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Biomedical subjects

R A Branch

Publications and source records attributed to R A Branch.

At least 235 records · Page 13Linked to original sources
PubMed1973

Determinants of serum antipyrine half-lives in patients with liver disease.

Antipyrine has been used as a model drug to investigate the effects of liver disease on drug metabolism in man. A prolongation in antipyrine half-life (T(1/2)) was found in patients with liver disease, patients with chronic liver disease showing a greater increase than those with acute, reversible pathology. The most marked prolongation in T(1/2) was found in association with hypoalbuminaemia and hypoprothrombinaemia, suggesting that the cause for these changes was defective protein synthesis of microsomal enzyme protein. This hypothesis was supported by demonstrating that enzyme-inducing agents, which are known to increase the amount of microsomal enzyme protein, reduced the antipyrine half-life.

Adult↗
PubMed1972

A clinical and experimental study of platelet function in chronic renal failure.

Coagulation and platelet function studies were performed on 24 normal subjects and 29 patients with chronic renal failure due to various causes. Thrombocytopenia was uncommon in the uraemic patients but there was reduced platelet retention in glass bead columns and platelet aggregation with adenosine diphosphate (ADP) and thrombin was slower and less complete than normal. The rate of platelet disaggregation in uraemic patients was significantly reduced. The abnormalities tended to be more severe in more uraemic subjects. In normal subjects no inter-relationships were observed between the various measurements of platelet activity. In patients there were significant interrelationships between the measurements of platelet aggregation with ADP and thrombin and between the measurements of aggregation and retention in glass bead columns. It is suggested that if a common pathway is involved in these reactions it is adversely affected in uraemia. Plasma coagulation defects were uncommon and present in only five of the uraemic subjects. Impaired prothrombin consumption apparently due to defective platelet function was present in half the patients but was not detected by a kaolin activation method. Although platelet coagulation function was activated during ADP aggregation and disaggregation in normal and uraemic subjects, it did not correlate in the latter with impairment of aggregation. It is suggested that aggregation and activation of platelet coagulant activity are not necessarily related aspects of platelet function. An effect of uraemic plasma on normal platelets was demonstrated by mixing experiments consistent with a humoral cause for the uraemic platelet defects.

Adenosine Diphosphate↗
PubMed1971

Incidence of uraemia and requirements for maintenance haemodialysis.

The biochemistry laboratory records of a 400-bed general hospital serving a population of about 120,000 showed that during the three-year period 1966-8 inclusive 487 patients had at some stage during their admission a blood urea of 100 mg/100 ml or more. Ninety per cent. were aged 50 or over, 79% were 60 or over, and 52% were 70 or over.The case notes of all patients with renal failure admitted during 1966 and 1967 were examined together with those of patients under 60 admitted during 1968. Three observers agreed about the most likely cause of the renal failure in 90% of patients whose case notes were available, or 74% of the total. The raised blood urea was thought to be due to "prerenal" factors in 60% of the patients, to acute tubular necrosis in 80%, to obstructive uropathy in 12%, and to "intrinsic" renal disease in 20%. Renal failure precipitated by such factors as cardiac failure, chest infections, cerebrovascular accidents, and shock was particularly common in old people.The hospital survey and replies to a questionnaire sent to all general practitioners in the area suggest that in the three-year period 14 patients may have been suitable for treatment by maintenance haemodialysis or renal transplantation. This represents a rate of about 39 per million per year under the age of 60 and 28 per million per year under 50.

Adolescent↗
PubMed1971

Clinical evaluation of fibreoptic sigmoidoscopy employing the Olympus CF-SB colonoscope.

Fifty-one patients with large bowel disease were examined with the Olympus CF-SB fibreoptic colonoscope. With adequate bowel preparation and employing inhalational analgesia administered by a self-demand valve the whole sigmoid colon could be examined in the majority of patients within 30 minutes. In 23% of cases (12/51) the diagnosis was either made or confirmed by this procedure alone. Fibreoptic sigmoidoscopy is especially helpful in patients with either equivocal or failed barium enemas and is indicated in patients with unexplained rectal bleeding, extending the search for polyps and cancer, and studying patients with inflammatory bowel disease.About one quarter of biopsies taken from a flat mucosal surface with the Olympus flexible biopsy forceps may be insufficient for detailed histology due to their small size. For this reason multiple biopsies may be taken. Adequate biopsies were always obtained from projecting lesions and could be very accurately sited. Colour photography employing automatic exposure control is used to supplement the information obtained. It is concluded that fibreoptic sigmoidoscopy is a valuable additional investigation in selected patients with suspected disease of the large bowel and to date has been without complications.

Anesthesia, Inhalation↗
PubMedDate not supplied

Hepatic and extrahepatic glucuronidation of lorazepam in the dog.

The pharmacokinetic disposition of lorazepam was investigated in sham-operated aneshetized dogs, dogs with hepatic devascularization, and dogs with total splanchnic devascularization following i.v. administration of 0.3 mg per kg of the drug. In sham-operated dogs, lorazepam distribution was extensive (100 +/- 15.2 liters) and clearance approximately expected liver blood flow (971 +/- 91 ml per min). Lorazepam glucuronide levels in plasma rose rapidly in the first hour and reached a plateau by 5 hr. Urinary recovery of the conjugate in 5 hr was 45% of administered dose. Hepatic devascularization resulted in 39% reduction in distribution volume, and 89% reduction in clearance; however, there was still 105 +/- 88 ml per min of extrahepatic lorazepam clearance. Five-hour urinary recovery of conjugate decreased by 80%. Total splanchnic devascularization resulted in 37% further reduction in extrahepatic clearance, almost complete inhibition of urinary recovery of conjugate, and further reduction in the volume of distribution. It is concluded that the liver is the major site for lorazepam metabolism in dogs; however, appreciable extrahepatic metabolism occurs, partly in nonhepatic components of the splanchnic organs which act as a reservoir during drug distribution.

Animals↗
PubMedDate not supplied

Drugs as indicators of hepatic function.

It is well recognized that liver disease may influence the disposition of many drugs. Conversely, it has been suggested that knowledge of the disposition of a model drug might provide an index of certain aspects of hepatic function. This review discusses the physiology of drug disposition and indicates how recent progress in understanding the determinants of drug disposition has provided useful indices of individual aspects of hepatic function. Topics which are discussed are the interpretation of pharmacokinetic parameters as indices of hepatic function, including half-life clearance, and intrinsic clearance. Utilizing the "intact hepatocyte hypothesis" as an operational model, an approach is described that uses the pharmacokinetic disposition of high and low intrinsic clearance drugs following p.o. and i.v. administration to provide quantitative estimates of hepatic function, flow to functioning hepatocytes, and the extent of portasystemic shunting through the liver. Thus, the theoretical basis for quantitation of certain aspects of hepatic function are available. It remains to be determined whether these indices will provide clinically useful measures to follow the natural history of hepatic disease.

Aminopyrine↗