Disfunción endotelial medida con flujimetría láser-doppler en pacientes con Síndrome de apneas-hipopneas del sueño. Efecto del tratamiento con presión positiva continua en la vía aérea / Endothelial dysfunction measured with a Laser-Doppler flowmetry in patients with sleep apnea-hypopnea syndrome. The effecto ftreatment with continuous positive airway pressure

INTRODUCCIÓN: El SAHS se relaciona con el desarrollo de enfermedades cardiovasculares, con un aumento de la mortalidad de los pacientes que lo padecen. Dentro del espectro de la afectación cardiovascular, cada día se reconoce como más importante la disfunción endotelial. MATERIAL Y MÉTODOS: Estudio prospectivo de pacientes diagnosticados de SAHS mediante poligrafía respiratoria con indicación de CPAP. La función endotelial se ha valorado mediante la técnica no invasiva de flujimetría láser-doppler, realizada de manera basal y tras 3 meses de tratamiento con CPAP. RESULTADOS: Hemos observado una correlación significativa entre los parámetros oximétricos de la poligrafía respiratoria y algunos parámetros de la flujimetría basal. Además, hemos encontrado un aumento significativo en el valor del área bajo la curva y una disminución del valor de la pendiente de la flujimetría láser doppler (que indica mejoría de la función endotelial) tras la realización del tratamiento con CPAP durante 3 meses

INTRODUCTION: Sleep apnea-hypopnea syndrome (SAHS) is linked to the development of cardiovascular diseases, with increased mortality among these patients. Within the range of cardiovascular affections, the importance of endothelial dysfunction is evermore recognized. MATERIAL AND METHODS: Prospective studies in patients with SAHS using respiratory polygraph with continuous positive airway pressure (CPAP). Endothelial function has been assessed using non-invasive Laser-Doppler Flowmetry, both basal and after 3 months of treatment with CPAP. RESULTS: A significant correlation was observed between the respiratory polygraph oximetry parameters and certain basal flowmeter parameters. Moreover, a significant increase in the value of the area under the curve(AUC) and a decrease in the slope of the Laser-Doppler flowmetry was seen (thus indicating an improvement of endothelial function) after a 3-month treatment with CPAP

Chronic hepatitis e in heart transplant recipients.

Chronic courses of hepatitis E virus (HEV) infections have been described in immunosuppressed patients. We aimed to study the role of HEV infections in heart transplant recipients (HTR). 274 HTR were prospectively screened for HEV infection using an anti-HEV-IgG ELISA and HEV-PCR. In addition, 137 patients undergoing cardiac surgery (non-HTR) and 537 healthy subjects were studied cross-sectionally. The anti-HEV-IgG seroprevalence was 11% in HTR, 7% in non-HTR and 2% in healthy controls (HTR vs. healthy controls p<0.0001; non-HTR vs. healthy controls p<0.01). Anti-HEV tested positive in 4.0% in control cohorts of other immunocompromised patients (n = 474). Four HTR (1.5%) were chronically infected with HEV as shown by HEV-PCR and all four patients had liver transaminases of >200 IU/L and histological or clinical evidence of advanced liver disease. In three patients ribavirin treatment was successful with a sustained biochemical and virological response while treatment failed in one cirrhotic patient after ribavirin dose reduction. Heart transplant recipients and patients undergoing cardiac surgery have an increased risk for HEV infections. Chronic hepatitis E may explain elevated liver enzymes in heart transplant recipients. Treatment of HEV infection with ribavirin is effective but the optimal dose and duration of ribavirin therapy remains to be determined.

Role of the Renin-Angiotensin system and aldosterone on cardiometabolic syndrome.

