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Biomedical subjects

M Murphy

Publications and source records attributed to M Murphy.

At least 19 recordsLinked to original sources
PubMed1992

Fatal myocardial infarction and use of psychotropic drugs in young women.

We have observed an unexpected 17-fold increase in risk of fatal [corrected] myocardial infarction (relative risk 16.9, 95% confidence interval 3.9-72.8) associated with current use of psychotropic drugs. This incidental finding, in a case-control study of cardiovascular mortality in women aged 16-39 not designed to test any hypothesis about psychotropic drugs, should be treated cautiously. There is, however, evidence of a relation between psychiatric morbidity and cardiovascular disease and the association recorded here requires further investigation.

Adolescent↗
PubMed1992

Tumor necrosis factor-alpha and IFN-gamma expression in human thymus. Localization and overexpression in Down syndrome (trisomy 21).

In vitro studies suggest that TNF-alpha and IFN-gamma regulate thymocyte proliferation, but little evidence exists for the constitutive production of these cytokines in normal human thymus. In paired experiments, we examined frozen sections of postnatal human thymus from four control children and four age-matched children with Down syndrome (DS) (trisomy 21) for TNF-alpha and IFN-gamma mRNA expression using in situ hybridization. We studied thymuses from children with DS because this aneuploid condition is associated with a greatly increased incidence of infection and has abnormal thymic anatomy and patterns of thymocyte maturation. We found cells expressing constitutive levels of TNF-alpha mRNA in the trabeculae, corticomedullary junctions, and medulla of both control and DS thymuses and the number of these cells was an average of 3.9-fold higher in DS thymuses than in age-matched control thymuses. DS thymuses also contained an average of 3 fold higher numbers of cells with mast cell morphology, identified by toluidine blue histologic staining and electron microscopy. In both DS and control thymuses the mast cells colocalized with TNF-alpha mRNA-expressing cells. In addition, TNF-alpha protein- expressing cells, identified by immunohistochemistry, displayed a granular pattern of staining that is characteristic of mast cells. These results suggest that mast cells may be one source of TNF-alpha in human postnatal thymus. Discrete cells expressing IFN-gamma mRNA were distinctly localized to the cortical region of both DS and control thymuses and were 2.4-fold more abundant in DS thymuses than in the controls. Our results demonstrate, for the first time, the constitutive production and location of TNF-alpha and IFN-gamma in postnatal human thymus. The overexpression of both of these cytokines in DS thymuses suggests a dysregulation in cytokine production in DS and may provide an explanation for the abnormal thymic anatomy and thymocyte maturation associated with this syndrome.

Down Syndrome↗
PubMed1992

Fatal stroke and use of oral contraceptives: findings from a case-control study.

A case-control study of women less than 40 years of age in England and Wales was performed to evaluate the risk of fatal stroke associated with the use of the newer, low-dose oral contraceptives. Included were 296 cases with subarachnoid hemorrhage, 105 cases with other hemorrhagic stroke, and 21 cases with occlusive stroke, all of which occurred during 1986-1988. Two living controls per case, matched for age and marital status, were chosen from the general practice lists. The power of the study was such that the minimum significant increased relative risk of subarachnoid hemorrhage associated with ever having used oral contraceptives that could have been detected with 90% certainty was 1.6; the equivalent value for occlusive stroke was 28.4. Relative risk was estimated by conditional logistic regression allowing for matching. The adjusted relative risk of subarachnoid hemorrhage associated with oral contraceptives was estimated to be 1.1 (95% confidence interval (CI) 0.6-1.9) for current use and 1.3 (95% CI 0.9-1.8) for ever use, while the equivalent relative risk of an occlusive stroke associated with ever use was 4.4 (95% CI 0.8-24.4). Oral contraceptive use may be associated with a small increase in the risk of subarachnoid hemorrhage. These data are consistent with a substantial increase in the risk of occlusive stroke associated with oral contraceptive use.

Adolescent↗
PubMed1992

Leukemia inhibitory factor promotes the neuronal development of spinal cord precursors from the neural tube.

