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Biomedical subjects

S F Murray

Publications and source records attributed to S F Murray.

At least 19 recordsLinked to original sources
PubMed2001

Tools for monitoring the effectiveness of district maternity referral systems.

It is widely accepted that substantial reductions in maternal mortality and severe morbidity are impossible to achieve without an effective referral system for complicated cases. Early detection and referral to higher levels of care might also substantially reduce neonatal deaths due to the complications of childbirth. The general goal of such a referral system is that patients are dealt with in the right place with effective treatment provided at the minimum of cost. There are real challenges, however, in monitoring the effectiveness of such referral systems once put in place. This paper describes some of the tools used to review pregnancy-related referrals in Lusaka, Zambia. The tool-mix used provided information for monitoring five different aspects of the referral system: the distribution of births across levels of facility and population coverage; the use of essential obstetric care (EOC) level facilities by women with complications; the progress towards a reduction of maternal mortality at referral facility level; inappropriate use of EOC level facility; and perinatal outcomes at peripheral facility level. Apart from the information on coverage, the data came from routinely collected facility statistics, registers and medical notes. Findings for Lusaka are reported. Consideration is given to issues of interpretation of specific indicators, and to how such tools might be used in conjunction with others, in order to help district managers to monitor the effectiveness of district maternity referral systems.

Female↗
PubMed2000

Relation between private health insurance and high rates of caesarean section in Chile: qualitative and quantitative study.

OBJECTIVES: To explore the circumstances and factors that explain the association between private health insurance cover and a high rate of caesarean sections in Chile. DESIGN: Qualitative analysis of audiotaped in-depth interviews with obstetricians and pregnant women; quantitative analysis of data from face to face semistructured interview survey conducted postnatally (with women who had given birth in the previous 24-72 hours), and of a review of medical notes at a public hospital, a university hospital, and a private clinic. SETTING: Santiago, Chile. PARTICIPANTS: Qualitative arm: 22 obstetricians, 21 pregnant women; quantitative arm: 540 postnatal women. MAIN OUTCOME MEASURES: Rates of caesarean section in different types of institutions; consultants' views on private practice; work patterns in private practice; women's reasons for choosing private care; women's preferences on method of delivery. RESULTS: Private health insurance cover requires the primary maternity care provider to be an obstetrician. In the postnatal survey, women with private obstetricians showed consistently higher rates of caesarean section (range 57-83%) than those cared for by midwives or doctors on duty in public or university hospitals (range 27-28%). Only a minority of women receiving private care reported that they had wanted this method of delivery (range 6-32%). With the diversification in the healthcare market, most obstetricians now have demanding peripatetic work schedules. Private maternity patients are a lucrative source of income. The obstetrician is committed to attend these private births in person, and the "programming" (or scheduling) of births is a common time management strategy. The rate of elective caesarean sections was 30-68% in women with private obstetricians and 12-14% in women not attended by private obstetricians. CONCLUSIONS: Policies on healthcare financing can influence maternity care management and outcomes in unforeseen ways. The prevailing business ethos in health care encourages such pragmatism among those doctors who do not have a moral objection to non-medical caesarean section.

Attitude of Health Personnel↗
PubMed2000

Training initiatives for essential obstetric care in developing countries: a 'state of the art' review.

Increased international awareness of the need to provide accessible essential or emergency obstetric and newborn care in developing countries has resulted in the recognition of new training needs and in a number of new initiatives to meet those needs. This paper reviews experience in this area so far. The first section deals with some of the different educational approaches and teaching methods that have now been employed, ranging from the traditional untheorized 'chalk and talk', to competency-based training, to theories of adult learning, problem solving and transferable skills. The second section describes a range of different types of indicators and data sources (learner assessments, user and community assessments, trainer assessments and institutional data) that have been used in the assessment of the effectiveness of such training. The final section of the paper draws together some of the lessons. It considers evaluation design issues such as the inclusion of medium and long term evaluation, the importance of methods that allow for the detection of iatrogenic effects of training, and the roles of community randomized trials and 'before, during and after' studies. Issues identified for the future include comparative work, how to keep training affordable, and where training ought to lie on the continuum between straightforward technical skills acquisition and the more complex learning processes required for demanding professional work.

Clinical Competence↗
PubMed2000

Phosphorothioate oligodeoxynucleotides distribute similarly in class A scavenger receptor knockout and wild-type mice.

