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Biomedical subjects

R Roberts

Publications and source records attributed to R Roberts.

At least 235 records · Page 13Linked to original sources

Impact of tissue plasminogen activator and heparin versus heparin alone on quantitative coronary angiographic findings in myocardial infarction. The Toronto Tissue Plasminogen Activator Trial Study Group.

The influence of tissue plasminogen activator (t-PA) and heparin versus heparin alone on anatomic characteristics of patent infarct-related coronary arteries and the development of these angiographic descriptors in coronary arteries that remain patent during the hospital course was examined in 108 patients who participated in a placebo-controlled trial of recombinant tissue-type plasminogen activator in acute myocardial infarction. Coronary angiography was performed 18 +/- 6 hours after treatment in 47 patients (group A) and at 10 days in 61 patients (group B). Quantitative coronary angiography of the infarct-related lesion was performed, and luminal irregularity was quantitated with an ulceration index. Of the 47 patients in group A, 7 (29%) treated with placebo had Thrombolysis in Myocardial Infarction grade 2 or 3 perfusion, whereas 18 (78%) treated with t-PA had grade 2 or 3 (p < 0.001); there was no difference between patients who had grade 2 or 3 perfusion in group B (placebo 59% vs t-PA 75%). In group A, at 10 days, the luminal area of the infarct artery had increased from 0.59 +/- 0.11 to 0.9 +/- 0.24 mm2 and from 0.75 +/- 0.16 to 1.31 +/- 0.39 mm2 for placebo- and t-PA-treated patients, respectively (p < 0.04). There was no change in the ulcerative index over time in either placebo- or t-PA-treated patients. It is concluded that early after infarction, t-PA produces marked and rapid improvement in overall patency as compared with heparin, although this difference was attenuated at 10 days because of spontaneous recanalization in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Short and long term prognosis of acute myocardial infarction since introduction of thrombolysis.

OBJECTIVE: To record prognosis and determinants of outcome in patients with acute myocardial infarction since thrombolysis was introduced. DESIGN: Observational study. SETTING: London district general hospital. PATIENTS: 608 consecutive patients admitted to the coronary care unit with acute myocardial infarction between 1 January 1988 and 31 December 1991. MAIN OUTCOME MEASURE: All cause mortality, non-fatal ischaemic events (myocardial infarction, unstable angina), and revascularisation. RESULTS: Of the 608 patients, 89 (14.6%) died in hospital. 507 [corrected] patients were followed up after discharge from hospital. Mortality (95% confidence interval) at 30 days, one year, and three years was 16.0% (13.4% to 19.2%), 21.7% (18.6% to 25.2%), and 29.4% (25.3% to 33.9%) respectively. Event free survival (survival without a non-fatal ischaemic event) was 80.4% (77.0% to 83.4%) at 30 days, 66.8% (62.8% to 70.5%) at one year, and 56.1% (51.3% to 60.6%) at three years. Survival in patients treated with thrombolysis was considerably higher than in those not given thrombolysis (three year survival: 76.7% v 54.3%), although the incidence of non-fatal ischaemic events was the same in the two groups. Multivariate determinants of six month survival were left ventricular failure, treatment with thrombolysis and aspirin, smoking history, bundle branch block, and age. For patients who survived six months, age was the only factor related to long term survival. CONCLUSIONS: Although patients treated by thrombolysis had a relatively good prognosis, long term mortality and the incidence of non-fatal recurrent ischaemic events remained high. Effective strategies for the identification and treatment of high risk patients need to be reassessed.

Age Factors↗

Effect of transforming growth factor-beta 1 on myocardial stunning in the intact dog.