Aldosterone facilitates cardiovascular damage by increasing blood pressure and through different mechanisms that are independent of its effects on blood pressure. In this respect, recent evidence involves aldosterone in the pathogenesis of metabolic syndrome. Although this relationship is complex, there is some evidence suggesting that different factors may play an important role, such as insulin resistance, renin-angiotensin-aldosterone system, oxidative stress, sodium retention, increased sympathetic activity, levels of free fatty acids, or inflammatory cytokines and adipokines. In addition to the classical pathway by which aldosterone acts through the mineralocorticoid receptors leading to sodium retention, aldosterone also has other mechanisms that influence cardiovascular tissue remodelling. Finally, overweight and obesity promote the adrenal secretion of aldosterone, increasing the predisposition to type 2 diabetes mellitus. Further studies are needed to better establish therapeutic strategies that act on the blockade of mineralocorticoid receptor in the treatment and prevention of cardiovascular diseases related to the excess of aldosterone and the metabolic syndrome.

The HELLP syndrome (hemolysis, elevated liver enzymes and low platelets): Clinical characteristics and maternal-fetal outcome in 172 patients.

OBJECTIVES: To analyze the frequency of the different clinical presentations of the disease in women with HELLP syndrome and the most important factors that can predict a different maternal and fetal outcome. STUDY DESIGN: This is a cross-sectional, consecutive, case-series study, the subjects being all patients with HELLP syndrome admitted to our Hospital within the last decade (1999-2009). RESULTS: The rate of maternal complications was 43.0% and perinatal mortality 14.1%. The severity of the syndrome, measured by The Mississippi Classification, influenced the rate of maternal complications but not fetal mortality: the rate of maternal complications among women in class 1 HELLP syndrome was 67.6%, compared to 49.3% in class 2 and 24.0% in class 3 HELLP syndrome, p<0.0001. In a 21.8% of women, the onset of the disease was after delivery. We highlight the fact that those cases with an early puerperium onset of the disease were those with a higher number of maternal complications (odds ratio: 2.38; CI: 1.05-5.44). CONCLUSIONS: These results suggest the possibility of an increased complication rate when the onset of the syndrome appears after delivery and the necessity of having a high grade of suspicion in every case to diagnose the disease, even when the gestation and delivery were normal.

Influence of polymorphism (RFLP-sstI) at the apolipoprotein C-III gene locus on the lipoprotein metabolism and insulin resistance in essential hypertensive patients. Interaction between gender and genetic polymorphism.

BACKGROUND AND AIM: With respect to the general population, hypertensive patients show an increase in plasma total cholesterol and triglycerides, a decrease in HDL-cholesterol (HDLc) and a higher degree of insulin resistance. Apolipoprotein C-III (apo C-III) plays a regulatory role in the catabolism of triacylglycerol-rich lipoproteins. The S2 allele has been associated with elevated plasma triglycerides concentration, blood pressure and increased risk of myocardial infarction, all of which are characteristic of an insulin resistant state. The aim of this study was to investigate the SstI polymorphism of the apo C-III gene locus on the lipoprotein metabolism, apolipoproteins and basal glucose and insulin levels in essential hypertensive patients. We also examined the influence of the S1S2 allele on blood pressure and the interaction of the mutation at the apo C-III gene and the gender. METHODS AND RESULTS: We studied 104 essential hypertensive patients (59 males and 45 females) determining the carriers of the S2 allele of the genetic polymorphism in the apo C-III gene by polymerase chain reaction, lipoprotein metabolism by standard laboratory methods and ultracentrifugation, apolipoproteins A-I and B by immunoturbidimetry and basal glucose and insulin levels by enzymatic method and radioimmunoassay, respectively. The frequency for the carriers of the SstI minor allele S2 (S1S2 genotype) was 0.17. Patients with the rare S2 allele compared with those with S1S1 allele showed higher plasma triglycerides, total cholesterol and apo B (255.9 +/- 114.6 vs 135.8 +/- 89.1; 250.6 +/- 56.6 vs 214.8 +/- 47.9 and 128.7 +/- 34.8 vs 103.1 +/- 28.6 respectively). Furthermore, basal glucose, insulin levels in S2 allele, and the rate Tg-VLDL/HDLc were increased in the same group. Subgroup analysis revealed that the association between these polymorphism and lipoprotein metabolism, apolipoprotein and basal glucose and insulin levels occurred predominantly in females. A study on the effect of the interaction between this mutation with gender revealed an additive effect on changes in total triglycerides levels. However age, blood pressure and body mass index were similar in both groups of patients (S1S1 and S1S2 genotypes). CONCLUSIONS: These results provide evidence of interaction between gender and the Sst1 polymorphism of the apo C-III on lipoprotein metabolism and insulin resistance in essential hypertensive patients. However, the studied mutation does not contribute to blood pressure levels in essential hypertensive patients (crossover study).

