Search PubMed⌕ Search

Biomedical subjects

J R Mitchell

Publications and source records attributed to J R Mitchell.

At least 145 records · Page 8Linked to original sources
PubMed1983

Venous thrombosis in diabetes mellitus.

The incidence over 7 days of isotopically-detected calf and popliteal vein thrombosis was determined in a group of 60 diabetic patients admitted to hospital with myocardial infarction, heart failure or stroke, or for abdominal surgery. The result was compared with the incidence in 60 control subjects matched for age, sex and presenting diagnosis. Twenty-one diabetic patients developed positive 125I-fibrinogen scans, compared with 19 control subjects; this difference is not significant. We conclude that diabetes is not associated with an enhanced risk of thrombosis in veins. It is therefore possible that the arterial and capillary abnormalities found in diabetes may arise from mechanisms other than a generalised thrombotic tendency.

Aged↗
PubMed1983

Mechanism of action of N-acetylcysteine in the protection against the hepatotoxicity of acetaminophen in rats in vivo.

N-Acetylcysteine is the drug of choice for the treatment of an acetaminophen overdose. It is thought to provide cysteine for glutathione synthesis and possibly to form an adduct directly with the toxic metabolite of acetaminophen, N-acetyl-p-benzoquinoneimine. However, these hypothese have not been tested in vivo, and other mechanisms of action such as reduction of the quinoneimine might be responsible for the clinical efficacy of N-acetylcysteine. After the administration to rats of acetaminophen (1 g/kg) intraduodenally (i.d.) and of [(35)S]-N-acetylcysteine (1.2 g/kg i.d.), the specific activity of the N-acetylcysteine adduct of acetaminophen (mercapturic acid) isolated from urine and assayed by high pressure liquid chromatography averaged 76+/-6% of the specific activity of the glutathione-acetaminophen adduct excreted in bile, indicating that virtually all N-acetylcysteine-acetaminophen originated from the metabolism of the glutathione-acetaminophen adduct rather than from a direct reaction with the toxic metabolite. N-Acetylcysteine promptly reversed the acetaminophen-induced depletion of glutathione by increasing glutathione synthesis from 0.54 to 2.69 mumol/g per h. Exogenous N-acetylcysteine did not increase the formation of the N-acetylcysteine and glutathione adducts of acetaminophen in fed rats. However, when rats were fasted before the administration of acetaminophen, thereby increasing the stress on the glutathione pool, exogenous N-acetylcysteine significantly increased the formation of the acetaminophen-glutathione adduct from 57 to 105 nmol/min per 100 g. Although the excretion of acetaminophen sulfate increased from 85+/-15 to 211+/-17 mumol/100 g per 24 h after N-acetylcysteine, kinetic simulations showed that increased sulfation does not significantly decrease formation of the toxic metabolite. Reduction of the benzoquinoneimine by N-acetylcysteine should result in the formation of N-acetylcysteine disulfides and glutathione disulfide via thiol-disulfide exchange. Acetaminophen alone depleted intracellular glutathione, and led to a progressive decrease in the biliary excretion of glutathione and glutathione disulfide. N-Acetylcysteine alone did not affect the biliary excretion of glutathione disulfide. However, when administered after acetaminophen. N-acetylcysteine produced a marked increase in the biliary excretion of glutathione disulfide from 1.2+/-0.3 nmol/min per 100 g in control animals to 5.7+/-0.8 nmol/min per 100 g. Animals treated with acetaminophen and N-acetylcysteine excreted 2.7+/-0.8 nmol/min per 100 g of N-acetylcysteine disulfides (measured by high performance liquid chromatography) compared to 0.4+/-0.1 nmol/min per 100 g in rats treated with N-acetylcysteine alone. In conclusion, exogenous N-acetylcysteine does not form significant amounts of conjugate with the reactive metabolite of acetaminophen in the rat in vivo but increases glutathione synthesis, thus providing more substrate for the detoxification of the reactive metabolite in the early phase of an acetaminophen intoxication when the critical reaction with vital macromolecules occurs.

Acetaminophen↗
PubMed1983

Influence of cooling rates and extenders upon post-thaw viability of bovine spermatozoa packaged in .25- and .5-ml French straws.

