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At least 613 records · Page 34Linked to original sources

Role of angiotensin subtype 2 receptor in neointima formation after vascular injury.

The role of angiotensin receptor subtypes 1 and 2 was assessed on neointima formation after injury in rat carotid artery. The effects of angiotensin converting enzyme inhibition by perindopril (3 mg.kg-1 x day-1 p.o.) and selective blockade of angiotensin subtype 1 receptors by DuP 753 (5 and 30 mg.kg-1 x day-1 p.o.) were compared on proliferative response to balloon injury. In rats treated 6 days before and for 14 days after injury, perindopril significantly reduced (-76%, p < 0.01) myointimal hyperplasia. In contrast, DuP 753 at 5 mg.kg-1 x day-1 did not modify the hyperplastic response to balloon catheterization. Only at 30 mg.kg-1 x day-1 was DuP 753 able to reduce neointima formation (-47%, p < 0.05). This dose was equipotent to perindopril on the renin-angiotensin system as assessed by the pressor response to angiotensin II and angiotensin I. Therefore, blockade of subtype 1 receptors was a less effective means of suppression of myointimal growth than angiotensin converting enzyme inhibition, suggesting that another angiotensin receptor subtype or converting enzyme substrates are involved in this process. For the determination of whether angiotensin subtype 2 receptors were implicated, the specific subtype 2 receptor antagonist CGP 42112A (1 mg.kg-1 x day-1) was continuously infused perivascularly for 14 days in the vicinity of the injured carotid artery. CGP 42112A was as effective in preventing neointima formation as perindopril (-73%, p < 0.01, versus -76%, p < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Two-dimensional echocardiographic assessment of left ventricular function in chronic obstructive pulmonary disease.

In 10 patients undergoing therapy for a mild exacerbation of their chronic obstructive pulmonary disease (COPD), a quantitative two-dimensional echocardiographic (2DE) study was performed together with hemodynamics to assess left ventricular (LV) function. From the 2DE examination, which was made up of parasternal, subcostal, and apical views, measurements of LV short axis end-diastolic and end-systolic areas (A) at the high papillary muscle level and long axis end-diastolic and end-systolic length (L) permitted us to calculate LV end-systolic and end-diastolic volumes (V) using the formula V = 5/6 AL. Compared with the same measurements obtained in a group of 12 normal volunteers, patients with COPD exhibited a markedly reduced LV cavity (LVES, 28.9 +/- 14.6 ml/m2 versus 51.5 +/- 11.0 ml/m2; LVEDV, 67.7 +/- 24.6 ml/m2 versus 103.2 +/- 19.9 ml/m2). An increased thickness of both left ventricular free wall and interventricular septum was also evidenced in patients with COPD. Left ventricular systolic function, assessed using both peak systolic blood pressure/end-systolic volume ratio and calculated left ventricular ejection fraction, was found to be clearly enhanced in patients with COPD. The influence of right ventricular enlargement on left ventricular diastolic function was also investigated in patients with COPD using progressive volume loading and 2DE right ventricular measurements. After a given threshold of volume loading, reduction in stroke index, opposite variations in right and left ventricular size and septal flattening, suggested the occurrence of ventricular interaction.

Adult↗

Retinal cotton-wool spots as the first sign of systemic sarcoidosis.

Isolated retinal cotton-spots have not yet been reported as the sign of ocular sarcoidosis. We describe three patients with retinal cotton-wool spots of initially unknown etiology in whom systemic sarcoidosis was diagnosed 6-16 months later. The diagnosis was confirmed by conjunctival biopsy. These observations indicate that sarcoidosis should be included in the differential diagnosis of retinal cotton-wool spots and patients with these lesions should be followed for the development of this disease.

Adult↗

The role of diffusion tensor imaging in establishing the proximity of tumor borders to functional brain systems: implications for preoperative risk assessments and postoperative outcomes.

