Search PubMed⌕ Search

Biomedical subjects

A Murray

Publications and source records attributed to A Murray.

At least 235 records · Page 13Linked to original sources

The dexamethasone suppression test and the diagnosis of depression in adults with severe and profound developmental disabilities.

The dexamethasone suppression test (DST) was administered to 40 adults with severe and profound mental retardation. All participants were free from known conditions which may have given misleading results from cortisol assay. Of nine participants who showed symptoms possibly indicating depression the DST results concurred in two cases (i.e. there were two true-positives). However there were four or five (depending on criteria adopted) false-positive DST results. There did not appear to be a consistent behavioural profile for positive DST responders. With sensitivity to possible depression estimated at 22%, and a diagnostic confidence of < 35%, these data do not support recommendations that the DST is useful for assisting in diagnosis of depression in this population.

Activities of Daily Living↗

Analysis of the body surface ECG measured in independent leads during ventricular fibrillation in humans.

The degree of myocardial electrical organization during ventricular fibrillation remains unknown. The aim of this study was to compare the characteristics of the surface ECG on three independent and approximately orthogonal leads. Ten recordings of ventricular fibrillation, each induced at electrophysiology study and successfully terminated by direct current shock, were analyzed. Each recording was divided into 1-second epochs for analysis. Frequency analysis using the Fast Fourier Transform showed that the frequency of the dominant spectral peak increased significantly from a mean of 4.1 +/- 0.8 Hz to 5.2 +/- 0.7 Hz during the first 5 seconds of ventricular fibrillation. In 95% of the epochs analyzed, a similar dominant frequency was observed on either two or three ECG leads. Frequency agreement tended to increase as ventricular fibrillation evolved. This study shows that the rate of ventricular fibrillation increases rapidly during the first 5 seconds but only gradually thereafter, and that similar signal characteristics are observed on independent ECG leads. These findings are not compatible with the traditional view of incoherent myocardial activity during ventricular fibrillation.

Body Surface Potential Mapping↗

A randomized controlled clinical study to quantify the effect of small changes in the design of pacing electrodes on threshold voltages.

A double-blind randomized study of three pacing leads, identical in all ways except for the surface of their electrodes, is presented. The leads were implanted in 30 patients. Ten patients (Group A) received a standard Laserdish lead (dish electrode with laser pores), 10 patients (Group B) received a platinum-iridium coated modified Laserdish electrode, and 10 patients (Group C) received a platinum-iridium coated dish electrode identical to that in Group B except for the absence of laser pores. All leads were implanted by the same operator via the subclavian vein and all patients received an Optima MPT pulse generator. Direct measurement at implantation of pacing threshold and endocardial electrograms showed no significant difference between the three groups (mean +/- standard deviation voltage thresholds 0.30 +/- 0.06 V at 0.5 ms and 0.21 +/- 0.05 V at 1.0-ms pulse durations, R wave amplitude 7.6 +/- 3.2 mV). Significant differences (P = 0.001) were found in threshold impedances at implant (Group A 940 omega, Group B 782 omega, Group C 673 omega). Ten further measurements of voltage threshold were made over the next 2 years. Overall, at a pulse duration of 1.0 ms, a significantly reduced (P < 0.025) threshold voltage was found for both the electrode with pores and platinum-iridium coating compared with pores alone (20%), and with pores and platinum-iridium coating compared with the coating alone (18%). There was no significant difference between using platinum-iridium alone or pores alone. We have shown that a controlled randomized study, using electrodes that are identical except for the characteristics being assessed, can enable effects of small differences in electrode design to be quantified.

Double-Blind Method↗

Evidence for electrical organization during ventricular fibrillation in the human heart.

INTRODUCTION: Ventricular fibrillation is a most dangerous cardiac arrhythmia that has received considerable attention, yet its pattern of electrical activation remains controversial. The aim of this study was to investigate the degree of organization during the clinical arrhythmia and to examine the phase relationship between deflections in independent ECG leads. METHODS AND RESULTS: Ten recordings of ventricular fibrillation were examined. Each had been provoked during routine electrophysiological study. The mean duration of ventricular fibrillation was 21 seconds (range 11 to 34). Independent and approximately orthogonal ECG leads I, aVF, and V2 were recorded to computer at a sampling rate of 250 Hz. The phase relationship of each ECG lead pair was measured from the lag of peaks in their cross-correlation function (CCF). In 61% of the 1-second ECG epochs analyzed, CCF peak lag changed by < 20 msec compared to the previous epoch. Thus, the overall phase relationship was stable most of the time. Changes in CCF peak lag tended to be either gradual or to punctuate periods of stability. CONCLUSIONS: This study provides evidence of organized myocardial activation during human ventricular fibrillation.