It has been suggested that binding of phosphorothioate oligodeoxynucleotides (P=S ODNs) to macrophage scavenger receptors (SR-AI/II) is the primary mechanism of P=S ODN uptake into cells in vivo. To address the role of scavenger receptors in P=S ODN distribution in vivo, several pharmacokinetic and pharmacological parameters were compared in tissues from scavenger receptor knockout mice (SR-A-/-) and their wild-type counterparts after i.v. administration of 5- and 20-mg/kg doses of P=S ODN. With an antibody that recognizes P=S ODN, no differences in cellular distribution or staining intensity in livers, kidneys, lungs, or spleens taken from SR-A-/- versus wild-type mice could be detected at the histological level. There were no significant differences in P=S ODN concentrations in these organs as measured by capillary gel electrophoresis as well, although the concentration of P=S ODN in isolated Kupffer cells from livers of SR-A-/- mice was 25% lower than that in Kupffer cells from wild-type mice. Furthermore, a P=S ODN targeting murine A-raf reduced A-raf RNA levels to a similar extent in livers from SRA-/- (92.8%) and wild-type (88.3%) mice. Finally, in vitro P=S ODN uptake studies in peritoneal macrophages from SR-A-/- versus wild-type mice indicate that other high- and low-affinity uptake mechanisms predominate. Taken as a whole, our data suggest that, although there may be some contribution to P=S ODN uptake by the SR-AI/II receptor, this mechanism alone cannot account for the bulk of P=S ODN distribution into tissues and cells in vivo, including macrophages.

Animals↗
PubMed1999

K252a induces cell cycle arrest and apoptosis by inhibiting Cdc2 and Cdc25c.

The indole carbazole K252a has been shown in previous studies to inhibit the platelet-derived growth factor signal transduction pathway in gliomas. Because K252a has nonspecific effects on protein kinase function, we studied its effect on cyclin-dependent kinases (CDK) and cell cycle blockade in glioma cells. K252a blocked T98G cells at the G1/S and G2/M checkpoints. Consistent with cell cycle arrest, K252a was shown to hypophosphorylate Rb, upregulate p21, and decrease Cdc2 and Cdc25c activity. Finally, cell cycle arrest in T98G cells resulted in apoptosis as determined by cell morphology and DNA laddering. K252a is a useful tool for studying the effects of CDK inhibition and cell cycle blockade in tumor cells.

Apoptosis↗
PubMed1997

Cesarean birth trends in Chile, 1986 to 1994.

BACKGROUND: Despite indications of high cesarean section rates in various parts of Latin America, relatively few comprehensive studies of national birth intervention trends have been conducted in that continent. Recent national statistics suggest that Chile may now have the highest reported cesarean section rate in the world. This paper examines cesarean birth trends in Chile with reference to changing patterns in health care financing. METHODS: The growth in the national cesarean birth rate is analyzed, with reference to regional patterns, differences according to insurance coverage, and recent shifts in the financing pattern of health care provision, using insurance fund data and hospital reporting systems data for both public and private sector care from the mid-1980s to mid-1990s. RESULTS: Chile had a cesarean birth rate of 37.2 percent for the 301,955 births covered by either the National Health Fund or private health insurance in 1994. This was a one-third increase from the 1986 rate of 27.7 percent. The private health insurance sector revealed consistently far higher cesarean section rates than the National Health Fund sector (59% vs 28.8% in 1994); intrasectoral rates remained fairly stable over the 8-year period. CONCLUSIONS: The overall increase in Chile's cesarean section rate correlates with the growth in the proportion of all births whose care was privately insured during these years (from 7.5% to 24.8%). This change may be partly explained by the doubling (to 32%) of the percentage of women with a personal obstetrician rather than a "duty" practitioner attending the birth of their baby.

Birth Rate↗
PubMed1997

Neonatal care in developing countries.

Worldwide, about eight newborn babies die every minute, yet interventions to reduce early neonatal mortality and morbidity are still not given high priority in most developing countries. It is often assumed that neonatal care is too costly for high coverage in poor populations, but in fact many deaths could be prevented or treated with low technology and improved care. There are four principles of basic newborn care: an atraumatic and clean delivery, maintenance of body temperature, initiation of spontaneous respiration and breast feeding shortly after birth. For the majority these could be facilitated at the health centre by nurse midwives or at home by TBAs or family members. Low cost special care for many of the 10%-15% who are sick or pre-term or low birth weight could be provided at district hospitals using appropriate simple technologies.

