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Biomedical subjects

E McGregor

Publications and source records attributed to E McGregor.

At least 19 recordsLinked to original sources

Identification and mapping of human saphenous vein medial smooth muscle proteins by two-dimensional polyacrylamide gel electrophoresis.

Changing smooth muscle phenotype and abnormal cell proliferation are important features of vascular pathology, including the failure of saphenous vein bypass grafts. We have characterised and mapped protein expression in human saphenous vein medial smooth muscle, using two-dimensional (2-D) polyacrylamide gel electrophoresis. The 2-D system comprised a nonlinear immobilised pH 3-10 gradient in the first dimension (separating proteins with isoelectric point values between pH 3-10), and 12%T total gel concentration sodium dodecyl sulphate polyacrylamide gel electrophoresis in the second dimension (separating proteins in the range 14,000-200,000 Daltons). Using a combination of peptide mass fingerprinting by matrix-assisted laser desorption/ionisation-time of flight mass spectrometry and partial amino acid sequencing by nanospray tandem mass spectrometry, a subset of 149 protein spots was analysed, with 129 protein spots being identified and mapped. The data presented here are an important addition to the limited knowledge of venous medial smooth muscle protein expression in vivo. Our protein map will facilitate the identification of proteins differentially expressed in human saphenous vein bypass grafts. In turn, this may lead to the elucidation of molecular events involved in saphenous vein bypass graft failure. The map should also provide a basis for comparative studies of protein expression in vascular smooth muscle of varying origins.

Electrophoresis, Gel, Two-Dimensional↗

Prognostic value of troponin T in hemodialysis patients is independent of comorbidity.

BACKGROUND: Patients on long-term hemodialysis have a high mortality. Various clinical and biochemical markers are of prognostic value. Cardiac troponin T (cTnT) is a sensitive and specific marker for myocardial damage. Asymptomatic dialysis patients have a high prevalence of cTnT concentrations above the diagnostic threshold for myocardial damage. There is controversy over whether this represents a false positive cTnT or an underlying pathology with a poor outcome. It is not known whether cTnT reflects comorbidity in these patients. METHODS: A cohort of 73 long-term hospital hemodialysis patients had cTnT estimated once prior to a mid-week dialysis. Samples were analyzed using the second-generation cTnT assay from Boehringer Mannheim on an Elecsys 1010 analyzer. The standard diagnostic threshold for myocardial damage of 0.1 ng/mL was used. A commonly employed measure of comorbidity (Khan) was applied at the time cTnT was measured. Patients were followed for 15 months. Mortality was used as the clinical end point. Kaplan-Meier survival analysis was employed and differences between groups were assessed using the Cox-Mantel log-rank test. RESULTS: Of the 73 patients, 20 were positive for cTnT and 53 were negative, at the cut-off of 0.1 ng/mL. At fifteen months, 65% of the positive patients were dead, whereas only 15% of the negative patients were dead. Survival analysis confirmed that this difference was statistically significant (P < 0.00001), and that the effect of cTnT on survival was independent of comorbidity. CONCLUSIONS: There is a high prevalence of positive cTnT in stable hemodialysis patients. A single estimation of cTnT in this group has significant prognostic value, independent of comorbidity.

Adult↗

The attitudes of teachers in Scotland to the integration of children with autism into mainstream schools.

Around 4600 school-age children in Scotland fall within the spectrum of autistic disorders, of whom 780 have been identified in schools. This study sought the views of 23 specialist and 49 mainstream teachers, 22 with experience of autism, 27 without. They were questioned about the advantages and disadvantages of integration into mainstream for autistic children, their own ability to cope and predictors of success. Questionnaires were issued to special units and to mainstream primary and secondary schools. A minority of mainstream respondents believed children with autism should be integrated where possible. Mainstream teachers with experience of autism showed more confidence to deal with the children than those without experience. Many expressed concerns about effects on mainstream pupils but most were willing to undertake more training. Specialist teachers were more positive, although they acknowledged possible disadvantages for both groups of children and stressed that the success of integration depends on the individual child.

Adult↗

Early echocardiographic changes and survival following renal transplantation.

