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Biomedical subjects

D Roberts

Publications and source records attributed to D Roberts.

At least 271 records · Page 15Linked to original sources
PubMed1991

Immunolocalization of tumour necrosis factor alpha in lung tissue from patients dying with adult respiratory distress syndrome.

Using a mouse monoclonal antibody raised against recombinant human tumour necrosis factor alpha (TNF alpha), we have studied immunostained paraffin-embedded autopsy lung tissues from 13 patients dying with adult respiratory distress syndrome and 10 control patients dying of unrelated conditions. Material from 12 of the 13 cases showed positive staining, strong in six, less strong in the remaining six. TNF alpha was located principally within epithelial cells resembling type II pneumocytes in both early and late stages of adult respiratory distress syndrome. In the early stages the TNF alpha positive cells were scattered and appeared disorganized, but in later cases they formed an epithelium. The cells were confirmed as epithelial by their staining pattern with monoclonal antibodies reactive with epithelial, cytokeratin and macrophage antigens, and by double staining for epithelial membrane antigen and TNF alpha. In the control group, staining for TNF alpha was confined to very occasional plump type II pneumocytes, and a weak reaction in bronchial lining cells. Macrophages were only weakly stained in either group. It is suggested that TNF alpha is synthesized (or possibly absorbed) by type II pneumocytes and may be involved in the production of, or recovery from, adult respiratory distress syndrome.

Adult↗
PubMed1991

Anthropometry and obesity in myelomeningocele.

Anthropometric data on 110 myelomeningocele (MMC) subjects in relation to age, sex, level of lesion and ambulation were studied to investigate growth and the occurrence of obesity in MMC. In 52 subjects, indices of obesity were validated against body composition analysis of total body fat (%BF) using body potassium and body water techniques. Most subjects were short and light compared to reference data and became relatively shorter and heavier with age. Overall trunk growth was not affected by the level of lesion, but sitting height was affected by kyphoscoliosis. Arm spans were similar to reference data, but were significantly greater in wheelchair users. Leg length was greatest in those who walked. Body composition data showed excess adipose in many MMC subjects, this tendency increasing with age. When correlated with %BF determined from body composition analysis, common clinical indices of obesity had variable r values (wt/ht2 0.78; wt/sitting ht2 0.77; upper arm fat area 0.75; triceps skinfold 0.74; wt/arm span2 0.68, with the 4 skinfold method correlating best, 0.82). Anthropometric measures, taken with cognizance of level of disability and mobility, can accurately assess body growth and the occurrence of obesity in MMC. The influence of ambulatory activity in promoting normal growth is emphasized.

Adolescent↗
PubMed1991

Examination of retail chickens and sausages in Britain for vero cytotoxin-producing Escherichia coli.

Samples from chickens and pork sausages were examined for the presence of Vero cytotoxin-producing Escherichia coli by using DNA probes for the Vero cytotoxin genes. Hybridization was detected in 25% of the 184 sausage samples, but none of the chickens was positive. No E. coli O157:H7 strains were isolated, and serotyping showed that the Vero cytotoxin-producing E. coli strains belonged to eight different O serogroups and that six strains had an unidentifiable O antigen.

Animals↗
PubMed1991

Renal interstitial hydrostatic pressure and PGE2 in pressure natriuresis.