Recent evidence from our laboratory has shown that leukemia inhibitory factor (LIF) can act early in peripheral nervous system development. We have investigated a potential role of LIF in the developing spinal cord. In explants and dissociated cultures of spinal cord primordium, LIF stimulated a profuse neurite outgrowth. To determine if these effects were related to neuronal differentiation, cells were plated at low cell density and stained for neurofilament. LIF stimulated an increase in the number of newly differentiated neurons, without inducing proliferation of the precursors. Given that LIF has previously reported effects as a cholinergic switching factor for sympathetic neurons, we investigated whether LIF had similar effects in these spinal cord cultures. LIF increased the number of cholinergic neurons in proportion to its overall effect on the stimulation of all neurofilament positive neurons in the culture. These data show that LIF stimulates the generation of spinal cord neurons from their precursors and further implicates a role for LIF in nervous system development.

Animals↗
PubMed1992

Steel factor is required for maintenance, but not differentiation, of melanocyte precursors in the neural crest.

Skin melanocytes are derived from neural crest cells that migrate into the dermis during embryogenesis. Two mouse mutants, Steel and White dominant-spotting, which have defects in melanocyte production, have recently been shown to have deletions in the genes that code for a new growth factor, steel factor (SLF), and its receptor, respectively. Here, we have investigated the role that SLF plays in melanogenesis using cultures of mouse neural crest and found that its primary action is the maintenance of melanocyte precursors. It has no effect on the final stage of melanocyte differentiation, the production of melanin, which appears to require an additional factor whose action is mimicked by the phorbol ester TPA (12-O-tetradecanoyl-phorbol-13-acetate).

Animals↗
PubMed1992

Down syndrome (DS) peripheral blood contains phenotypically mature CD3+TCR alpha, beta+ cells but abnormal proportions of TCR alpha, beta+, TCR gamma, delta+, and CD4+ CD45RA+ cells: evidence for an inefficient release of mature T cells by the DS thymus.

Down syndrome (DS) thymocytes have a markedly diminished proportion of cells expressing high levels of the alpha, beta T cell receptor (TCR alpha, beta) and the associated CD3 molecule. Thus, we examined the surface expression of TCR alpha, beta and CD3 as well as TCR gamma, delta, CD4, CD8, CD16, and CD45RA on peripheral blood lymphocytes (PBL) from 13 noninstitutionalized subjects with DS and 13 closely age-matched sibling controls using immunofluorescence and flow cytometry. DS PBL expressed high surface levels of TCR alpha, beta and CD3, but, as compared to controls, they had a lower proportion of cells expressing TCR alpha, beta (61% vs. 68%, respectively; P less than or equal to 0.05). Moreover, the absolute number of TCR alpha, beta+ cells was considerably lower for DS subjects than for controls (1634 +/- 229 vs. 2763 +/- 530, respectively; P less than or equal to 0.05). DS subjects had a markedly higher proportion of cells expressing TCR gamma, delta than did the controls (12% vs. 7%, respectively; P less than or equal to 0.02). In addition, DS subjects had a lower proportion of CD4+CD45RA+ cells than controls (22% vs. 35%, respectively; P less than or equal to 0.02), representing naive T cells which have recently emigrated from the thymus. The imbalance in the proportions of T cell subpopulations we have observed in DS PBL may contribute to the increased susceptibility to infection associated with DS and may represent a diminished efficiency in the production of newly differentiated T cells by the DS thymus.

Adolescent↗
PubMed1992

Influence of blood handling techniques on lactic acid concentrations.

Despite the popularity of measuring blood lactic acid concentrations, many of the common variations in technique have not been evaluated. The purposes of this study were to: 1) establish the relationship between plasma and blood lactate concentrations, 2) determine the inter-analyzer reliability, and 3) assess the stability of lactate concentration in blood stored for up to one week. Blood was sampled from 26 volunteers before exercise, at 80% of estimated maximum heart rate, and 5 minutes after a treadmill run to exhaustion. Inter-machine reliability was tested between two Yellow Springs Instruments analyzers with buffer treated with a lysing agent and between two without. Blood lactate levels at all three levels could be predicted from plasma with R2 greater than .95. Correlations between duplicates on the same machine were greater than .96 for blood and .97 for plasma. In the worst cases, between duplicate differences and between machine differences were 2%. Lactate in stored blood was in some cases significantly different after 24 hours of storage. Moderate and high lactate concentrations in plasma were not significantly altered after 2 days of storage.

Adult↗
PubMed1992

A cluster of vancomycin-resistant Enterococcus faecium in an intensive care unit.