Developing Countries↗
PubMed1997

K252a inhibits proliferation of glioma cells by blocking platelet-derived growth factor signal transduction.

Growth factors are known to regulate glioma proliferation. The glioma cell lines U87 and T98G were examined for evidence of an autocrine stimulatory loop involving the neurotrophin family of growth factors. Although neurotrophin-3 and TrkC RNA were detected by reverse transcription-PCR, there was no evidence of significant interaction between neurotrophin-3 and its cognate receptor TrkC. The microbial alkaloid K252a has been described to inhibit both Trk tyrosine kinase activity and neuroblastoma cell proliferation. K252a inhibited proliferation in U87 (IC50 = 1170 nM) and T98G (IC50 = 529 nM) but induced apoptosis in U87 cells only. At concentrations of 500 nM to 1 microM, K252a blocked only platelet-derived growth factor (PDGF)-mediated receptor autophosphorylation. These results suggest that an autocrine loop involving PDGF is functional and important for maintaining tumor growth. There is no evidence to support the existence of a neurotrophin-mediated autocrine loop. K252a, through inhibition of PDGF signal transduction, may be a novel therapeutic agent in the treatment of human gliomas.

Apoptosis↗
PubMed1995

Involvement of multiple cis elements in basal- and alpha-adrenergic agonist-inducible atrial natriuretic factor transcription. Roles for serum response elements and an SP-1-like element.

In the present study, cis elements in the 5'-flanking sequence (FS) of the rat atrial natriuretic factor (ANF) gene involved in regulating basal and alpha 1-adrenergic-inducible transcription were investigated. Truncation analyses using ANF-luciferase reporter constructs transfected into primary neonatal rat cardiac myocytes showed that an A/T-rich serum response element (SRE) at -114 bp of the ANF 5'-FS, which bound serum response factor (SRF), was required for basal and inducible transcription. In constructs composed of 134 bp of rat ANF 5'-FS driving luciferase (ANF-134Luc), mutations in the SRE at -114 bp disrupted SRF binding and ANF promoter activity. However, the same mutations in ANF-638Luc had little effect, suggesting a collaborating role for more distal sequences, such as the other SRE in ANF-638 at -406 bp. In ANF-638Luc, mutations in the SRE at -406 bp that disrupted SRF binding to that site decreased ANF reporter activity by only 25%; however, mutating both of the SREs completely blocked alpha 1-adrenergic-inducible activity. Mutation analyses showed that an ... (SP-1)-like site at -69 bp, shown previously to confer inducibility in reporters with 134 bp of ANF 5'-FS, was not required in ANF-638Luc. However, double mutants in the SP-1-like region and either SRE completely blocked alpha 1-adrenergic-inducible ANF promoter activity. These findings emphasize that no single element is responsible for alpha 1-adrenergic agonist-regulated ANF transcription but that the SREs at -114 and -406 bp and the SP-1-like sequence at -69 bp mediate the effect in collaboration.

Adrenergic alpha-Agonists↗
PubMed1994

Brain natriuretic peptide is induced by alpha 1-adrenergic agonists as a primary response gene in cultured rat cardiac myocytes.

To better understand the molecular basis for increased atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) expression during overload-induced cardiac hypertrophy, we studied the induction of the genes in primary myocardial cells by the alpha 1-adrenergic agonist, phenylephrine (PE), a potent hypertrophic agent. PE augmented the transcription of both genes to similar extents, although the time course of mRNA accumulation differed. Increases in ANF mRNA were evident only after 6-8 h of PE exposure, when transcript levels were 2-4-fold over control. However, similar increases in BNP mRNA were observed as soon as 1 h of PE exposure. Moreover, while ANF mRNA levels continued to increase through 24 h of PE treatment, maximal levels of BNP mRNA (8-10-fold over control) were observed at 4 h, after which transcript levels declined to about 3-fold over control. The early induction of the BNP mRNA by PE was independent of protein synthesis, whereas the late induction of both genes required protein synthesis. Interestingly, the early BNP induction was only partially blocked by the transcription inhibitor, actinomycin D, indicating that, in part, the inductive effects of PE might be the result of transcript stabilization. Indeed, the BNP transcript, which was shown to possess a half-life of less than 1 h in control cells, was stabilized by the addition of PE, while the ANF transcript possessed a half-life of at least 24 h under all conditions. These data indicate that the induction of BNP by alpha 1-adrenergic agonists has characteristics of both a primary and secondary response gene, while ANF is a typical secondary response gene. Moreover, alpha 1-adrenergic stimulation enhances BNP expression through both transcriptional activation and transcript stabilization, while ANF expression is enhanced primarily transcriptionally.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1993

