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Biomedical subjects

R Charles

Publications and source records attributed to R Charles.

At least 19 recordsLinked to original sources

Glucose intolerance and other cardiovascular risk factors in Haiti. Prevalence of Diabetes and Hypertension in Haiti (PREDIAH).

AIMS: To assess the prevalence of diabetes and other forms of glucose intolerance and to examine their relationship with some cardiovascular risk factors in a population representative of the capital of Haiti. METHODS: This cross-sectional survey was conducted in the metropolitan area of Port-au-Prince, Haiti. A population-based sample of 1620 adults was randomly selected using a two-stage cluster method, stratified in 3 age groups: 20-39, 40-64 and > or =65 years of age. Diagnosis of diabetes and pre-diabetes (IFG and IGT) was based on the 2003 Expert Committee criteria. RESULTS: The total response rate was 69%. The age-standardized prevalence of diabetes was 4.8% in men and 8.9% in women (P=0.0014), with, overall, 70.6% of previously diagnosed cases. Standardized for the Segi world population aged 30-64 years, its prevalence was 7.4% in men and 11.1% in women (NS). The age-standardized prevalence of pre-diabetes was 6.4% in men and 8.0% in women (NS). Hypertension was found in 48.7% in men and 46.5% in women (NS). Its rates in people > or =40 years old were 69.1% in men and 67.2% in women (NS). Abdominal obesity was strongly independently associated with diabetes and pre-diabetes in both genders. Hypertension was shown to be risk factor for pre-diabetes and total glucose intolerance in women. High education was associated with lower risk of diabetes in men. CONCLUSION: Prevalence of diabetes and pre-diabetes is moderately high in Port-au-Prince, Haiti. In people aged > or =40 years, the rate of normal blood pressure is less than 25%. Intervention programs to prevent simultaneously and manage diabetes and hypertension are imperative, and prevention strategies through lifestyle modifications should be cost-effective.

Adult↗

Value of transoesophageal echocardiography for diagnosis of intraoperative tumour embolization.

Malignant neoplasms such as renal cell carcinoma may invade the inferior vena cava leading to a risk of pulmonary tumour embolization during surgical excision. Although massive pulmonary tumour embolism occurs relatively rarely, it can have catastrophic consequences. We report the case of an acute intraoperative pulmonary tumour embolism during resection of a renal cell carcinoma. The use of transoesophageal echocardiography allowed the immediate diagnosis and appropriate management of the underlying cause of acute haemodynamic instability. The role of transoesophageal echocardiography in the diagnosis of pulmonary embolism is discussed.

Carcinoma, Renal Cell↗

Pharmacology of low molecular weight heparins.

Although intravenous heparin has been the treatment of choice for acute VTE disease, LMWHs are gaining wider recognition and support as not only a new option but also as the standard of care. Each LMWH is viewed as a unique drug by regulatory agencies because of their differing physical and pharmacokinetic attributes. LMWHs have high absorption, high bioavailability, and long half-lives enabling once- or twice-daily dosing with predictable dose-response relationships. These factors enable the LMWHs to be used without laboratory monitoring and at home for acute DVT management. Studies continue to show that LMWH preparations are as at least as effective as heparin in a variety of settings, including VTE disease prophylaxis, management of acute VTE disease, unstable angina, and NSTEMI. They are at least as safe as heparin relative to hemorrhagic complications. Heparin-induced thrombocytopenia is less of a problem with LMWHs. Use of LMWHs has resulted in cost benefits in the treatment of acute DVT, unstable angina, and NSTEMI as well as in prophylaxis against venous thromboembolism. Emergency physicians, because of their unique position at the forefront of acute care, will soon regularly use LMWHs.

Age Factors↗

Ceramide-coated balloon catheters limit neointimal hyperplasia after stretch injury in carotid arteries.

