Impact of thyroid function and polymorphisms in the type 2 deiodinase on blood pressure: the Rotterdam Study and the Rotterdam Scan Study

Introduction  Thyroid function and genetic variation in the hypothalamus–pituitary–thyroid axis have been implicated in blood pressure regulation and susceptibility to hypertension. However studies conducted thus far were small with controversial results.
Objective  To examine whether serum thyroid parameters and polymorphisms in the type 2 deiodinase and the TSH receptor are associated with blood pressure and the presence of hypertension in two large cohorts of elderly subjects.
Design and participants  We studied a random sample of 1444 subjects of the Rotterdam study, and 997 subjects of the Rotterdam Scan study, two population-based cohort studies among elderly individuals aged 55–90 years.
Outcome measurements  Data on blood pressure and hypertension were obtained, and serum thyroid parameters, D2-Thr92Ala, D2-ORFa-Gly3Asp and TSHR-Asp727Glu polymorphisms were determined.
Results  In contrast to previous findings, no consistent and/or significant associations were found between serum TSH and FT4 and blood pressure in both cohorts. In addition, the D2-Thr92Ala, D2-ORFa-Gly3Asp and TSHR-Asp727Glu polymorphisms were not associated with blood pressure or the risk of hypertension.
Conclusions  In two large populations of elderly subjects, neither serum thyroid parameters nor polymorphisms in the type 2 deiodinase and the TSH receptor, were associated with blood pressure or the presence of hypertension. Our data suggest that thyroid function is not an important determinant of hypertension in elderly Dutch subjects.     

No difference in clinical progression between patients infected with the predominant human immunodeficiency virus type 1 circulating recombinant form (CRF) 02_AG strain and patients not infected with CRF02_AG,in Western and West-Central Africa: a four-year prospective multicenter study

To compare human immunodeficiency virus (HIV) type 1 disease progression in patients infected by the predominant strain circulating recombinant form (CRF) 02_AG in western and west-central Africa and in patients infected by other strains, a prospective multicenter cohort study was conducted in Cameroon and Senegal. Among the 335 patients, a broad HIV-1 group M subtype diversity was observed in the envelope V3-V5 region, but strain CRF02_AG predominated in both Cameroon and Senegal (61.2% and 62.9%, respectively; P<.8). Multivariate analyses showed no difference between patients infected by CRF02 strains and those infected by other strains in terms of survival (adjusted hazards ratio [HR], 1.16; 95% confidence interval [CI], 0.76-1.78; P=.5), clinical disease progression (HR, 0.79; 95% CI, 0.50-1.25; P=.3), or square root CD4 cell decline (regression coefficient, -0.01; 95% CI, -0.82 to 0.81; P=.9). This study suggests that the predominance of HIV-1 CRF02_AG strain in western and west-central Africa should have no major clinical consequences.     

Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation

BACKGROUND/AIMS: Biliary strictures are a serious cause of morbidity after liver transplantation. We have studied the role of altered bile composition as a mechanism of bile duct injury after human liver transplantation. METHODS: In 28 liver transplant recipients, bile samples were collected daily posttransplantation for determination of bile composition. Hepatic expression of bile transporters was studied before and after transplantation. Histopathological criteria as well as biliary concentrations of alkaline phosphatase (ALP) and gamma-glutamyltransferase (gamma-GT) were used to quantify bile duct injury. RESULTS: Early after transplantation, bile salt secretion increased more rapidly than phospholipid secretion, resulting in high biliary bile salt/phospholipid ratio (BA/PL). In parallel with this, mRNA levels of the bile salt transporters NTCP and BSEP increased significantly after transplantation, whereas phospholipid translocator MDR3 mRNA levels remained unchanged. Bile duct injury correlated significantly with bile salt secretion and was associated with a high biliary BA/PL ratio. CONCLUSIONS: Bile salt secretion after human liver transplantation recovers more rapidly than phospholipid secretion. This results in cytotoxic bile formation and correlates with bile duct injury. These findings suggest that endogenous bile salts have a role in the pathogenesis of bile duct injury after liver transplantation.     

