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Biomedical subjects

A Murray

Publications and source records attributed to A Murray.

At least 127 records · Page 7Linked to original sources
PubMed2000

Computer model for study of cardiac repolarization.

INTRODUCTION: We propose a new and simple method to model repolarization in the left ventricle and the corresponding T waves on the surface ECG. METHODS AND RESULTS: We modeled the cardiac cell action potentials (APs) in the left ventricle (LV) with differences in only the duration of the plateau phase. Using published experimental data on the epicardial and endocardial repolarization sequences, for each point on the left ventricular surface we set a different AP repolarization starting time, determined by the duration of the plateau phase. The surface source model was used to compute potentials on the surface of the torso, generated by repolarization of the LV. Both the torso and the LV had homogeneous and isotropic conductivity. We simulated T waves on the 12-lead ECG and compared our results with measured T waves from five normal subjects. The orientation and shape in each lead were reproduced. In each lead we computed the root mean square error between simulated and measured T waves. The average error across the 12 leads was small, with a mean value of 0.11 mV across all the subjects. CONCLUSION: Repolarization of the LV can be modeled independently of the depolarization sequence and AP duration gradients. This method is an easy and powerful tool to describe the ECG features of repolarization.

Action Potentials↗
PubMed2000

Comparison of three serological tests and an interferon-gamma assay for the diagnosis of paratuberculosis in experimentally infected sheep.

OBJECTIVE: To compare the diagnostic performance of a complement fixation test, an agar gel immunodiffusion test, an enzyme-linked immunosorbent assay, and a whole-blood interferon-gamma assay for paratuberculosis in 14 sheep experimentally infected with Mycobacterium avium subsp paratuberculosis. EXPERIMENTAL DESIGN: Longitudinal study. RESULTS: The IFN-gamma assay detected more experimentally infected sheep, and earlier, than any of the serological tests. None of the antibody assays was able to detect all sheep with histologically confirmed paratuberculosis. CONCLUSIONS: The superior performance of the IFN-gamma assay in detecting infected sheep in this small experimental population warrants its further evaluation in a larger population of sheep naturally exposed to M a paratuberculosis.

Animals↗
PubMed2000

Vaccination against paratuberculosis of lambs already infected experimentally with Mycobacterium avium subspecies paratuberculosis.

OBJECTIVE: To assess the protective value of a live-attenuated vaccine in sheep already exposed to Mycobacterium avium subsp paratuberculosis and to investigate the progression of a systemic immune response in experimentally infected sheep. STUDY DESIGN: Twenty-eight lambs, aged 1 to 1.5 months, were dosed via stomach tube with approximately 4.4 x 10(8) M a paratuberculosis organisms. Two weeks later, 14 of these 28 animals received subcutaneous injections of 1 mL of a live-attenuated vaccine. Thirteen additional lambs were neither dosed nor vaccinated (negative controls). Antigen-induced production of IFN-gamma in blood, and antibody concentrations in serum were sequentially monitored in vaccinated, unvaccinated and control animals for 1 year. Each sheep was examined for infection by an IS900-based PCR test on samples of ileum and ileocaecal lymph node and histological examination at the time of necropsy. RESULTS: Seven of 14 unvaccinated and two of 14 vaccinated sheep developed clinical paratuberculosis that was later confirmed by histological examination and/or the IS900-based PCR test. The granulomatous inflammation in the jejunal and ileal mucosa was less severe in vaccinated than in unvaccinated sheep. Acid-fast organisms were detected only in the unvaccinated group. The PCR assay on ileal samples gave positive reactions in two vaccinated and eight unvaccinated sheep. Both the antibody response and IFN-gamma response were detected earlier and were more substantial in vaccinated than in unvaccinated sheep. Furthermore, in experimentally infected but unvaccinated sheep, the IFN-gamma concentrations were higher in those animals without acid-fast organisms than in those with them. CONCLUSIONS: Vaccination of lambs with live-attenuated vaccine 2 weeks after oral inoculation with M a paratuberculosis stimulated the host response against the organism and led to a reduced mycobacterial burden. The diminished IFN-gamma responses in experimentally infected sheep with acid-fast organisms suggest a positive relationship between the magnitude of the systemic cell-mediated immune response and an animal's ability to control infection.

Animals↗
PubMed2000

Use of the polymerase chain reaction assay for the detection of Mycobacterium avium subspecies paratuberculosis in blood and liver biopsies from experimentally infected sheep.

