Demonstration of Single-Barium-Ion Sensitivity for Neutrinoless Double-Beta Decay Using Single-Molecule Fluorescence Imaging.

A new method to tag the barium daughter in the double-beta decay of ^{136}Xe is reported. Using the technique of single molecule fluorescent imaging (SMFI), individual barium dication (Ba^{++}) resolution at a transparent scanning surface is demonstrated. A single-step photobleach confirms the single ion interpretation. Individual ions are localized with superresolution (∼2 nm), and detected with a statistical significance of 12.9σ over backgrounds. This lays the foundation for a new and potentially background-free neutrinoless double-beta decay technology, based on SMFI coupled to high pressure xenon gas time projection chambers.

Disordered eating in French high-level athletes: association with type of sport, doping behavior, and psychological features.

PURPOSE: Over the last few years, disordered eating in athletes has received increasing attention. According to several studies, athletes could be more vulnerable to disordered eating and some characteristics specific to the athletic community could be in favour of an increased risk of poor body image and disturbed eating habits in athletes. However, the literature is sparse and some methodological issues in studies have been pointed out. In this context, we aimed at determining the prevalence of disordered eating in French high-level athletes using clinical interviews of three different clinicians and identifying what are the factors associated with disordered eating in athletes. METHODS: In France, all athletes registered on the French high-level list have to undergo a yearly evaluation. Data collected during the somatic assessment, the dietary consultation, and the psychological of the yearly evaluation were used. Multivariate analysis was performed for identification of factors associated with disordered eating. RESULTS: Out of the 340 athletes included, 32.9% have been detected with a disordered eating. They were difficult to detect by clinicians, as usual criteria did not seem to be reliable for athletes. Competing in sports emphasizing leanness or low body weight was associated with disordered eating; however, gender was not. CONCLUSION: These results highlight the need for the development of specific screening tools for high-level athletes. Furthermore, the identification of factors associated with disordered eating could improve early detection and prevention program effectiveness.

Impact of salbutamol on muscle metabolism assessed by ³¹P NMR spectroscopy.

The potential ergogenic effects of oral salbutamol intake were demonstrated for decades but the underlying mechanisms remain to elucidate. We hypothesized that improved exercise performance after acute oral salbutamol administration is associated with changes in muscle metabolism. Twelve healthy, nonasthmatic, moderately trained, male subjects were recruited to compare in a double-blind crossover randomized study, an oral dose of salbutamol (4 mg) and a placebo. After treatment administration, subjects performed repetitive plantar flexions to exhaustion in a 3T magnet. Continuous (31) P nuclear magnetic resonance spectroscopy assessment of the calf muscles was performed at rest, during exercise, and during recovery. No significant difference between treatments was detected in metabolite concentration at rest (P > 0.05). Creatine phosphate and inorganic phosphate changes during and immediately after exercise were similar between treatments (P > 0.05). Intramuscular pH (pHi) was significantly higher at rest, at submaximal exercise but not at exhaustion with salbutamol (pHi at 50% of exercise duration, 6.8 ± 0.1/6.9 ± 0.1 for placebo and salbutamol, respectively, P < 0.05). The maximal power (28 ± 7 W/23 ± 7 W; P = 0.001) and total work (1702 ± 442 J/1381 ± 432 J; P = 0.003) performed during plantar flexions were significantly increased with salbutamol. Salbutamol induced significant improvement in calf muscle endurance with similar metabolic responses during exercise, except slight differences in pHi. Other mechanisms than changes in muscle metabolism may be responsible for the ergogenic effect of salbutamol administration.

Pegfilgrastim and daily granulocyte colony-stimulating factor: patterns of use and neutropenia-related outcomes in cancer patients in Spain--results of the LEARN Study.