Previous studies have demonstrated that transforming growth factor-beta (TGF-beta) can accelerate wound healing, inhibit free radical formation and limit myocardial ischemia/reperfusion injury in a variety of experimental models. However, it is unknown whether exogenous TGF-beta 1 can attenuate the prolonged contractile dysfunction that is observed after a brief, reversible ischemic insult (myocardial stunning). Thus, open-chest dogs undergoing a 15-min left anterior descending coronary artery occlusion and 4 h of reperfusion were given TGF-beta 1 as an intravenous bolus (250 micrograms) at 24 h and again at 1 h before coronary occlusion (n = 5). Control dogs (n = 7) received equivalent amounts of vehicle. The two groups were similar with respect to occluded bed size, collateral blood flow and rate-pressure product. Fundamental physiological parameters, such as body temperature, arterial pH, PO2 and hematocrit, were within normal limits throughout the experiment. In control dogs, regional myocardial function (assessed as systolic thickening fraction) remained depressed throughout the 4 h reperfusion period, indicating severe myocardial stunning. TGF-beta 1 did not produce any significant improvement in the recovery of regional function; 4 h after reperfusion, paradoxical systolic thinning was still present in both treated and control groups, with thickening fraction being -22.5 +/- 6.1% and -31.0 +/- 5.3% of baseline, respectively (P = N.S.). These results demonstrate that a large dose of TGF-beta 1 given before ischemia fails to attenuate myocardial stunning in the open-chest dog, suggesting that this growth factor does not exert protective effects in the setting of reversible myocardial ischemia/reperfusion injury.

Acute Disease↗

Ethical dilemmas in continuing a zidovudine trial after early termination of similar trials.

Ethical dilemmas caused by external events and an interim subset analysis raised concerns about continuing a long-term VA clinical trial comparing early with later zidovudine therapy for symptomatic human immunodeficiency virus (HIV) infection. The first external event was the early termination of other, apparently similar, trials conducted by the AIDS Clinical Trials Group (ACTG) and the announced clear benefits for the zidovudine-treated patients. Interim analysis of the VA trial at this time did not show similar benefits. Subset analyses were performed to explore factors that might explain the different results. These suggested a difference in response to zidovudine in white and minority groups. The Data Monitoring Board and a special advisory panel reviewed these data and concluded that, since the VA results were neutral overall and the subset analyses based on small numbers, the trial should continue. By conference call, the study cochairmen and biostatistician discussed this decision with study personnel without revealing interim results, and study personnel passed the information on to patients at the participating centers. The second event was in March 1990, when the Food and Drug Administration (FDA) approved earlier use of zidovudine, which applied to patients still in the VA trial. Patients were asked to reaffirm their participation by signing a new informed consent that explained the findings reported by the ACTG, the FDA-approved revised recommendations, and the rationale for continuation of the VA trial. The consent form emphasized that continued masked therapy was optional and that unmasked treatment and follow-up would be provided to patients requesting it. Seventy-four percent of the participants chose to continue masked therapy. We conclude that when new external data are announced, informed participation in a long-term clinical trial may require a revised consent form and that it is ethical and practical to present this without disclosure of interim study results.

Acquired Immunodeficiency Syndrome↗

Gender differences in occupational mobility and structure of employment in the British Civil Service.

In all industrialized societies health status in adults has been found to vary with social position. Attempts to explain this are usually grouped under headings of artefact, material, lifestyle and selective mobility of the healthiest. Such attempts have to date been unsuccessful in fully accounting for this relationship, and whilst they have merit have left unconsidered the effects of the process whereby social stratification occurs. The present study is a prelude to subsequent studies that will endeavour to distinguish between three separate influences on health--the effects of current social position, the long term effects stemming from one's initial class position, and the effects of the processes governing mobility. The purpose of our present investigation is to describe patterns of occupational mobility, that will enable us to identify possible predictors of subsequent mobility and therefore to indicate to what extent mobility might be a process governed by social rules. The work presented in this paper comprises part of the Whitehall II study of occupational, social and lifestyle influences upon health in a Civil Service population. Using multiple regression techniques almost half the variation in mobility is modelled in terms of educational level, fathers' social class, gender, marital status, age on entry into the Civil Service, length of time in Civil Service employment and grade of entry into the Civil Service. Using estimates derived from this model it is suggested that a number of sub-groups within the Civil Service suffer adverse mobility (mobility appears particularly restricted for women and for those entering the Civil Service above 30 years of age). The results obtained suggest that the issue of obstructed opportunity at the workplace could become a focus for fruitful investigation, linking issues of personal autonomy, expectations and control to health. A number of methodological problems in this kind of work are considered together with discussion of how the model can be used to increase our understanding of mobility.

