Testing for recombinant erythropoietin

Erythropoietin (Epo) is a glycoprotein hormone that promotes the production of red blood cells. Recombinant human Epo (rhEpo) is illicitly used to improve performance in endurance sports. Doping in sports is discouraged by the screening of athletes for rhEpo. Both direct tests (indicating the presence of exogeneous Epo isoforms) and indirect tests (indicating hematological changes induced by exogenous Epo administration) can be used for Epo detection. At present, the test adopted by the World Anti Doping Agency is based on a combination of isoelectric focusing and double immunoblotting, and distinguishes between endogenous and rhEpo. However, the adopted monoclonal anti-Epo antibodies are not monospecific. Therefore, the test can occasionally lead to the false-positive detection of rhEpo (epoetin-beta) in post-exercise, protein-rich urine, or in case of contamination of the sample with microorganisms. An improved preanalytical care may counteract a lot of these problems. Adaptation of the criteria may be helpful to further refine direct Epo testing. Indirect tests have the disadvantage that they require blood instead of urine samples, but they can be applied to detect a broader range of performance improving techniques which are illicitly used in sports.     

Domestication of the donkey: timing, processes, and indicators

Domestication of the donkey from the African wild ass transformed ancient transport systems in Africa and Asia and the organization of early cities and pastoral societies. Genetic research suggests an African origin for the donkey, but pinpointing the timing and location of domestication has been challenging because donkeys are uncommon in the archaeological record and markers for early phases of animal domestication are hard to determine. We present previously undescribed evidence for the earliest transport use of the donkey and new paleopathological indicators for early phases of donkey domestication. Findings are based on skeletal data from 10 approximately 5,000-year-old ass skeletons recently discovered entombed in an early pharaonic mortuary complex at Abydos, Middle Egypt, and a concurrent study of 53 modern donkey and African wild ass skeletons. Morphometric studies showed that Abydos metacarpals were similar in overall proportions to those of wild ass, but individual measurements varied. Midshaft breadths resembled wild ass, but midshaft depths and distal breadths were intermediate between wild ass and domestic donkey. Despite this, all of the Abydos skeletons exhibited a range of osteopathologies consistent with load carrying. Morphological similarities to wild ass show that, despite their use as beasts of burden, donkeys were still undergoing considerable phenotypic change during the early Dynastic period in Egypt. This pattern is consistent with recent studies of other domestic animals that suggest that the process of domestication is slower and less linear than previously thought.     

Old or frail: what tells us more?

BACKGROUND: Selecting elderly persons who need geriatric interventions and making accurate treatment decisions are recurring challenges in geriatrics. Chronological age, although often used, does not seem to be the best selection criterion. Instead, the concept of frailty, which indicates several concurrent losses in resources, can be used. METHODS: The predictive values of chronological age and frailty were investigated in a large community sample of persons aged 65 years and older, randomly drawn from the register of six municipalities in the northern regions of the Netherlands (45% of the original addressees). The participants' generative capacity to sustain well-being (i.e., self-management abilities) was used as the main outcome measure. RESULTS: When using chronological age instead of frailty, both too many and too few persons were selected. Furthermore, frailty related more strongly (with beta values ranging from -.25 to -.39) to a decline in the participants' self-management abilities than did chronological age (with beta values ranging from -.06 to -.14). Chronological age added very little to the explained variances of all outcomes once frailty was included. CONCLUSIONS: Using frailty as the criterion to select older persons at risk for interventions may be better than selecting persons based only on their chronological age.     

Women at risk of coronary heart disease experience barriers to diagnosis and treatment: A qualitative interview study

Objective To describe the types of patients admitted to the first Dutch general practitioner (GP) hospital, their health-related quality of life and its substitute function.

Design A prospective observational study.

Setting The remaining 20-bed ward of a former district general hospital west of Amsterdam; a region with 62?000 inhabitants and 26 GPs.

Subjects All patients admitted during the 12 months between 1 June 1999 and 1 June 2000.

Main outcome measures Patients’ health-related quality of life (Medical Outcome Study 36-item Short Form Health Survey, Groningen Activities Restriction Scale), GPs assessments of severity of illness (DUSOI/WONCA Severity of Illness Checklist) and alternative modes of care.