Daily granulocyte colony-stimulating factors [(G-CSFs); e.g. filgrastim, lenograstim] are frequently used to reduce the duration of chemotherapy-induced neutropenia (CIN) and the incidence of febrile neutropenia (FN) in cancer patients. A pegylated formulation of filgrastim, pegfilgrastim, which is administered once per cycle, was introduced in Spain in 2003. LEARN was a multi-centre, retrospective, observational study in Spain comparing patterns of use of daily G-CSF and pegfilgrastim, and CIN-related outcomes in adults with non-myeloid malignancies receiving myelosuppressive chemotherapy. Outcome measures were the percentage of patients receiving G-CSF for primary prophylaxis versus secondary prophylaxis/treatment, duration of treatment with G-CSF and incidence of CIN-related complications. Medical records from consecutive patients with documented pegfilgrastim (n = 75) or daily G-CSF (n = 111) use during 2003 were included. The proportion of patients receiving primary or secondary prophylaxis was comparable between the pegfilgrastim (39 and 48% respectively) and daily G-CSF (40 and 48% respectively) groups. However, there was a trend towards less frequent use to treat a neutropenic event such as FN or neutropenia in the pegfilgrastim group (17 versus 30% with daily G-CSF). Chemotherapy-induced neutropenia-related complications were less frequent in patients receiving pegfilgrastim (e.g. FN 11 versus 24% with daily G-CSF). This is the first study to show the potential benefits of pegfilgrastim over daily G-CSF in Spanish clinical practice.

Methodological aspects of crossover and maximum fat-oxidation rate point determination.

AIM: Indirect calorimetry during exercise provides two metabolic indices of substrate oxidation balance: the crossover point (COP) and maximum fat oxidation rate (LIPOXmax). We aimed to study the effects of the analytical device, protocol type and ventilatory response on variability of these indices, and the relationship with lactate and ventilation thresholds. METHODS: After maximum exercise testing, 14 relatively fit subjects (aged 32+/-10 years; nine men, five women) performed three submaximum graded tests: one was based on a theoretical maximum power (tMAP) reference; and two were based on the true maximum aerobic power (MAP). Gas exchange was measured concomitantly using a Douglas bag (D) and an ergospirometer (E). RESULTS: All metabolic indices were interpretable only when obtained by the D reference method and MAP protocol. Bland and Altman analysis showed overestimation of both indices with E versus D. Despite no mean differences between COP and LIPOXmax whether tMAP or MAP was used, the individual data clearly showed disagreement between the two protocols. Ventilation explained 10-16% of the metabolic index variations. COP was correlated with ventilation (r=0.96, P<0.01) and the rate of increase in blood lactate (r=0.79, P<0.01), and LIPOXmax correlated with the ventilation threshold (r=0.95, P<0.01). CONCLUSION: This study shows that, in fit healthy subjects, the analytical device, reference used to build the protocol and ventilation responses affect metabolic indices. In this population, and particularly to obtain interpretable metabolic indices, we recommend a protocol based on the true MAP or one adapted to include the transition from fat to carbohydrate. The correlation between metabolic indices and lactate/ventilation thresholds suggests that shorter, classical maximum progressive exercise testing may be an alternative means of estimating these indices in relatively fit subjects. However, this needs to be confirmed in patients who have metabolic defects.

Difference of catecholamine responses to exercise in men with trisomy 21, with or without chronotropic incompetence.

