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Biomedical subjects

L Murray

Publications and source records attributed to L Murray.

At least 109 records · Page 6Linked to original sources

Depressed mothers' speech to their infants and its relation to infant gender and cognitive development.

The speech of depressed and well mothers during play with their infants at two months was compared on dimensions of structure and semantics. No differences between maternal groups were found on measures of complexity and syntax. However, the speech of depressed women expressed more negative affect, was less focused on infant experience, and tended to show less acknowledgement of infant agency. Speech style of depressed women also varied according to infant gender. Regression analyses indicated that the quality of maternal communication with the infant, and particularly the focus of speech, mediated the association between depression and infant cognitive development in the first 18 months.

Adult↗

Effect of simvastatin on plasma lipid and lipoprotein concentrations and low-density lipoprotein metabolism in the nephrotic syndrome.

1. The effect of inhibiting the rate-limiting enzyme (3-hydroxy-3-methylglutaryl-CoA reductase, EC 1.1.1.88) in cholesterol synthesis on plasma lipid and lipoprotein concentrations was investigated in 16 patients with primary glomerular disease, heavy proteinuria, well-preserved renal function and hypercholesterolaemia. 2. Detailed studies of low-density lipoprotein metabolism were performed on eight patients before and after 12 weeks of simvastatin therapy. Radioiodinated tracers were used to quantify the fractional catabolic rate of low-density lipoprotein by apolipoprotein B/E receptors and alternative pathways. 3. Simvastatin produced consistent reductions in total plasma cholesterol concentration (median 36.9%), plasma low-density lipoprotein-cholesterol concentration (43.6%) and apolipoprotein B pool size (29.9%). 4. In contrast, the changes in kinetic parameters of low-density lipoprotein metabolism showed no clear pattern. Although an increase in the receptor-mediated catabolism of low-density lipoprotein was demonstrated in five patients, no change or a slight decrease was seen in three patients. Production rates were not significantly altered, although there was a slight decrease in the median value (from 12.4 to 9.7 mg day-1 kg-1). Plasma lathosterol concentration was reduced in all eight patients (range 34-71%), indirectly confirming significant inhibition of cholesterol synthesis. 5. These results suggest that, as in patients with primary moderate hyperlipidaemia, the significant cholesterol-lowering effect of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors in the nephrotic syndrome is accompanied by variable changes in lipoprotein metabolism. The reasons for this heterogeneous response are unclear. This reflects our limited understanding of the metabolic basis of nephrotic hyperlipidaemia and the relationship between hepatic sterol synthesis and plasma lipoprotein kinetics.

Adult↗

The impact of postnatal depression on infant development.

A large sample of primiparous women was screened for depression after childbirth. Those identified as depressed, women with a previous history of depression and a control group were followed up to 18 months, when their infants were assessed on measures of cognitive, social and behavioral development. Infants of postnatally depressed mothers performed worse on object concept tasks, were more insecurely attached to their mothers and showed more mild behavioural difficulties. Postnatal depression had no effect on general cognitive and language development, but appeared to make infants more vulnerable to adverse effects of lower social class and male gender.

Child↗

Activities of various quinolone antibiotics against Mycobacterium leprae in infected mice.

Previously, pefloxacin and ofloxacin were found to be active against Mycobacterium leprae in vitro, in experimental animals, and in clinical trials of lepromatous leprosy patients. In this study, we compared certain more recently developed fluoroquinolones (lomefloxacin, PD 124816, WIN 57273, temafloxacin, and sparfloxacin) with pefloxacin and ofloxacin in M. leprae-infected mice at doses of 50, 150, and 300 mg/kg given five times weekly. All seven of the fluoroquinolones studies were active against M. leprae; temafloxacin and sparfloxacin were the most active, being fully bactericidal at all three dosage schedules. Additionally, sparfloxacin was found to be fully bactericidal at 15 and 30 mg/kg given five times weekly.

Animals↗

Vaccination of mice with a soluble protein fraction of Mycobacterium leprae provides consistent and long-term protection against M. leprae infection.