Post-thaw survival of bovine spermatozoa was compared for semen packaged in either .25- or .5-ml French straws and frozen at three different cooling rates in moving N2 vapor. Using a split ejaculate technique, nine ejaculates were extended in heated skim milk, egg yolk-citrate and egg yolk-Tris and packaged in .25- and .5-ml French straws. Semen packaged in the .25- and .5-ml straws was frozen simultaneously at initial N2 vapor temperatures of -140, -110 or -80 C. Semen was thawed in a water bath at 35 C for 1 min. Recovery of spermatozoa was evaluated immediately post-thaw (0 h) and again after 3 h of incubation at 37 C. Motility estimates and motility counts were made using phase contrast microscopy; percentage of spermatozoa possessing intact acrosomes was quantitated using differential interference contrast microscopy. There was a packaging unit X cooling rate interaction (P less than .05) for all three viability measures. However, there was no consistent trend with regard to cooling rate or packaging unit among the three extenders examined. Post-thaw viability for each characteristic varied (P less than .01) among extenders, but not for cooling rate or packaging unit (P greater than .05). Spermatozoa extended and frozen in egg yolk-Tris had greater (P less than .05) post-thaw viability than those extended in skim milk or egg yolk-citrate regardless of cooling rate or volume of the seminal package.

Acrosome↗
PubMed1983

Plasma glutathione and glutathione disulfide in the rat: regulation and response to oxidative stress.

Plasma GSH and GSSG concentrations were examined after the administration of compounds that deplete intracellular GSH either by adduct formation or by production of oxidative stress. A modified assay based on the GSSG reductase method was developed that minimizes the artifactual auto-oxidation of GSH to GSSG and mixed disulfides by rapid addition of bis(3-carboxy-4-nitrophenyl)disulfide or N-ethylmaleimide directly to whole blood or tissue samples. Control arterial plasma GSH and GSSG concentrations were found to be 16.5 +/- 0.7 and 0.3 +/- 0.1 microM, respectively. Depletion of GSH by fasting or by the administration of acetaminophen or diethyl maleate was associated with a proportional decrease in the arterial plasma GSH concentrations (r = 0.94) consistent with the hypothesis that the liver in vivo is a major source of plasma GSH. Diquat and t-butyl hydroperoxide, but not acetaminophen or diethyl maleate, elicited large increases in arterial plasma GSSG concentrations (17- and 115-fold, respectively) and several-fold increases in biliary GSSG levels without markedly increasing hepatic GSSG levels (2.7- and 1.2-fold, respectively). In contrast, treatment with paraquat produced substantial increases in arterial plasma GSSG levels (22-fold) without large increases in the bile (3-fold). Assessment of the arteriovenous difference for GSSG across the lungs after paraquat administration demonstrated that the lung may be a significant source of plasma GSSG. In conclusion, plasma GSH concentrations appear to reflect mainly intrahepatic GSH concentration, whereas plasma GSSG appears to arise from both hepatic and extrahepatic sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1982

Platelet aggregation in whole blood determined using the Ultra-Flo 100 Platelet Counter.

The Ultra-Flo 100 Whole Blood Platelet Counter has proved a useful tool for measuring platelet aggregation in whole blood, the extent of aggregation being deduced from the number of single platelets that remain. The technique has allowed us to show that platelets aggregate spontaneously in citrated blood and in heparinized blood but not in whole blood collected into EDTA. The aggregation occurs during storage but its rate is enhanced by stirring and it occurs more readily when the whole blood has been exposed to plastic rather than glass. It occurs much more readily in whole blood from some individuals than from others and the process may involve adenosine diphosphate (ADP). The rate of aggregation in whole blood is enhanced by several aggregating agents including collagen, ADP and sodium arachidonate which are more usually studied in platelet-rich plasma.

Adenosine Diphosphate↗
PubMed1982

Early reporting of myocardial infarction: impact of an experiment in patient education.

Many deaths from myocardial infarction occur before medical help is sought. A campaign was mounted in Nottingham ("Nottingham Heartwatch") to encourage early reporting. A total of 13 828 men and women aged 40 and over registered with three general practices were asked to telephone a hospital-based number if they developed chest pain lasting for more than 10 minutes. Patients from study practices reported chest pain earlier after our invitation than they had before and also earlier than patients from control practices. While accepting the advice to call early some patients from the study practices ignored our special number and telephoned their general practitioner. The calls received on the Heartwatch line yielded a lower percentage of definite and probable infarcts than the calls received by the patients' own doctors. The way in which the characteristics of the study practices might have influenced this difference is discussed since it has considerable implications for larger-scale attempts to bring patients with suspected myocardial infarction under medical care at the earliest opportunity.

Adult↗
PubMed1982

Rhesus diploid rabies vaccine (adsorbed), a new rabies vaccine. Results of initial clinical studies of preexposure vaccination.

To meet the need for a safe, efficacious, and low-cost rabies vaccination program, the Michigan Department of Public Health developed a new rabies vaccine: rhesus diploid rabies vaccine, adsorbed (RDRV). Initial clinical studies were conducted in 534 volunteers using preexposure protocols consisting of two injections of RDRV given 1, 2, or 4 weeks apart. This new rabies vaccine induced an excellent rabies virus antibody response two to three weeks after vaccination: antibody levels were superior to those reported after duck embryo rabies vaccine and were similar to those reported with human diploid rabies vaccine. In addition, vaccination with RDRV was associated with an acceptable level of local and constitutional symptoms.

