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Biomedical subjects

D Murray

Publications and source records attributed to D Murray.

At least 163 records · Page 9Linked to original sources

Childbirth: life event or start of a long-term difficulty? Further data from the Stoke-on-Trent controlled study of postnatal depression.

BACKGROUND: This paper reports further data from the Stoke study of postnatal depression and examines whether psychosocial characteristics and symptom profiles differ between postnatal and control depression. METHOD: Two hundred and thirty-two postnatal and non-postnatal control women were screened with the Edinburgh Postnatal Depression Scale; all high scorers and a sample of low scores were interviewed with the Standardised Psychiatric Interview and modified Social Maladjustment Schedule. Depression was diagnosed using the Research Diagnostic Criteria. RESULTS: Postnatal but not control depression was associated with a poor relationship with the woman's own mother and greater occupational instability. Depression in control women was associated with low income, having three or more children, performing manual work and occupational dissatisfaction, but postnatal depression was not. There were no differences in the symptom profiles of the postnatal and control women nor between early and late onset postnatal depression. CONCLUSION: Depression is a common and socially disabling disorder affecting mothers of young children. Postnatal depression is more contingent on acute biopsychosocial stresses caused by the arrival of a new family member. Depression in women with older children is more closely related to longer term social adversity.

Adult↗

Mechanisms of cyclophosphamide resistance in a human myeloid leukemia cell line.

The 4-hydroperoxycyclophosphamide (4HC)-resistant B5-180(3) subline of the cloned KBM-7/B5 cell line was developed as a model of induced cyclophosphamide resistance in human myeloid leukemia. Based on IC90 values, this subline was approximately 20-fold resistant to 4HC. Furthermore, it was significantly cross-resistant to phosphorodiamidic mustard (PM), whose cytotoxicity is independent of aldehyde dehydrogenase (ADH). Using alkaline elution we found that the resistant line had decreased initial levels of DNA interstrand cross-links (ISCs) following 4HC but not PM treatment. The resistant cells also appeared to remove ISCs from their DNA more rapidly than the parental cells. Our data therefore suggest that 4HC resistance in the B5-180(3) subline is multifactorial; ADH is an important mediator of its resistance to ISC induction by 4HC, while a second process, which may involve an increased ability to tolerate drug-induced DNA damage, appears to be important for its resistance to both 4HC and PM. The B5-180(3) cells were also cross-resistant to gamma-radiation (approximately 1.7-fold at a surviving fraction of 0.1); if generally applicable, such effects could have important clinical implications, since pretransplant total body irradiation is a major component of the eradication of leukemic cells.

Aldehyde Dehydrogenase↗

Onward and upward with managed care.

Pediatricians are among the big gainers from managed care, according to the latest Medical Economics Continuing Survey. These findings will let you compare your managed-care participation and earnings with those of your colleagues.

Humans↗

Evaluation of weight reduction in a community intervention for cardiovascular disease risk: changes in body mass index in the Minnesota Heart Health Program.

This paper describes the effectiveness of the Minnesota Heart Health Program (MHHP) in modifying mean body mass index (BMI) in whole communities. The MHHP is a 13-year research and demonstration project designed to reduce cardiovascular risk. One member of each of three pairs of matched communities received 7 years of community intervention activities that included risk factor screening, mass media education, adult education classes, worksite interventions, home correspondence programs, school-based programs, restaurant programs, and point-of-purchase education in supermarkets. Weight gain prevention was emphasized for all adults and weight loss was encouraged among those who were obese or who had elevated risk factors known to be responsive to weight loss (e.g., high blood pressure). A strong upward secular trend in weight was noted in all MHHP communities over time. Intervention effects were evaluated conservatively with community as the unit of analysis. This analysis showed no overall effect of the MHHP intervention program on mean BMI. However, a positive intervention effect was noted early in the intervention among those with elevated cholesterol or a history of obesity-related disease. Possible reasons for this relatively weak community effect are discussed, including secular forces overwhelming intervention effects, an intervention effort not sufficiently focused on obesity, ceiling effects for weight concern in a population that was highly aware of the issue at baseline, and inherent limitations in educational approaches for this recalcitrant public health problem.