Apolipoprotein E gene polymorphism is related to metabolic abnormalities, but does not influence erythrocyte membrane lipid composition or sodium-lithium countertransport activity in essential hypertension.

The aim of this study was to analyze the influence of the apolipoprotein E (apoE) gene polymorphism on insulin resistance and plasma lipid composition of essential hypertensive patients. A secondary objective was to analyze if differences regarding plasma lipids had an effect on the erythrocyte membrane lipid composition and the activity of the erythrocyte membrane sodium-lithium countertransport. We studied 128 untreated nondiabetic essential hypertensive patients enrolled from our outpatient clinic. We considered as hyperinsulinemic all subjects having more than 80 mU/L of plasma insulin 120 minutes after a 75-g oral glucose intake. The number of hyperinsulinemic subjects among carriers of the epsilon4 allele was higher that in epsilon4 noncarrier subjects (13 of 19 v45 of 109, P < .05; odds ratio [OR], 3.08; confidence interval [CI], 0.99-10.57). Plasma insulin at baseline and plasma insulin and glucose at 120 minutes after overload was higher in carriers of the epsilon4 allele (respectively, 17.5 +/- 6.9 v 12.4 +/- 4.9 mU/L, P < .01; 111.9 +/- 39.9 v 88.7 +/- 48.2, P < .05; and 143.8 +/- 29.3 v 121.2 +/- 30.8 mg/dL, P < .005). Subjects with the epsilon4 allele had a plasma lipid profile more atherogenic than those without this allele. This profile was mainly characterized by higher levels of low-density lipoprotein (LDL) cholesterol (150.1 +/- 31.2 v 133.0 +/- 34.3 mg/dL, P < .05) and very-low-density lipoprotein (VLDL) triglycerides (134.7 +/- 85.5 v 99.2 +/- 68.8 mg/dL, P < .05) and by lower levels of high-density lipoprotein (HDL) cholesterol (41.8 +/- 10.7 v 50.0 +/- 14.7 mg/dL, P < .05). There were no differences between groups regarding erythrocyte membrane cholesterol or phospholipids composition and sodium-lithium countertransport (SLC) activity.

Gordon's syndrome: increased maximal rate of the Na-K-Cl cotransport and erythrocyte membrane replacement of sphingomyelin by phosphatidylethanolamine.

OBJECTIVE: Gordon's syndrome comprises hypertension, hyperchloremic acidemia, hyperkalemia and intact renal function. We hypothesize that disturbances of one or more cell membrane ion carriers, handling sodium, chloride and potassium, might be relevant in this disorder and, furthermore, that such disturbances might be related to altered.cell membrane composition. DESIGN AND METHODS: In a patient diagnosed with Gordon's syndrome, we assessed the kinetics (K(m) and maximal rate) of four membrane sodium transport systems in sodium-enriched erythrocytes, according to the technique of Garay. We also measured the lipid composition of erythrocyte membrane in this patient and 69 essential hypertensive controls, using the latroscan technique. RESULTS: Compared to reference values of patients with essential hypertension, this patient exhibited a marked increase in the maximal rate of the Na+-K+-2Cl(-)-cotransport (964.0 micromol/l per cell versus the 391.6 +/- 222 micromol/l per cell in essential hypertensives). Also, there was an increased concentration of erythrocyte membrane phosphatidylethanolamine and a reduced concentration of sphingomyelin (27.9 and 11.1% versus 17.9 +/- 3.8% and 18.2 +/- 3.4%, respectively). CONCLUSIONS: We conclude that this abnormality in membrane Na+-K+-2Cl- cotransport could be responsible for the hyperkalemia, hyperchloremic acidemia and increased reabsorption of sodium observed in this condition and, furthermore, that such disturbance in membrane cotransport might be related to altered phospholipid concentration in cell membranes.