OBJECTIVE: Our purpose was to analyse if catecholamine responses to exercise would be different in Down syndrome (DS) with or without chronotropic incompetence. RESEARCH DESIGN AND METHODS: Twenty five men with DS (mean age 22.2 ± 3.2) and twenty six controls (CONT, mean age 22.5 ± 1.4) participated in the study, and are divided into 3 groups: CONT, DS with chronotropic incompetence (DS+) and DS without chronotropic incompetence (DS-). During two treadmill incremental tests, blood samples were collected for the determination of hormonal and metabolic variables. RESULTS: Ten out of 25 DS had chronotropic incompetence whereas no CONT. At rest, compared to CONT, despite similar physical activity, DS with chronotropic incompetence had significantly higher subcutaneous fat mass (p<0.001), lower epinephrine concentration (p<0.01), and higher leptin (p<0.01) and insulin concentrations (p<0.05). At peak exercise, all DS had lower heart rate, oxygen uptake and blood lactate concentrations than controls (p<0.001). During a 'Submaximal incremental test', DS with chronotropic incompetence had lower HR and lactate values (p<0.001) compared to CONT and DS without chronotropic incompetence (p<0.01). They also had blunted epinephrine and impaired norepinephrine responses to exercise compared to DS without chronotropic incompetence and CONT (p<0.01 and p<0.05 respectively). CONCLUSIONS: Our results indicate that catecholamine adaptations to exercise are not adequate in DS+ and are associated with exercise intolerance. Thus, this endocrine profile at rest and during exercise may limit endurance performance of DS.

Long-term acyclovir prophylaxis for prevention of varicella zoster virus infection after autologous blood stem cell transplantation in patients with acute leukemia.

Twenty-one adult patients with acute leukemia who underwent autologous blood stem cell transplantation (ABSCT) and who received acyclovir during the first 6 months after transplant to prevent varicella zoster virus (VZV) infection were studied retrospectively to determine the incidence and outcome of VZV infection after ABSCT. The cumulative risk of VZV infection was 32% by 1 year after transplant. No patient developed VZV while on prophylactic acyclovir but five (24%) had localized herpes zoster within 1 month of acyclovir withdrawal. There were no deaths related to VZV infection and only one patient had disseminated disease and post-herpetic neuralgia. These preliminary results suggest that the incidence and outcome of VZV infection after ABSCT largely parallel those reported in marrow transplant patients and that long-term acyclovir prophylaxis delays but does not prevent VZV infection. Prophylaxis of VZV infection after ABSCT requires new therapeutic approaches.

Acute myeloblastic leukemia with minimal myeloid differentiation (FAB AML-M0): a study of eleven cases.

The main clinical, morphological, cytochemical, immunological features and therapy results of eleven patients diagnosed as acute myeloblastic leukemia M0 (AML-M0) are reported here. There were no clinical characteristics, abnormalities on physical examination or initial laboratory parameters that distinguished these eleven patients. Bone marrow aspirates were hypocellular in four patients. The leukemic cells were undifferentiated by light microscopy and myeloperoxidase (MPO) and/or Sudan Black B (SBB) stains were negative in all cases. Myeloid differentiation antigens were present on the leukemic cells of all eleven patients, whereas B and T cell markers were clearly negative except for CD4 and CD7 antigens. Whatever the treatment employed survival was very short. Eight of the eleven patients were treated and two achieved complete remission (CR) but only one of them is alive in continuous CR. Our results like those previously reported, suggest that AML-M0 patients have a very poor prognosis with standard induction therapies and should perhaps be considered for experimental therapeutic approaches.

Characterization and mechanisms of the cardiovascular and haemodynamic alterations induced by scorpion venom in rats.

The scope of this work was to investigate the nature, chronology and mechanisms of the cardiovascular disorders induced by scorpion envenomation. Anaesthetized rats were instrumented for measurement of cardiac output (CO), renal (RBF) and muscular (HBF) blood flows (pulsed Doppler flowmetry), blood pressure, heart rate and dP/dt. Buthus occitanus venom (BO) was administered intravenously in the absence/presence of different pre-treatments. BO dose-dependently (150-300 microg/kg) increased blood pressure, dP/dt, total peripheral (TPR), renal (RVR) and muscular (HVR) vascular resistances, and decreased CO, RBF and HBF. Recovery occurred after 150 but not after 300 microg/kg. BO, 600 microg/kg, produced qualitatively similar effects but arrhythmias developed and mortality increased. Pre-treatment with phentolamine prevented the rises in TPR, RVR, HVR and blood pressure and the decreases in CO, RBF and HBF induced by BO, 300 microg/kg. Pre-treatment with propranolol prevented the rise in dP/dt and the occurrence of arrhythmias and limited the rise in RVR and the drop in RBF induced by BO, 300 microg/kg. Phentolamine, propranolol and their combination also prevented BO, 600 microg/kg-induced mortality. Other pre-treatments (bosentan, losartan, diltiazem, mepyramine) were almost ineffective vs. BO effects. Finally, BO, 300 microg/kg, induced a 30-40-fold increase in plasma epinephrine and norepinephrine levels, but no change in plasma endothelin-1 levels. Thus in anaesthetized rats, the pattern of the cardiac and systemic and regional haemodynamic effects of BO is typically that of and results from catecholamine outpouring-induced alpha- and beta-adrenoceptor stimulation.