Groups of BALB/c mice were vaccinated intradermally with either Freund's incomplete adjuvant (FIA) alone, 10(7) heat-killed Mycobacterium leprae organisms in FIA, or a number of fractions of M. leprae containing soluble and/or cell wall components. At 1, 3, 6, 9, and 12 months later, vaccinated mice were challenged in the right hind footpad with 5,000 live M. leprae organisms, and vaccine protection was assessed 6 to 8 months later, at the peak of M. leprae multiplication in the negative control (FIA alone), by the two-sample rank-sum test. In these studies, a cell wall fraction rich in peptidoglycan was consistently ineffective. Both heat-killed M. leprae and a fraction containing cell wall and fixed proteins generally protected when the interval between vaccination and challenge was 1 or 3 months but not subsequently. On the other hand, soluble proteins of M. leprae alone or in combination (with cell wall fractions) consistently (14 of 14 instances) afforded highly significant protection (P less than or equal to 0.01) at all challenge intervals up to 1 year after vaccination. These results suggest that the soluble protein fraction of M. leprae offers promise for a vaccine against leprosy.

Animals↗

Abnormal T cells from lpr mice down-regulate transcription of interferon-gamma and tumor necrosis factor-alpha in vitro.

We have studied the ability of isolated T cell subpopulations from the autoimmune mouse MRL/MPJ/lpr/lpr (lpr) to proliferate and to undergo changes in cytokine gene transcription in vitro, in the presence or absence of cytokines. The lpr mouse develops lupus-like symptoms and massive lymphadenopathy due to accumulation of abnormal CD4-/CD8- T lymphocytes, which are unusual in coexpressing Thy1 and B220. FACS-purified B220+/Thy1+ lpr lymph node cells showed little proliferative response to cytokines, even in the presence of PMA, and failed to proliferate in response to stimulation through the CD3/TcR complex. Polymerase chain reaction was used to examine the presence of cytokine gene transcripts in B220-/Thy1+ and B220+/Thy1+ ("abnormal") T cells, before and after in vitro culture. The high level of transcripts of IFN-gamma and TNF-alpha genes observed in freshly isolated B220+/Thy1+ cells decreased after 10 hr of in vitro culture, while levels of TNF-beta, IL-6 and TGF-beta transcripts were maintained. These results suggest that a positive stimulus for IFN-gamma and TNF-alpha gene transcription by lpr B220+/Thy1+ cells may exist in vivo but is removed upon purification of this abnormal T cell subset.

Animals↗

Estimating psychiatric morbidity by logistic regression: application to post-natal depression in a community sample.

The use of logistic regression to estimate the prevalence of psychiatric morbidity in community samples is illustrated here with data from a study of post-natal depression in 702 primiparous Cambridge mothers. The method is also used to validate the primary screening instrument (in this case the Edinburgh Postnatal Depression Scale--EPDS), and to estimate the effects of cofactors, such as maternal age, previous psychiatric history and social class.

Adult↗

The validation of the Edinburgh Post-natal Depression Scale on a community sample.

The Edinburgh Post-natal Depression Scale (EPDS) was validated on a community sample of 702 women at six weeks post-partum using Research Diagnostic Criteria for depression. The estimates of sensitivity, specificity and positive predictive value, being based on a large random sample, offer improved guidelines for the use of the EPDS by the primary care team.

Adult↗

Recurrent hematomas following craniotomy for traumatic intracranial mass.

Of 850 patients who underwent craniotomy for evacuation of a traumatic intracranial mass, 59 (6.9%) developed a second hematoma at the operation site, which required a second operation. Compared to those who did not, patients who developed postcraniotomy hematoma (PCH) had a significantly higher incidence of evidence of alcohol intake and preoperative mannitol administration; a higher percentage had a bad outcome. Coagulopathy was frequent in PCH patients. Although three-quarters of the initial hematomas were intradural, 69% of the PCH's were predominantly extradural. The large potential space underlying a craniotomy bone flap may predispose to development of a PCH. Intracranial pressure (ICP) was monitored in 39 of the 59 PCH patients, which allowed earlier detection of the PCH in 22 (56%). In 17 patients, the ICP failed to rise despite clinical deterioration, and detection of the PCH was delayed, significantly worsening the outcome in this group.

Adult↗

Charge densities of atoms of conjugated styryl ketones having activity against L1210 leukemia cells.