OBJECTIVE: To evaluate a polymerase chain reaction-based assay for the detection of Mycobacterium avium subsp paratuberculosis in blood and liver biopsies from subclinically infected sheep. STUDY DESIGN: A direct PCR assay for the detection of M a paratuberculosis was applied to liver biopsy specimens and to samples of blood that were sequentially collected over 53 weeks from 14 sheep infected experimentally with the organism. RESULTS: Of 117 blood samples from the 14 experimentally infected sheep, two tested positive in the PCR assay. Both positive results were obtained in two subclinically infected sheep that had paratuberculosis later confirmed by histological examination at necropsy. However, the assay failed to detect the target DNA in samples of blood from five other sheep with histologically confirmed paratuberculosis. Similarly, the PCR assay on liver biopsy specimens collected 32 weeks after administration of M a paratuberculosis gave only two positive results, both of which were obtained in sheep with histological evidence of paratuberculosis. CONCLUSIONS: The PCR assay on blood and liver biopsies does not provide a useful method for the diagnosis of M a paratuberculosis infection in subclinically infected sheep.

Animals↗
PubMed2000

FRAXA and FRAXE: the results of a five year survey.

We report the results of a five year survey of FRAXA and FRAXE mutations among boys aged 5 to 18 with special educational needs (SEN) related to learning disability. We tested their mothers using the X chromosome not transmitted to the son as a control chromosome, and the X chromosome inherited by the son to provide information on stability of transmission. We tested 3738 boys and 2968 mothers and found 20 FRAXA and one FRAXE full mutations among the boys and none among the mothers. This gives an estimated prevalence of full mutations in males of 1 in 5530 for FRAXA and 1 in 23 423 for FRAXE. We found an excess of intermediate and premutation alleles for both FRAXA and FRAXE. For FRAXA this was significant at the 0.001 level but the excess for FRAXE was significant only at the 0.03 level. We conclude that the excess of intermediate and premutation sized alleles for FRAXA may well be a contributing factor to the boys' mental impairment, while that for FRAXE may be a chance finding. We studied approximately 3000 transmissions from mother to son and found five instabilities of FRAXA in the common or intermediate range and three instabilities of FRAXE in the intermediate range. Thus instabilities in trinucleotide repeat size for FRAXA and FRAXE are rare, especially among alleles in the common size range.

Adolescent↗
PubMed2000

Assessing rbf networks using DELVE.

In this paper, different methods for training radial basis function (RBF) networks for regression problems are described and illustrated. Then, using data from the DELVE archive, they are empirically compared with each other and with some other well known methods for machine learning. Each of the RBF methods performs well on at least one DELVE task, but none are as consistent as the best of the other non-RBF methods.

Algorithms↗
PubMed2000

Risk of recurrence of bipolar disorder in pregnant and nonpregnant women after discontinuing lithium maintenance.

OBJECTIVE: Pregnancy poses major challenges for the treatment of bipolar disorder, and information to guide clinical care remains very sparse. The authors sought to determine the illness recurrence risk for women with bipolar disorder who discontinue lithium maintenance during pregnancy. METHOD: The authors retrospectively compared recurrence rates and survival functions for 101 women with DSM-IV bipolar disorder (68 type I, 33 type II) during pregnancy and postpartum (N=42) or during equivalent periods (weeks 1-40 and 41-64) for age-matched nonpregnant subjects (N=59) after either rapid (1-14 days) or gradual (15-30 days) discontinuation of lithium. Recurrence rates also were obtained for the year before discontinuing lithium. RESULTS: Rates of recurrence during the first 40 weeks after lithium discontinuation were similar for pregnant (52%) and nonpregnant women (58%) but had been much lower for both in the year before treatment was discontinued (21%). Among subjects who remained stable over the first 40 weeks after lithium discontinuation, postpartum recurrences were 2.9 times more frequent than recurrences in nonpregnant women during weeks 41-64 (70% versus 24%). Depressive or dysphoric-mixed episodes were more prevalent in pregnant than nonpregnant women (63% versus 38% of recurrences). Recurrence risk was greater after rapid than after gradual discontinuation, and for patients with more prior affective episodes, but was similar for diagnostic types I and II. CONCLUSIONS: Rates of recurrence during the first 40 weeks after lithium discontinuation were similar for pregnant and nonpregnant women but then sharply increased postpartum. Risk was much lower during preceding treatment and less with gradual discontinuation. Treatment planning for potentially pregnant women with bipolar disorder should consider the relative risks of fetal exposure to mood stabilizers versus the high recurrence risks after discontinuing lithium.

Age of Onset↗
PubMed2000

Pyoderma gangrenosum in a patient with essential thrombocythemia.

BACKGROUND: Pyoderma gangrenosum is an uncommon ulcerative condition associated with inflammatory bowel disease, arthritis, and hematologic disease. We report a patient with essential thrombocythemia and pyoderma gangrenosum. OBJECTIVE: This article is a review of the associations between pyoderma gangrenosum and other diseases. RESULTS: There have been two previous reports of patients with pyoderma gangrenosum and essential thrombocythemia. CONCLUSION: There may be a possible association between pyoderma gangrenosum and essential thrombocythemia. The diagnosis of pyoderma gangrenosum should be considered in patients with essential thrombocythemia and cutaneous ulcers.