Genetic variation in the beta-3-adrenergic receptor in essential hypertension.

We investigated the role of the beta-3-adrenergic receptor polymorphism in membrane lipid composition and erythrocyte membrane sodium transport in essential hypertensive patients. We studied 87 essential hypertensive patients determining: The Trp64Arg mutation of the beta-3-adrenergic receptor by PCR, lipoprotein profile by standard laboratory methods, membrane lipid composition by IATROSCAN and erythrocyte sodium lithium countertransport by Canessa technique. Patients with the mutation as compared with those without it showed lower membrane cholesterol, membrane cholesterol phospholipids ratio and erythrocyte sodium lithium countertransport, however blood pressure and the other studied variables were similar in both groups of patients. After adjusting by sex sodium lithium countertransport activity remained significant. These data suggest that although the Trp64Arg mutation of the beta-3-adrenergic receptor is related with a different membrane lipid composition and erythrocyte sodium lithium countertransport values it does not contribute to blood pressure levels in essential hypertensive patients.

[Decreased activity of 11-beta-hydroxysteroid dehydrogenase in patients with Cushing's syndrome]. / Disminución de la actividad de la 11-beta-hidroxiesteroide deshidrogenasa en pacientes con síndrome de Cushing.

BACKGROUND: To study 11 beta-hydroxysteroid dehydrogenase activity in Cushing's syndrome. PATIENTS AND METHOD: Measurements of free cortisol, cortisone, tetrahydrocortisol and tetrahydrocortisone in 24 h urine samples of patients with Cushing's syndrome and controls. RESULTS: The cortisol to cortisone and tetrahydrocortisol to tetrahydrocortisone relationship was significant (in controls, r = 0.70; p < 0.0001, and r = 0.75; p < 0.0001) respectively, but it was not in patients with Cushing's syndrome. CONCLUSIONS: 11 beta-hydroxysteroid dehydrogenase activity is decreased in patients with Cushing's syndrome.

[Prevalence of dyslipidemia and its phenotypes in recently diagnosed essential arterial hypertension]. / Prevalencia de dislipemia y de sus distintos fenotipos en la hipertensión arterial esencial de comienzo reciente.

BACKGROUND: To know the prevalence of phenotypic dyslipidemias and their clinical and metabolic characteristics in recently diagnosed hypertensive patients. METHODS: Consecutive study of 158 essential hypertensive patients without previous pharmacological treatment. RESULTS: 69.6% of the patients had some kind of dyslipidemia, being the isolated increase of Lp(a) (27.3%) the most prevalent and the hyperapobetalipoproteinemia the less (10.0%). Age, sex, smoking, alcohol consumption, uric acid, systolic and pulse pressure and serum glucose were different among phenotypes. CONCLUSIONS: Essential hypertensive patients have high and heterogeneous prevalence of dyslipidemias.

Non-invasive assessment of vascular function; paradoxical vascular response to intravenous glucose in coronary heart disease.