[Results of hemograms of a series of top-level cyclists: an example of a factor of biological variability]. / Résultats d'hémogrammes d'une série de cyclistes de haut niveau: exemple d'un facteur de variation biologique.

We report data about 50 caucasian top-level cyclists (45 males, 5 women, aged between 16 and 36 years, mean 25 +/- 4.5). Recruitment was by controlling top-level athletes in order to follow their blood cell counts to detect variation in haemoglobin concentration and hematocrit level (prevention of erythropoietin abuse). All samples were drawn in the morning, when the cyclists were at rest, according to a standardized protocol. Erythroblastic serie was abnormal in several cases (4 anaemias, 3 macrocytosis, 6 low haematocrit level, 10 mean cell haemoglobin higher than 32 pg, low reticulocyte count). White blood cells showed a trend toward low counts for neutrophils and lymphocytes. Two cyclists had platelets counts below 150.109/l. Our data indicated that top-level cyclism had some effects on the blood cell counts, which is likely to indicate an effect of intense aerobic training on physiological status.

Maximal and submaximal treadmill tests in a young adult with fragile-X syndrome.

Fragile X syndrome is associated with expansion of a CGG triplet repeat in the FMR1 gene, which abolishes production of the FMRP protein. This abnormality is expressed as a number of neuro-endocrine disorders (the adrenal axis, macroorchidism) and the emergence of significant behavioural stress. Here, we report on the hormonal status of a young adult with fragile X syndrome, with a focus on catecholamine and cortisol changes during a submaximal treadmill test. The patient showed abnormally high epinephrine and norepinephrine concentrations. During a submaximal incremental test, cortisol levels were higher than the laboratory reference range. Although the submaximal incremental test has a significant "stressful" effect, this young adult was able to complete the entire protocol without any maladaptive behaviour or withdrawal.

Are hormonal responses to exercise in young men with Down's syndrome related to reduced endurance performance?

The aim of the present study was to analyse whether hormonal responses could explain an exercise limitation in Down's syndrome (DS). Fourteen young men with DS (mean age 22.5 +/- 0.7 years) and 15 controls (CONT, mean age 22.5 +/- 0.3 years) participated in the study. During a treadmill submaximal incremental test, blood samples were collected for determination of hormonal and metabolic variables. Compared to CONT, DS individuals showed lower VO(2max) (P < 0.05), and lower duration of submaximal incremental exercise (P < 0.001). At rest, DS individuals showed greater catecholamines, insulin and leptin values (P < 0.05), but lower testosteronemia and cortisolemia (P < 0.05), compared to CONT. During submaximal incremental tests, catecholamines and cortisol were not increased, whereas the insulin concentration of DS individuals was significantly higher (P < 0.01) compared to CONT. Glycaemia increased significantly at the end of submaximal incremental test for CONT but not for DS individuals (P < 0.01). Maximal fat oxidation was lower (P < 0.01), whereas non-esterified fatty acids concentrations rose significantly during submaximal exercise in DS individuals. These results indicate an altered hormonal response to exercise in DS individuals. This endocrine profile at rest and during exercise may limit endurance performance in DS individuals.