Diffusion Tensor Imaging (DTI) is a new MRI imaging technique sensitive to directional movements of water molecules, induced by tissue barriers. This provides a new form of contrast that allows the identification of functional white matter tracts within the brain, and has been proposed as a technique suitable for presurgical planning in brain tumor patients. Resection of primary brain tumors improves survival, functional performance, and the effectiveness of adjuvant therapies, provided that surgically-induced neurological deficits can be avoided. Diffusion Tensor Imaging (DTI) has the potential to establish spatial relationships between eloquent white matter and tumor borders, provide information essential to preoperative planning, and improve the accuracy of surgical risk assessments preoperatively. We present our experience in a series of 28 brain tumor patients where the integration of functional magnetic resonance imaging (fMRI) and DTI data was used to determine key anatomic spatial relationships preoperatively. Twice as many functional systems were localized to within 5 mm of tumor borders when DTI and fMRI were utilized for preoperative planning, compared to that afforded by fMRI alone. Our results show that the combined use of fMRI and DTI can provide a better estimation of the proximity of tumor borders to eloquent brain systems sub-serving language, speech, vision, motor and premotor functions. Additionally, a low regional complication rate (4%) observed in our series suggests that preoperative planning with these combined techniques may improve surgical outcomes compared to that previously reported in the literature. Larger studies specifically designed to establish the accuracy and predictive value of DTI in brain tumor patients are warranted to substantiate our preliminary observations.

Adult↗

Impact of bone marrow hematopoiesis failure on T-cell generation during pathogenic simian immunodeficiency virus infection in macaques.

Experimental infection of macaques with pathogenic strains of simian immunodeficiency virus (SIV) represents one of the most relevant animal models for studying HIV pathogenesis. In this study, we demonstrated a significant decrease in the generation of CD4+ T cells from bone marrow (BM) CD34+ progenitors in macaques infected with SIVmac251. This decrease appears to result from changes in the clonogenic potential of BM progenitors of both the myeloid and lymphoid lineages. We also demonstrated a significant decrease in the numbers of the most immature long-term culture-initiating cells (LTC-ICs). Hematopoietic failure occurred as early as primary infection, in the absence of CD34+ BM cell infection and was not related to plasma viral load. No major change was observed in the phenotype of BM CD34+ cells from infected macaques, including apoptosis markers such as annexin V staining and BcL-2 expression, but a significantly higher that normal proportion of cells were in the G0/G1 phase. This is the first demonstration that failure of BM hematopoiesis results in impaired T-cell production, which may contribute to the disruption of T-lymphocyte homeostasis characteristic of pathogenic lentiviral infections in primates.

Animals↗

Polymorphism in the fractalkine receptor CX3CR1 as a genetic risk factor for coronary artery disease.

Coronary atherosclerosis is a major cause of death in industrialized countries. Monocytes, which play a key role in atherosclerosis, migrate into the vessel wall, presumably guided by specific chemoattractant and adhesion molecules. A compelling candidate for this role is the chemokine receptor CX3CR1, which is expressed on monocytes and acts as either a chemotactic receptor or an adhesion molecule, depending on whether its ligand, fractalkine, is presented free or membrane bound. A common variant of CX3CR1 was recently identified, encoded by the alleles I249 and M280, which form a common I(249)M(280) haplotype. When CX3CR1 genotypes were analyzed in 151 patients with acute coronary syndromes and in 249 healthy controls, CX3CR1 I249 heterozygosity was associated with a markedly reduced risk of acute coronary events, independent of established acquired coronary risk factors (eg, smoking, diabetes). The adjusted odds ratio for this allele was 0.43 (95% confidence interval, 0.26-0.72; P =.001). Consistent with this, functional analysis of peripheral blood mononuclear cells showed that CX3CR1 I249 heterozygosity was associated with a significant decrease in the number of fractalkine binding sites per cell. The results show that CX3CR1 I249 is an independent genetic risk factor for coronary artery disease and that CX3CR1 may be involved in the pathogenesis of atherosclerotic disease. (Blood. 2001;97:1925-1928)

Acute Disease↗

Estrone and dehydroepiandrosterone sulfatase activities in normal and pathological human endometrium biopsies.