Chromosome 11q rearrangements in B non Hodgkin''s lymphoma

The clinical features, morphology and immunophenotype of 20 cases of B non Hodgkin's lymphoma (B-NHL) with chromosome abnormalities involving 11q13-14 were studied, to determine if this abnormality was closely associated with a specific sub-type of B-NHL. A t(11;14)(q13;q32) was found in 11 cases of intermediately differentiated lymphocytic lymphoma (IDLL). A breakpoint in the major translocation cluster of the BCL-1 locus was found in six of these cases. These patients were male with lymphomatous involvement of the bone marrow, marked splenomegaly and frequently had mucosa associated lymphoid tissue involvement. One patient with IDLL had a t(8;11)(p21;q13) and a rearranged BCL-1 locus, suggesting that this may be a variant of t(11;14)(q13;q32). Diagnoses of IDLL, chronic lymphocytic leukaemia, lymphoplasmacytic lymphoma and monocytoid B cell lymphoma were made in all but one of the remaining cases. These cases had either a translocation involving 11q13-14 and various partner chromosomes or an 11q13 deletion. This study demonstrates that 11q abnormalities occur mainly in a group of low-grade B-NHL of non follicle centre cell lineage.     

Influence of Bleeding Risk on Outcomes of Radial and Femoral Access for Percutaneous Coronary Intervention: An Analysis From the GLOBAL LEADERS Trial

BackgroundRadial artery access has been shown to reduce mortality and bleeding events, especially in patients with acute coronary syndromes. Despite this, interventional cardiologists experienced in femoral artery access still prefer that route for percutaneous coronary intervention. Little is known regarding the merits of each vascular access in patients stratified by their risk of bleeding.MethodsPatients from the Global Leaders trial were dichotomized into low or high risk of bleeding by the median of the PRECISE-DAPT score. Clinical outcomes were compared at 30 days.ResultsIn the overall population, there were no statistical differences between radial and femoral access in the rate of the primary end point, a composite of all-cause mortality, or new Q-wave myocardial infarction (MI) (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.42-1.15). Radial access was associated with a significantly lower rate of the secondary safety end point, Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding (HR 0.55, 95% CI 0.36-0.84). Compared by bleeding risk strata, in the high bleeding score population, the primary (HR 0.47, 95% CI 0.26-0.85; P = 0.012; P_interaction = 0.019) and secondary safety (HR 0.57, 95% CI 0.35-0.95; P = 0.030; P_interaction = 0.631) end points favoured radial access. In the low bleeding score population, however, the differences in the primary and secondary safety end points between radial and femoral artery access were no longer statistically significant.ConclusionsOur findings suggest that the outcomes of mortality or new Q-wave MI and BARC 3 or 5 bleeding favour radial access in patients with a high, but not those with a low, risk of bleeding. Because this was not a primary analysis, it should be considered hypothesis generating.     

Pathology-supported genetic testing as a method for disability prevention in multiple sclerosis (MS). Part II. Insights from two MS cases

Metabolic Brain Disease - In Part I of this Review we evaluated the scientific evidence for a Metabolic Model of multiple sclerosis (MS). Part II outlines the implementation of an adaptive...     

The value of serologic markers in indeterminate colitis: a prospective follow-up study