Neointimal hyperplasia at the site of surgical intervention is a common and deleterious complication of surgery for cardiovascular diseases. We hypothesized that direct delivery of a cell-permeable growth-arresting lipid via the balloon tip of an embolectomy catheter would limit neointimal hyperplasia after stretch injury. We have previously demonstrated that sphingolipid-derived ceramide arrested the growth of smooth muscle cell pericytes in vitro. Here, we show that ceramide-coated balloon catheters significantly reduced neointimal hyperplasia induced by balloon angioplasty in rabbit carotid arteries in vivo. This ceramide treatment decreased the number of vascular smooth muscle cells entering the cell cycle without inducing apoptosis. In situ autoradiographic studies demonstrated that inflating the balloon catheter forced cell-permeable ceramide into the intimal and medial layers of the artery. Intercalation of ceramide into vascular smooth muscle cells correlated with rapid inhibition of trauma-associated phosphorylation of extracellular signal-regulated kinase and protein kinase B. These studies demonstrate the utility of cell-permeable ceramide as a novel therapy for reducing neointimal hyperplasia after balloon angioplasty.

Angioplasty, Balloon, Coronary↗

NO regulates PDGF-induced activation of PKB but not ERK in A7r5 cells: implications for vascular growth arrest.

In addition to the well-documented role of nitric oxide (NO) as a vasodilator, NO has also been implicated in vascular smooth muscle cell (VSMC) growth arrest. Signaling mechanisms responsible for growth factor receptor-mediated VSMC proliferation include the extracellular signal-regulated kinase (ERK) and possibly the protein kinase B (PKB) cascade. Thus the present study was designed to test the hypothesis that, in A7r5 vascular smooth muscle-derived cells, platelet-derived growth factor (PDGF)-induced activation of either ERK or PKB is regulated by NO, which then modulates cellular proliferation and/or apoptosis. PKB-alpha was the predominant isoform of PKB expressed in A7r5 cells and was also expressed in rabbit carotid arteries and aortae. Phosphorylation of PKB-alpha and ERK induced by PDGF-BB was maximal within 5-15 min in A7r5 cells. Preincubation of A7r5 cells with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) resulted in a biphasic regulation of PDGF-stimulated PKB-alpha phosphorylation and bioactivity. Acute exposure to SNAP significantly augmented PDGF-induced activation of PKB-alpha, whereas prolonged incubation led to a marked diminution in PDGF-induced activation of PKB-alpha. In contrast, SNAP did not affect PDGF-induced activation of ERK at any time point. The cGMP-independent effects of SNAP on PDGF-induced activation of PKB-alpha were established with the use of an inhibitor of soluble guanylyl cyclase, ODQ, as well as a cell-permeable analog of cGMP, 8-bromo-cGMP. Prolonged treatment of A7r5 cells with SNAP led to a significant decrease in DNA synthesis without an appreciable increase in apoptosis. These data suggest that, after prolonged exposure to SNAP, NO selectively attenuates PDGF-induced increase in PKB-alpha activation, which in turn may contribute to diminished VSMC proliferation by mechanisms involving growth arrest but not apoptosis.

Animals↗

The challenge of disseminating innovations to direct care providers in health care organizations.

Innovation is the discipline of applying new knowledge gained from multiple sources, including, but not limited to, scientific research. What is known and believed about knowledge generation, sharing, and dissemination of innovative ideas is discussed, with emphasis on applications to nursing and health care. The US Department of Veterans Affairs' virtual learning center is an example of a technology-based center that provides the opportunity to nurture social learning. Expanding the understanding of the generation and spread of innovations, and applying this knowledge in health care settings are critical to rapid changes in our social systems.

Diffusion of Innovation↗

Developmental changes in rat cardiac DNA, RNA and protein tissue base: implications for the interpretation of changes in gene expression.

During cardiac development the expression levels of many genes change as determined by Northern blot, dot blot, RNase protection, quantitative RT-PCR. Western blot or immunoprecipitation analyses. It is not always realized that the total amount of RNA or protein per gram of heart, dubbed tissue base, may change significantly during development as well. If this would be the case, this has to be taken into account. So far, the (changing) tissue base has not been established during cardiac development. To this end developmental profiles of cardiac DNA, RNA and protein concentration were determined in rats ranging in age from embryonic day 13 until neonatal day 121. The profiles show significant development changes in each parameter, that closely match the distinct growth phases of the developing heart and provide the parameters that are essential for an adequate interpretation of changes in the amount of a distinct mRNA and/or protein. In a comparison between in situ hybridization and Northern blot analysis it is demonstrated that the same developmental profile leads to an almost opposite conclusion depending on whether or not the changing tissue base is taken into account. These findings are of great interest for studies aimed at unravelling the molecular mechanisms underlying the regulation of gene expression during cardiac development.