Electrocardiography↗

Identification of mycobacterium tuberculosis DNA sequences encoding exported proteins by using phoA gene fusions.

The activity of bacterial alkaline phosphatase (PhoA) is dependent on it being exported across the plasma membrane. A plasmid vector (pJEM11) allowing fusions between phoA and genes encoding exported proteins was constructed to study protein export in mycobacteria. Introduction of the Mycobacterium fortuitum beta-lactamase gene (blaF*) into this vector led to the production in M. smegmatis of protein fusions with PhoA activity. A genomic library from M. tuberculosis was constructed in pJEM11 and screened in M. smegmatis for clones with PhoA activity. Sequences of the M. tuberculosis inserts directing the production of protein fusions in these PhoA-positive clones were determined. They include part of the already-known exported 19-kDa lipoprotein, a sequence with similarities to the exported 28-kDa antigen from M. leprae, a sequence encoding a protein sharing conserved amino acid motifs with stearoyl-acyl-carrier-protein desaturases, and unknown sequences. This approach thus appears to identify sequences directing protein export, and we expect that more extensive screening of such libraries will lead to a better understanding of protein export in M. tuberculosis.

Alkaline Phosphatase↗

Comparison of automatic QT measurement techniques in the normal 12 lead electrocardiogram.

OBJECTIVE: To undertake a quantitative assessment of different automatic QT measurement techniques and investigate the influence of electrocardiogram filtering and algorithm parameters. DESIGN: Four methods for identifying the end of the T wave were compared: (1) threshold crossing of the T wave (TH); (2) threshold crossing of the differential of the T wave (DTH); (3) intercept of an isoelectric level and the maximum T wave slope (SI); and (4) intercept of an isoelectric level and the line passing through the peak and the point of maximum slope of the T wave (PSI). Automatic QT measurements were made by all techniques following different electrocardiogram filtering and, when appropriate, with four different isoelectric levels and with three different threshold levels. SUBJECTS: 12 simultaneous standard electrocardiogram leads, containing at least two electrocardiogram complexes, were recorded from 25 healthy volunteers relaxing in a semirecumbent position. MAIN OUTCOME MEASURE: Mean and standard deviation of differences between reference and automatic QT measurements were compared for the four techniques. RESULTS: The mean automatic QT measurements varied by up to 62 ms, which was greater than has been found between manual measurements by experienced clinicians. Technique TH was particularly poor. The other techniques produced consistent results for most electrocardiogram filter, isoelectric level, and threshold level setting; but technique SI underestimated QT relative to the other techniques. CONCLUSION: Different QT measurement techniques produced results which were influenced, to varying degrees, by filtering and technique variables. This is relevant for the inter-comparison of studies using different techniques. Technique TH, a common approach, is not recommended.

Adult↗

Study of the immunohistochemistry and T cell clonality of enteropathy-associated T cell lymphoma.

Specimens from 23 patients with enteropathy-associated T cell lymphoma were studied by immunohistochemistry after antigen retrieval. Specimens from 14 of these patients were investigated for the presence of clonal T cell gene rearrangements in both the tumor and the adjacent enteropathic intestine by the polymerase chain reaction. Primers for T cell receptor beta and gamma genes were used in a combination that permits the identification of approximately 90% of T cell receptor rearrangements. Clonal rearrangements of the T cell receptor were found in 13 of the 14 tumors studied. Specimens of enteropathic bowel resected with the tumor, but showing no morphological or immunohistochemical evidence of tumor involvement, showed clonal T cell receptor gene rearrangements in 11 cases. In 10 of these, the amplified DNA was of the same molecular weight in the enteropathic bowel as in the corresponding tumor. In 2 cases, sequencing the polymerase chain reaction product showed identical T cell receptor gene rearrangements in the tumor and in the adjacent intestine. Uniform staining for p53 was seen in 22 of the 23 tumors. In 9 of 19 cases studied, collections of small lymphocytes in the enteropathic bowel expressed p53. In all but one of these specimens, a clonal rearrangement of the T cell receptor genes was identified. We interpret these findings as support for the concept that enteropathy-associated T cell lymphoma arises on a background of gluten-sensitive enteropathy with evolution of neoplastic T cell clones from the reactive T cell population present in the enteropathic bowel.