BACKGROUND & AIMS: In the absence of pathognomonic markers for Crohn's disease (CD) and ulcerative colitis (UC), the diagnosis of inflammatory bowel disease depends on a compendium of clinical, radiographic, endoscopic, and histologic criteria that bears imperfect specificity to the individual disorders. In 10% of cases of colitis, no differentiation can be made between CD and UC; these patients are diagnosed with indeterminate colitis (IC). We evaluated the value of anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) to increase diagnostic accuracy in categorizing IC. METHODS: Since 1996, 97 patients with IC from 3 centers (Leuven, Lille, and Vienna) were enrolled, analyzed for pANCA and ASCA, and followed up prospectively. RESULTS: A definitive diagnosis has been reached for 31 of 97 patients (32%). In these patients, ASCA+/pANCA- correlated with CD in 8 of 10 patients, whereas ASCA-/pANCA+ correlated with UC in 7 of 11 patients. The remaining 4 cases became CD, clinically behaving as UC-like CD. Almost half of the patients (47 of 97 [48.5%]) were negative for ASCA and pANCA, and 40 remain diagnosed with IC to date. Only 7 seronegative cases (14.9%) became CD or UC compared with 48% (24 of 50) of seropositive patients (P < 0.001). CONCLUSIONS: Results so far show that ASCA+/pANCA- predicts CD in 80% of patients with IC and ASCA-/pANCA+ predicts UC in 63.6%. Interestingly, 48.5% of patients do not show antibodies against ASCA or pANCA. Most of these patients remain diagnosed with IC during their further clinical course, perhaps reflecting a distinct clinicoserological entity.     

Effects of a home visiting program for older people with poor health status: a randomized, clinical trial in The Netherlands

OBJECTIVES: To evaluate the effectiveness of a home visiting program on health-related measures in a population of older people with poor health status.
DESIGN: Randomized, clinical trial.
SETTING: Community-dwelling citizens in the Netherlands.
PARTICIPANTS: Three hundred thirty people aged 70 to 84 randomly assigned to an intervention group (n=160) or a control group (n=170).
INTERVENTION: Eight home visits, lasting 1 hour or more, with telephone follow-up, over an 18-month period, conducted by experienced home nurses under supervision of a public health nurse; key elements of the (systematic) visits were assessment of health problems and risks, advice, and referral to professional and community services.
MEASUREMENTS: Self-rated health, functional status, quality of life, and changes in self-reported problems.
RESULTS: No differences were found between the intervention and control group in these and other outcome measures at the end of the intervention period (18 months).
CONCLUSION: The home visiting program did not appear to have any effect on the health status of older people with poor health and are probably not beneficial for such persons.     

TMC114/ritonavir substitution for protease inhibitor(s) in a non-suppressive antiretroviral regimen: a 14-day proof-of-principle trial

OBJECTIVE: To evaluate antiviral activity, tolerability, and safety of the protease inhibitor (PI) TMC114 boosted with low-dose ritonavir (RTV). DESIGN: A randomized, open-label, controlled, phase IIA clinical trial in 15 sites in Europe with 50 HIV-1-infected patients who had taken multiple PIs. METHODS: At entry, PIs in non-suppressive regimens were replaced with TMC114/RTV (300/100 or 600/100 mg twice daily, or 900/100 mg once daily) or left unchanged for 14 days. The time-averaged difference (DAVG) in HIV-1 RNA from baseline, change in HIV-1 RNA from baseline, proportions achieving plasma HIV-1 RNA < 400 copies/ml and > or = 0.5 and > or = 1.0 log10 copies/ml reductions in HIV-1 RNA, and safety were assessed. RESULTS: DAVG responses in all TMC114/RTV groups (range, -0.56 to -0.81 log10 copies/ml) were significantly greater (P < 0.001) than in the controls (-0.03 log10 copies/ml). Median change at day 14 was -1.38 and +0.02 log10 copies/ml for all TMC114/RTV groups and the control group, respectively. A reduction of > or = 0.5 and > or = 1.0 log10 copies/ml was attained by 97% and 76% of patients, respectively, in all TMC114/RTV groups and by 25% and 17%, respectively, in the control group. HIV-1 RNA < 400 copies/ml at any time during treatment was achieved by 40% in the TMC114/RTV groups and 8% in the control group. Most common reported adverse events were gastrointestinal and central nervous system disorders (mild to moderate severity). No dose relationship was observed. Biochemical, haematological and electrocardiographic parameters showed no significant changes. CONCLUSIONS: TMC114/RTV demonstrated a potent antiretroviral effect over 14 days in multiple-PI-experienced patients and was generally well tolerated.