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Biomedical subjects

W F Clark

Publications and source records attributed to W F Clark.

At least 73 records · Page 4Linked to original sources

Failure to demonstrate renal uptake of labelled platelets in chronic glomerulonephritis.

1. Renal localization of autologous 111In-labelled platelets was studied in patients with chronic glomerulonephritis. External imaging was performed with a gamma-camera fitted with a medium energy collimator and the images were collected by a computer. 2. Images of 111In-labelled platelet distribution showed that there was a marked contribution to the radioactivity within each renal silhouette from adjacent spleen or liver. It was not possible to demonstrate renal accumulation of 111In-labelled platelets. 3. The application of 111In-labelled platelets to the study of intrarenal platelet consumption in chronic glomerulonephritis is limited by the sensitivity of current techniques and the scatter from adjacent splenic and hepatic radioactivity.

Adult↗

Acute interstitial nephritis due to drugs: Review of the literature with a report of nine cases.

Acute interstitial nephritis due to drugs commonly presents as acute renal failure and may be commoner than is presently realized. Drugs implicated include not only methicillin and other penicillins but also diuretics and nonsteroidal anti-inflammatory agents. The mechanism of injury likely involves an immunologic disturbance, possibly a delayed hypersensitivity reaction. Differential diagnosis from other causes of acute renal failure may be difficult, but coincident evidence of an acute allergic reaction may help, as may the detection of eosinophils in the urine or avid uptake of 67Ga by the kidneys. Definitive diagnosis may require renal biopsy, which will reveal normal glomeruli and a patchy but usually heavy interstitial infiltrate with lymphocytes, plasma cells, and eosinophils. Diagnosis of acute interstitial nephritis is important, because withdrawal of the offending agent will usually result in rapid improvement in renal function, and steroid therapy may reduce residual chronic renal damage.

Acute Disease↗

Platelet aggregation and release associated with immune complex formation in pig plasma.

The correlation between the formation of immune complexes and platelet aggregation and release was studied in pig plasma. The pigs were hyperimmunized with a multivalent antigen, horse ferritin. The ability of the antisera to form precipitating (insoluble) and soluble immune complexes was measured and correlated with the concomitant platelet aggregation and release of serotonin and LDH. Aggregation ws measured by aggregometry, differential centrifugation, and electron microscopy, and release by [14C]serotonin and LDH loss. Aggregation correlated with release (r = 0.84, p < 0.001), but no correlation was found between antibody titer or varying antigen concentrations and platelet [14C]serotonin release. A positive correlation was found between platelet [14C]serotonin release and precipitating immune complexes (r = 0.68, p < 0.001) and a negative correlation with soluble complexes (r = -0.78, p < 0.001). Maximal precipitation of insoluble complexes was complete within 30 sec or less, was independent of temperature, and obeyed the laws of mass action and of optimal ratios of antigen and antibody concentrations (equivalence zone). Platelet aggregation and serotonin release in plasma and precipitating immune complex formation were both maximal at antigen-antibody equivalence and undetectable at marked antigen or antibody excess. These results suggest that immune complex precipitation may initiate platelet aggregation and release in plasma and that the reaction may be at least partially blocked by soluble immune complexes.

Animals↗

Intrarenal insoluble immune complex formation.

In the rabbit, intrarenal insoluble immune complex formation results in a mesangiopathic lesion with focal glomerulosclerosis. In swine we have examined in vivo the relation between intrarenal insoluble immune complex formation, glomerular deposition and associated renal vein platelet and basophil changes, pattern of scarring and degree of persistent functional impairment. Swine, as opposed to rabbits, were selected because their platelets more closely resemble human platelets in immune reactions. Direct renal antigen challenge was performed on two occasions at weekly intervals in swine maintained in persistent antibody excess. Immune complex glomerular deposition was observed in renal biopsies performed 20 minutes following antigen challenge. A significant renal vein thrombocytopenia and decline in basophil count was detected at the time of intrarenal insoluble immune complex formation. When basophil count was expressed relative to white cell count change, a weak association was detected. These in vivo changes in contrast to the soluble immune complex challenge in the rabbit has led us to postulate that in this model the direct platelet spontaneously pecipitating (insoluble) immune complex reaction may provide the permeability factors to facilitate glomerular immune complex deposition. A scarring mesangiopathic lesion with a persistent decrement in glomerular filtration is noted in swine studied one week after two consecutive renal antigen challenges. This type of intrarenal immune reaction results in a pattern of functional and histologic damage observed in progressive mesangiopathic forms of glomerulonephritis in man.

Animals↗

Serum vitamin A levels and associated abnormalities in patients on regular dialysis treatment.

Multivitamin preparations are commonly administered to regular dialysis treatment (RDT) patients. Serum Vitamin A was measured in 72 patients on RDT. Elevated serum Vitamin A levels (102.29 +/- 26.95 microgram/dl [3.57 +/- 0.94 mumoles/l]) were found in the dialysis population (normal 40.98 +/- 6.71 microgram/dl [1.43 +/- 0.23 mumoles/l]; P less than 0.0005). Serum Vitamin A levels increased with duration (months) of dialysis but not with frequency of dialysis (twice or thrice weekly). Patients taking a VitaminA-containing multivitamin preparation had higher serum Vitamin A levels than those on a non-Vitamin A supplemented diet. Bilaterally nephrectomized patients had the highest serum Vitamin A levels while patients with obstructive uropathy had the lowest levels. Serum Vitamin A levels did not correlate with symptoms of uremia. Positive correlations were found with serum levels of calcium, cholesterol and triglycerides. Patients receiving a Vitamin A supplement had higher serum cholesterol levels than non-supplemented patients. Vitamin A might be a factor in the high incidence of cardiovascular disease in RDT patients. We therefore advise discontinuing the long-term administration of Vitamin A-containing multivitamin supplements to patients on RDT.