Adult↗

Mycobacterium paratuberculosis and inflammatory bowel disease: frequency distribution in serial colonoscopic biopsies using the polymerase chain reaction.

An association between Mycobacterium paratuberculosis and Crohn's disease is suspected but the evidence remains controversial. Using a one-step DNA extraction procedure with the thermophilic protease PRETAQ and amplification by the polymerase chain reaction, M. paratuberculosis DNA was detected in 22% of patients with Crohn's disease, and in 13% of patients with ulcerative colitis. M. paratuberculosis DNA was not found in any biopsy tissue from control non-inflammatory bowel disease patients. The biopsy tissues in which M. paratuberculosis was detected all came from regions which were inflamed when viewed microscopically. Overall, 7.7% of biopsies from such inflamed areas were positive. This low frequency of detection could be explained on the basis of extremely low abundance of the organism in relation to the area of mucosa sampled, or be consistent with a non-aetiological role for M. paratuberculosis in inflammatory bowel disease.

Animals↗

Cholinergic activity of intestinal muscle in vitro taken from horses with and without equine grass sickness.

Equine grass sickness (EGS) is a pan-dysautonomia of horses that involves central and peripheral neuronal degeneration and ultimately depletion. This is the first reported functional study on the motility of equine intestine taken immediately post mortem from horses with EGS. Strips of smooth muscle from the small intestine of healthy and EGS-affected horses were suspended in an organ bath and their motility was measured isometrically. The activity of the cholinergic system was studied. Physostigmine enhanced the motility of all muscle strips. Tissues taken from horses suffering from acute grass sickness (AGS) had the longest latency before a measurable response could be obtained (p < 0.05). The ileum appeared to be damaged by EGS to a greater extent than the duodenum. For the duodenal strips the enhanced rate of spontaneous contractions was significant (p < 0.05) for both normal tissue and that affected by grass sickness but this was not the case for the ileal strips. Muscarinic receptor sensitivity investigation using bethanecol suggested a hypersensitivity of receptors with AGS material.

Acetylcholine↗

Transcervical endometrial cryoablation (ECA) for menorrhagia.

OBJECTIVE: To evaluate endometrial cryoablation (ECA) as a treatment for menorrhagia. METHOD: Prospective study of 67 women. ECA uses the Joule Thompson principle of expanding gases. The ECA probe has a channel to inject saline solution into the uterine cavity. The probe is introduced into the uterine cavity, which is distended with 5 ml saline solution. The device is activated for two freeze-thaw cycles. The saline solution forms an ice mold of the uterine cavity which can be observed by ultrasound scan. RESULTS: No surgical or long-term complications were observed. Two-thirds of patients followed up for > 3 months were completely satisfied. CONCLUSIONS: ECA is technically very easy, can be learned quickly, is free of complications and led to improvement of menstrual symptoms in 63% of patients followed up for 3-18 months. The device is virtually maintenance-free and requires only a small initial investment, while running costs are negligible.

Adult↗

Cell cycle checkpoints.

Checkpoints help ensure that cell cycle events occur in the correct order. Studies on mammalian cells identified inhibitors of complexes of cyclins and cyclin-dependent kinases as components of cell cycle checkpoints and provide the first glimpse of the molecular pathways that prevent cells with damaged DNA from replicating their DNA. In embryos, the extent to which checkpoints arrest the cell cycle reflects the relative strength of inhibitory checkpoints and the machinery driving the cell cycle forward.

Animals↗

Automated measurement of the cyclic activity of respiratory muscles.