Electron density calculations were undertaken on several atoms in a series of 3-substituted-4-phenyl-3-buten-2-ones in order to gain insight into the molecular features which affect charge densities. The results indicate that substituents at position 3 alter the electron densities of the olefinic group but have little effect on the acetyl function. The compounds were tested against L1210 cells in vitro, and the results suggest that electronic--but not steric--factors are important in affecting cytotoxicity. The most active compound was 3-phenylmethylene-2,4-pentanedione (1c) with an ED50 value of 1.06 x 10(-8) M.

Animals↗

Detection of cellular platinum using the monoclonal antibody 1C1.

A monoclonal antibody, 1C1, developed using a trans-R,R-1,2-diamminocyclohexane (DACH) modified platinum analog (DACH-Pt-SO4) complexed with DNA was shown, using the enzyme-linked immunosorbent assay (ELISA), to have the ability to bind to both free drug DACH-Pt-SO4 and to the drug-DNA complex. Using competitive ELISA, 1C1 was found to recognize non-DACH-containing platinum compounds, such as cis-dichlorodiammine platinum (II) (CDDP). 1C1 exhibited strong binding to slot-blotted, DACH-Pt-SO4-treated DNA and moderate binding to the CDDP-DNA complex, but was unable to detect DACH containing methyliminodiacetato-trans-R,R-1,2-diamminocyclohexane platinum (II) (MIDP)-modified DNA. Immunocytochemical staining studies using 1C1 antibody on CDDP-treated BRO melanoma cells showed preferential staining of the cytosol compared with the nucleus. Although the extent of staining was dose dependent, a heterogeneous staining pattern was observed. Multicellular spheroids of MDA886LN squamous carcinoma cells treated with CDDP showed intense staining on the growing periphery compared with weak but homogeneous staining within the spheroid. Cell cycle-dependent uptake of CDDP in synchronized BRO cells may partly explain the observed heterogeneity of platinum distribution.

Antibodies, Monoclonal↗

Changes in hemodynamic variables during hypothermic cardiopulmonary bypass. Effects of flow rate, flow character, and arterial pH.

During hypothermic cardiopulmonary bypass, the effects on hemodynamic variables of alternating pump flow rate between 1.5 and 2.0 L.min-1.m-2, flow character between nonpulsatile and pulsatile perfusion, and acid-base management between pH- and alpha-stat control were studied in a crossover factorial experiment. Twenty-four patients who were undergoing elective coronary artery bypass grafting were studied during stable hypothermic (27 degrees to 29 degrees C) cardiopulmonary bypass. A minimum of two (when time allowed, three) consecutive 10-minute periods (period 1, 2, or 3) were investigated. Only stage of the study period during cardiopulmonary bypass, flow rate, and interaction between stage and acid-base management were found to have significant effects on mean arterial pressure. In all patients, there were average increases in mean arterial pressure from period 1 to period 2 of 9.4 (95% confidence interval 5.8, 13.0) mm Hg, from period 2 to period 3 of 6.3 (95% confidence interval 1.2, 11.4) mm Hg, and from period 1 to period 3 of 15.7 (95% confidence interval 10.6, 20.9) mm Hg. At 2.0 L.min-1.m-2, mean arterial pressure was 7.2 (95% confidence interval 1.6, 12.9) mm Hg higher than at 1.5 L.min-1.m-2. Peripheral vascular resistance was significantly affected only by stage and flow rate. There were, in all patients, mean increases in peripheral vascular resistance from period 1 to period 2 of 239 (95% confidence interval 135, 343) dynes.sec.cm-5, from period 2 to period 3 of 85 (-64, 234) dynes.sec.cm-5, and from period 1 to period 3 of 324 (95% confidence interval 175, 473) dynes.sec.cm-5. At 1.5 L.min-1.m-2, the peripheral vascular resistance was 316 (95% confidence interval 152, 480) dynes.sec.cm-5 higher than at 2.0 L.min-1.m-2. Alteration in flow rate, but not flow character or arterial pH, had a significant effect on peripheral vascular resistance. It is hypothesized that the increase in peripheral vascular resistance during the course of cardiopulmonary bypass results from an active capillary mechanism, whereas the increase that is associated with reduction in flow rate reflects a passive mechanism. The increase in peripheral vascular resistance with decrease in flow rate indicates impaired tissue perfusion, unlike that occurring with stage.

Blood Pressure↗