The role of a baseline casual blood pressure measurement and of blood pressure changes in middle age in prediction of cardiovascular and all-cause mortality occurring late in life: a cross-cultural comparison among the European cohorts of the Seven Countries Study

OBJECTIVE: The first objective was to study the long-term association of a casual measurement of systolic blood pressure (SBP) with cardiovascular deaths (CVD) and all causes of death (ALL) occurring during 35 years of follow-up in different population samples of men aged 40-59 years in five European countries. The second objective was to study the predictive power of early change in SBP levels (years 0-10) in relation to late fatal events (years 10-35). DESIGN, SETTING AND PARTICIPANTS: A single measurement of SBP was considered in cohorts in Finland, The Netherlands, Italy, Serbia and Greece for a total of 6507 men. Three partitioned proportional hazards models were solved, one for each independent and subsequent time block of 10 years, after excluding data from the first 5 years, to predict the risk of cardiovascular disease deaths of atherosclerotic origin (CVD) and all cause mortality (ALL). Independently, the predictive power of SBP changes (Delta-SBP) occurred during the first 10 years of follow-up was explored as a possible additional risk factor in relation to CVD and ALL deaths occurring between year 10 and year 35 of follow-up. RESULTS: Partitioned hazard scores derived from the three partitioned functions were cumulated. The resulting curves showed a continuous and significant association of baseline SBP with CVD and ALL deaths during three decades, although the strength of association declined significantly from the first to the third decade. The relative risk for 20 mmHg of SBP (and its 95% confidence intervals) in predicting CVD deaths was 1.65 (1.54-1.77) for the first 10-year block; 1.33 (1.24-1.42) for the second block; and 1.22 (1.13-1.31) for the last 10-year block. The corresponding levels of ALL deaths were 1.41 (1.34-1.49), 1.26 (1.19-1.32) and 1.11 (1.05-1.17). Changes in SBP during 10 years (Delta-SBP) added predictive power to baseline measurements in a direct and significant way, with a relative risk for a change of 10 mmHg of 1.14 (1.10-1.17) for CVD deaths and 1.11 (1.09-1.13) for ALL deaths. CONCLUSION: A single measurement of systolic blood pressure in middle-aged men maintains a strong relationship with fatal CVD and ALL deaths during the next 35 years, although for late events the strength of the association definitely declines. Changes in systolic blood pressure levels during the first 10 years of follow-up add predictive power, while baseline measurements retain their predictive power.     

Disseminated Infection with a New Genovar of Encephalitozoon cuniculi in a Renal Transplant Recipient

Disseminated microsporidiosis is a life-threatening opportunistic infection. Here, we report about a previously undescribed genovar of Encephalitozoon cuniculi causing disseminated infection in a non-HIV-infected renal transplant recipient. Disseminated microsporidiosis must be considered in the differential diagnosis of chronic fever in renal allograft recipients, even those without urinary symptoms.     

Acetyl-L-carnitine affects nonassociative learning processes in the leech Hirudo medicinalis

Acetyl-L-carnitine is a natural molecule widely distributed in vertebrate and invertebrate nervous system. It is known to have significant effects on neuronal activity playing a role as neuroprotective and anti-nociceptive agent, as well as neuromodulatory factor. About its capability of affecting learning processes the available data are controversial. In the present study, we utilized the simplified model system of the leech Hirudo medicinalis to analyze the effects of acetyl-L-carnitine, assessing whether and how it might affect elementary forms of nonassociative learning processes. In leeches with the head ganglion disconnected from the first segmental ganglion, repetitive application of weak electrical shocks onto the caudal portion of the body wall induces habituation of swim induction whereas brush strokes on the dorsal skin produces sensitization or dishabituation when the nociceptive stimulus is delivered on previously habituated animals. Herein, the effects of different concentrations of acetyl-L-carnitine (2 mM - 0.05 mM) have been tested at different times on both sensitization and dishabituation. The results show that a single treatment of acetyl-L-carnitine blocked the onset of sensitization in a dose- and time-dependent manner. In fact, the most effective concentration able to block this process was 2 mM, which induced its major effects 11 days after the treatment, whereas 0.05 mM was unable to affect the sensitization process at all considered time points. On the contrary, acetyl-L-carnitine did not completely abolish dishabituation at the tested concentrations and at every time point. Finally, acetyl-L-carnitine also impaired the habituation of swim induction, but only 11 days after treatment.     