Age Factors↗

In situ measurement of glutamate concentrations in the periportal, intermediate, and pericentral zones of rat liver.

We developed a quantitative histochemical assay for measurement of local glutamate concentrations in cryostat sections of rat liver. Deamination of glutamate by glutamate dehydrogenase (GDH) was coupled to the production of formazan and formazan precipitation was used for colorimetric visualization. The method was tested and validated with gelatin model sections with known glutamate concentrations. Calibration graphs showed linear relationships with high correlation coefficients (> 96%) between glutamate concentrations or section thickness and absorbance values. The method was reproducible, with a constant percentage of 60 +/- 5% of glutamate being converted in gelatin model sections containing glutamate concentrations of 2 mM and higher. Glutamate concentrations were estimated in periportal, intermediate, and pericentral zones of liver lobules that contain low, intermediate, and high GDH activity, respectively. In fed adult male rat livers, periportal zones contained the highest concentrations of glutamate (approximately 14 mM) and intermediate and pericentral zones approximately 13 and 9 mM, respectively. On starvation, glutamate concentrations increased only in the small rim of pericentral cells that express glutamine synthetase, to approximately 15 mM. In livers of fetal and newborn rats, glutamate was homogeneously distributed, with a concentration of approximately 5 mM. In suckling rat liver, distribution of glutamate was still homogeneous but the concentration was increased to approximately 8 mM. These glutamate distribution patterns were in agreement with those detected immunohistochemically.

Age Factors↗

[Mass screening programs for breast cancer in France. Comparative evaluation].

OBJECTIVE: The purpose of this work was to comparatively assess the results of mass screening programs for breast cancer implemented in six French departments in 1986, within the scope of the National Fund for Health Prevention, Education and Information of the National Health Insurance Office of Salaried Workers. MATERIAL AND METHODS: The data collected by the screening centres were analyzed by ten assessment teams that were independent from the program promotion staff, all using the same evaluation form. A complementary population study performed in eight French districts then, allowed assessing the frequency of self-referred screening (mammography performed out of program). RESULTS: The rate of participation in screening programs, in relation to the invited population, ranged from 21 to 48%, according to the district (36% in average). This low participation was probably related to the extent of self-referred screening. In fact, 19 to 40% of women, according to the district, had previously had a screening mammographic coverage: rate was around 68% in women aged 50 to 69 years. Positive findings with mammography ranged from 4.5 to 15.8% (10.1% in average), while intervention rates ranged from 0.7 to 1.6% and detection rates from 3.8 to 6.2%. The ratio between benign tumors and cancers ranged from 0.7 to 2.1 according to the district. In order to enlighten the judgement on French results, we propose a comparison with the international standards in force. CONCLUSION: The various experiences with breast cancer screening in France show that this screening is technically feasible on the basis of existing medical structures. However, some criteria are still below the expected values, especially if compared with international standards. This result is probably accounted for by the high rate self-referred screening before age 40 in France. In these conditions, the question is whether extending breast cancer screening programs in France is an appropriate course of action.

Breast Neoplasms↗

The dynamics of local kinetic parameters of glutamate dehydrogenase in rat liver.

Kinetic parameters of glutamate dehydrogenase (GDH, EC 1.4.1.2) for glutamate were determined in periportal and pericentral zones of adult male and female rat liver lobules under normal fed conditions and after starvation for 24 h. GDH activity was measured as formazan production over time against a range of glutamate concentrations in serial cryostat sections using image analysis. Captured gray value images were transformed to absorbance images and local initial velocities (Vini) were calculated. A hyperbolic function was used to describe the relationship between substrate concentration and local Vini. Under fed conditions, Vmax values were similar in male and female rats (8 +/- 2 and 16 +/- 2 mumol min-1 cm-3 liver tissue in periportal and pericentral zones, respectively). Starvation increased Vmax, especially in pericentral zones of females (to 27 +/- 1 mumol min-1 cm-3 liver tissue). Under fed conditions, the affinity of GDH for glutamate was similar in male and female rats (2.5 +/- 0.5 mM and 3.5 +/- 0.8 mM in periportal and pericentral zones, respectively). Starvation had no effect on K(m) values in male rats, but in female rats affinity for glutamate decreased significantly in both zones (K(m) values of 4.0 +/- 0.1 mM and 8.6 +/- 0.8 mM, respectively). These local changes in the kinetic parameters of GDH indicate that conversion of glutamate to alpha-oxoglutarate cannot be predicted on the basis of GDH concentrations or zero-order activity in the different zones of liver lobules alone.