Adult↗

Heparin neutralizing activity in patients with renal disease on maintenance haemodialysis.

Heparin neutralizing activity (HNA) was increased in plasma of patients with end-stage renal disease treated by maintenance haemodialysis. It was not raised in non-dialyzed patients with chronic renal failure, nor in patients with normal renal function who had been exposed to the extracorporeal circulation of the heart-lung bypass 48--72 hr before testing. It is postulated that the trauma of extracorporeal circulation causes platelets to release HNA which is not cleared by the dialysis membranes of the artificial kidney but is by the human kidney. This may have therapeutic implications for heparin dosage schedules during haemodialysis.

Coronary Artery Bypass↗

Immunologic findings, thrombocytopenia and disease activity in lupus nephritis.

Twenty patients with nephritis due to systemic lupus erythematosus were followed up for a mean of 34 months after renal biopsy with serial determinations of total serum complement and C3 and C4 concentrations, binding of deoxyribonucleic acid (DNA), antinuclear antibody pattern and platelet count. There were 25 episodes of nonhematologic observed disease activity in 16 of the 20 patients; elevated DNA binding and thrombocytopenia correlated well with these episodes. The mean platelet count during episodes of observed disease activity was 96 +/- 42 X 10(9)/L, which was significantly different from the mean count of 248 +/- 90 X 10(9)/L during disease quiescence. The proportion of false-positive results with the immunologic tests varied from 25% to 67% and with platelet counts it was 11%. It is suggested that thrombocytopenia may be a simple and accurate index of disease activity in lupus nephritis.

Antibodies, Antinuclear↗

Protective effect of prostaglandin [PGE2] and in glycerol-induced acute renal failure in rats.

1. Acute renal failure was induced in female Sprague-Dawley rats by the subcutaneous injection of glycerol. 2. Four groups of rats were studied; all animals received a glycerol challenge. Group A (control) were sham-operated only, group B received an infusion of sodium chloride solution (150 mmol/l; saline) for 24 h, group C received an infusion containing prostaglandin E2 (PGE2, 1.7 micronmol/l) in saline and group D a solution containing PGE2 (3.4 micronmol/l) in saline. 3. All rats were killed 48 h after glycerol challenge. The degree of renal impairment was assessed by serum creatinine concentration, which did not differ in sham-operated animals and the group receiving saline alone. The group of rats receiving the lower dose dose of PGE2 has a significantly lower mean serum creatinine concentration than the saline-infused control rats (P less than 0.0025). Creatinine concentration was further lowered by the higher dose of PGE2 but there was not a significant difference in the number of rats showing severe tubular necrosis histologically. 4. The study demonstrates that intravenous infusion of prostaglandin E2 has a protective influence on glycerol-induced renal failure in the rat; the protection afforded may be due to the vasodilator effect of PGE2 and/or an effect on glomerular permeability.

Acute Kidney Injury↗

Ristocetin and the thrombin clotting time.

The addition of the antibiotic ristocetin to plasma accelerated the thrombin clotting time (TCT) in 20 out of 22 subjects. Prior incubation of ristocetin with thrombin or plasma did not alter its effect on the TCT. Ristocetin accelerated clotting greatly at low but not at high levels of thrombin. A simple linear correlation between heparin concentrations and the TCT was demonstrated when ristocetin at 2.5 mg per ml was added to plasma containing between 0.05 and 0.5 unit of heparin per ml. There are implications for assay procedures involving heparin and the TCT.

Blood Coagulation Tests↗

Correctable factors contributing to the anemia of dialysis patients.

Twelve out of 60 patients undergoing regular dialysis treatment were found to have an inappropriate degree of anemia. This was not related to duration on dialysis, square meter hours of dialysis or underlying renal disease. Radioactive methods were used to determine blood losses in the dialyzer, lines, at cannulation and from the gastrointestinal tract in the "anemic" patients. Ten of these patients were found to have excessive blood losses and appropriate measures to correct this produced a significant rise in hematocrit in all cases.

Anemia↗

Intrarenal platelet consumption in the diffuse proliferative nephritis of systemic lupus erythematosus.

1. Platelet survival and an index of the localization of platelets in the kidney were studied in patients with the proliferative nephritis of systemic lupus erythematosus, either focal or diffuse, and in control subjects. Platelet survival was reduced in patients with proliferative lupus nephritis, more in those with diffuse rather than focal renal involvement. 2. The index of renal platelet localization in patients with diffuse proliferative nephritis suggested an intrarenal platelet consumption not found in other groups. 3. A patient with the classical platelet autoantibody disease, idiopathic thrombocytopenic purpura, also showed reduced platelet survival but localization of platelets was in the spleen rather than the kidney. 4. Intrarenal platelet consumption in diffuse proliferative lupus nephritis may be an epiphenomenon of pre-existing scarring or platelet aggregation secondary to immune complex-formation, which contributes to the progressive sclerosing lesions of this form of nephritis.

Adult↗