BACKGROUND: In healthy individuals, insulin administration causes an increase in forearm blood flow which is dependent on the effects of insulin on the vascular endothelium. Glucose, administered as an intravenous bolus, produces a transient hyperinsulinaemic response. We hypothesized that the insulin response to an intravenous glucose challenge during the intravenous glucose tolerance test might lead to increases in forearm blood flow in healthy individuals, and that such a response might be altered in patients with coronary heart disease. METHODS AND RESULTS: Healthy individuals (n=10, aged 41.6+/-3. 0 years, mean+/-SEM) and patients with angiographically proven coronary heart disease (n=13, aged 65.5+/-2.4 years) underwent an intravenous glucose tolerance test with simultaneous measurement of right forearm blood flow at 28 time points, using mercury-in-silastic venous occlusion plethysmography. In controls, forearm blood flow increased to a mean of 31.7% above baseline values at 7 min and remained above baseline up to 180 min after intravenous glucose. In contrast, patients with coronary heart disease exhibited an opposite response, with forearm blood flow decreasing to a mean of -16.2% below baseline values at 7 min and -25.8% at 180 min. Marked group differences emerged in net changes from baseline in forearm blood flow throughout the intravenous glucose tolerance test, expressed as incremental areas under the forearm blood flow profiles (controls: +351.3+/-121.7; coronary heart disease patients: -244.3+/-72.4 min ml(-1). 100 ml(-1), P=0. 001). CONCLUSIONS: We have demonstrated for the first time that in healthy individuals forearm blood flow increases after an intravenous bolus of glucose, and that paradoxically, this response is reduced below baseline forearm blood flow in patients with coronary heart disease. Further studies are needed to determine whether plethysmographic measurement of forearm blood flow after an intravenous bolus of glucose could provide a clinically useful non-invasive test for the diagnosis of occult coronary heart disease.

Sodium transport kinetics, cell membrane lipid composition, neural conduction and metabolic control in type 1 diabetic patients. Changes after a low-dose n-3 fatty acid dietary intervention.

BACKGROUND: A decreased content of n-3 fatty acids in erythrocyte membrane of type 1 diabetic patients, which is inversely related to plasma levels of HbA(1c), has been reported previously. Our aim in this study was to observe the changes after a low-dose n-3 fatty acid (330 mg/day docosahexaenoic acid and 630 mg/day eicosapentanoic acid) dietary intervention in the lipid composition of cell membrane and metabolic control (measured according to plasma HbA(1c) levels). Since changes in both parameters may alter transmembrane sodium transport or influence parameters measuring target organ damage, we also studied the neural conduction quality and activity of four sodium transporters. METHODS: Eighteen type 1 diabetic patients were randomly assigned to continue their usual diet (control group) or to supplement their diet with a daily low dose of n-3 fatty acids (supplemented group). The changes between baseline and end values of the following parameters were compared: HbA(1c), lipid and phospholipid composition of cell membrane, activity of four ion carriers and neural conduction quality. RESULTS: The dietary supplementation caused statistically significant changes in membrane lipid composition, particularly an increase of C22:6 (n-3) and the total n-3 fatty acid (respectively +0.90+/-1.14% vs. -0.44+/-1.23% and +1.36+/-1.62% vs. -0.5+/-1.80%, p<0.05). After the dietary supplementation, we also observed a significant decrease of HbA(1c) (-2.00+/-1.9% vs. -0.13+/-0.48%, p<0.05), without significant changes in the dose of insulin required, an increase in the motor conduction velocity by the median nerve (+2.12 +/-1.35 m/s vs. -0.8+/-2.34 m/s, p<0.05) and a decrease of the V(max) of the Na(+)-Li(+) countertransport (-96.6+/-111.2 vs. +58.1+/-81.3 micromol/l cell/h(-1), p<0.01). CONCLUSION: A low-dose omega-3 fatty acid dietary supplementation may change the fatty acid composition of the cell membrane and improve the metabolic control of diabetes. Using this dose, we also observed a decrease of the maximal rate of Na(+)-Li(+) countertransport and a slight improvement of neural conduction.

Cryptococcal peritonitis: report of a case and review of the literature.