Value of basal serum cortisol to detect corticosteroid-induced adrenal insufficiency in elite cyclists.

The frequent use of glucocorticoids by athletes necessitates testing for adrenal insufficiency because of the risk of death in cases of associated severe stress (trauma, infection). During the 2001 and 2002 sporting seasons, we assessed the value of measuring baseline serum cortisol concentrations and the frequency of corticosteroid use during compulsory medical tests carried out by the French Cycling Federation on 659 elite cyclists (585 men and 74 women); the risk of adrenal insufficiency is negatively correlated with the basal serum cortisol level. Adrenal insufficiency was suspected in 34 cyclists (5.2%; 22 in 2001 and 12 in 2002) on the basis of below normal cortisol concentrations and in three cyclists (in 2001) because they had received corticosteroid treatment. In 2001, 10 of the 25 cyclists convoked underwent baseline follow-up serum cortisol determinations and 15 underwent dynamic exploration of adrenal function with the short ACTH test. Adrenal function was found to be deficient in four of these cyclists, at the limits of the normal range in four and normal in seven. Based on these results, the FFC sent a questionnaire in 2002 to all the cyclists to assess the use of corticosteroid in this population. This survey revealed that 85 of 538 cyclists (15.8%) had received corticosteroid treatment in the previous 3 months. Moreover, 11 of the 12 cyclists (92%) with low basal serum cortisol concentrations had received corticosteroid therapy. These results show that basal serum cortisol is relevant to detect adrenal insufficiency in sportsmen, in particular in cases of values below the normal range. The high frequency of corticosteroid use among elite cyclists, and in particular road cyclists who are at risk of trauma and infection, justifies screening tests to detect adrenal insufficiency.

Laboratory running test vs. field roller skiing test in cross-country skiers: a longitudinal study.

Laboratory treadmill running tests are commonly used to assess the effect of training programs and to prescribe training intensity for cross-country skiers. The present study compared the physiological parameters during a treadmill running (R) test and a field roller skiing (RS) test both at the beginning (Beg) and at the end (End) of a 6-month specific training program in seven competitive cross-country skiers. Oxygen uptake (VO2) and blood lactate concentration ([La]) were assessed for exercise intensity corresponding to 70%, 80%, 90% of maximal heart rate (HRmax) and to HRmax.VO2 was lower for the RS test compared to the R test at any HR levels at Beg only (p<0.05). Maximal VO2 increased from Beg to End for the RS test only (+23.7+/-10.4; p<0.05). [La] was lower for the R test compared to the RS test during both testing periods at 90% HRmax (p<0.05), and no significant modification in [La] from Beg to End at any HR levels was observed (p>0.05). The [La]/V.O2 curve shifted toward the right from Beg to End to a greater extent for the RS test compared to the R test. The present study emphasised the importance of exercise specificity in order to assess the effect of specific training program in competitive cross-country skiers.

[Thyroid dysfunction in women with suspected fibromyalgia]. / Disfunción tiroidea en mujeres con sospecha de fibromialgia.

BACKGROUND AND OBJECTIVE: Due to its prevalence, morbidity, and frequency rate, fibromyalgia (FM) represents a health problem and produces high healthcare resource utilization. Serum thyrotropin (TSH) measurement is recommended as a first-line laboratory test to exclude hypothyroidism as a cause of FM syndrome. The aim of this study was to analyze the prevalence of thyroid dysfunction (TD), the frequency of TSH measurement, the effect of levothyroxine treatment, and whether screening for TD is justified in women with suspected FM. PATIENTS AND METHODS: A cross-sectional descriptive study was performed in 400 consecutive female outpatients with suspected FM and in 384 controls from January 2001 to October 2004. TSH measurement was used as the first line test to detect TD. RESULTS: The prevalence of TD in patients with suspected FM (40/400; 10%; 95% CI: 7-13%) and controls was similar (46/384; 12%; 95% CI: 9-15%). No differences were found in the types and grades of TD. The prevalence of TD was higher in patients with suspected FM and connective tissue diseases (12%) than in those without these diseases (5%). The most frequent TD was subclinical hypothyroidism (5.5% in suspected FM and 6.7% in controls), and in 93% of these cases TSH concentrations were <10 mIU/L. FM persisted in all women with hypothyroidism even after euthyroidism was achieved with levothyroxine. A total of 870 TSH determinations were performed in 360 euthyroid patients with suspected FM. CONCLUSIONS: The prevalence of TD in women with suspected FM does not differ from that in the general population. Screening for TD does not appear to be justified in women without diseases that increase their risk. In many cases the request for thyroid function tests is excessive. Treatment for hypothyroidism does not affect FM.

