Health sector reform and rise of caesarean birth in Chile.
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Cesarean Section↗
Biomedical subjects
S F Murray
Publications and source records attributed to S F Murray.
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Reducing perinatal mortality.
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Developing Countries↗
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↗
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↗
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↗
Selection and evaluation of blood- and tribologically compatible journal bearing materials.
A critical issue in the Cleveland Clinic Foundation (CCF) Innovative Ventricular Assist System (IVAS) blood pump is the selection of materials for the blood-lubricated journal bearing. Under normal operating conditions, the journal bearing geometry creates a thick blood film that separates the rotating and stationary surfaces. However, since start-up and certain transients could cause temporary contact, the material pair selected for these surfaces must be both tribologically and blood compatible. Combinations of two biocompatible alloys were tested: a titanium-zirconium-niobium alloy (Ti-13Zr-13Nb) and a zirconium-niobium alloy (Zr-2.5Nb). A standard pin-on-disk tester was used, with the contact surfaces lubricated by glycerol/saline mixtures simulating the viscosity range of blood. One test series evaluated start-up conditions; the other modeled a high-speed rub that might occur if the fluid film broke down. Results showed that the preoxidized Zr-2.5Nb pin/Ti-13Zr-13Nb disk combination was superior at all sliding velocities; a self-mated Zr-2.5Nb pair also showed promise. The oxide film on a self-mated Ti-13Zr-13Nb pair, and a Ti-13Zr-13Nb pin and Zr-2.5Nb disk combination did not show adequate wear life. More work remains to explain distinct performance differences of certain combinations, with more data needed on mechanical properties of thin, hard coatings on softer metal substrates.
Alloys↗