Menopause, insulin resistance, and risk factors for cardiovascular disease

OBJECTIVE: In this retrospective analysis of the European Group for the Study of Insulin Resistance database, a clamp data pooling project, a cardiovascular risk score (CVS) was assessed to verify whether hyperinsulinemia and/or insulin resistance were independent cardiovascular risk factors and to investigate how menopause affected CVS and insulin resistance. DESIGN: Information was obtained on whole-body glucose uptake (M), determined by the euglycemic hyperinsulinemic clamp technique, normalized by fat-free mass (FFM), and insulin concentration (I) at a steady state. Body composition was estimated using a labeled water technique or bioimpedance. Other parameters measured included blood pressure, lipid levels, and waist-to-hip ratio. CVS was computed using a structural equation model that included age, body mass index, blood lipids, and blood pressure. The study population included 523 normal and overweight patients. Women were grouped according to fertility status, and men, according to age (cutoff 50 y). RESULTS: M/kg(FFM)/I significantly decreased after menopause (12.41 +/- 3.40 vs 10.96 +/- 3.68; P < 0.01) and in men 50 years and older (11.39 +/- 3.47 vs 10.32 +/- 3.77 micromol x min(-1) x kg(-1) x microUI/mL; P < 0.02). CVS was lowest in fertile women (-0.414 +/- 0.57 vs 0.107 +/- 0.43; P < 0.0001) and highest in men 50 years and older (0.045 +/- 0.455 vs 0.257 +/- 0.51; P < 0.001). CVS significantly correlated with M/kg(FFM)/I in men 49 years and younger (r(o) = -0.27, P < 0.0001) and 50 years and older (r(o) = -0.38, P < 0.0001) and with fasting insulin in fertile women (r(o) = -0.29, P < 0.01) and in the other groups (r(o) ranging from 0.37 to 0.45, P < 0.0001). CONCLUSIONS: Menopause does not seem to strictly relate to a decrease in insulin sensitivity as postmenopausal women had the same insulin sensitivity as age-matched men. In the population studied, the best predictor of CVS was fasting insulin rather than insulin sensitivity.     

Prevalence of intestinal parasites including microsporidia in human immunodeficiency virus-infected adults in Cameroon: a cross-sectional study

To assess the prevalence of intestinal parasites in a cohort of human immunodeficiency virus (HIV)-infected adults in Cameroon, a cross-sectional study was conducted. Detection of parasites was performed in 181 stool samples from 154 HIV-infected patients with a mean CD4 cell count of 238 cells/mm(3). Only 35 patients (22%) were receiving antiretroviral therapy at the time of stool sampling, and 46 (29%) had diarrhea. Opportunistic protozoa were found in 15 patients (9.7%), 8 of whom (53%) had diarrhea. Enterocytozoon bieneusi was found in eight patients, C. parvum in six patients, and Isospora belli in three patients. All E. bieneusi isolates tested belonged to the same genotype. The prevalence of opportunistic protozoa among patients with CD4 cell counts less than 50/mm(3) was 32%.     

The protective effect of L-carnitine in peripheral blood human lymphocytes exposed to oxidative agents

Literature data indicate L-carnitine (LC), a trans-mitochondrial carrier of acetyl and long chain groups, as an agent possessing protective effects against oxidative stress in mammalian cells. However, the major factor involved in the protective mechanism is not known. The protection activity exerted by this agent against reactive oxygen species induced by hydrogen peroxide (H2O2) and t-butylhydroperoxide (t-butyl-OOH) treatment in isolated human peripheral blood lymphocytes (PBLs) has been studied. Human lymphocytes cells were isolated and pre-incubated with 5 mM LC before H2O2 (100 microM) and t-butyl-OOH (400 microM) treatment. The protective effect of LC on treated PBLs was measured by single cell gel electrophoresis and the analysis of chromosomal aberrations. Results show that lc treated cells exhibited a significant decrease in the number of oxidative induced single-strand breaks and chromosomal aberrations.     