OBJECTIVE: To describe the epidemiology of a cluster of vancomycin-resistant Enterococcus faecium (VAREC) in a cardiothoracic surgery intensive care unit. DESIGN: A case series of patients identified through review of surveillance data on nosocomial infections, review of microbiologic records, and culture survey of patients in the unit. RESULTS: Six patients in the cardiothoracic surgery intensive care unit had VAREC with identical antimicrobic susceptibility patterns over a 6-month period. Four patients were identified with VAREC through prospective surveillance and 2 through retrospective review. Prior vancomycin use was seen more commonly in patients with VAREC (6/6, 100%) than in those without VAREC (3/12, 25%) (Fisher's exact test, p = .01). Six of the 7 patients with prior infection developed VAREC (85.7%). A prior nosocomial infection and prior exposure to vancomycin were found to be important variables in a logistic regression analysis. VAREC also was isolated from the environment. A combination of cohorting of patients and staff, and modifications of standard contact isolation practices eliminated the presence of VAREC from the cardiothoracic surgery intensive care unit. CONCLUSIONS: The results suggest that prior administration of vancomycin, especially in the patient who develops nosocomial infection, can influence the acquisition of vancomycin-resistant enterococci and that VAREC may be transmitted from patient to patient. Using a modification of the standard infection control practice of isolation, we were able to control the spread of this resistant strain of E faecium.

Cross Infection↗
PubMed1992

Risk factors for fatal venous thromboembolism in young women: a case-control study.

A case-control study of fatal venous thromboembolism in young women is described. Sixty women aged between 16 and 39 who died from thromboembolism in England and Wales between 1986 and 1988 were included in the study. Two living controls matched for age and marital status were sought from the records of the general practitioner with whom each case was registered. Some 115 controls were included in the study. The cases had a significantly higher prevalence of a history of major illness, particularly thrombotic episodes, than the controls. The odds ratio (OR) of a fatal thromboembolism in women who had a history of venous thrombosis was 4.0 (95% Cl: 1.4-11.5). There was also a significantly higher frequency of a recent operation or accident amongst the cases than the controls (OR = 11.1, 95% Cl: 1.3-92.5). There was no significant excess or oral contraceptive use amongst the cases. The overall OR associated with current use of oral contraceptives was 1.6 (95% Cl: 0.7-3.4), while the corresponding OR for 'idiopathic' diseases was 2.1 (95% Cl: 0.8-5.2). These risks are considerably smaller than those observed in previous studies. The observed risk may be low because the dosage of oestrogen in modern oral contraceptive preparations has been reduced, but it may also be because the cases of fatal venous thromboembolism included in this study represent only a small proportion of all cases of venous thrombeombolism; a disease which is rarely fatal in young women. These results cannot necessarily be extrapolated to nonfatal venous thromboembolism.

Adolescent↗
PubMed1992

Space time clustering of births in SIDS: do perinatal infections play a role?

The aetiology of sudden infant death syndrome (SIDS) remains uncertain; many causal pathways have been proposed. In this paper we have examined firstly the variation in the risk of SIDS with age, month of death and month of birth; and secondly the space time clustering of SIDS deaths, and, separately, space time clustering of their births. Data were obtained from the Office of Populations, Censuses and Surveys on all certified SIDS deaths in the period; children were assigned grid references for the address of birth and of death. Data on number of births were abstracted from published material. A log-linear modelling technique was used to investigate the separate effects of age, month of death and month of birth on the risk of SIDS. The Knox method was used to investigate space time clustering of deaths and of births of children who died of SIDS. Separate, statistically significant effects were found for age, month of death and month of birth. There was minor space time clustering of SIDS births and deaths at large time and space intervals, and a marked space time clustering of births in short space time intervals in the first quarter of the year. The finding of an effect of month of birth on the risk of SIDS, and of space time clustering of births suggest that a perinatal hazard--possibly of infectious origin--may play a role in the aetiology of SIDS.

Birth Intervals↗
PubMed1992

Twin peaks, extramarital conceptions, and virgin births: is there a connection?

The trends in British twin and higher multiple birth rates inside and outside marriage from 1938 to 1989 were reviewed for evidence of the probable impact of the use of ovulatory stimulants. After adjustment for maternal age monozygotic twin rates within marriage rose to a significant excess (of 12%) over those outside during the last two decades; a similar increase of higher multiple births within marriage to a significant excess (of 50%) over those outside was also seen for 1980-9. The dizygotic twin rate within marriage exceeded that outside in 1989 for only the second time in 50 years, as the difference in rates narrowed in the last decade. It is concluded that ovulation induction and techniques of assisted conception are apparently more available to the married, with a stronger effect on higher multiple birth rates than on dizygotic twin rates. Monozygotic twin trends support the suggestion that part of the infertility treatment regimen also promotes zygote splitting.

