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.

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.

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.

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.

Experience with ifosfamide combinations (etoposide or DDP) in non-small cell lung cancer.

In all, 171 patients with histologically verified non-small cell lung carcinoma were treated with ifosfamide 2.0 g/m2 on days 1-5 in combination with (91 patients) etoposide 120 mg/m2 on day 1. Therapeutic regimens were repeated after 4 weeks. Supportive treatment with mesna (20% of the ifosfamide doses at 0, 4, and 8 h) was performed. Cisplatin treatment was supported by mannitol-induced diuretic hydration. The overall response rate of ifosfamide/etoposide was calculated to be 27%, with 1 complete and 24 partial remissions. The median survival time for all patients was 8.5 months, for responders 14 months (P less than 0.05), for patients with no change 9.5 months, and for patients with tumor progression 4 months. With ifosfamide/cisplatin, there were 4 complete and 21 partial remissions (response rate 35%). The median survival time for all patients was 8.3 months, for responders 11.5 months, and for patients with tumor progression 4 months. Age, sex, and histological tumor type had no significant effect on survival. Patients with better performance stage and limited disease lived significantly longer. The main side-effects of the cisplatin combination were vomiting, bone marrow depression, and neuropathy. The etoposide combination was tolerated better. Urotoxicity was not significant, as a consequence of treatment with mesna. The results show that the combination ifosfamide/etoposide or ifosfamide/cisplatin are effective in the treatment of non-small cell lung cancer, being comparable to other combinations of etoposide/cisplatin and vindesine/cisplatin. Because of the better tolerability, the combination ifosfamide/etoposide is superior to cisplatin combinations.

The rate of transbilayer movement of erythrocyte membrane cholesterol is correlated with sodium-lithium countertransport.

Hypertension is associated with some abnormalities in cell membrane structure, including an impaired distribution of cholesterol into the monolayers of erythrocyte membrane. Transbilayer movement of membrane cholesterol modulates the formation of these structural cholesterol domains. We tested whether the rate of cholesterol movement may influence on the erythrocyte Na(+)-Li+ countertransport, that is a marker of human essential hypertension. In single regression analysis, the half-time for the decrease in specific radioactivity of cholestenone (inverse of membrane cholesterol transbilayer movement) was negatively related to the erythrocyte cation flux mediated by Na(+)-Li+ countertransport (r = -0.8983, P < 0.0001 for control subjects; r = -0.8191, P < 0.005 for normocholesterolaemic hypertensive patients; r = -0.7664, P < 0.005 for hypercholesterolaemic hypertensive patients). These data suggest that changes in the transbilayer movement of membrane cholesterol interfere with the main cation transport system which is implicated in the pathophysiology of essential hypertension. This also provides a new link between kinetic cholesterol pools and cell membrane functions.

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.

Ambulatory blood pressure monitoring in physicians working in a hospital: is there an increase in the number of subjects with high workplace blood pressures?

Sixty-two physicians from our hospital who were normotensives, as supported by casual blood pressure measurements, underwent 24-h blood pressure monitoring which included their normal work, home rest and sleep periods. During working hours, 19% of the subjects showed mean diastolic and/or diastolic plus systolic blood pressures higher than those admitted as normal by the WHO for casual measurements for out of work subjects. Both mean systolic and diastolic blood pressure measurements, during the work at the hospital, were significantly higher in males (P < 0.01 and P < 0.005, respectively) than the mean of the readings obtained during the 24-h period, but this phenomenon did not occur among the females. Male's mean systolic (129.8 +/- 10.6 vs. 117.1 +/- 9.7 mmHg, P < 0.0001) and diastolic pressures (83.4 +/- 8 vs. 74.9 +/- 7.3 mmHg, P < 0.001) were significantly higher during the working period in relation to those of the female group. Discussing the influence of the kind of work on blood pressure, we came to the conclusion of the existence in our environment of a group of subjects (generally males), presenting high blood pressure values during their working period at the hospital and normal or borderline values during the rest of the day. This should be of interest, since it has been reported that subjects with high workplace blood pressure have an increased risk of hypertension and target-organ damage.

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.

[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.

[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.

[Influences of hyperinsulinemia in the lipid profile of hypertensive patients]. / Influencias de la hiperinsulinemia en el perfil lipídico de los pacientes hipertensos.

BACKGROUND: Hypertension and dyslipemia are associated with a greater frequency than that randomly expected. The increase in insulinic resistance hyperinsulinemia is one of the factors implicated in the pathogenesis of this association. In the present study the lipid profile of hypertensive patients is analyzed according to the degree of insulinemia. METHODS: The lipid profile (total cholesterol, fraction linked to low density lipoproteins cLDL, high density cHDL, triglycerides and plasma apolipoproteins A1 and B were determined in 87 patients with essential high blood pressure. Moreover an oral overdose of 75 g of glucose was administered with determinations of glycemia, insulinemia and C peptide at the time of glucose administration, 60 and 120 minutes. RESULTS: Upon separation of the hypertense patients into two groups according to the insulinemia achieved following an oral overload of glucose, those hypertensives with a greater degree of insulinemia showed a significant increase in triglycerides (p < 0.05) and also a significant decrease in cHDL (p < 0.001). The hypertensive patients with lower insulinemia showed a significant increase in total cholesterol (p < 0.05) and fraction linked to LDL although the latter was not significant. CONCLUSIONS: Two different lipid profiles may be observed in hypertensive patients: one linked to hyperinsulinemia and characterized by an increase in triglycerides and a decrease in cHDL and another with no relation with hyperinsulinemia which is manifested by an increase in total cholesterol and cholesterol transported by the LDL.

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.

Pilomatrix carcinoma: role played by MR imaging.

We report the magnetic resonance imaging (MRI) of a pilomatrix carcinoma. We found a soft tissue tumor of the back entering the spinal canal and compressing the spinal cord and we monitored a good response to radiotherapy and chemotherapy. We have concluded that MRI played an important role in determination of the volume, extension and management of this rare malignant tumor.

[Chemotherapy of non-small cell bronchial cancer with ifosfamide in combination with cisplatin, etoposide or vindesine]. / Die Chemotherapie des nicht-kleinzelligen Bronchialkarzinoms mit Ifosfamid in Kombination mit Cisplatin, Etoposid oder Vindesin.

192 untreated patients with a histologically verified non-small cell lung carcinoma were treated within 3 phase-II studies with different chemotherapy regimens: ifosfamide 2 g/m2 day 1-5 and cis-platinum 75 mg/m2 on day 1 (study I); ifosfamide 2 g/m2 days 1-5 and etoposide 120 mg/m2 days 1-3 (study II); ifosfamide 2 g/m2 days 1-5 and vindesine 3 mg/m2 on days 1 and 8 (study III). All chemotherapy combinations were repeated every 4 weeks. One therapy with at least 2 courses was the minimum criterion for evaluating the remission rate. We observed complete remissions in 5 patients, and partial remissions in 54 patients (remission rate 31%). The median duration of remission was 7 months, the time to progression 5 months. The median survival time of all 192 patients was calculated as 8.5 months. The performance status had a significant influence on the remission state and the survival time of the patients. The sex and age of the patients as well as the extension and the histological type of the tumor had no influence. Concerning the remission rate and the survival time, there was no significant difference between the 3 therapy regimens. Due to the lesser toxicity, the combination ifosfamide/etoposide was the best.