BACKGROUND: Left ventricular hypertrophy, ventricular dilatation and poor systolic function prior to renal transplantation are associated with increased mortality. However, whether the improvement in these echocardiographic indices that is reported to follow renal transplantation improves patient survival has not been investigated. METHODS: We studied 67 patients who underwent renal transplantation in our unit between 1988 and 1990 and in whom echocardiography was performed immediately prior to transplant surgery and 4 months later. Pre- and post-transplantation echocardiographic parameters were compared between the 20 patients who have since died and surviving patients and a descriptive survival analysis was performed. RESULTS: Following transplantation there was no significant change in left ventricular mass index (LVMI) or end diastolic diameter (EDD). End systolic diameter (ESD) improved in 60% of patients (median 3.3 vs 3. 7 cm; P=0.031) as did fractional shortening in 67% (0.33 vs 0.29; P=0.001). However, improvement was not associated with survival benefits. We also found that prior to transplantation, fractional shortening, ESD and EDD were strongly associated with outcome; this was no longer the case following transplantation. In contrast, LVMI provided a stronger association with adverse outcome (albeit of limited statistical significance) following transplantation. CONCLUSIONS: In this Preliminary Report, we conclude that echocardiographic parameters are associated with adverse outcome in patients receiving renal replacement therapy (RRT). Different echocardiographic parameters are associated with adverse outcome before and after renal transplantation and improvement of pre-transplant abnormalities (e.g. poor LV systolic function) following transplantation does not necessarily confer survival benefits. Whether this is a genuine observation or a reflection of the interpretation of echocardiographic measurements in dialysis patients requires further investigation.

Adolescent↗

Pre-operative echocardiographic abnormalities and adverse outcome following renal transplantation.

BACKGROUND: Premature cardiovascular disease is now the leading cause of death in renal transplant recipients. Although patients with progressive renal disease have many of the conventional risk factors for cardiovascular disease these do not have the same predictive power as they do in the general population. Echocardiographic abnormalities, notably left ventricular hypertrophy, have been shown to be associated with adverse outcome in patients on dialysis. METHODS: The echocardiograms were studied from 141 patients who were examined on the eve of renal transplantation between 1988 and 1990 to try to identify factors predicting outcome. Thirty-four patients have since died, 22 of cardiovascular disease. Ninety-three of the survivors and 27 of the dead patients had echocardiographic traces suitable for analysis. RESULTS: Left ventricular mass index was increased in those patients who died (median 167 vs 134 g/m2; P=0.03), as were end-systolic (4.3 vs 3.4 cm; P<0.01) and end-diastolic (5.8 vs 5.2 cm; P<0.01) diameters. Systolic function was also more severely impaired (fractional shortening, 27 vs 33%; P<0.01). Apart from age, only systolic function and end systolic diameter were independent predictors of outcome in multivariate analysis. CONCLUSIONS: This pattern of echocardiographic abnormality is similar to that reported in long-term dialysis populations, despite the adverse effects on survival. Moreover, despite potential benefits of transplantation on cardiac function, left ventricular hypertrophy, ventricular dilatation and systolic dysfunction were all associated with adverse outcome following transplantation. We conclude that echocardiography identifies markers for premature death following transplantation and provides targets for therapeutic intervention.

Adolescent↗

Accuracy and precision of the TAS analyser for near-patient INR testing by non-pathology staff in the community.

AIMS: To assess the accuracy and precision of INR measurement by trained practice and district nursing staff using the Thrombolytic Assessment System (TAS) analyser. METHODS: Seventeen nurses from four practices were trained to measure INR using the TAS analyser on citrated capillary blood samples. Quality control (QC) consisted of: daily internal QC using normal and abnormal commercial plasmas; monthly local external QC scheme using fresh citrated venous blood; and registration of all analysers in the NEQAS (national external quality assessment scheme) main users scheme. RESULTS: Analysis of internal QC results demonstrated satisfactory interanalyser and intra-analyser precision with no evidence of analytical drift in any of the four practice analysers over an eight month period. Local and national external QC results confirmed the interanalyser precision but INR was underestimated by the TAS analysers compared with the CA 1000 using either Diagen rabbit brain thromboplastin or Innovin, and with other NEQAS users. CONCLUSIONS: The TAS analyser has many features to commend it for use by nonpathology staff to determine INR. Local internal and external QC and entry into the NEQAS main users group are possible because the TAS analyses citrated plasma or blood. The TAS analyser underestimates INR when the geometric mean normal prothrombin time (GMNPT) is determined by conventional methods. A local correction factor can be introduced by adjusting the normal PT to give INR results comparable with the local laboratory. This is particularly desirable when INRs are measured using both near-patient and laboratory analytical systems on different occasions.

Anticoagulants↗

The effect of cefodizime on phagocyte function in non-patient volunteers and patients with chronic renal failure. In vitro and ex vivo studies.

