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Biomedical subjects

M Murphy

Publications and source records attributed to M Murphy.

At least 361 records · Page 20Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Binding and retrograde transport of leukemia inhibitory factor by the sensory nervous system.

Leukemia inhibitory factor (LIF), a peptide growth factor with multiple activities, has recently been shown to support the generation and survival of sensory neurons in cultures of mouse neural crest and dorsal root ganglia (DRG). We have conducted binding experiments with 125I-LIF on cultures of DRG to determine the receptor distribution for LIF on these cells and found that at least 60% of the sensory neurons in the cultures bound 125I-LIF, all of which could be eliminated by the addition of unlabeled LIF. The other cells in the culture, which morphologically appeared to be Schwann cells, did not bind appreciable quantities of 125I-LIF. In order to investigate whether LIF is retrogradely transported to sensory neurons in vivo, 125I-LIF was injected into the footpads and gastrocnemius muscles of newborn and adult mice, following sciatic nerve ligation. Radioactivity accumulated in the distal portion of the sciatic nerve, indicating retrograde transport of LIF. Subsequent experiments on mice with unligated sciatic nerves showed that 125I-LIF is specifically transported into the sensory neurons of the DRG. There was no apparent transport of 125I-LIF into motor neurons in the spinal cord. These experiments demonstrate that LIF can specifically bind to and be transported by sensory neurons and further support the idea that LIF acts as a target-derived neurotrophic factor, analogous to NGF.

Animals↗

How accurate is antenatal sonographic identification of discordant birthweight in twins?

The association between discordant birth weight in twins and poor perinatal outcome is well recognised. Antenatal identification of discordant fetal growth in twins using ultrasound has been previously reported. In this study we have assessed the accuracy of interpair percentage estimated fetal weight difference determination (interpair EFW%) in identifying an interpair percentage birth weight difference (interpair BW%) of greater than or equal to 20% and greater than or equal to 25% in 85 twin pregnancies. The maximum sensitivity, specificity, positive and negative predictive values we noted were 54.5, 98.5, 75 and 94.4%, respectively. These results suggest that interpair EFW% results should be interpreted with caution when used in the antenatal assessment of birth weight in twin pregnancies.

Abdomen↗

Generation of sensory neurons is stimulated by leukemia inhibitory factor.

The processes that regulate the development of peripheral neurons from their precursors in the embryonic neural crest are essentially unknown. In this report, we show that leukemia inhibitory factor stimulates the generation of neurons in cultures of mouse neural crest. These neurons have the morphology of sensory neurons and contain neuropeptides found in mammalian sensory neurons. Consistent with these neurons being of the sensory lineage is the finding that they arise from nondividing precursors within the neural crest. In addition, we show that leukemia inhibitory factor supports the generation and/or maturation of sensory neurons in cultures of cells obtained from embryonic dorsal root ganglia. In cultures of postnatal dorsal root ganglia, which contain mature sensory neurons, leukemia inhibitory factor acts directly as a survival molecule on the majority of neurons.

Animals↗

Fibroblast growth factor-mediated proliferation of central nervous system precursors depends on endogenous production of insulin-like growth factor I.

Fibroblast growth factor stimulates proliferation and subsequent differentiation of precursor cells isolated from the neuroepithelium of embryonic day 10 mice in vitro. Here we show that fibroblast growth factor-induced proliferation is dependent on the presence of insulin-like growth factors (IGFs) and that IGF-I is endogenously produced by the neuroepithelial cells. Blocking of endogenous IGF-I activity with anti-IGF-I antibodies results in complete inhibition of fibroblast growth factor-mediated proliferation and in cell death. IGF-I alone acts as a survival agent. These observations correlate with the detection of transcripts for IGF-I and basic fibroblast growth factor in freshly isolated neuroepithelium and are consistent with an autocrine action of these factors in early brain development in vivo.

Animals↗

Establishment and characterization of a human leptomeningeal cell line.

Human leptomeningeal cells grown in culture were immortalized via transfection with an SV40 large T antigen gene construct under the control of the Rous sarcoma virus promoter. This cell line, designated LTAg2B, maintained the polygonal morphology characteristic of primary cultures, and stained positively in early passage for cytokeratin, a specific marker for arachnoid cells of the leptomeninges. Additional immunofluorescent staining revealed that these cells express vimentin and desmoplakin as well; these antigens have been found together only in normal arachnoid tissue and in meningiomas, which are the neoplastic derivatives of leptomeningeal cells. Significantly, LTAg2B cells demonstrate a greatly increased life span and growth rate relative to primary cultures. The establishment of this cell line should thus facilitate studies on the cellular and molecular biology of leptomeningeal cells, as well as elucidate their roles in certain pathological situations involving the leptomeninges, such as meningitis and meningioma tumor formation.

Antigens, Polyomavirus Transforming↗

Cell lines derived from mouse neural crest are representative of cells at various stages of differentiation.

In order to study mammalian neural crest differentiation in vitro, a series of clonal neural crest (NC) cell lines have been generated by infection of migrating mouse neural crest cells with two recombinant retroviruses containing either the c-myc or N-myc proto-oncogenes. Many cell lines were generated which could be subdivided into three groups based on their appearance in culture. Eleven of these cell lines representative of each of the morphological groups were characterized for the expression of six antigenic markers expressed by neural cells. In addition, mRNA was prepared from these cell lines and analyzed for the expression of a number of neural specific genes. These analyses show that the cell lines are representative of the following cell types: (1) neural crest-like cell lines that do not differentiate in 10% serum; (2) progenitor cell lines, some of which can partially differentiate in culture; and (3) mature neuronal cell lines or bipotential cell lines. Southern blot analysis of DNA from these lines indicated that they have multiple integration sites for the provirus and suggest that phenotypically different cell types have arisen from a single cell. None of the cell lines showed any proliferative or morphological response to nerve growth factor (NGF), whereas over two-thirds of the lines showed both marked proliferative and morphological responses to fibroblast growth factor (FGF). These data indicate that we have generated a range of cell lines representative of a spectrum of mouse neural crest derivatives.

Animals↗

Basic fibroblast growth factor upregulates steady-state levels of laminin B1 and B2 chain mRNA in cultured neuroepithelial cells.

The growth of purified populations of murine neuroepithelial cells isolated from 10 day embryonic (E10) telencephalon and mesencephalon can be specifically enhanced by supplementing growth culture media with basic fibroblast growth factor (bFGF). One effect of bFGF on cultured neuroepithelial cells was to enhance the amount of laminin expressed at the protein level as detected by immunofluorescence. This was correlated with significant upregulation of steady-state levels of laminin B1 and B2 chain expression as analyzed at the mRNA level. When E12 neuroepithelial cells were split into precursor neuronal or glial subpopulations on the basis of differential expression of major histocompatibility class-1 antigens, only the glial progenitor fraction was found to be capable of detectable laminin synthesis. It is thus possible that a primary action of FGF is to increase the synthesis and release of extracellular matrix molecules from neural cells which act back in a paracrine manner to stimulate differentiation.

Animals↗