The properties of estrone (E1) and dehydroepiandrosterone (DHEA) sulfatase activities are reported. Endometrial biopsy specimens were obtained using a Novak curette. Cycle stage was assessed from histological dating of endometrium, plasma estradiol and progesterone levels, and patient history. Both sulfatases are membrane-bound enzymes. The optimum pHs in Tris-HCl buffer were 6.5 for E1 sulfatase and 7.3 for DHEA sulfatase. Lowest activities and different optimum pHs were obtained with imidazole, maleate, or acetate buffers. DHEA sulfatase is more sensitive to thermal inactivation than E1 sulfatase. From kinetic studies, apparent Km values of 3.1 microM for E1 sulfatase and 5.7 microM for DHEA sulfatase were calculated. Noncompetitive inhibition of E1 sulfatase by DHEA sulfate and of DHEA sulfatase by E1 sulfate were demonstrated. The effects of inorganic ions and unconjugated steroids were also tested. These results are consistent with two different activities hydrolyzing E1 or DHEA sulfates. Neither activity varies during normal menstrual cycles nor is not correlated to plasma progesterone or 17 beta-estradiol levels. An isolated increase in E1 sulfatase occurred in the proliferative phase of irregular menstrual cycles, postantibiotic-treated salpingitis, or hyperplastic endometrium.

Dehydroepiandrosterone↗

Lesion-induced pseudo-dominance at functional magnetic resonance imaging: implications for preoperative assessments.

OBJECTIVE: To illustrate how lesion-induced neurovascular uncoupling at functional magnetic resonance imaging (fMRI) can mimic hemispheric dominance opposite the side of a lesion preoperatively. METHODS: We retrospectively reviewed preoperative fMRI mapping data from 50 patients with focal brain abnormalities to establish patterns of hemispheric dominance of language, speech, visual, or motor system functions. Abnormalities included gliomas (31 patients), arteriovenous malformations (AVMs) (11 patients), other congenital lesions (4 patients), encephalomalacia (3 patients), and tumefactive encephalitis (1 patient). A laterality ratio of fMRI hemispheric dominance was compared with actual hemispheric dominance as verified by electrocortical stimulation, Wada testing, postoperative and posttreatment deficits, and/or lesion-induced deficits. fMRI activation maps were generated with cross-correlation (P < 0.001) or t test (P < 0.001) analysis. RESULTS: In 50 patients, a total of 85 functional areas were within 5 mm of the edge of a potentially resectable lesion. In 23 of these areas (27%), reduced fMRI signal in perilesional eloquent cortex in conjunction with preserved or increased signal in homologous contralateral brain areas revealed functional dominance opposite the side of the lesion. This suggested possible lesion-induced transhemispheric cortical reorganization to homologous brain regions (homotopic reorganization). In seven patients, however, the fMRI data were inconsistent with other methods of functional localization. In two patients with left inferior frontal gyrus gliomas and in one patient with focal tumefactive meningoencephalitis, fMRI incorrectly suggested strong right hemispheric speech dominance. In two patients with lateral precentral gyrus region gliomas and one patient with a left central sulcus AVM, the fMRI pattern incorrectly suggested primary corticobulbar motor dominance contralateral to the side of the lesion. In a patient with a right superior frontal gyrus AVM, fMRI revealed pronounced left dominant supplementary motor area activity in response to a bilateral complex motor task, but right superior frontal gyrus perilesional hemorrhage and edema subsequently caused left upper-extremity plegia. Pathophysiological factors that might have caused neurovascular uncoupling and facilitated pseudo-dominance at fMRI in these patients included direct tumor infiltration, neovascularity, cerebrovascular inflammation, and AVM-induced hemodynamic effects. Sixteen patients had proven (1 patient), probable (2 patients), or possible (13 patients) but unproven lesion-induced homotopic cortical reorganization. CONCLUSION: Lesion-induced neurovascular uncoupling causing reduced fMRI signal in perilesional eloquent cortex, in conjunction with normal or increased activity in homologous brain regions, may simulate hemispheric dominance and lesion-induced homotopic cortical reorganization.

