Adjuvant intra-arterial hepatic fotemustine for high-risk uveal melanoma patients.

Uveal melanoma metastases occur most commonly in the liver. Given the 50% mortality rate in patients at high risk of developing liver metastases, we tested an adjuvant intra-arterial hepatic (i.a.h.) chemotherapy with fotemustine after proton beam irradiation of the primary tumour. We treated 22 high-risk patients with adjuvant i.a.h. fotemustine. Planned treatment duration was 6 months, starting with four weekly doses of 100 mg/m(2), and after a 5-week rest, repeated every 3 weeks. The survival of this patient group was compared with that of a 3 : 1 matched control group randomly selected from our institutional database. Half of the patients experienced > or =grade 3 hepatotoxicity (one patient developing cholangitis 8 years later). Catheter-related complications occurred in 18%. With a median follow-up of 4.6 years for the fotemustine group and 8.5 years for the control group, median overall survival was 9 years [95% confidence interval (CI) 2.2-12.7] and 7.4 years (95% CI 5.4-12.7; P=0.5), respectively, with 5-year survival rates of 75 and 56%. Treatment with adjuvant i.a.h. fotemustine is feasible. However, toxicities are important. Although our data suggest a survival benefit, it was not statistically significant. Confirming such a benefit would require a large, internationally coordinated, prospective randomized trial.

Hypertension portate et infection par le VIH [Portal hypertension and HIV infection]

In the era of antiretroviral therapies, the outcome of patients with chronic HIV infection has considerably changed and their prolonged survival allows the development of chronic liver diseases as a major cause of mortality. Although viral hepatitis, alcoholic and non alcoholic steatohepatitis account forthe majority of chronic liver damage in these patients, there is a growing number of cases with unexplained liver disease, many of which are associated with clinical manifestations of portal hypertension. Inthissituation, nodularregenerative hyperplasia is a frequent finding, characterized at histology by the presence of a nodular architecture in the absence of significant fibrosis, resulting from progressive obliteration of small portal veins. This article describes the clinical presentation, diagnostic aspects, pathogenic mechanisms, as well as the management of this emergent non cirrhotic liver disease in HIV-infected patients.

Fructose-rich diet-induced abdominal adipose tissue endocrine dysfunction in normal male rats.

We have currently studied the changes induced by administration of a fructose-rich diet (FRD) to normal rats in the mass and the endocrine function of abdominal (omental) adipose tissue (AAT). Rats were fed ad libitum a standard commercial chow and tap water, either alone (control diet, CD) or containing fructose (10%, w/vol) (FRD). Three weeks after treatment, circulating metabolic markers and leptin release from adipocytes of AAT were measured. Plasma free fatty acids (FFAs), leptin, adiponectin, and plasminogen activator inhibitor-1 (PAI-1) levels were significantly higher in FRD than in CD rats. AAT mass was greater in FRD than in CD rats and their adipocytes were larger, they secreted more leptin and showed impaired insulin sensitivity. While leptin mRNA expression increased in AAT from FRD rats, gene expression of insulin receptor substrate, IRS1 and IRS2 was significantly reduced. Our study demonstrates that administration of a FRD significantly affects insulin sensitivity and several AAT endocrine/metabolic functions. These alterations could be part of a network of interacting abnormalities triggered by FRD-induced oxidative stress at the AAT level. In view of the impaired glucose tolerance observed in FRD rats, these alterations could play a key role in both the development of metabolic syndrome (MS) and beta-cell failure.

Prevalences of masked and white-coat hypertension in the Lausanne population: the Hercules Study