Anti-Inflammatory Agents↗
PubMed2000

Excision of nasopharyngeal angiofibroma facilitated by intra-operative 3D-image guidance.

The latest 3D-image guidance systems to assist surgeons have greatly improved over earlier models. We describe the use of an optical infra-red system to assist in the removal of a juvenile nasopharyngeal angiofibroma. The specific advantages of this system in pre-operative assessment, intra-operative evaluation and excision of the angiofibroma are discussed.

Adult↗
PubMed2000

Genomic arrangement of a putative operon involved in maltose transport in the Mycobacterium tuberculosis complex and Mycobacterium leprae.

A Mycobacterium bovis gene coding for a putative MalE maltose binding protein was cloned and its full-length sequence determined. Database searches revealed 99.9% identity with IpqY, encoding a putative sugar uptake protein from Mycobacterium tuberculosis strain H37Rv. The deduced protein product showed high sequence similarity to MalE-like proteins from a variety of bacterial species, including Mycobacterium leprae. Analysis of flanking database sequences from M. tuberculosis and M. leprae revealed the presence of malF-, malG- and malK-like genes. Comparison of these mycobacterial sequences with other maltose operons has allowed us to deduce a unique genomic arrangement of the genes involved in the uptake of maltose in members of the Mycobacterium tuberculosis complex and M. leprae.

ATP-Binding Cassette Transporters↗
PubMed1999

Fulminant hepatic failure resulting from lamivudine-resistant hepatitis B virus in a renal transplant recipient: durable response after orthotopic liver transplantation on adefovir dipivoxil and hepatitis B immune globulin.

BACKGROUND: Mutations in the hepatitis B virus (HBV) genome may occur during therapy. METHODS: We report an asymptomatic HBV carrier who underwent transplantation for end-stage renal disease. She developed an HBV flare 6 months after transplantation and was placed on lamivudine. After initial rapid improvement, she relapsed clinically and virologically. She decompensated with jaundice, peripheral edema, ascites, encephalopathy, coagulopathy, and hepatorenal syndrome. A liver biopsy specimen revealed submassive necrosis. RESULTS: Emergency liver transplantation was performed: lamivudine was discontinued. Hepatitis B immunoglobulin and adefovir dipivoxil were initiated. Sixteen months after orthotopic liver transplantation, she is HBV DNA seronegative with normal liver enzymes. Sequencing of HBV polymerase gene from preliver transplantation sera did not detect the usual lamivudine resistance mutations in the YMDD motif but instead two other mutations (F514-->L, L528-->M). Lamivudine resistance was demonstrated in vitro. CONCLUSIONS: Asymptomatic HBV carriers may reactivate following renal transplantation after immunosuppression. Resistance to lamivudine may result in severe hepatic damage in immunocompromised patients.

Adenine↗
PubMed1999

Splicing mutations in KCNQ1: a mutation hot spot at codon 344 that produces in frame transcripts.

BACKGROUND: Long-QT syndrome is a monogenic disorder that produces cardiac arrhythmias and can lead to sudden death. At least 5 loci and 4 known genes exist in which mutations have been shown to be responsible for the disease. The potassium channel gene KCNQ1, previously named KVLQT1, on chromosome 11p15.5 is one of these. METHODS AND RESULTS: We initially analyzed one family using microsatellite markers and found linkage to KCNQ1. Mutation detection showed a G to C change in the last base of exon 6 (1032 G-->C) that does not alter the coded alanine. Restriction digest analysis in the family showed that only affected individuals carried the mutation. A previous report suggested that a G to A substitution at the same position may act as a splice mutation in KCNQ1, but no data was given to support this hypothesis nor was the transcription product identified. We have shown by reverse-transcription polymerase chain reaction that 2 smaller bands were produced for the KCNQ1 gene transcripts in addition to the normal-sized transcripts when lymphocytes of affected individuals were analyzed. Sequencing these transcripts showed a loss of exon 7 in one and exons 6 and 7 in the other, but an in-frame transcript was left in each instance. We examined other families in whom long-QT syndrome was diagnosed and found another unreported splice-site mutation, 922-1 G-->C, in the acceptor site of intron 5, and 2 of the previously reported 1032 G-->A mutations. All these showed a loss of exons 6 and 7 in the mutant transcripts, validating the proposal that a consensus sequence is affected in the exonic mutations and that the integrity of the base at position 1032 is essential for correct processing of the transcript. CONCLUSIONS: The 6 cases already reported in the literature with the 1032 G-->A transition, the novel 1032 G-->C transversion, and a recent G-->T transversion at the same base show that codon 344 is the second most frequently mutated after codon 341, suggesting at least two hotspots for mutations in KCNQ1.

Child, Preschool↗