Cefodizime has previously been shown to possess a number of immunomodulating properties in vivo and in vitro using several different test systems. Since most in vitro studies have been performed with cells from normal individuals, we first investigated whether cells from chronic renal failure patients would respond in vitro to cefodizime in the same way as healthy subjects. Subsequently, we investigated the effect of cefodizime (10 g over 10 days in 2-g doses) on phagocyte function ex vivo in an open study of 26 chronic renal failure patients and 16 healthy subjects. Polymorphonuclear leukocytes were tested for their ability to polarize in response to cefodizime and/or f-met-leu-phe peptide. Polymorphonuclear leukocytes and monocytes were tested for their ability to produce chemiluminescence on stimulation with either phagocytic (zymosan) or soluble phorbol myristate acetate stimuli. Phagocyte and lymphocyte membrane receptor expression was compared after exposure to cefodizime. Exposure to cefodizime in vitro causes a significant increase in polarization of polymorphonuclear leukocytes from both normal individuals and renal failure patients (both P < 0.001). It also caused increased chemotaxis and chemokinesis in a modified Boyden chamber assay. Cefodizime did not affect lucigenin-enhanced chemiluminescence and there were only minor effects on cell membrane antigen levels. In the ex vivo study there was a significant increase in polymorphonuclear leukocyte polarization (P < 0.001) attributable to cefodizime, but other investigations showed no significant differences. The results suggest that cefodizime may act as a mild priming agent for some functions, particularly chemotaxis.

Adult↗

Non-steroidal anti-inflammatory drugs and hospitalization for acute renal failure.

Non-steroidal anti-inflammatory drugs (NSAIDs) have been implicated in the aetiology of acute renal failure (ARF), but epidemiological studies examining this association have produced disparate results. We conducted a case-control study using a purpose-built record-linkage database for a population of 420,600 patients, resident in Tayside since May 1990. Patients (n = 207) hospitalized with a diagnostic code for ARF between 1990 and 1992 had their diagnosis validated by a renal physician. Six community controls and two hospital controls, matched for age and sex, were generated for each of these cases. Exposure to dispensed oral NSAIDs, topical NSAIDs and aspirin during the 90 days prior to the index date were investigated (recent exposure), as was exposure at any time since January 1989 (previous exposure). The most significant associations were modelled using conditional logistic regression. When community controls were used, recent exposure to NSAIDs and previous exposure to aspirin were independently associated with hospitalization for ARF, with adjusted odds ratios of 2.20 (1.49-3.25) and 2.19 (1.46-3.30), respectively. Only recent exposure to oral NSAIDs was associated when hospital controls were used: 1.84 (1.14-2.93). No significant interactions were present with previous chronic renal failure, other possible causes of ARF or whether the diagnosis was primary or secondary. There is an approximate doubling of the risk of hospitalization for ARF with use of oral NSAIDs.

Acute Kidney Injury↗

The spectrum of chronic liver disease in renal transplant recipients.

Chronic liver disease has been reported to be an important cause of late morbidity and mortality in renal transplant recipients. We have examined the prevalence and nature of chronic liver disease among 538 patients with functioning renal allografts managed at the Western Infirmary, Glasgow, between 1980 and 1989. Thirty-seven patients (7 per cent) satisfied biochemical criteria for chronic liver dysfunction. Liver biopsies were obtained from 24 of these, and autopsy tissue was available from three other patients. Chronic hepatitis of variable severity was present in 15 patients, haemosiderosis in 12 patients and nodular regenerative hyperplasia in five patients. Nineteen patients (51 per cent) had serological evidence of infection with the hepatitis C virus, and one of these developed chronic hepatitis B and D infection as well. Although a variety of chronic liver diseases occurred in our transplant population, the frequency of serious sequelae from liver dysfunction was much lower than that reported from transplant centres in other countries.

Chronic Disease↗

Emerging careers.

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Career Choice↗

Retinal changes in malignant hypertension.

To assess the diagnostic and prognostic importance of papilloedema in malignant hypertension a two part study was undertaken. Four observers reviewed 56 photographs of fundi from patients with grade 3 or 4 hypertensive retinopathy. Complete agreement on the presence or absence of haemorrhages was recorded in 52 cases and on exudates in 53 cases. Opinion on papilloedema, however, was divided, all four observers agreeing in only 34 cases. In the second part of the study survival in 139 consecutive hypertensive patients with bilateral retinal haemorrhages and exudates was examined by life tables. Ten year survival was 46% in patients with bilateral haemorrhages and exudates alone (n = 43) and 48% when papilloedema was also present (n = 96). Multivariate analysis confirmed that papilloedema was not related to survival. These results suggest that papilloedema is an unreliable physical sign and does not adversely influence prognosis in hypertensive patients who already have bilateral retinal haemorrhages and exudates when effective treatment is available. Papilloedema should no longer be regarded as a necessary feature of malignant hypertension.

Actuarial Analysis↗