A microcomputer-based system developed for the automated analysis of the electromyogram (EMG) recorded from respiratory muscles in a variety of situations is described. In addition, an assessment of the performance of the system is presented, along with data relating intercostal EMG activity to ribcage movement in seated subjects. Studies were performed on sixteen normal subjects--non smokers, mean (+/- SD) age 31 (+/- 6) years, mean (+/- SD) mass 78 (+/- 8) kg--of which fifteen studies proved suitable for analysis. Each study lasted for a period of five minutes, during which time recordings of intercostal EMG, ribcage postero-anterior displacement (RCPA) and airflow were made. For every breath taken by each of the subjects, the peak integrated EMG activity (iEMGpeak) was measured both by hand and by the automated system. The automated and manual measurements of iEMGpeak, which ranged from 0.0 to 91.3 microV, differed by only -0.82 +/- 3.34 microV (mean +/- SD). The index iEMGpeak and two additional indices of iEMG activity (iEMGmean, iEMGarea) were evaluated with respect to RCPA, a measure of overall respiratory activity. The indices of iEMG were observed to show an exponential dependence on RCPAamp, the amplitude of ribcage motion. Following a log transformation to linearise the relationship, the correlation of each index with RCPAamp was evaluated; iEMGpeak and iEMGarea correlated similarly with RCPAamp (no significant difference at 5% level), but iEMGmean was found to be a significantly different (p < 0.001) and poorer correlate. We conclude that the automated analysis of respiratory iEMG as described in this paper can provide results showing consistency with manual measurement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Modulation of cytokine production in vivo by dietary essential fatty acids in patients with colorectal cancer.

1. The effects of essential fatty acids (gamma-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid), at a dose of 4.8 g/day, given in combination as dietary supplements, on cytokine production were investigated in patients with colorectal cancer. 2. Total serum cytokines--interleukin (interleukin-1 beta, 2, 4 and 6), tumour necrosis factor-alpha and interferon-gamma--were analysed using the enzyme-linked immunosorbent assay technique at different time intervals during the course of essential fatty acid supplementation. 3. Fatty acid uptake and patient compliance were confirmed by a significant increase in serum levels of gamma-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid in all three fractions: tricylglycerol, cholesterol and phospholipid. 4. There was no significant alteration in total serum cytokine concentration/levels in the first 2 months of essential fatty acid ingestion, but the levels of serum cytokines steadily declined thereafter, reaching minimum levels after 6 months of essential fatty acid supplementation. 5. Essential fatty acids, at the dose and duration (6 months) used in this study, reduced total serum interleukin-1 beta levels by 61% (P = 0.044), interleukin-2 by 63% (P = 0.05), interleukin-4 by 69% (P = 0.025), interleukin-6 by 83% (P = 0.030), tumour necrosis factor-alpha by 73% (P = 0.040) and interferon-gamma by 67% (P = 0.050). 6. Three months after cessation of essential fatty acid intake, however, these cytokine levels returned to presupplementation values. 7. This present study has shown that long-term n-3 and n-6 EFA ingestion results in a significant reduction in circulating key cytokines. The precise mechanism of this reduction is unclear.

Aged↗

A comparison of the polymerase chain reaction with standard laboratory methods for the detection of EHV-1 and EHV-4 in archival tissue samples.

A detection system incorporating the polymerase chain reaction was compared with the use of histopathology and virus isolation to determine the presence of equid herpesvirus type 1 or equid herpesvirus type 4 in equine tissues submitted to a diagnostic laboratory. When the polymerase chain reaction was performed, these tissues had been stored for up to 3 years. Thirty-eight tissues representing 14 cases had been stored embedded in paraffin wax. Analysis of these tissues using the PCR gave predictive values of 1.0 and 0.91 for a positive and negative result respectively, and sensitivity and specificity values of 75% and 100% respectively. Fifty-three tissues representing 28 cases had been stored immersed in 10% formalin. Analysis of these tissues gave predictive values of 0.44 and 0.42 for a positive and negative result respectively, and sensitivity and specificity values of 28% and 57% respectively. The poor results obtained with this group of tissues was attributed to contamination of the samples during wax embedding. Viral DNA could not be amplified from older tissues. These results indicate that under appropriate conditions the polymerase chain reaction is reliable when applied to tissues collected for routine diagnosis. However, it is less reliable when samples for analysis are handled collectively. Also, storage of tissues in wax blocks for 14 or more years inhibits later amplification of viral DNA from these tissues. The implications of these results to the application of the polymerase chain reaction to routine laboratory diagnosis are discussed.

Journal Article↗