Adult↗

DNA ploidy of hydatidiform moles and nonmolar conceptuses: a study using flow and tissue section image cytometry.

This study was performed to investigate the role of DNA cytometry in the evaluation of molar and nonmolar pregnancies. DNA ploidy analysis was performed on paraffin-embedded tissue from 53 molar (35 complete, 18 partial) and 24 nonmolar (13 hydropic, 11 nonhydropic) conceptuses. Nuclear suspensions were analyzed by both flow and image cytometry and there was excellent correlation (96%) in the classification of DNA diploid, triploid, and tetraploid cases using these two methods. DNA ploidy analysis revealed a high proportion of tetraploid nonmolar conceptuses (42%) and complete moles (47%). The majority of partial moles were triploid (89%). Tissue sections from all cases were also studied by image cytometry to identify the cellular subpopulations (decidua, villous stromal cells, inner trophoblast, and extravillous trophoblast) with abnormal DNA content. In the triploid cases, all of the villous cell subtypes had an abnormal DNA content consistent with the development of partial moles from a triploid conceptus. In contrast, the majority of tetraploid cases showed high proliferative activity of the extravillous trophoblast whereas the other villous cell subtypes were diploid. These results suggest that tetraploid complete moles may arise from a diploid conceptus with the development of tetraploidy related to polyploidization of the hyperplastic extravillous trophoblast. Tissue section image cytometric DNA analysis can aid in our interpretation of ploidy results and our understanding of the biology of molar pregnancies.

Cell Nucleus↗

The role of DNA damage in the resistance of human chronic myeloid leukemia cells to cyclophosphamide analogues.

We examined 4-hydroperoxycyclophosphamide (4HC) and phosphorodiamidic mustard (PM)-mediated cytotoxicity and DNA interstrand cross-link (ISC) induction in a 4HC-resistant subline, B5-180(3), that was derived from the subcloned human myeloid leukemia cell line KBM-7/B5. Based on the ratio of the 50% inhibitory concentration values, B5-180(3) cells were approximately 35-fold resistant to 4HC compared with the parental cells. 4HC-induced ISC levels (as measured by alkaline elution) were approximately 9-fold lower in the 4HC-resistant line than the parent line. To determine whether the approximately 9-fold reduction of initial 4HC-induced ISCs was related to elevated aldehyde dehydrogenase (ADH), we examined PM-mediated cytotoxicity and ISC induction in the two cell lines. Unlike 4HC, the cytotoxicity of PM is independent of ADH activity. B5-180(3) cells were between 5- and 7-fold resistant to the cytotoxic effects of PM and were only slightly (approximately 1.3-fold) resistant to PM-mediated ISC induction. Furthermore, when cells were exposed to 4HC in the presence of 40 micrograms/ml cyanamide, an efficient inhibitor of ADH, the resistance index based on the 50% inhibitory concentration values was decreased to approximately 8. Elevated ADH can therefore explain most of the decrease in 4HC-induced ISCs, with elevated GSH levels probably accounting for the remaining small increment of resistance. Thus, decreased levels of ISC induction can account for a factor of approximately 9 of the total approximately 35-fold resistance to 4HC. The remaining increment of resistance to 4HC, as well as the cross-resistance to PM, appears to relate to an enhanced ability of the resistant subline to tolerate drug-induced ISCs. Thus, multiple factors appear to be involved in the resistance of these cells to the cytotoxic and DNA-damaging effects of 4HC, with elevated ADH and temporal factors (related to the processing of DNA damage) being the most important of these.

Aldehyde Dehydrogenase↗

Endometrial cancer and abdominal wound recurrence.

A 65-year-old woman had a total abdominal hysterectomy and bilateral salpingo-oophorectomy through a Pfannenstiel incision for a Stage Ib, Grade 2 endometrial adenocarcinoma with extension to the middle third of the myometrium. No adjuvant treatment was given. She presented 7 years later with a large suprapubic mass and the entire lower central abdominal wall was removed and closed with Marlex mesh. Pathology revealed a moderately well-differentiated adenocarcinoma, very similar to the previous cancer with follow-up at 15 months revealing no evidence of recurrence. This case represents growth of implanted tumor cells in the incision that occurred 7 years previously at the time of an uneventful hysterectomy without tumor transgression. It is felt that there was intraoperative tumor cell extrusion through the cervical os with subsequent growth of viable tumor cells.