Background and Objectives: Few population-based data on the prevalences of masked and white-coat hypertension exist. We collected 24-hour ambulatory blood pressure (BP) and urine in a random subset of participants to the population-based CoLaus study. Methods: Clinic BP was measured using an Omron HEM 907 device and ambulatory BP (ABP) using a Diasys Integra device. Masked hypertension (MH) was defined as clinic BP < 140/90mm Hg and 24-hour ABP >¼135/85mmHg. White coat hypertension (WCH) was defined as clinic BP >¼ 140/90mm Hg and ABP <135/85mm Hg. Microalbuminuria was defined as present if urinary albumin excretion was > 20mg/min. Results: The 198 men and 213 women were aged (mean_SD) 56.2_10.7 and 57.2_10.3 years and had mean urinary excretion of 148_65 and 122_52 mmol/24 h for sodium and 70_24 and 5721 mmol/24 h for potassium, respectively. In men and women, the prevalences were 34.9% and 31.0% for clinic hypertension, 42.9% and 32.9% for ambulatory hypertension, 12.6% and 5.6% for MH, and 4.5% and 3.8% for WCH, respectively. The higher prevalence of MH in men was explained, in part, by higher alcohol consumption and smoking. Participants with MH tended to have higher microalbuminuria (13.5% vs 5.8%, P¼0.067). Participants with WCH had no microalbuminuria. Conclusions: In the Lausanne population aged 38 to 78 years, the prevalence of hypertension based on ABP was high, despite moderate dietary salt intake. Men had higher prevalence of MH then women. The prevalence of WCH was low and similar in men and women. MH tended to be associated with early kidney damage.

Monitoring compliance in resistant hypertension: an important step in patient management.

Poor compliance with antihypertensive drug regimens is one recognized cause of inadequate blood pressure control. Compliance is difficult to measure, so poor adherence to treatment remains largely undiagnosed in clinical practice. When the therapeutic response to a drug is not the one expected, it is a major challenge for many physicians to decide whether the patient is a non-responder or a non-complier. Poor compliance is therefore often incorrectly interpreted as a lack of response to treatment. Not detecting non-compliance can lead to the wrong measures being taken. Electronic monitoring of compliance provides important longitudinal information about drug-intake behaviour that cannot be obtained in the clinic. Such monitoring can improve both compliance and blood pressure control, and help physicians to make more rational therapeutic decisions. A reliable assessment of compliance could have a great impact on medical costs by preventing unnecessary investigations or dose adaptations in patients who are not taking their drugs adequately, or potentially reducing the number of hospitalizations. Side-effects and lack of effectiveness are two frequent causes of poor compliance. The right choice of antihypertensive drug can therefore contribute to compliance. In this respect, it is important to find a drug regimen that is effective, long-acting and well tolerated. Long-acting antihypertensive drugs that provide good blood pressure control beyond the 24-h dosing period should perhaps be considered as drugs of choice in non-compliant patients with hypertension because they help to prevent the consequences of occasional drug omissions.

Hypertension and microvascular remodelling

In the present review, microvascular remodelling refers to alterations in the structure of resistance vessels contributing to elevated systemic vascular resistance in hypertension. We start with some historical aspects, underscoring the importance of Folkow's contribution made half a century ago. We then move to some basic concepts on the biomechanics of blood vessels, and explicit the definitions proposed by Mulvany for specific forms of remodelling, especially inward eutrophic and inward hypertrophic. The available evidence for the existence of remodelled resistance vessels in hypertension comes next, with relatively more weight given to human, in comparison with animal data. Mechanisms are discussed. The impact of antihypertensive drug treatment on remodelling is described, again with emphasis on human data. Some details are given on the three studies to date which point to remodelling of subcutaneous resistance arteries as an independent predictor of cardiovascular risk in hypertensive patients. We terminate by considering the potential role of remodelling in the pathogenesis of end-organ damage and in the perpetuation of hypertension.

Treatment of advanced ovarian cancer with surgery, chemotherapy, and consolidation of response by whole-abdominal radiotherapy.

Between April 1981 and June 1985, 195 patients with ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) Stages IIB, IIC, III, and IV, entered a trial that consisted of surgery and chemotherapy with cisplatin (P) and melphalan (PAM) with or without hexamethylmelamine (HexaPAMP or PAMP regimens) every 4 weeks for 6 cycles. Because the intent was to study the outcome by treatment after evaluation of first-line chemotherapy, patients were evaluable only if the response was assessed by a second-look operation or if measurable disease progression was documented. One hundred fifty-eight patients (81%) were evaluable for response. Forty-five (28%) achieved pathologically confirmed complete remissions (pCR), and 24 of these patients received whole-abdominal radiation (WAR) for consolidation of response. Five patients with complete remission after WAR relapsed, as did nine of the 21 with complete remission who had not undergone WAR. The 3-year time to progression percentage (TTP +/- SE) from second-look operation was 70% +/- 7% for all patients who achieved pCR, 83% +/- 8% for those who received WAR, and 49% +/- 15% for those who did not receive WAR (this was not a randomized comparison). The 3-year TTP percentage for the 49 partial responders was 21% +/- 6%, identical for the 19 who had WAR and the 30 who had no radiation therapy. Additional or alternative methods for consolidation of pCR are needed since patients continue to relapse despite optimal initial response to therapy.