The relationship of age, blood pressure, serum cholesterol and smoking habits with the risk of typical and atypical coronary heart disease death in the European cohorts of the Seven Countries Study

OBJECTIVE: To explore whether "typical" coronary heart disease (CHD) such as fatal myocardial infarction and sudden death relate to major cardiovascular risk factors in the same way as the "atypical" CHD, such as fatal heart failure and chronic arrhythmias. DESIGN AND SETTING: Ten cohorts (6633 cardiovascular disease-free men, aged 40-59) in five European countries were examined, age and three major risk factors were measured (systolic blood pressure, serum cholesterol, and smoking habits) and 35-year mortality data were collected. Proportional hazard models were solved with typical and atypical CHD deaths treated separately. RESULTS: Death rates from typical and atypical CHD were inversely related among the five countries. Mean age at death was significantly higher for atypical than typical (75.8 versus 71.6 years; p < 0.001). In the multivariate analysis conducted on pools of 5 countries (adjusted for countries), the relationship of risk factors with typical CHD was direct and significant for age (hazard ratio-HR-for 5 years of age 1.44 (95% CI 1.36-1.52)), systolic blood pressure (HR for 20 mm Hg, 1.39 (95% CI 1.32-1.47)), serum cholesterol (HR for 1 mmol/l of 1.22 (95% CI 1.16-1.27)) and smoking habits (HR smokers versus non-smokers of 1.39 (95% CI 1.24-1.57)). For atypical CHD, age had a larger HR of 2.27 (95% CI 2.05-2.52), systolic blood pressure had a smaller HR of 1.28 (95% CI 1.16-1.41), serum cholesterol had an inverse non-significant HR of 0.90 (0.58-1.58) and smoking habits had a larger HR of 1.54 (95% CI 1.26-1.89). CONCLUSIONS: Age and serum cholesterol were differently related with typical and atypical CHD deaths, suggesting different etiologies for these coronary diseases.     

Anti-allergic properties of a new all-D synthetic immunoglobulin-binding peptide

Using a combinatorial chemistry approach, we identified a tetrameric tripeptide, denoted Protein A Mimetic (PAM) or TG19318, able to bind to immunoglobulins of different classes and species. The inverso variant, with the tripeptide in the all-D configuration (D-PAM or TG19320), is described as retaining binding properties to Ig. This peptide has now been assayed as a binder for E class immunoglobulins, in linear and competitive ELISA experiments, dot-blot and surface plasmon resonance (SPR) analyses. We show that D-PAM binds IgE with high specificity and selectivity, the interaction being sufficient to inhibit anaphylactic release of beta-hexosaminidase from RBL 2H3 cells, with an IC50 value of 10 microg/mL. Intradermal administration of D-PAM suppresses PCA in the rat, with an IC50 of 1.25 microg/kg dose of peptide, while its intraperitoneal injection inhibits mouse PCA with an IC50 of about 7 mg/kg and an efficacy comparable to that of ketotifen. Similarly, D-PAM inhibits ACA in the mouse, with 50% suppression at 10 mg/kg. The results presented here show that the peptide is active on the studied models, with effective doses below toxicity level, hence the molecule is a promising candidate for development of a new class of anti-allergic drugs.     

Anaphylaxis during the first course of high-dose methotrexate: a case report and literature review

What is known and Objective: Methotrexate (MTX) is widely used in the management of paediatric cancer with a generally favourable benefit/risk profile. We report an unusual adverse drug reaction with the first course of high‐dose MTX in a paediatric patient and review the literature for similar cases. Case summary: An 11‐year‐old boy with small‐cell osteoblastic osteosarcoma in the lower limb experienced a case of life‐threatening anaphylaxis during the first course of high‐dose MTX. The adverse event occurred during the first course, likely due to an immune‐mediated mechanism. We postulate that prior antineoplastic treatment might have contributed to the immune response to MTX. What is new and Conclusion: Given that this reaction has rarely been reported, we discuss the present case with a review of other similar cases. Further studies are needed to substantiate this ‘signal alarm’ for serious MTX‐related hypersensitivity reactions.