England↗
PubMed1992

Predicting mortality from cancer of the uterine cervix from 1991-2001.

STUDY OBJECTIVE: The aim was to provide benchmarks by which to judge the success of behaviour change and the cervical cancer screening programme in England and Wales in reducing mortality from this disease over the next decade. DESIGN: Log-linear models and cervical cancer mortality data by age and marital status from 1959-88 were used to predict future mortality in England and Wales. MEASUREMENTS AND MAIN RESULTS: Recombining "predicted" deaths in marital status groups for 1984-88 gave a closer agreement to total mortality observed in those years than predictions based on past trends from 1959-83 among women of all statuses combined. Mortality for 1989-2003 was then predicted, using the data for 1959-1988. CONCLUSIONS: The reaggregated marital status forecasts of mortality provide an upper boundary which future observed mortality should not cross if primary and secondary prevention measures are working effectively. The method allows swift comparison of observation with expectation and therefore the rapid evaluation of the overall performance of preventive strategies.

Adult↗
PubMed1992

A role for tumor necrosis factor-alpha and interferon-gamma in the regulation of interleukin-4-induced human thymocyte proliferation in vitro. Heightened sensitivity in the Down syndrome (trisomy 21) thymus.

The influence of recombinant interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF) on IL-4-induced proliferation of postnatal human thymocytes from eight children with Down syndrome (DS, trisomy 21) and 18 control children was evaluated. DS thymuses were studied because they are characterized by cortical depletion and abnormal thymocyte differentiation. IL-4, without mitogen, induced a dose-dependent proliferation of both DS and control thymocytes. The proliferation was comparable to that induced by IL-2 and far greater than the proliferation mediated by IL-1 beta in the absence of mitogen. The level of IL-4 responsiveness correlated with the proportion of cells expressing the gamma, delta chains of the T cell receptor. Furthermore, thymocyte preparations greatly enriched for T cell receptor gamma, delta-bearing cells were found to vigorously proliferate when treated with IL-4. Both IFN-gamma and TNF inhibited IL-4-driven proliferation in a dose-dependent manner, but DS thymocytes were found to be significantly more sensitive to inhibition by both cytokines. Our studies suggest an important role for IL-4 in the proliferation of T cell receptor gamma, delta+ thymocytes and demonstrate regulatory functions for IFN-gamma and TNF in human thymocyte proliferation. The increased sensitivity of DS thymocytes to IFN-gamma and TNF may explain anatomical abnormalities in DS thymuses and suggests the involvement of genes encoded on human chromosome 21 in the responses to both IFN-gamma and TNF.

Cell Division↗
PubMed1992

Phlebotomy practices/needles stick injuries/hepatitis B status/among interns in a Dublin hospital.

Needlestick injury is the most important risk event for human immunodeficiency virus (HIV) and hepatitis B Virus (HBV) transmission to health-care workers. We examined phlebotomy practices, the frequency of needle stick injuries, the reporting of such injuries and hepatitis B status among interns in St James's Hospital during a six month period. This study took the form of a questionnaire. The response rate was 100%. 72% had at least one needlestick injury during this time period, 23% had injuries from known HIV sero-positive or hepatitis B surface antigen positive patients, less than 5% of all injuries were reported and only 41% of interns were definitely hepatitis B immune. The majority (77%) resheated needles by hand.

Accidents, Occupational↗
PubMed1992

Toxoplasma pneumonitis: fatal presentation of disseminated toxoplasmosis in a patient with AIDS.

Toxoplasma gondii infection is an uncommon cause of pneumonitis in patients with acquired immune deficiency syndrome (AIDS). We report a case of fatal pulmonary toxoplasmosis, which clinically resembled Pneumocystis carinii pneumonia (PCP). Conventional diagnostic methods for toxoplasmosis lack sensitivity. Bronchoscopy and histological evaluation of transbronchial biopsy specimens failed to identify the infecting organism. At autopsy there was evidence of disseminated infection.

Acquired Immunodeficiency Syndrome↗