Usefulness of intra-articular bupivacain and lidocain adjunction in MR or CT arthrography: a prospective study in 148 patients.

PURPOSE: To evaluate the influence of shorter- and longer-acting intra-articular anaesthetics on post-arthrographic pain. MATERIALS AND METHODS: 154 consecutive patients investigated by MR or CT arthrographies were randomly assigned to one of the following groups: 1--intra-articular contrast injection only; 2--lidocain 1% adjunction; or 3--bupivacain 0.25% adjunction. Pain was assessed before injection, at 15 min, 4 h, 1 day and 1 week after injection by visual analogue scale (VAS). RESULTS: At 15 min, early mean pain score increased by 0.96, 0.24 and 0 in groups 1, 2 and 3, respectively. Differences between groups 1 & 3 and 1 & 2 were statistically significant (p=0.003 and 0.03, respectively), but not between groups 2 & 3 (p=0.54). Delayed mean pain score increase was maximal at 4 h, reaching 1.60, 1.22 and 0.29 in groups 1, 2 and 3, respectively. Differences between groups 1 & 2 and 2 & 3 were statistically significant (p=0.002 and 0.02, respectively), but not between groups 1 & 2 (p=0.46). At 24 h and 1 week, the interaction of local anaesthetics with increase in pain score was no longer significant. Results were independent of age, gender and baseline VAS. CONCLUSION: Intra-articular anaesthesia may significantly reduce post-arthrographic pain. Bupivacain seems to be more effective than lidocain to reduce both early and delayed pain.

Augmented myocardial methionine-enkephalin in a murine model of cardiac angiotensin II-overexpression.

INTRODUCTION: The endogenous opioid system has been reported to interact with both the cardiac sympathetic and renin-angiotensin systems in exerting a local regulatory action on the heart. The goal of this investigation was to examine how cardiac levels of enkephalin production are altered in the development of normotensive primary hypertrophy due to elevated intra-cardiac angiotensin II (Ang II) production. METHODS: Atrial and ventricular methionine-enkephalin (ME) levels were measured by quantitative radioimmunoassay in 14 and 28-week-old male transgenic mice (TG1306/1R) and control mice. The TG1306/1R exhibit cardiac specific Ang II overexpression and cardiac hypertrophy, but not hypertension. RESULTS: TG1306/1R mice had significantly higher heart/body weight ratios (15-20%) than control littermates at both 14 (p=0.02) and 28 weeks (p=0.04). Relative to controls, ME content was significantly elevated (approximately two-fold) in atria and ventricles in the older 28-week TG1306/1R mice only. A significant inverse correlation between heart size and ME level was observed for 28-week TG1306/1R only. CONCLUSIONS: We have provided evidence that a marked elevation of myocardial enkephalin level is observed in the established (but not early) phase of cardiac hypertrophy associated with cardiac-specific Ang II-overexpression. This study identifies a potentially important relationship between two endogenous peptidergic signalling systems involved in the regulation of growth and function of the hypertrophic heart.

1999-2009 trends in prevalence, unawareness, treatment and control of hypertension in Geneva, Switzerland.