Animals↗

Gender-dependent regulation of glutamate dehydrogenase expression in periportal and pericentral zones of rat liver lobules.

We studied the level(s) at which glutamate dehydrogenase (GDH; EC 1.4.1.2) expression is regulated in the livers of fed male and female rats. The cellular content of GDH mRNA, protein, and enzyme activity was determined quantitatively using image analysis for measurement of the absorbance in consecutive serial sections that were processed for in situ hybridization, immunohistochemistry, and enzyme histochemistry. In both males and females, GDH protein and activity patterns were similar, with pericentral values being twice as high as periportal values. GDH mRNA distribution patterns in female liver lobules reflected those of GDH protein and activity, but GDH mRNA distribution patterns in male rat livers were found to be homogeneous owing to a more than twofold lower cellular mRNA content in pericentral zones than in female rats. We conclude that gender affects GDH expression selectively in pericentral zones at posttranscriptional and pretranslational levels.

Animals↗

Isolation and characterization of the rat gene for carbamoylphosphate synthetase I.

Carbamoylphosphate synthetase I (CbmPS) is first expressed in rat hepatocytes shortly before birth. After birth, expression of CbmPS gradually becomes confined to the hepatocytes surrounding the portal veins. To obtain insight into the spatiotemporal regulation of its expression, the rat CbmPS gene was isolated and characterized. The gene is 110 kb in length and contains 38 exons. The basal promoter comprises the first 161 nucleotides upstream of the transcription-initiation site. Determination of the state of methylation of the 5' portion of the gene identified a CCGG sequence at -6.3 kb that is selectively demethylated in adult tissues which express CbmPS. This site remains methylated before birth, however, despite recruitment of all hepatocytes for CbmPS synthesis, indicating that its demethylation is a consequence of rather than a condition for expression of CbmPS. Transient expression assays revealed that the region surrounding the CCGG site at 6.3 kb functions as an enhancer. In FTO-2B hepatoma cells and Rat-1 fibroblasts, this enhancer is constitutively active when tested in front of the basal viral thymidine kinase promoter. When tested in front of the basal CbmPS promoter in hepatoma cells, however, the activity of this enhancer is dependent on the presence of glucocorticoids. In Rat-1 fibroblasts, the presence of both glucocorticoids and cyclic AMP is required for full activity, suggesting that the hepatocyte-specific expression of CbmPS is related to tissue-specific differences in the sensitivity to cyclic AMP. Matrix-attachment regions (MAR) are present upstream and downstream of the CbmPS gene. The downstream MAR defines the 3' boundary of the gene. The upstream MAR is located midway between the basal promoter and the enhancer, and may function as a hinge point to facilitate the positioning of the enhancer in the vicinity of the basal promoter.

Animals↗

Image analysis and image processing as tools to measure initial rates of enzyme reactions in sections: distribution patterns of glutamate dehydrogenase activity in rat liver lobules.

To analyze regional differences in the activity of glutamate dehydrogenase in rat liver in situ, we developed an image recording and processing system for monitoring the formation of a colored final reaction product in time. All absorbance measurements of test and control reactions in time in consecutive sections were used to fit the data to a quadratic curve, with the derivative at t = 0 representing the initial velocity of formazan formation. The images of sections incubated for test and control reactions were topographically matched with an affine transformation using the positions of vessels as fiducials. Specific enzyme activity was calculated by subtracting the coefficients representing the initial velocity at corresponding locations in the test and control reactions and appeared to be 8 and 4 mumoles glutamate converted per min per cm3 of tissue at 20 degrees C in pericentral and periportal zones of fasted female rats, respectively. Those values are in agreement with biochemical data. The ability to construct two-dimensional images of cellular distribution patterns of enzyme activity in liver lobules is particularly useful for the study of metabolic zonation in this organ.

Animals↗