01). Protein synthesis was inhibited with 100 ng after 24 and 48 hr (P less than .01). There was a reduction in ODC activity with 200 ng CsA (P less than .05). Methods for simulating transplant-related injuries were then developed. Under ischemic conditions, 18 hr were required before a synergistic effect with CsA produced a reduction in replication (P less than .05). Incubation of MDCK cells in preservative solution at 4 degrees C under hypoxic conditions resulted in a time-dependent reduction in synthetic and replicative capacity that plateaued at 24 hr (P less than .01). The next step was to simulate the clinical situation by combining treatments. MDCK cells were incubated for 24 hr in preservative solution under hypoxic conditions at 4 degrees C, and then CsA was added at defined intervals. The addition of CsA before 24 hr resulted in a significant decrease in cell replication (P less than .05) compared with CsA addition after 48 hr. Similar results were obtained with cells incubated for 48 hr in preservative solution with hypoxia. These data suggest that renal injury from ischemia and cold storage requires a period of cellular repair and replication. Administration of CsA before this period results in further renal injury. Our analysis offers an explanation of CsA nephrotoxicity seen in the human situation and, therefore, may provide a model for studying human nephrotoxicity.

Cell Survival↗
PubMed1985

Surgical adjuvant treatment of locally advanced breast cancer.

The reported incidence of local recurrence after mastectomy for locally advanced breast cancer (TNM Stage III and IV) is between 30% and 50%. The purpose of this study was to evaluate the effect of radiation therapy (XRT) followed by total mastectomy on the incidence of local recurrence in patients with locally advanced breast cancer. Fifty-three patients who presented with locally advanced breast cancer, without distant metastases, were treated with XRT (4500-5000 R) to the breast, chest wall, and regional lymph nodes. Five weeks after completion of XRT, total mastectomy was performed. There were no operative deaths. The complications that occurred in 22 patients after surgery were flap necrosis, wound infection, and seroma. Patients have been followed from 3 to 134 months. Twenty-five patients are alive (3-134 months), 12 free of disease; 28 patients have died with distant metastases (6-67 months). Isolated local recurrence occurred in only two patients. Four patients had local and distant recurrence (total local recurrence is 6/53). The remaining patients all developed distant metastases. We have devised a treatment strategy which significantly decreases the incidence of local recurrence in patients with locally advanced breast cancer. However, the rapid appearance of distant metastases emphasizes the need for systemically active therapy in patients with locally advanced breast cancer.

Breast Neoplasms↗
PubMed1983

Inability of thoracic duct drainage to prevent hyperacute rejection.

Serum and lymph albumin and Ig levels were measured during 6 weeks of lymphocyte depletion by thoracic duct drainage (TDD) in 21 patients prior to renal allotransplantation. In ten of these patients, the amount of protein lost from all sources (blood sampling, dialysis, and lymph centrifugation) was measured. The total amount of albumin lost was significantly greater than the amount of IgG lost. However, serum IgG declined at a faster rate and to a greater extent than albumin. Hyperacute or acute humoral rejection occurred in 14 grafts in 10 patients prepared by TDD despite negative crossmatch tests. These data suggest that removal of lymphocytes by TDD, rather than protein loss alone, affects IgG levels. On the other hand, TDD and IgG depletion do not prevent hyperacute or acute humoral rejection. This is most likely due to the inability of currently employed crossmatch tests to predict accurately which patients will manifest antibody-mediated graft rejection.

Drainage↗
PubMed1982

Successful surgical treatment of anuria caused by renal artery occlusion.

Anuria resulting from obstruction of the renal arteries to both Kidneys or to a solitary kidney is unusual. The tolerance of the kidney to this ischemia is largely dependent upon the presence of collaterals, stimulated by pre-existing arterial disease. Our experience with six patients with anuria caused by renal artery occlusion supports the role of revascularization in the recovery of significant renal function. Four of these patients had hypertension, impaired renal function, and the existence of collateral circulation to an ischemic kidney, prior to occlusion, while two patients had normal renal function (serum creatinine = 0.5 and 0.9 mg/dl) before occlusion. The intervals of anuria for the two previously normal kidneys were six hours and five days, and 2 to 14 days in the four patients with vascular disease. Isotope scanning suggested renal artery occlusion in two patients, but arteriograms confirmed the diagnosis in all six. A thrombectomy restored blood flow through the two previously normal renal arteries. Grafts from the aorta or celiax axis were used for three patients and the splenic artery was used for the sixth patient. Urine flow began during or soon after operation in all patients. Dialysis was necessary for 30 and 45 days in the two patients with normal kidneys, but in only one of the four patients with previous disease (for ten days). Serum creatinine decreased to <2.0 mg/dl after operation, except in the man with a solitary kidney, who five years later has a creatinine of 3 mg/dl. All four patients with previous arterial disease died from cardiac failure within 1 to 30 months after operation. Therefore, anuria of acute onset should be evaluated by renal scan and arteriogram to detect those patients with proximal renal artery occlusion in preparation for revascularization.