Identification of the receptor subtype responsible for endothelin-mediated protein kinase C activation and atrial natriuretic factor secretion from atrial myocytes.

Endothelin-1 (ET-1) is a potent stimulator of atrial natriuretic factor (ANF) secretion from myocardial cells. In heart tissue there are two ET receptor subtypes (ETA-R and ETB-R), which can be pharmacologically distinguished by the ET isopeptides ET-1 and ET-3. However, the identification of the ET-R subtype responsible for the rapid enhancement of ANF release, which occurs within minutes of exposing cardiac myocytes to ET, has not been investigated. In the present study ET-1 was about 100-fold more potent than ET-3 at stimulating membrane phosphoinositide hydrolysis, protein kinase C activation, and ANF release from purified primary atrial myocytes. These responses were completely abolished by BQ123, an ETA-R antagonist. Radioligand binding analyses showed that competitor peptides displaced 125I-ET-1 binding to atrial myocyte ET-Rs with a rank order of potency of ET-1 >> BQ123 > ET-3, a characteristic ETA-R pharmacological profile. While neither ET-1 or ET-3 altered forskolin-stimulated cAMP levels, suggesting the absence of the ETB-R, basal cAMP levels were also unaffected by the ETs. Northern analysis using ET-R subtype-specific probes demonstrated that the ETA-R transcript was present in the cultures at levels at least 50-fold greater than the ETB-R transcript. These findings demonstrate that the stimulation of the phosphatidylinositol/protein kinase C pathway, which is required for maximal ET-stimulated ANF release from primary atrial myocytes, is associated with the activation of only the ETA-R, thus defining a specific function for an endogenous ET-R in myocardial cells.

Animals↗
PubMed1993

Myocardial alpha-thrombin receptor activation induces hypertrophy and increases atrial natriuretic factor gene expression.

The protease, alpha-thrombin (alpha Th), affects myocardial cell contractility, a feature common among agents that induce hypertrophy. However, it is not known whether cardiac myocytes possess alpha Th receptors (alpha Th-R), or if long term treatment with alpha Th can enhance growth and gene expression. In the present study primary neonatal rat ventricular myocytes expressed a 3.6-kilobase mRNA species that hybridized with a rat alpha Th-R-specific probe. After 48 h, alpha Th induced hypertrophy, sarcomeric organization, and enhanced atrial natriuretic factor (ANF) expression, all of which were blocked by the alpha Th-selective protease inhibitor, D-Phe-Pro-Arg-chloromethyl ketone. The alpha Th-R agonist peptide, SFLLRNPND, was a potent activator of ANF expression, however, the non-agonist, FLLRNPND, was inactive. Transfection experiments showed the enhancement of ANF expression by alpha Th to be transcriptional. The abilities of alpha Th to induce myocyte hypertrophy and to augment ANF transcription and peptide production were inhibited by the protein kinase C inhibitor, chelerythrine, and by the tyrosine kinase inhibitor, tyrphostin. Thus, myocardial cell alpha Th-Rs are stimulated by the specific proteolytic actions of alpha Th, and pathways involving both protein kinase C and protein tyrosine kinases are required for subsequent hypertrophy and ANF expression. Further, these findings suggest a new role for extracellular proteases as regulators of myocardial cell gene expression and growth.

Alkaloids↗
PubMed1992

Women physicians in dual-physician relationships compared with those in other dual-career relationships.