The present study tested the hypothesis that the presence of renal prostaglandin E2 (PGE2) is necessary for full natriuretic response to increased renal interstitial hydrostatic pressure (RIHP) during increased renal perfusion pressure (RPP). In control untreated pentobarbital-anesthetized dogs (n = 7), fractional excretion of sodium (FENa) was 1.17 +/- 0.48, 1.07 +/- 0.24, and 2.69 +/- 0.57% at RPP of 90, 122, and 148 mmHg, respectively. These changes in FENa were associated with effective renal blood flows (ERBF) of 1.43 +/- 0.20, 1.49 +/- 0.23, and 1.99 +/- 0.40 ml.min-1.g kidney wt-1, respectively. Similarly, glomerular filtration rate (GFR) was 0.53 +/- 0.10, 0.71 +/- 0.10, and 0.72 +/- 0.14 ml.min-1.g kidney wt-1, respectively. Treatment with indomethacin, a cyclooxygenase inhibitor, significantly lowered FENa to 0.45 +/- 0.13, 0.77 +/- 0.21, and 1.19 +/- 0.59% at RPP of 91, 121, and 146 mmHg, respectively. Additionally, indomethacin treatment lowered ERBF (0.51 +/- 0.15, 0.52 +/- 0.10, and 0.85 +/- 0.21 ml.min-1.g kidney wt-1) and GFR (0.28 +/- 0.09, 0.34 +/- 0.09, and 0.47 +/- 0.09 ml.min-1.g kidney wt-1) at low, middle, and high RPP, respectively. PGE2 replacement (n = 6) into renal artery at 0.01 microgram.min-1.kg body wt-1 returned FENa, ERBF, and GFR to control levels over the same range of RPP, whereas prostacyclin (PGI2) infusion (n = 7) at the same dose did not. RIHP was 4.2 +/- 1.2, 4.2 + 0.5, and 7.5 +/- 1.7 mmHg with increasing RPP in control untreated group and increased to similar levels with indomethacin treatment and during PGE2 or PGI2 replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Diltiazem overdose: pharmacokinetics of diltiazem and its metabolites and effect of multiple dose charcoal therapy.

We describe a 38 year-old female who ingested 900 mg of diltiazem. She experienced hypotension, bradycardia and heart block but responded well to supportive care that included normal saline infusion and vasopressors. Calcium administration was not beneficial. Serial plasma concentrations of diltiazem, N-demethyldiltiazem and desacetyldiltiazem were quantified. By comparing the elimination half-life for diltiazem with historical controls, it is concluded that multiple dose charcoal therapy was not beneficial for our patient.

Adult↗
PubMed1990

Smoking cessation in the workplace: evaluation of relapse factors.

Relapse factors associated with a well-supported worksite smoking cessation program were examined in a prospective study. Of 104 employee-participants, 81 (78%) were confirmed as abstinent at 8 days after quit day. Forty-six employees (44%) continued to report total abstinence at 1 year. Stepwise regression analysis of baseline variables found two significant, but weak, predictors of 1-year smoking status: Fagerstrom score and number of other smokers residing in the home. Analysis of tobacco withdrawal symptom data of confirmed abstainers found only self-reported anxiety scores to be predictive of smoking status at 1 year. Early abstainers with elevated anxiety scores appear to be at high risk for smoking relapse.

Anxiety↗
PubMed1990

Acute embolic lower limb ischaemia is associated with decreased red cell deformability.

Red cell deformability is an important determinant of peripheral blood flow. In this study the red cell filtration rate (RFR) was measured in 17 patients admitted for acute embolic lower limb ischaemia. The severity of the limb ischaemia on admission was scored from 0 to 6 depending on the degree of pain, and loss of motor and sensibility functions in the ischaemic extremity. Patients who presented with very severe ischaemia on admission underwent early embolectomy whereas those with less severe ischaemia (range from 0 to approximately 3 in ischaemic score) initially were treated conservatively with heparin. Red cell filtration rate was assessed with a standard microfiltration method and expressed in microliters/sec. On admission the RFR averages 30 +/- 5 microliters/sec (mean +/- S.D.), significantly lower than the corresponding value in a normal population of similar age (50 +/- 5 microliters/sec). There was an inverse relationship (r = 0.74, P less than 0.001 by use of linear regression analysis) between the ischaemic score and the RFR on admission, with low RFR values being related to high ischaemic scores. Forty-eight hours after revascularisation, the RFR had improved significantly in the patients having undergone successful revascularisation, whereas it was unchanged in conservatively treated patients. It is concluded that patients with acute embolic lower limb ischaemia have an impaired red cell filtration rate suggesting decreased red cell deformability, the impairment being related to the severity of the ischaemia. A poor red cell filtration rate on admission is related to increased risk of postoperative gangrene and/or cardiac death. Successful revascularisation, but not conservative heparin treatment is associated with increasing deformability.