Adult↗

Assessment of lifestyle effects on the overall antioxidant capacity of healthy subjects.

Oxidative damage is increasingly recognized as playing an important role in the pathogenesis of several diseases such as cancer and cardiovascular diseases. Using a biologic test based on whole blood resistance to free-radical aggression, we sought to evaluate lifestyle factors that may contribute to the normal variability of the overall antioxidant status. We assessed this global antiradical defense capacity in 88 men and 96 women in relation to information on lifestyle obtained by questionnaire. In our relatively young, healthy population, we found a weak negative relation between male sex or aging and the resistance to oxidant stress. Among the factors studied, nonsmoking, vitamin and/or mineral supplementation, and regular physical activity were closely associated with an increased overall antioxidant capacity. Conversely, the antioxidant potential was negatively related to tobacco smoking; psychologic stress; alcohol consumption; moderate vegetable, low fruit, and low fish consumption; and, to a lesser extent, high natural ultraviolet light exposure. Thus, we were able to determine "unhealthy" and "healthy" lifestyle patterns that truly contributed to the variation of individual antioxidant capacity. We conclude that lifestyle determinants of cancer and cardiovascular risks were associated with a decreased overall antioxidant status as dynamically measured by means of a biologic test. Thus, the evaluation of the total human resistance against free-radical aggression, taking into account nutritional habits, lifestyle, and environmental factors, may be useful in preventive medicine as a precocious diagnosis to identify healthy subjects who are at risk for free-radical-mediated diseases.

Adult↗

Effects of a combination of evening primrose oil (gamma linolenic acid) and fish oil (eicosapentaenoic + docahexaenoic acid) versus magnesium, and versus placebo in preventing pre-eclampsia.

In a placebo controlled, partially double-blinded, clinical trial, a combination of evening primrose oil and fish oil was compared to Magnesium Oxide, and to a Placebo in preventing Pre-Eclampsia of Pregnancy. All were given as nutritional supplements for six months to a group of primiparous and multiparous pregnant women. Some of these women had personal or family histories of hypertension (21%). Only those patients who received prenatal care at the Central Maternity Hospital for Luanda were included in the study. Compared to the Placebo group (29%), the group receiving the mixture of evening primrose oil and fish oil containing Gamma-linolenic acid (GLA), Eicosapentaenoic acid (EPA), and Docosahexaenoic acid (DHA) had a significantly lower incidence of edema (13%, p = 0.004). The group receiving Magnesium Oxide had statistically significant fewer subjects who developed hypertension of pregnancy. There were 3 cases of eclampsia, all in the Placebo group.

Adolescent↗

Evolution of consanguinity in a French alpine valley: the Vallouise in the Brianfon region (17th-19th Centuries).

The present study considers the evolution of consanguinity in the Vallouise, a high glacial valley in the French Alps. The genealogical method was used to estimate consanguinity in this Alpine population from the 17th to the 19th centuries. This method was then compared with three other methods used to measure consanguinity. The results indicate that while consanguinity increased through time (marriage dispensations and genealogies), the structural consanguinity (isonymy) was very stable throughout the entire period.

Consanguinity↗

Social structure and consanguinity in a French mountain Population (1550-1849).