Neural networks for the biochemical prediction of bone mass loss.

Neural networks are specialized artificial intelligence techniques that have shown high efficiency in dealing with complex problems. Paradigms such as backpropagation have been successfully applied in a number of biomedical applications, but not in attempts to identify women at risk of postmenopausal osteoporotic complications. In this paper, several neural networks were trained using different combinations of biochemical variables as inputs. Bone densitometric measurements in Ward's triangle and in the spinal column were used as separate classification criteria (outputs) between slow and fast bone mass losers. The most parsimonious model with the best performance included plasma concentrations of estrone, estradiol, osteocalcin, parathyrin and urine concentrations of calcium and hydroxyproline (expressed as ratio to creatinine excretion) as input neurons; ten neurons in a single hidden layer; and one neuron in the output layer. Diagnostic efficiency was 76% in Ward's triangle and 74% in the spinal column; sensitivity was 70 and 81%, and specificity was 77 and 65%, respectively. Linear discriminant analysis showed a diagnostic efficiency of 66% in Ward's triangle and 64% in the spinal column, sensitivity was 55 and 86%, and specificity was 75 and 13%, respectively. We conclude that performance of the stepwise discriminant analysis was not superior to the neural networks.

Does hypothyroidism increase the prevalence of chondrocalcinosis?

To investigate whether or not there is an association between hypothyroidism (HPT) and chondrocalcinosis (CC) 100 HPT patients and 100 controls matched for the age and sex were evaluated prospectively. All the patients were examined clinically, and X-rays of knees, wrists and pelvis, and biological evaluation of thyroid hormones, calcium, uric acid, iron and alkaline phosphatase levels were recorded. X-rays were assessed independently by two radiologists blind to the thyroid status of the patient. The prevalence of CC was 17% in the HPT patients and 10% in the controls (NS). No correlation was found between CC duration and mechanism or treatment of HPT. We suggest that HPT and CC are two diseases that may co-exist in patients but without any causal or mechanistic relationship.

Pathologic rupture of the spleen as the initial manifestation in acute lymphoblastic leukemia.

Pathologic splenic rupture is a rare and life-threatening complication of acute leukemia. It is even more uncommon as the initial manifestation, and only a few cases has been reported in the literature. Early recognition of this complication is vital because the prognosis is fatal without immediate treatment by splenectomy. We report the case of a spontaneous spleen rupture irreversibly complicating the onset of acute lymphoblastic leukemia in a 19-year-old man, in spite of splenectomy. In our case abdominal ultrasound was a good, non-invasive diagnostic test. Therefore, we believe that the course of the underlying disease and the physical condition of the patient dramatically influenced the disease evolution.

[Transfusion policy toward a patient with an anti-Cartwright antibody (anti-Yta)]. / Actitud transfusional frente a un paciente con un anticuerpo anti-Cartwright (anti-Yta).

We have observed one patient with hepatic cirrhosis showing on her antibody screening an anti-Yta. We studied the 51 Cr-labelled erythrocyte survival using either Yt (a+) and autologous blood red cells. She was transfused two Yt (a+) red blood cell concentrates without any adverse reaction.