Results In total, 218 admissions were recorded divided into 3 bed categories: GP beds (n=131), rehabilitation beds (n=62) and nursing home beds (n=25). The mean age of all patients was 76 years. Main reasons for admission were immobilization due to trauma at home (GP beds), rehabilitation from surgery (rehabilitation beds) and stroke (nursing home beds). Overall, patients showed a poor health-related quality of life on admission. If the GP beds had not been available, the GPs estimated that the admissions would have been almost equally divided among home care, nursing home and hospital care. The severity of the diagnosis on admission of the ‘hospital-care group’ appeared to be significantly higher than the other care groups.

Conclusion The GP hospital appears to provide a valuable alternative to home care, nursing home care and hospital care, especially for elderly patients with a poor health-related quality of life who are in need of short medical and nursing care.     

Cold acclimation recruits human brown fat and increases nonshivering thermogenesis

In recent years, it has been shown that humans have active brown adipose tissue (BAT) depots, raising the question of whether activation and recruitment of BAT can be a target to counterbalance the current obesity pandemic. Here, we show that a 10-day cold acclimation protocol in humans increases BAT activity in parallel with an increase in nonshivering thermogenesis (NST). No sex differences in BAT presence and activity were found either before or after cold acclimation. Respiration measurements in permeabilized fibers and isolated mitochondria revealed no significant contribution of skeletal muscle mitochondrial uncoupling to the increased NST. Based on cell-specific markers and on uncoupling protein-1 (characteristic of both BAT and beige/brite cells), this study did not show “browning” of abdominal subcutaneous white adipose tissue upon cold acclimation. The observed physiological acclimation is in line with the subjective changes in temperature sensation; upon cold acclimation, the subjects judged the environment warmer, felt more comfortable in the cold, and reported less shivering. The combined results suggest that a variable indoor environment with frequent cold exposures might be an acceptable and economic manner to increase energy expenditure and may contribute to counteracting the current obesity epidemic.     

Montelukast reduces asthma exacerbations in 2- to 5-year-old children with intermittent asthma

The PREVIA study was designed to investigate the role of montelukast, a leukotriene receptor antagonist, in the prevention of viral-induced asthma exacerbations in children aged 2 to 5 years with a history of intermittent asthma symptoms. The study was a 12-month multicenter, double-blind, parallel-group study of patients with asthma exacerbations associated with respiratory infections and minimal symptoms between episodes. Patients were randomized to receive oral montelukast 4 or 5 mg (depending on age) (n = 278) or placebo (n = 271) once per day for 12 months. Caregivers recorded children's symptoms, beta-agonist use, and health care resource use in a diary card. Over 12 months of therapy, montelukast significantly reduced the rate of asthma exacerbations by 31.9% compared with placebo. The average rate of exacerbation episodes per patient was 1.60 episodes per year on montelukast compared with 2.34 episodes on placebo. Montelukast also delayed the median time to first exacerbation by approximately 2 months (p = 0.024), and the rate of inhaled corticosteroid courses (p = 0.027) compared with placebo. Montelukast effectively reduced asthma exacerbations in 2- to 5-year-old patients with intermittent asthma over 12 months of treatment and was generally well tolerated.     

Long-term outcome in acquired aplastic anemia treated with an intensified dose schedule of horse antilymphocyte globulin in combination with androgens

Aplastic anemia (AA) is a rare hematopoietic stem cell disease, which can be treated with horse antilymphocyte globulin (ALG) for patients not eligible for bone marrow transplantation. ALG gives about 60% overall survival rate (OS) after 5 years, a 30% of persistent complete remission and a 20% early death rate related to failure. ALG has been incriminated in the emergence of 10 to 20% therapy-related AML/MDS (t-AML/MDS) with the usual doses. Questions remain whether higher doses of ALG could improve the response and OS rates and whether the combination with androgens is able to protect patients from t-AML/MDS. We have carried out a single institutional retrospective study of 87 AA treated with higher doses of ALG, twice the usual posology (140 mg/kg instead of 75 mg/kg), combined to androgens. The overall response rate was 77% and the OS rate at 5 years was 78%. Androgens in combination with ALG improved response and OS rates. At diagnosis, 6% of AA had an abnormal karyotype using conventional cytogenetic not related to any time-to-event. Two patients displayed a cytogenetic conversion related to the occurrence of secondary malignancies. The incidence of t-AML/MDS was 2.3% with an estimated 10-year cumulative incidence of 3.1. Our results show that higher doses of ALG combined to androgens are feasible and give results close to those recently describe with the immunosuppressive treatments including ALG associated to cyclosporine, with a low SMD/AML incidence rate.     