Aged↗
PubMed1990

Red kidney bean poisoning in the UK: an analysis of 50 suspected incidents between 1976 and 1989.

Between July 1976 and February 1989, 50 incidents of suspected red kidney bean poisoning were reported in the UK. Nine incidents in which nausea, vomiting and diarrhoea developed within 1-7 h of ingestion, were confirmed by the detection of haemagglutinin in the beans. The diagnosis was made on a further 23 incidents on the basis of symptoms, incubation time and the description of preparation of beans prior to consumption. The haemagglutinin (lectin), which occurs naturally in the red kidney bean, is inactivated by thorough cooking of well soaked beans. In many of the outbreaks reported the implicated beans were consumed raw or following an inadequate heat process.

Cooking↗
PubMed1990

Identification and preliminary characterization of protein-cysteine farnesyltransferase.

Ras proteins must be isoprenylated at a conserved cysteine residue near the carboxyl terminus (Cys-186 in mammalian Ras p21 proteins) in order to exert their biological activity. Previous studies indicate that an intermediate in the mevalonate pathway, most likely farnesyl pyrophosphate, is the donor of this isoprenyl group. Inhibition of mevalonate synthesis reverts the abnormal phenotypes induced by the mutant RAS2Val-19 gene in Saccharomyces cerevisiae and blocks the maturation of Xenopus oocytes induced by an oncogenic Ras p21 protein of human origin. These results have raised the possibility of using inhibitors of the mevalonate pathway to block the transforming properties of ras oncogenes. Unfortunately, mevalonate is a precursor of various end products essential to mammalian cells, such as dolichols, ubiquinones, heme A, and cholesterol. In this study, we describe an enzymatic activity(ies) capable of catalyzing the farnesylation of unprocessed Ras p21 proteins in vitro at the correct (Cys-186) residue. This farnesylating activity is heat-labile, requires Mg2+ or Mn2+ ions, is linear with time and with enzyme concentration, and is present in all mammalian cell lines and tissues tested. Gel filtration analysis of a partially purified preparation of protein farnesyltransferase revealed two peaks of activity at 250-350 kDa and 80-130 kDa. Availability of an in vitro protein farnesyltransferase assay should be useful in screening for potential inhibitors of ras oncogene function that will not interfere with other aspects of the mevalonate pathway.

Alkyl and Aryl Transferases↗
PubMed1990

Platelet thrombospondin modulates endothelial cell adhesion, motility, and growth: a potential angiogenesis regulatory factor.

Components of the extracellular matrix have been shown to modulate the interaction of endothelial cells with their microenvironment. Here we report that thrombospondin (TSP), an extracellular matrix component, induces adhesion and spreading of murine lung capillary (LE-II) and bovine aortic (BAEC) endothelial cells. This TSP-induced spreading was inhibited by heparin and fucoidan, known to bind the amino-terminal globular domain of the molecule. In addition, endothelial cells were induced to migrate by a gradient of soluble TSP (chemotaxis). The chemotactic response was inhibited by heparin and fucoidan, as well as by the mAb A2.5, which also binds to the amino-terminal domain. These data are in agreement with our previous observation that the TSP aminoterminal heparin binding region is responsible for the induction of tumor cell spreading and chemotactic motility. The inhibition of chemotaxis and spreading by antibodies against the beta 3 but not the beta 1 chain of the integrin receptor points to a role for the integrins in the interaction of endothelial cells with TSP. We also found that TSP modulates endothelial cell growth. When added to quiescent LE-II cells, it inhibited the mitogenic effects of serum and the angiogenic factor bFGF, in a dose-dependent manner. The inhibition of DNA synthesis detected in the mitogenic assay resulted in a true inhibition of BAEC and LE-II cell growth, as assessed by proliferation assay. This work indicates that TSP affects endothelial cell adhesion, spreading, motility and growth. TSP, therefore, has the potential to modulate the angiogenic process.