Adolescent↗
PubMed1981

Renal transplantation after thoracic duct drainage.

Forty-seven patients treated by at least 28 days of thoracic duct drainage (TDD) before cadaveric renal transplant are compared with 63 patients treated with standard immunosuppression. The TDD patients were begun on half the dosage of steroids, and at 30 days were receiving approximately two-thirds the dose that the non-TDD patients received. Acute rejection occurred in 35% of the TDD group, as compared with 61% of the non-TDD group. Graft survival in the TDD patients was twice as good as the non-TDD patients at all time intervals. The patient survival rates were not significantly different between the two groups. TDD pretransplant favorably affects cadaveric renal allograft survival for at least five years.

Adult↗
PubMed1979

Pulmonary vascular response to endotoxin in normal and lymphocyte depleted sheep.

The cardiopulmonary effects of intravenously administered Escherichia coli endotoxin were studied in unanesthetized sheep. One group of animals was depleted of circulating T-lymphocytes while a non-depleted group served as control. T-lymphocyte depletion was accomplished by chronic thoracic duct drainage of lymph, removal of lymphocytes by continuous flow centrifugation and return of the cell free lymph intravenously. The T-lymphocyte depleted sheep demonstrated markedly obtunded increases in pulmonary arterial pressure and pulmonary vascular resistance following endotoxin when compared to the effects of the lipopolysaccharide in control animals. additionally, the lymphocyte depleted group showed a significant augmentation of myocardial contractility which occurred at the same time as marked systemic hypotension. This period of extreme hypotension following endotoxin is presumed to be accompanied by a reflex increase in the activity of the sympathetic nervous system. The control sheep, although equally hypotensive at this time, did not demonstrate a significant increase in myocardial contractility from the preendotoxin value. The results of these experiments indicate that T-lymphocytes may mediate some of the pathophysiological effects of bacterial endotoxin on the cardiovascular system.

Animals↗
PubMed1979

Results of parathyroidectomy for autonomous hyperparathyroidism.

Autonomous hyperparathyroidism occurred in 15% of 152 patients maintained by long-term home dialysis during the past nine years. Twenty-two patients with elevated serum parathormone levels and progressive bone disease in the presence of normal serum phosphate and calcium levels were treated by subtotal parathyroidectomy. All had parathyroid hyperplasia. Eighteen of the 22 patients are presently alive and undergo dialysis. Symptoms of bone pain, pruritus, and muscle cramps had improved in three fourths of the patients. The serum parathormone level decreased from a preoperative average of 576 muLEq/mL to an average of 188 muLEq/mL postoperatively. All 18 patients, observed for six to 77 months, showed improvement in x-ray films of their bone disease. The autonomous hyperparathyroidism of end-stage renal disease is corrected by subtotal parathyroidectomy, and the effect is sustained.

Adult↗
PubMed1977

The risk of anticoagulation in hemodialysis patients.

The risks of intermittent anticoagulation with heparin for hemodialysis and longterm anticoagulation with warfarin to prevent clotting of arteriovenous shunts were assessed in a group of 125 home dialysis patients. Over a 7-year period, there were nine bleeding complications attributable to heparin anticoagulation for an incidence of one complication for every 40 patient year on dialysis. In contrast, 20 of 48 patients anticoagulated with warfarin for an average of 2 years each, had a total of 50 hemorrhagic complications requiring 542 days in the hospital and 15 operative procedures. Concersion to an alternative form of vascular access, the internal arteriovenous fistula, obviated the need for warfarin therapy and its unacceptably high complication rate in this population of patients.

Blood Coagulation↗