Abdominal Injuries↗

Classification and treatment of closed sagittal band injuries.

Twenty-eight nonrheumatoid patients were treated for sagittal band injuries. The digits involved, in order of frequency, were long, small, index, and ring. We observed three clinical types of sagittal band injuries: type I, injury without extensor tendon instability; type II, injury with tendon subluxation; and type III, injury with tendon dislocation. Eight of nine patients with small finger involvement had radial sagittal band injuries; four of them presented with abduction deformity of the small finger. Satisfactory results were achieved with nonoperative treatment when it was initiated within 3 weeks of injury. Splinting was the initial treatment for all patients. Ten patients were treated either by centralization of the extensor tendon of the central two digits to provide pain-free stability or tendon transfer to correct small finger abduction deformity.

Adolescent↗

Correlation between gamma-ray-induced DNA double-strand breakage and cell killing after biologically relevant doses: analysis by pulsed-field gel electrophoresis.

We examined the degree of correlation between gamma-ray-induced lethality and DNA double-strand breaks (dsbs) after biologically relevant doses of radiation. Radiation lethality was modified by treating 14C-labelled Chinese hamster ovary cells with either of two aminothiols (WR-1065 or WR-25591) and the associated effect on dsb induction was determined by pulsed-field gel electrophoresis (PFGE). The use of phosphorimaging to analyse the distribution of 14C-activity in the gel greatly improved the low-dose resolution of the PFGE assay. Both WR-1065 and WR-25591 protected against dsb induction and lethality to a similar extent after low doses of radiation, although this correlation broke down when supralethal doses were used to induce dsbs. Thus, the level of dsbs induced in these cells as measured by PFGE after survival-curve doses of gamma-radiation is consistently predictive of the degree of lethality obtained, implying a case-effect relationship between these two parameters and confirming previous results obtained using the neutral filter elution assay for dsbs.

Animals↗

HIV seroprevalence in a London same-day testing clinic.

OBJECTIVES: To determine the prevalence of HIV infection among people attending a confidential, non-genitourinary medicine based testing clinic that provides HIV antibody test results on the day of consultation. METHODS: Retrospective analysis of data collected on 2635 individuals attending the Same-Day HIV Testing Clinic at the Royal Free Hospital, London between March 1992 and February 1993. RESULTS: A total of 1612 men and 1023 women were tested for HIV antibody. The primary risk for HIV infection was heterosexual (71.7%; 1889 out of 2635) and homosexual contact (24.5%; 646 out of 2635). Fifty-four individuals were given positive HIV test results (46 men, median age 34 years; eight women, median age 27 years). Overall HIV seroprevalence was 2.0% (95% confidence interval, 1.5-2.5). HIV seroprevalence was highest among homosexual men (6.5%; 41 out of 635) and injecting drug users (5.7%; four out of 70). The rates for heterosexual men and women were 0.2% (two out of 915) and 0.7% (seven out of 974), respectively. Of the 54 individuals who were HIV-antibody-positive, 44 were Centers for Disease Control and Prevention stage II/III, eight stage IV and one was tested at the time of seroconversion (stage I; data were not available for one patient). Of the total numbers attending this clinic 27% (702 out of 2635) had previously been tested and received a negative result. Of a total of 54 HIV-antibody-positive individuals, 40% (21) had previously received a negative test result. CONCLUSIONS: The data suggest that seroprevalence amongst homosexual men attending a designated HIV testing clinic in London is lower than that reported by genitourinary clinic based testing sites. The large number of repeat testers who subsequently became infected with HIV suggests that there is a population requiring specific targetting for HIV risk reduction.

AIDS Serodiagnosis↗

Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes. Central role of tumor necrosis factor-alpha.