Relation between abdominal obesity, insulin resistance and left ventricular hypertrophy diagnosed by electrocardiogram and magnetic resonance imaging in hypertensive patients

Obesity is related to left ventricular hypertrophy (LVH). Whether LVH on electrocardiography (ECG-LVH) is a result of increased cardiac electrical activity or due to increased left ventricular mass (LVM) remains to be determined. The aims of the present study were to investigate the relation between obesity and ECG-LVH and LVM by magnetic resonance imaging (MRI-LVM) in patients with hypertension and to investigate the relation of insulin resistance (IR) and LVH. Patients with hypertension (n = 421) were evaluated using Sokolow-Lyon voltage, Cornell voltage, and cardiac magnetic resonance imaging. Waist circumference was used as a measure of abdominal obesity. Linear regression analysis revealed an inverse relation (adjusted β = -0.02, 95% confidence interval -0.02 to -0.01) between waist circumference and Sokolow-Lyon voltage, indicating a decrease of 0.02 mV per 1-cm increase in waist circumference. There was a positive relation between waist circumference and MRI-LVM (β = 0.49, 95% confidence interval 0.32 to 0.67). Patients in the highest quartile of LVM had a worse metabolic profile than patients with the Sokolow-Lyon voltage criterion. The relations of IR with ECG-LVH and MRI-LVM were similar to those of waist circumference in relation to ECG-LVH and MRI-LVM. In conclusion, there is an inverse relation between waist circumference and ECG-LVH and a positive relation between waist circumference and MRI-LVM. This study indicates that obesity has a different relation to voltage criteria for LVH compared to anatomic criteria for LVH, supporting the hypothesis that IR decreases electrocardiographic voltages, despite an increase in MRI-LVM. The clinical implication is that especially in patients with IR, Sokolow-Lyon voltage is low in contrast to high MRI-LVM.     

Ferroportin Q248H mutation,hyperferritinemia and atypical type 2 diabetes mellitus in South Kivu

BackgroundThe ferroportin Q248H mutation is relatively common in sub-Saharan Africa. No previous study examined its relationship with atypical diabetes mellitus (DM) in this area.ObjectiveTo determine the potential interactions between ferroportin Q248H mutation, hyperferritinemia and DM in South Kivu (RDC).MethodologyPresence of ferroportin Q248H mutation and iron status were investigated in diabetic patients (n = 179, age (mean) 57.7 years, CRP (median) 0.16 mg/L) and non-diabetic subjects (n = 86, age 44.5 years, CRP 0.07 mg/L) living in the city of Bukavu. Hyperferritinemia was considered for values greater than 200 and 300 μg/L in women and in men, respectively.ResultsThe prevalence of ferroportin Q248H mutation [12.1%] was non-significantly higher in diabetics than non-diabetics [14.0% vs. 8.1%, p = 0.17]. Similarly, hyperferritinemia frequency was higher in diabetic patients with Q248H mutation [44.0% vs. 14.3%, p = 0.16] and in mutation carriers [37.0% vs 16.5%, p = 0.001] than in the control groups, respectively. The association between Q248H mutation and DM was nevertheless not significant [adjusted OR 1.70 (95% CI: 0.52–5.58), p = 0.37], whereas hyperferritinemia [OR 2.72 (1.24–5.98), p = 0.01] showed an independent effect after adjustment for age and metabolic syndrome.ConclusionsThe present work suggests a potential association between abnormal iron metabolism, ferroportin Q248H mutation and atypical DM in Africans, which may be modulated by environmental factors.