This study compared the career and domestic responsibilities of women physicians whose domestic partners were physicians (WP-Ps) with those of women physicians whose domestic partners were not physicians (WP-NPs). In 1988 the authors surveyed 602 women physicians in a large midwestern city regarding their career and domestic roles; 390 were physicians in training (students and residents), and 212 were physicians in practice (academic medicine and private practice). Overall, 382 (63%) responded; of the 382, 247 (65%) had domestic partners; of these 247, 91 (37%) were WP-Ps and 156 (63%) were WP-NPs. The WP-Ps were found to be twice as likely as the WP-NPs to interrupt their careers to accommodate their partners' careers. The WP-Ps also assumed significantly more domestic responsibilities and worked fewer hours practicing medicine than did the WP-NPs. The 163 women physicians in training (44-48%-of the WP-Ps and 119-76%-of the WP-NPs) demonstrated a more egalitarian division of labor overall, with no significant differences between the WP-Ps and the WP-NPs. The authors recommend that longitudinal studies be undertaken to determine whether women physicians in training continue this trend as they enter the practice of medicine.

Adult↗
PubMed1992

Comparing the transfusion medicine content of the NBME's examinations in 1984-1985 and 1989-1990.

Recognition of the seriousness of transfusion-transmitted diseases has been demonstrated by U.S. medical schools through the integration of transfusion medicine (TM) content into their curricula. To evaluate the degree to which these changes in curricula have been reflected in the National Board of Medical Examiners' (NBME) examinations, a study conducted in 1991 evaluated the proportions of TM-related items on Parts I and II of the NBME examinations for 1984-1985 versus 1989-1990. Both Part I (basic sciences) and Part II (clinical sciences) demonstrated significant gains in TM items between the comparison periods (p less than .001), with Part II having the higher gain. An analysis of students' knowledge revealed that students in 1989-1990 tended to perform better on TM items than on examination items generally. The increases in TM content and student performance on TM items on the 1989-1990 examinations suggest that the national effort to expand and improve teaching of TM in U.S. medical schools has been effective.

Blood Transfusion↗
PubMed1992

The cosecretional maturation of atrial natriuretic factor by primary atrial myocytes.

Cardiac myocytes store the 126-amino acid precursor of atrial natriuretic factor (pro-ANF), yet the mature, bioactive 28-amino acid peptide, ANF-(99-126), and the resulting N-terminal product, ANF-(1-98), are the forms of the hormone that are released by the heart and found in the circulation. Although previous studies have shown that the maturation of ANF takes place in the heart, it is not known whether it occurs in or on the myocyte concurrently with secretion, or whether cleavage takes place postsecretionally on either the myocyte surface or the surface of a nonmuscle cardiac cell. To address these questions, experiments were carried out in the present study using primary atrial cultures that had been prepared such that greater than 90% of the cells were myocytes. Reversed-phase and ion-exchange HPLC, coupled with immunoprecipitation of biosynthetically labeled ANF, showed that the stored peptide, pro-ANF, was cleaved between residues 98 and 99 such that ANF-(1-98) and (99-126) accumulated in the medium. Coupling biosynthetic labeling with timed secretion experiments showed that the extent of ANF processing was not dependent on the time after secretion; maximal levels of processing were observed at all secretion times examined. Additionally, the processing-competent myocyte-enriched cultures were unable to cleave exogenously added pro-ANF. These results indicate that the myocyte is the cell type responsible for pro-ANF maturation and that this cleavage event takes place cosecretionally.

Animals↗
PubMedDate not supplied

Sodium vanadate inhibits apoptosis in malignant glioma cells: a role for Akt/PKB.

The dual signal hypothesis of apoptosis holds that a common signal can activate both apoptotic and proliferative pathways. The fate of a cell is dependent on which of these two pathways predominates. In the MAPK family of kinases, ERK and JNK have been proposed to mediate apoptosis whereas the PI3K-stimulated kinase, Akt/PKB, has been shown to inhibit apoptosis. The object of this study was to determine the role of these kinases in a glioma model of apoptosis. We have previously shown that K252a induces apoptosis and inhibits kinase activity. In this study we confirm these results and show that the protein tyrosine phosphatase inhibitor sodium vanadate activates ERK, JNK and Akt/PKB, but does not stimulate proliferation. Vanadate did protect T98G cells from K252a-induced apoptosis, an effect that was abolished by addition of the PI3K inhibitor wortmannin. This suggests that PI3K and Akt/PKB may be responsible for mediating vanadate's protective effect on glioma cells. We conclude that the intracellular balance between protein phosphorylation pathways is a critical determinant of both cell proliferation and cell death.

Androstadienes↗