Animals↗
PubMed1990

Adverse effects of captopril in hospital outpatients with hypertension.

Hypertensive patients prescribed captopril while attending a hospital hypertension clinic were studied, to identify the benefits of the drug, its adverse effects and factors predisposing to them. One hundred and eighty two patients were followed for a mean of 18 months; 24 received captopril alone, and 158 combinations of captopril and other antihypertensive drugs, especially loop diuretics (91/158), or thiazide diuretics (57/158), or other vasodilators (57/158). The mean final dose of captopril was 67 mg/day. Blood pressure (BP) was effectively controlled in 73% of patients (mean fall in systolic BP 29 mmHg, CI 24 to 34, P less than or equal to 0.001; mean fall in diastolic BP 18 mmHg, CI 16 to 20, P less than or equal to 0.001). Blood urea and creatinine rose slightly in all patients (urea by 0.9 mmol/l [13%], CI 0.5-1.3, P less than or equal to 0.001 and creatinine by 9 mumols/l [8%], CI 4-13, P less than or equal to 0.001). Twenty six patients were withdrawn from captopril therapy: 6 because of poor control of their blood pressure, two because it was no longer necessary and 12 (7.7%) because of extrarenal adverse effects--10 for rashes, one each for gastric upset and impotence. Captopril was withdrawn in a further 6 patients, because of deteriorating renal function. Factors discriminating those at risk of renal dysfunction were high doses of captopril, concomitant high dose diuretic therapy and undiagnosed renovascular disease.

Adult↗
PubMed1990

Autosomal dominant transmission of autoantibodies to thyroglobulin and thyroid peroxidase.

The inheritance of autoantibodies to thyroglobulin and thyroid peroxidase (thyroid microsomal antigen) has been reevaluated with newly developed ultrasensitive assays that depend on the direct interaction between antibody and radiolabeled antigen. In a study of 16 families with autoimmune thyroid disease, autoantibodies to thyroid peroxidase (TPO) were found to be inherited as a dominant Mendelian trait in females with reduced penetrance in males. Similar results were obtained with thyroglobulin (Tg) autoantibodies. Genetic linkage analysis of the loci for TPO and Tg autoantibodies with 28 polymorphic serological markers (including HLA and Gm allotypes) was carried out in 9 families. LOD scores for some serological markers (such as Gm) were uninformative, but linkage with other markers, notably the HLA antigens -A, B, -DR, -DQ, and BF on chromosome 6, could be excluded. Further studies using a comprehensive panel of gene probes to analyze DNA from families with autoimmune thyroid disease should permit the localization of the gene cluster responsible for regulating the ability to produce autoantibodies to TPO and Tg in man.

Adolescent↗
PubMed1990

Early predictors of mortality for hospitalized patients suffering cardiopulmonary arrest.

Few if any prearrest or intraarrest variables have been identified as highly predictive of inhospital mortality following cardiopulmonary arrest. A total of 310 consecutive patients requiring advanced cardiac life support during the calendar years 1985 and 1986 were reviewed with respect to eight specific variables. These included age, diagnosis, location, mechanism of the event, duration of resuscitation, whether the event was witnessed or unwitnessed, the initial observed rhythm and medications administered. A total of 37.1 percent of the patients were successfully resuscitated, but only 9.7 percent survived until discharge. Factors strongly associated with inhospital mortality included unwitnessed events (p = 0.0316), the need for epinephrine (p = 0.0003), identification of electromechanical dissociation or asystole as initial rhythms (p = 0.0000), and cardiac vs respiratory mechanism of arrest (p = 0.0000).

Age Factors↗