Sociocultural factors play a crucial role in the variation of consanguinity in a population. The choice of specific matrimonial strategies can favor the closure or opening of the group to the outside, whereas differential fertility affects the gene flow from one generation to another. In the present study we analyzed the role of socioprofessional groups in the maintenance of endogamy and consanguinity in a French Alpine valley: Vallouise in the Briançon area. In mountain environments, where the reproductive space is limited and quickly saturated, the autochthonous families adopt diversified matrimonial strategies. These marriage practices tend to prevent fragmentation of agricultural property. We analyzed the matrimonial behavior in the two main social groups of this population (décideurs and farmers) from 1550 to 1849. To better understand the behavior of the two social groups, we considered the two components of consanguinity, close and distant. Our study showed that the two groups had similar behavior regarding consanguinity. The way to prevent fragmentation of the patrimony was to choose a consanguineous spouse. This type of strategy inevitably leads to a high percentage of endogamy, which in this region of the Alps exceeded 90% through many centuries.

Anthropology, Cultural↗

Cardiopulmonary effects of a single oral dose of almitrine at rest and on exercise in patients with hypoxic chronic airflow obstruction.

Almitrine, a new triazine derivative, was studied in a double-blind, randomized, parallel study in 16 patients with hypoxic chronic airflow obstruction (eight almitrine and eight placebo). At rest, compared to placebo, a 3 mg/kg single dose of almitrine given orally significantly increased the partial pressure of oxygen (mean increase: +12.0 +/- SEM 2.1 mm Hg, p less than 0.001) and decreased the partial pressure of carbon dioxide (mean decrease: -6.0 +/- 0.7 mm Hg, p less than 0.001); this improvement in arterial blood gases persisted on exercise. The lack of significant change in ventilation and the decrease in the alveolar-arterial oxygen gradient (mean decrease -10.0 +/- 1.9 mm Hg; p less than 0.001) at rest suggests a change in the distribution of the ventilation-perfusion ratio in the lung; such a change was confirmed by a krypton 81m isotopic study. Pulmonary hemodynamic responses were studied at rest and on exercise; a significant but slight increase in mean pulmonary artery pressure at rest (+4.0 +/- 1.5 mm Hg, p less than 0.05) was found.

Administration, Oral↗

Folate deficiencies and cardiovascular pathologies.

Although folates are widely distributed in foods, folate deficiencies may be more frequent than expected because their true availability may be impaired due to their lability under various food cooking and processing conditions. Folate deficiency is frequently observed in elderly people, smokers, alcoholics and oral contraceptive users. It is also associated with the mutation leading to the thermolabile variant of N5,10-methylenetetrahydrofolate reductase which is observed in about 10% of the population. In addition to the essential role of the intracellular pool of polyglutamates in de novo biosynthesis of deoxyribonucleotides which allow cell growth and division, the reduced and methylated form of folate, N5-methyltetrahydrofolate, is required for the remethylation of homocysteine to methionine. By inhibiting this remethylation pathway, folate deficiency induces homocysteine efflux into the circulation. Many studies have shown a negative correlation between plasma folate, particularly N5-methyltetrahydrofolate, and circulating homocysteine levels. In addition, folate deficiency is a major cause of hyperhomocysteinemia which is fully recognised as an independent risk factor for atherothrombosis. Epidemiological and recent experimental studies have demonstrated that folate deficiency might increase the risk of cardiovascular disease by increasing circulating homocysteine levels. Thus, the clinical efficiency of folate supplementation, especially N5-methyltetrahydrofolate, in reducing homocysteine-dependent cardiovascular risk should be evaluated.

Cardiovascular Diseases↗

Determination of plasma methoxyamines.

The determination of plasma methoxyamines is the most informative parameter for the diagnosis of pheochromocytoma. Very good sensitivity and specificity are necessary for this. The measurement of deconjugated (free plus sulfate-conjugated) metanephrines is more useful. Concentrations are 10-fold higher than free metanephrine concentrations. The methodology generally uses a column purification and high performance liquid chromatography with electrochemical detection. We have tested six commercial columns used for the purification step. We chose a rapid and reliable method with a mixture of strong cation-exchange and strong anion-exchange groups bonded onto a silica column. This protocol has been validated with samples of plasma from normal subjects, healthy elderly people, renal failure patients and patients with pheochromocytoma.

Chromatography, High Pressure Liquid↗