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Biomedical subjects

J R Mitchell

Publications and source records attributed to J R Mitchell.

At least 235 records · Page 13Linked to original sources
PubMed1977

Renin-aldosterone profiling in hypertension.

Renin-aldosterone profiling was used to classify patients with hypertension: 243 patients with essential hypertension were classified by renin-urinary sodium indexing; 107 were reclassified by response to administration of furosemide and intravenous saline; 45 were further classified by response to a low-sodium diet. Arbitrary "normal ranges" were determined in 89, 32, and 38 volunteers, respectively. Patients with low-renin apparently do not have "high-volume" hypertension. Rather, they show a primary renal abnormality in renin secretion and become relatively deficient in angiotensin II and aldosterone when they are subjected to diuresis. They can maintain aldosterone secretion under normal conditions because their adrenal aldosterone receptor is supersensitive to angiotensin II. No evidence of abnormal sympathetic neural activity was found among the renin subgroups. Renin-aldosterone profiling in current clinical practice seems useful mainly in the detection of patients with curable forms of secondary hypertension. Aldosterone/renin ratios may be particularly helpful in diagnosis when obtained after a patient has undergone expansion or contraction of his extracellular fluid volume.

Aldosterone↗
PubMed1977

The aetiology of acute pulmonary embolism and the identification of high risk groups.

Although the cause of venous thrombosis remains obscure, preventive methods have been described. The fact that pulmonary embolism continues to cause a high death toll suggests that there is still a failure to recognize the need for prevention or to employ those prophylactic methods that are known to be effective. While it may be impracticable to offer prophylactic treatment to all patients at risk, an awareness of the important predisposing factors and the application of effective prophylaxis to high risk cases could bring about a reduction in the mortality rate from a disease that at present causes as many unnecessary deaths as motor vehicle accidents.

Acute Disease↗
PubMed1976

Warfarin sodium in prevention of deep venous thrombosis and pulmonary embolism in patients with fractured neck of femur.

In a prospective controlled randomised trial, the prophylactic value of warfarin sodium (in doses aimed at maintaining a "Thrombotest" value of 10% and given from the day of admission until independent mobility had been achieved or for 3 mo, whichever was the sooner) was assessed in 160 elderly patients who had sustained a fracture of the femoral neck. Treatment significantly reduced the frequency of deep venous thrombosis (D.V.T.), whether indicated by the 125I-fibrinogen test during life or assessed by detailed post-mortem studies. Pulmonary embolism was eliminated in treated patients, but the difference in mortality between the treatment and control groups was not significant, indicating that causes of death other than pulmonary embolism are of major importance in these elderly patients. A case is made out for prophylactic anticoagulation on a selective basis.

Aged↗
PubMed1976

Biochemical changes after hepatic injury by allyl alcohol and N-hydroxy-2-acetylaminofluorene.

Administration of hepatotoxic doses of allyl alcohol and N-hydroxy-2-acetylaminofluorene (N-OH-AAF) TO adult male rats produced periportal necrosis and functional derangement of the hepatic endoplasmic reticulum within 24 h. The rates of N-demethylation of ethylmorphine and p-hydroxylation of aniline were decreased 6 h following allyl alcohol administration, but cytochromes P-450 and b5 were unchanged. In contrast, administration of NOH-AAF decreased cytochromes P-450 and b5 and the rate of aniline p-hydroxylation, but did not change the rate of N-demethylation of ethylmorphine or the activities of cytochrome c reductase and glucose-6-phosphatase. No decrease was observed in the activity of the cytosol enzyme, DT diaphorase, following allyl alcohol treatment. The changes by these periportal hepatotoxins were compared with those produced both by central and midzonal hepatotoxins and with changes occurring in the liver after surgical partial hepatectomy.

Acetaminophen↗
PubMed1976

Isoniazid and iproniazid: activation of metabolites to toxic intermediates in man and rat.

Acetylhydrazine, a metabolite of isoniazid, a widely used antituberculosis drug, and isopropylhydrazine, a metabolite of iproniazid, an antidepressant removed from clinical use because of high incidence of liver injury, were oxidized by cytochrome P-450 enzymes in human and rat liver microsomes to highly reactive acylating and alkylating agents. Covalent binding of these metabolites to liver macromolecules paralleled hepatic cellular necrosis. The metabolites formed from these and probably other monosubstituted hydrazines are reactive electrophiles.

Animals↗
PubMed1976

Role of interferon in prophylaxis of rabies after exposure.

Rhesus monkeys were completely protected from rabies by a single dose of experimental, highly concentrated, rabies virus vaccine prepared from virus propagated in cultures of human diploid cells and administered several hours after infection with street rabies virus. Protection seemed to be related to the high antigenicity of the vaccine and to its ability to induce interferon in vaccinated animals. Only partial protection was afforded by one or three inoculations of less concentrated vaccines that were prepared from cultures of human diploid cells or primary hamster kidney cells and that were not capable of inducing interferon. The level of virus-neutralizing antibody induced by vaccination could not be correlated with the final outcome of the disease. The simultaneous inoculation of vaccine and interferon inducers (polyribocytidylic acid homopolymer pair or Newcastle disease virus) did not improve the results obtained with vaccine along, a fact which indicates that factors other than interferon and antibody may play an important role in the treatment of rabies after exposure.

Animals↗
PubMed1976

Biochemical changes after hepatic injury from toxic doses of acetaminophen or furosemide.

The effects of hepatotoxic doses of acetaminophen and furosemide on the function and composition of hepatic endoplasmic reticulum were compared from 3 to 24 h after administration. Acetaminophen caused a significant decrease in microsomal protein concentration as early as 3 h after its administration, but furosemide did not affect the microsomal protein concentration until 24 h after the dose. Both acetaminophen and furosemide decreased the concentrations of cytochrome P-450 and cytochrome b5 in microsomes, and the activity of microsomal ethylmorphine N-demethylase and aniline hydroxylase. Glucose-6-phosphatase and UDP-glucuronyl transferase were not significantly affected by acetaminophen or furosemide administration, and neither diene conjugation nor hepatic triglycerides were increased. Incorporation of 3H-L-leucine into liver proteins was decreased by 50% after the administration of either acetaminophen or furosemide.

Acetaminophen↗
PubMed1976

The role of biotransformation in chemical-induced liver injury.

The role of drug metabolism in chemical-induced liver injury is reviewed. Parameters for studying the formation of chemically reactive metabolites are discussed and the factors that alter the formation and covalent binding of reactive metabolites are selectively emphasized. Some of the experimental work that led to these concepts is discussed, especially the chemical toxicology of the hepatic injury produced by acetaminophen, bromobenzene, furosemide, isoniazid and iproniazid.

Acetaminophen↗