We describe a patient diagnosed with AIDS and cirrhosis who had recently suffered a self-limited and non-specific esophageal ulceration. After this, he was hospitalized because of an oral bleeding with fatal evolution, and Cryptococcus neoformans was isolated from ascitic fluid during a routine paracenteses. We have reviewed the literature and, since 1963, only another 10 cases of cryptococcal peritonitis have been reported. A liver disease and not the AIDS (surprisingly, our case is the only report of cryptococcal peritonitis in a subject having both diseases) was the most common underlying disease (72.7%) and was associated with the worst prognosis (only one patient survived). An oral or upper gastrointestinal bleeding was the most common associated circumstance although recent steroid or antibiotic therapy has been also reported. Finally, diagnosis was delayed in many patients. The reasons for these delays are discussed.

Erythrocyte Na(+)-Li+ countertransport in essential hypertension: correlation with membrane lipids levels.

OBJECTIVE: To examine whether Na(+)-Li+ countertransport (SLC) activity is linked to erythrocyte membrane lipid content. DESIGN: An observational case-control study. The maximal efflux rate of SLC, plasma cholesterol, triglycerides, phospholipids, low- and high-density lipoprotein cholesterol levels and the erythrocyte membrane cholesterol, phospholipids and fatty acids contents were determined both in fasting normolipaemic normotensive subjects and in hypertensive patients. METHODS: The Li(+)-stimulated Na+ efflux was measured in Li(+)-preloaded erythrocytes. Membrane cholesterol and phospholipids levels were determined by the latroscan technique. Membrane fatty acids were identificated by gas chromatography. Several derived indices were also obtained. RESULTS: Erythrocyte membranes of hypertensive patients showed an increase in cholesterol: phospholipid ratio and a decrease in the total amount of polyunsaturated fatty acids, mainly at the expense of arachidonic acid and docosatetraenoic acid. SLC activity was higher in hypertensive patients and correlated positively with the plasma triglycerides level and negatively with the ratio of C20:4 to C20:3. CONCLUSION: Our data from untreated normolipaemic hypertensive patients show that a higher SLC activity was accompanied by parameters that indicate a lower membrane fluidity.

Modifications induced by -10 degrees Trendelenburg's posture in sodium tubular handling in patients with essential hypertension.

In essential hypertensive patients "exaggerated natriuresis" is a response to acute volume expansion. However, the underlying mechanisms for this remain to be determined. We studied 19 patients with essential hypertension (HP) and 9 normotensive subjects (NS). In all examined subjects the response to acute central volume expansion, without the plasma compositional change that Trendelenburg's position involves, was evaluated during 90 min (period T) after a similar period of deambulation (period D). Mean blood pressure (MBP), tubular sodium handling by the lithium clearance technique, plasma renin activity (PRA), plasma aldosterone (PA), plasma catecholamines and urine prostaglandine E2 and kallikrein were assessed after D and T. MBP was significantly higher in HP than in NS (p = 0.00001). HP showed "exaggerated natriuresis" after T (fractional excretion of sodium increased from 0.55 +/- 0.1% after D to 1.20 +/- 0.2% after T, p < 0.01). This was because of a decrease in their proximal fractional reabsorption of sodium (from 74.96 +/- 1.8% after D to 62.50 +/- 2.8% after T, p < 0.01). Plasma epinephrine and plasma dopamine after T were significantly lower than in standing position in HP (p < 0.01) but no in NS. The decrease in plasma renin activity after T in HP was 53%, and 32% in NS. There were not any significant differences between groups in the other neurohormonal systems studied. We conclude that the major determinant of "exaggerated natriuresis" in hypertensive patients is a higher stimulation of the cardiopulmonary receptors following Trendelenburg's position and consequently stronger reflex inhibition of sympathetic system activity and renin-angiotensin II activity. The "exaggerated natriuresis" after Trendelenburg's position in HP was an expression of abnormal pressure natriuresis.