Adult↗

Symptomatic bradycardia following the administration of sublingual nitroglycerin.

A case of severe bradycardia with junctional escape immediately following sublingual nitroglycerin is described. Bradycardia is a rare, but well-documented, complication of nitroglycerin and is often reported in the setting of myocardial ischemia or infarction. This particular case reported was complicated by the presence of an angiographically documented congenital coronary anomaly, but did not have either electrocardiographic or enzymatic evidence of ischemia or infarction during this event. Previously reported cases were reviewed, as well as potential mechanisms for this phenomenon. All cases reported to date were easily corrected with passive leg elevation or atropine.

Administration, Sublingual↗

A prospective study to identify the risk factors associated with acute reactions to platelet and red cell transfusions.

It is generally assumed that febrile nonhemolytic transfusion reactions are an immunologically mediated reaction involving the recipient's plasma and the white cells in the donor unit. This has led to the use of white cell reduction and pretransfusion medication, to try to minimize these reactions. To better understand febrile transfusion reactions, a prospective study was performed in which all patients receiving platelet and red cell transfusions in a tertiary-care medical center were interviewed before and after transfusion to obtain information about the typical presentation of the syndrome. It was found that transfusion reactions were much more frequently associated with platelet transfusion (30.8%) than with red cell transfusion (6.8%, p < 0.0005). The routine use of antipyretics prevented most episodes of fever but did not prevent the occurrence of other symptoms such as chills, cold, and discomfort. The application of logistic regression analysis revealed that the dominant factor determining the risk of a reaction was not white cell contamination, but the age of the component (p < 0.005). The significant relationship between reaction and the increasing age of the component suggests that cytokines released in the component during storage may be responsible for many reactions to blood components.

Adolescent↗

Maternally transmitted partial direct tandem duplication of mitochondrial DNA associated with diabetes mellitus.

Mitochondrial DNA from a 38 year old male with diabetes mellitus and features of mitochondrial dysfunction was analysed and shown to include a population with a partial duplication. The partially duplicated mitochondrial DNA molecules were evident in both muscle and blood. The region of mitochondrial DNA duplicated includes the origin of heavy strand replication, but not the light strand origin. This patient has features in common with other cases of partial direct tandem duplications and with a family which was reported to harbour a 10.4 kb mtDNA deletion. Initial restriction enzyme analysis of our case produced results consistent with a partial deletion of mitochondrial DNA. This leads us to propose that the rarity of reports of partial mitochondrial DNA duplications may stem in part from the classification of such mutants as partial deletions.

Adult↗

The techniques and complications of out-patient uterine washing in the assessment of endometrial function.

The complications of a consecutive series of 90 uterine washings performed among 52 women were studied. The amount of discomfort was significantly less than that of endometrial biopsy but greater than that of cervical smear or blood sampling. Incomplete recovery of fluid (< 8 ml from 10 ml flushing fluid) was reported in only 3% of cases. Vaginal bleeding, pelvic infection and delayed abdominal pain were not encountered. The techniques of uterine washing are simple and may have important implications in the study of endometrial function.

Adult↗

The role of ERCP and endoscopic sphincterotomy in the era of laparoscopic cholecystectomy.