Adolescent↗
PubMed1982

Arrest and extravasation of neoplastic cells. An electron microscopy study of serial sections at sequential stages.

The morphological aspects of the arrest and extravasation of malignant cells of human origin (K-562 cell line) in the lungs of athymic (nude) and asplenic-athymic (lasat) mice were studied by electron microscopy examination of serial sections. The specimens were obtained at sequential stages after the sc inoculation into newborn mice of 10(7) malignant cells. K-562 cells (10(5)) were also injected iv into control groups of nude and lasat mice to assess the influence of the route of inoculation on the in vivo behavior of K-562 cells. Our results demonstrated that K-562 cells were arrested and proliferated within the pulmonary capillaries without the participation of platelets or fibrin. The neoplastic cells extravasated by attrition and penetration of the endothelium (rather than by diapedesis) and continued to proliferate in the interstitial tissue of the lung, developing into neoplastic nodules. Following iv injection, K-562 cells induced the formation of platelet-tumor cell aggregates within the pulmonary capillaries. However, under these conditions, the neoplastic cells did not adhere to the endothelium nor did they proliferate or extravasate. These aggregates were flushed out by the circulation, restoring the permeability of the capillaries.

Animals↗
PubMed1982

Absence of morphological, chromosomal and antigenic changes in the K-562 cell line growing as localized or disseminated tumours in nude mice.

Transplantation of K-562 cells into adult and newborn nude mice led to the development of localized s.c. and disseminated myelosarcomas, respectively. This age-associated, changing pattern of in vivo proliferation of K-562 cells derived from a single aliquot was consistently repeated throughout sequential passages. The only variable in this experimental system was the age of the recipient mice. Not only did the mice have an identical genetic background, but also the transplanted K-562 cells were derived from a single culture passage. As shown by cytological and histological examinations, the characteristic morphology and percentage composition of the subpopulations of the K-562 cell line were preserved in successive in vitro and in vivo passages. The K-562 cells had no prevailing phenotypic traits which could be associated with the growth either in the s.c. tissue or in the viscera. Furthermore, the cells maintained the human karyotype, including their typical chromosomal abnormalities and antigenic determinants, as demonstrated by the binding of a specific antibody, throughout all passages. Our results demonstrate that heterotransplanted K-562 cells may change their behaviour in vivo without undergoing modifications associated with different types of growth. These findings would indicate that the ability of neoplastic cells to proliferate in various environments (metastases) is not the consequence of predetermined cellular characteristics but is functionally conditioned.

Animals↗
PubMed1982

The distribution and associations of blood pressure in an adolescent population.

In this report we describe the distributions of blood pressure and its associations in adolescence. Six hundred and twenty-five subjects aged 13 to 18 were drawn from three general practices in different urban and rural settings. Systolic pressures were higher and rose with age in boys (mean = 119 mm Hg) compared with girls (mean = 114 mm Hg), who showed no age association. Diastolic pressures (phase 5) were higher in girls (mean = 64 mm Hg) than in boys (mean = 60 mm Hg) and showed no association with age in either sex. Initial blood pressures were generally higher than those recorded after a further five minutes' rest in the sitting position, although diastolic pressures rose on the second reading in the older subjects. Systolic pressures of subjects from the suburban practice and in the late autumn were relatively low; diastolic pressures tended to be lower in the spring and in subjects from the rural practice. Systolic pressures were lower in the morning and this was found to be primarily related to fasting status. Individuals with a positive family history of hypertension had significantly higher blood pressures than those with a negative history. Boys who frequently played sports had lower diastolic pressures, largely accounting for the above sex difference. We conclude that although blood pressure measurement in adolescence is a difficult screening procedure it should be offered to selected groups such as those with a family history of hypertension.

Adolescent↗
PubMed1982

Relevance of lipids to heterotransplantation of human malignancies.

Although the transplantation of human neoplasms in immunodeficient mice is now a well-established procedure, the majority of primary malignancies cannot be successfully maintained for long periods of time in adult athymic (nude) and asplenic-athymic (lasat) mice. Various lipids such as cholesterol, cholesterol oleate, stearic and palmitic acid esters markedly depress the RES phagocytic activity and immunocompetence of mammals. In view of the immunosuppressive properties of certain lipids and in order to graft and grow as many tumors as possible, further studies into the effects of lipids on the growth of heterotransplanted human tumors is warranted. Lipids may enhance local growth and facilitate the development of metastases rarely seen in nude and lasat mice bearing xenogeneic cancer cells. Lipids may accelerate human malignant cell proliferation in mice by both depressing further the defense of host and modifying the cancer cell membrane. The relationship of lipids to the onset and progression of 'spontaneous' tumors in humans is not known.

Cholesterol↗