Insulin resistance is an important metabolic abnormality often associated with infections, cancer, obesity, and especially non-insulin-dependent diabetes mellitus (NIDDM). We have previously demonstrated that tumor necrosis factor-alpha produced by adipose tissue is a key mediator of insulin resistance in animal models of obesity-diabetes. However, the mechanism by which TNF-alpha interferes with insulin action is not known. Since a defective insulin receptor (IR) tyrosine kinase activity has been observed in obesity and NIDDM, we measured the IR tyrosine kinase activity in the Zucker (fa/fa) rat model of obesity and insulin resistance after neutralizing TNF-alpha with a soluble TNF receptor (TNFR)-lgG fusion protein. This neutralization resulted in a marked increase in insulin-stimulated autophosphorylation of the IR, as well as phosphorylation of insulin receptor substrate 1 (IRS-1) in muscle and fat tissues of the fa/fa rats, restoring them to near control (lean) levels. In contrast, no significant changes were observed in insulin-stimulated tyrosine phosphorylations of IR and IRS-1 in liver. The physiological significance of the improvements in IR signaling was indicated by a concurrent reduction in plasma glucose, insulin, and free fatty acid levels. These results demonstrate that TNF-alpha participates in obesity-related systemic insulin resistance by inhibiting the IR tyrosine kinase in the two tissues mainly responsible for insulin-stimulated glucose uptake: muscle and fat.

Adipose Tissue↗

Prospective study of decubitus ulcers in two long term care facilities.

The incidence and prevalence of decubitus ulcers, and their complications and microbiology were studied prospectively in two large long term care facilities in Winnipeg, Manitoba between January 1, 1989 and December 30, 1990. The initial prevalence of decubitus ulcers was 2.6 and 1.6% at the two institutions, with an incidence of 3.4 and 4.8 per 100,000 resident days, respectively. The incidence of decubitus ulcer infection was 1.4 per 1000 ulcer days. The only other complication identified was in one resident who required an indwelling catheter to permit ulcer healing. An average of 2.4 organisms grew from surface swabs of ulcers; anaerobes were isolated from 14% of cultures. Aspirates from clinically noninfected ulcers had bacteria isolated in 30% of specimens. Two-thirds of organisms isolated were considered potentially pathogenic. Concurrent bacteriuria was present for 75% of sampling episodes. Organisms present in the urine were simultaneously isolated from decubiti in only 5% of specimens. Decubitus ulcers are uncommon in long term care institutions. The urinary tract of the bacteriuric elderly appears to be an infrequent source of organisms colonizing decubiti.

Adult↗

DNA image cytometry of prostatic carcinoma: a comparison of needle core biopsy and subsequent prostatectomy specimens.

DNA ploidy has recently been identified as an objective prognostic factor in prostatic carcinoma. Although the diagnosis of prostatic carcinoma is increasingly being made with the use of needle core biopsies, the optimal method for the cytometric analysis of these specimens has yet to be determined. In addition, the degree to which the biopsy is representative of the subsequent prostatectomy specimen with respect to DNA heterogeneity has not been adequately addressed. In this study, image cytometric (ICM) DNA analysis was performed on tissue sections from 12 prostatic needle core biopsies and the results were compared with similar ICM analysis of the subsequent prostatectomy specimens. Multiple blocks (n = 48) of the prostatectomy specimens were utilized to prepare tissue sections and nuclear suspensions and each set of preparations were analyzed by ICM in a parallel comparison study. There was concordance of 0.80 in the classification of DNA diploid and aneuploid tumors by ICM analysis of tissue sections and nuclear suspensions from paraffin blocks. In all of the discordant cases, DNA aneuploid populations were identified by ICM analysis of tissue sections only. This is attributed to difficulties in obtaining a representative nuclear suspension from disaggregated paraffin-embedded prostatic tissue which often has a very desmoplastic stroma. ICM analysis of tissue sections seems to be an optimal method for DNA ploidy analysis of prostatic carcinoma and is well suited to small volume biopsy material. Determination of DNA ploidy status in prostatic biopsies was predictive of the subsequent prostatectomy specimens with a concordance of 0.92.

Aged↗