The advent of laparoscopic cholecystectomy (LC) has led to some controversy regarding the best method of managing bile duct calculi. This paper reviews the cases of 38 patients who underwent LC and endoscopic retrograde cholangiopancreatography (ERCP), from a series of 600 consecutive laparoscopic cholecystectomies. Twenty-nine patients had ERCP performed pre-operatively because of suspicion of choledocholithiasis. Duct stones were confirmed in eight patients. Recent or current jaundice was the best predictor of bile duct stones. Nine patients had ERCP done postoperatively because of duct stones seen on operative cholangiography. In two patients bile duct cannulation was not possible and a third procedure, open duct exploration, was necessary. Techniques in laparoscopic management of duct stones are improving and the role of ERCP and sphincterotomy should be limited to jaundiced patients or those with proven bile duct stones in whom laparoscopic procedures have been unsuccessful.

Adult↗

Development and validation of laboratory procedures for preimplantation diagnosis of Duchenne muscular dystrophy.

In order to develop and validate methods for the preimplantation diagnosis of Duchenne muscular dystrophy (DMD), we have established and evaluated PCR assays for the analysis of four loci within the DMD gene and for two Y chromosome sequences in single cells. A model system using buccal cells picked from mouthwash samples has been used for an extensive evaluation of the sensitivity and specificity of the assays, and each assay has been tested in samples containing single cells, two cells, and three cells per tube. The four DMD and two Y assays have been combined in duplex and triplex reactions to enable simultaneous diagnosis of DMD and of fetal sex. One of the DMD markers is a highly polymorphic simple tandem repeat locus which produces a basic DNA profile, and provides a control for contamination by foreign DNA. Amplification of DMD or Y sequences was observed in 78 to 92% of single male cells, rising to 96% and 97% in tubes containing two or three male cells respectively. Coamplification of both a DMD and a Y sequence together occurred with a mean success of 74% in single male cells, increasing to 93% with two, and 95% with three cells per tube. With appropriate precautions, we believe that it is now possible to proceed to clinical application of these procedures.

Base Sequence↗

Ictal/postictal SPECT in the pre-surgical localisation of complex partial seizures.

Single photon emission computed tomography (SPECT) used in conjunction with HM-PAO (Ceretec-Amersham International) was used to image regional cerebral blood flow (rCBF) in 28 patients with medically intractable complex partial seizures during or soon after a seizure, and interictally. Changes from interictal rCBF were seen in 26/28 (93%) patients. The main findings were; 1) During the seizure--hyperperfusion of the whole temporal lobe; 2) Up to 2m postically--hyperperfusion of the hippocampus with hypoperfusion of lateral temporal structures; 3) From 2-15m postically--hypoperfusion of the whole temporal lobe. When compared with EEG and MRI data, correct localisation to one temporal lobe was obtained in 23 patients. In one further patient bilateral temporal foci, and in a further two patients frontal foci, were correctly identified. There were no disagreements between EEG and SPECT localisation. Temporal lobe surgery was successful (by the criterion of at least 90% reduction in seizure frequency) in all but one of the 23 patients operated on. It is concluded that ictal/postictal SPECT is a reliable technique for the presurgical localisation of complex partial seizures. The data indicate a likely sequence of changes in rCBF during and after complex partial seizures of temporal lobe origin.

Adolescent↗

Prevalence of small opacities in chest radiographs of nickel sinter plant workers.

Radiographs from 745 nickel sinter plant workers were taken and classified by five readers using the International Labour Office (1980) protocol. Each reader worked independently and the films were randomly mixed with films from a non-dust exposed office population and also with films from subjects known to have silicosis or asbestosis. The prevalence of small irregular opacities was selected as the outcome of interest. In the sinter workers this was within the range identified in cigarette smokers or in workers exposed to dusts of low fibrogenicity. Only minimal evidence of small round opacities was noted. There was no evidence from the chest radiographs that exposures to high concentrations of dusts containing compounds of nickel caused an inflammatory or fibrogenic response in the lungs of the exposed population.