BACKGROUND: There are no time trends in prevalence, unawareness, treatment, and control of hypertension in Switzerland. The objective of this study was to analyze these trends and to determine the associated factors. METHODS/FINDINGS: Population-based study conducted in the Canton of Geneva, Switzerland, between 1999 and 2009. Blood pressure was measured thrice using a standard protocol. Hypertension was defined as mean systolic or diastolic blood pressure ≥140/90 mmHg or self-reported hypertension or anti-hypertensive medication. Unawareness, untreated and uncontrolled hypertension was determined by questionnaires/blood pressure measurements. Yearly age-standardized prevalences and adjusted associations for the 1999-2003 and 2004-2009 survey periods were reported. The 10-year survey included 9,215 participants aged 35 to 74 years. Hypertension remained stable (34.4%). Hypertension unawareness decreased from 35.9% to 17.7% (P<0.001). The decrease in hypertension unawareness was not paralleled by a concomitant absolute increase in hypertension treatment, which remained low (38.2%). A larger proportion of all hypertensive participants were aware but not treated in 2004-2009 (43.7%) compared to 1999-2003 (33.1%). Uncontrolled hypertension improved from 62.2% to 40.6% between 1999 and 2009 (P = 0.02). In 1999-2003 period, factors associated with hypertension unawareness were current smoking (OR = 1.27, 95%CI, 1.02-1.59), male gender (OR = 1.56, 1.27-1.92), hypercholesterolemia (OR = 1.31, 1.20-1.44), and older age (OR 65-74yrs vs 35-49yrs  = 1.56, 1.21-2.02). In 1999-2003 and 2004-2009, obesity and diabetes were negatively associated with hypertension unawareness, high education was associated with untreated hypertension (OR = 1.45, 1.12-1.88 and 1.42, 1.02-1.99, respectively), and male gender with uncontrolled hypertension (OR = 1.49, 1.03-2.17 and 1.65, 1.08-2.50, respectively). Sedentarity was associated with higher risk of hypertension and uncontrolled hypertension in 1999-2003. CONCLUSIONS: Hypertension prevalence remained stable since 1999 in the canton of Geneva. Although hypertension unawareness substantially decreased, more than half of hypertensive subjects still remained untreated or uncontrolled in 2004-2009. This study identified determinants that should guide interventions aimed at improving hypertension treatment and control.

Performance of blood pressure-to-height ratio at a single screening visit for the identification of hypertension in children.

BACKGROUND: The diagnosis of hypertension in children is difficult because of the multiple sex-, age-, and height-specific thresholds to define elevated blood pressure (BP). Blood pressure-to-height ratio (BPHR) has been proposed to facilitate the identification of elevated BP in children. OBJECTIVE: We assessed the performance of BPHR at a single screening visit to identify children with hypertension that is sustained elevated BP. METHOD: In a school-based study conducted in Switzerland, BP was measured at up to three visits in 5207 children. Children had hypertension if BP was elevated at the three visits. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) for the identification of hypertension were assessed for different thresholds of BPHR. The ability of BPHR at a single screening visit to discriminate children with and without hypertension was evaluated with receiver operating characteristic (ROC) curve analyses. RESULTS: The prevalence of systolic/diastolic hypertension was 2.2%. Systolic BPHR had a better performance to identify hypertension compared with diastolic BPHR (area under the ROC curve: 0.95 vs. 0.84). The highest performance was obtained with a systolic BPHR threshold set at 0.80 mmHg/cm (sensitivity: 98%; specificity: 85%; PPV: 12%; and NPV: 100%) and a diastolic BPHR threshold set at 0.45 mmHg/cm (sensitivity: 79%; specificity: 70%; PPV: 5%; and NPV: 99%). The PPV was higher among tall or overweight children. CONCLUSION: BPHR at a single screening visit had a high performance to identify hypertension in children, although the low prevalence of hypertension led to a low PPV.

Blood pressure monitoring through pharmacies and team-based care of hypertension.

In the last issue of Blood Pressure Monitoring, (James K, Dolan E, O'Brien E. Making ambulatory blood pressure monitoring accessible in pharmacies. Blood Press Monit 2014;19:134-139) elegantly reported for the first time the characteristics of patients attending pharmacies for ambulatory blood pressure measurement (ABPM) and showed that they were similar to those undergoing ABPM through primary care practices. The authors concluded that pharmacies could be a valuable resource to perform ABPM. In the continuity of this study, we would like to emphasize the results of recent studies as well as recommenda-tions of pharmacist involvement in the management of hypertension, more specifically in a team approach.

Modification du style de vie : une alternative au traitement pharmacologique lors d'hypertension modérée

[But de l'étude] Il s'agit d'effectuer un projet pilote afin de développer la méthodologie pour une large étude et d'en examiner les possibilités de réalisation. Cette large étude devrait permettre de tester l'hypothèse qu'une thérapeutique non médicamenteuse de l'hypertension artérielle modérée est une alternative valable au traitement chimiothérapeutique en termes de résultats cliniques et de rapport coût/efficacité. [Auteurs, p. 4]