Adult↗

Hypertrophic cardiomyopathy mutation is expressed in messenger RNA of skeletal as well as cardiac muscle.

BACKGROUND: The beta-myosin heavy chain (beta-MHC) gene has been identified as a major locus for familial hypertrophic cardiomyopathy (FHCM). We recently showed that one of the common mutations associated with FHCM is expressed in the cardiac muscle messenger RNA (mRNA) of an affected individual. Since beta-MHC is a major sarcomeric protein of cardiac and skeletal muscle, studies were performed to determine whether the mutation is also expressed in skeletal muscle. METHODS AND RESULTS: Biopsies were obtained of skeletal muscle (biceps brachii) from a proband with FHCM known to have the missense mutation in exon 13 of the beta-MHC gene. RNA was extracted from skeletal muscle and lymphocytes by the RNAzol method. First-strand complementary DNA was synthesized by reverse transcription using an antisense primer to exon 16. Polymerase chain reaction (PCR) was performed using primers to exons 12 and 14 to amplify the segment encompassing exon 13. The PCR products were digested with Ddel restriction endonuclease. Undigested PCR product in the control and the proband was 321 base-pairs (bp). Ddel digestion of the PCR product from normal skeletal and lymphocytes showed two DNA fragments of 181 and 140 bp as expected, whereas digestion of the PCR product from the proband's skeletal muscle and lymphocytes showed four DNA fragments of 181, 149, 140, and 32 bp due to the mutation in exon 13. This indicates that the mutation in affected individuals is also expressed in the mRNA of skeletal muscle and lymphocytes. CONCLUSIONS: To our knowledge, this is the first documentation of a beta-MHC gene mutation expressed in skeletal muscle. This finding is provocative. Does it impair skeletal muscle function? If so, how? If not, why not? Is the impairment, or lack of it, a clue to the molecular defect of cardiac muscle? Furthermore, skeletal muscle provides a readily accessible source of mRNA for expression studies and for purification of the beta-MHC protein, which is probably essential to future investigation designed to unravel the molecular basis of this disorder.

Adult↗

The Australian National Non-Acute Inpatient Project.

The Australian National Non-Acute Inpatient Project has produced a casemix classification system for non-acute inpatients (NAIP). The daily classification has 19 final classes which bring together descriptions of a patient's clinical type (from admission diagnosis) and functional ability (from automated nursing care plans). Data on salary cost relating to care of 786 patients were collected at three large metropolitan teaching hospitals for six months during 1991, yielding a total sample of 15,013 non-acute bed-days. The NAIP classification was built from first principles, combining clinician input and statistical testing using an analysis of variance model (PC Grouper). Overall variance reduction on the full set of 15,013 records was 26.15 per cent.

Activities of Daily Living↗

A comparison of pentastarch and lactated Ringer's solution in the resuscitation of patients with hemorrhagic shock.

Pentastarch is a colloid that is chemically similar to Hetastarch. It has a shorter half-life (12 hr), and produces volume expansion at least 1.5 times the administered volume. We compared Pentastarch to Ringer's lactate in 41 patients (21 Pentastarch, 20 Ringer's lactate) presenting with hemorrhagic shock. The groups were similar in age, sex, race, and type of injury. Significantly less volume of Pentastarch was required initially to resuscitate to a normal blood pressure and urine output than Ringer's lactate (P < 0.005). Coagulation parameters (prothrombin time, partial thromboplastin time, fibrinogen, and factor VIII) were measured for 48 hr post-resuscitation, and no abnormalities were noted in the Pentastarch group. Serum albumin was the same in both groups throughout the study period; however, serum colloid oncotic pressure was elevated at 1 hr post-resuscitation in the Pentastarch group (P < 0.005). There was no difference in ventilatory parameters, blood gases, pulmonary function tests, ventilator days, or hospital days between the two groups. We conclude that Pentastarch is safe and effective for the initial resuscitation from hemorrhagic shock.

Blood Coagulation↗