Inhibition of Na(+)-K(+)-ATPase by digoxin and its relation with energy expenditure and nutrient oxidation rate.

This study investigates the effects of digoxin, an inhibitor of the Na+ pump (Na(+)-K(+)-ATPase), on resting metabolic rate (RMR), respiratory quotient (RQ), and nutrient oxidation rate. Twelve healthy male subjects followed a double-blind protocol design and received either 1 mg/day digoxin or a placebo 2 days before indirect calorimetry measurements. Digoxin induced a 0.22 +/- 0.07 kJ/min or 3.8 +/- 1.5% (mean +/- SE, P = 0.01) decrease in RMR and a 0.40 +/- 0.13 kJ/min (P = 0.01) decrease in fat oxidation rate, whereas carbohydrate and protein oxidation rates did not change significantly. A dose-response relationship between serum digoxin and RQ was observed. These results suggest that digoxin reduces not only RMR but also fat oxidation rate by mechanisms that remain to be elucidated. Because a linkage and an association between genes coding the Na(+)-K(+)-ATPase and the RQ have been previously observed, the present demonstration of an effect of Na(+)-K(+)-ATPase inhibition on fat oxidation rate strengthens the concept that the activity of this enzyme may play a role in body weight regulation.

Dose-dependent effect of atrial natriuretic peptide on blood pressure, heart rate, and skin blood flow of normal volunteers.

Synthetic atrial natriuretic peptide, containing 26 amino acids in the rat sequence, L-364, 343 (Ileu-ANP), was infused intravenously at increasing rates (1-40 micrograms/min) into four normal volunteers. Mean intraarterial blood pressure decreased and heart rate increased in cumulative-dose-dependent fashion. Skin blood flow as measured with a laser Doppler device rose already with a cumulative dose of 55 micrograms Ileu-ANP and further rises were directly related to dose. The only side effects observed were those accompanying symptomatic hypotension at higher doses. These findings provide strong evidence that Ileu-ANP acts as a vasodilator in normal volunteers.

High rate of severe radiation dermatitis during radiation therapy with concurrent cetuximab in head and neck cancer: results of a survey in EORTC institutes.

OBJECTIVE: Examination of the rate of grade III or grade IV radiation dermatitis during treatment of head and neck cancer (HNC) with radiotherapy (RT) and concurrent cetuximab in EORTC centres. MATERIALS AND METHOD: A questionnaire was sent to all members of the EORTC Radiation Oncology Group and Head and Neck Group (111 institutions) to evaluate the widespread use of cetuximab and radiotherapy in HNC and to estimate the frequency of grades III and IV skin reactions in the radiation portals associated with this protocol. Co-morbidities, RT schedules and co-medications were also recorded. RESULTS: We received responses from 28 institutions in 11 countries. A total of 125 HNC patients from 15 institutions were treated with cetuximab and concurrent RT. Information about the skin reactions was available from 71 patients. Of these 36 had no grade III/IV adverse effects in the RT field, 15 had a grade III and 20 had grade IV radiation dermatitis. No detectable relation of grades III and IV radiation dermatitis with co-morbidities such as liver insufficiency or renal dysfunction was found. CONCLUSION: According to the results of the questionnaire, grade III/IV radiation dermatitis is observed in 49% of HNC patients treated with cetuximab and concurrent RT. A systematic clinical monitoring of cutaneous side effects during RT plus cetuximab is advised to ensure the safety of this protocol.

Fatigue shifts and scatters heart rate variability in elite endurance athletes

PURPOSE: This longitudinal study aimed at comparing heart rate variability (HRV) in elite athletes identified either in 'fatigue' or in 'no-fatigue' state in 'real life' conditions. METHODS: 57 elite Nordic-skiers were surveyed over 4 years. R-R intervals were recorded supine (SU) and standing (ST). A fatigue state was quoted with a validated questionnaire. A multilevel linear regression model was used to analyze relationships between heart rate (HR) and HRV descriptors [total spectral power (TP), power in low (LF) and high frequency (HF) ranges expressed in ms(2) and normalized units (nu)] and the status without and with fatigue. The variables not distributed normally were transformed by taking their common logarithm (log10). RESULTS: 172 trials were identified as in a 'fatigue' and 891 as in 'no-fatigue' state. All supine HR and HRV parameters (Beta+/-SE) were significantly different (P<0.0001) between 'fatigue' and 'no-fatigue': HRSU (+6.27+/-0.61 bpm), logTPSU (-0.36+/-0.04), logLFSU (-0.27+/-0.04), logHFSU (-0.46+/-0.05), logLF/HFSU (+0.19+/-0.03), HFSU(nu) (-9.55+/-1.33). Differences were also significant (P<0.0001) in standing: HRST (+8.83+/-0.89), logTPST (-0.28+/-0.03), logLFST (-0.29+/-0.03), logHFST (-0.32+/-0.04). Also, intra-individual variance of HRV parameters was larger (P<0.05) in the 'fatigue' state (logTPSU: 0.26 vs. 0.07, logLFSU: 0.28 vs. 0.11, logHFSU: 0.32 vs. 0.08, logTPST: 0.13 vs. 0.07, logLFST: 0.16 vs. 0.07, logHFST: 0.25 vs. 0.14). CONCLUSION: HRV was significantly lower in 'fatigue' vs. 'no-fatigue' but accompanied with larger intra-individual variance of HRV parameters in 'fatigue'. The broader intra-individual variance of HRV parameters might encompass different changes from no-fatigue state, possibly reflecting different fatigue-induced alterations of HRV pattern.

Machine learning analysis and modeling of interest rate curves

The present research deals with the review of the analysis and modeling of Swiss franc interest rate curves (IRC) by using unsupervised (SOM, Gaussian Mixtures) and supervised machine (MLP) learning algorithms. IRC are considered as objects embedded into different feature spaces: maturities; maturity-date, parameters of Nelson-Siegel model (NSM). Analysis of NSM parameters and their temporal and clustering structures helps to understand the relevance of model and its potential use for the forecasting. Mapping of IRC in a maturity-date feature space is presented and analyzed for the visualization and forecasting purposes.

Fast low-specific absorption rate B0 -mapping along projections at high field using two-dimensional radiofrequency pulses.

PURPOSE: At 7 Tesla (T), conventional static field (B0 ) projection mapping techniques, e.g., FASTMAP, FASTESTMAP, lead to elevated specific absorption rates (SAR), requiring longer total acquisition times (TA). In this work, the series of adiabatic pulses needed for slab selection in FASTMAP is replaced by a single two-dimensional radiofrequency (2D-RF) pulse to minimize TA while ensuring equal shimming performance. METHODS: Spiral gradients and 2D-RF pulses were designed to excite thin slabs in the small tip angle regime. The corresponding selection profile was characterized in phantoms and in vivo. After optimization of the shimming protocol, the spectral linewidths obtained after 2D localized shimming were compared with conventional techniques and published values from (Emir et al NMR Biomed 2012;25:152-160) in six different brain regions. RESULTS: Results on healthy volunteers show no significant difference (P > 0.5) between the spectroscopic linewidths obtained with the adiabatic (TA = 4 min) and the new low-SAR and time-efficient FASTMAP sequence (TA = 42 s). The SAR can be reduced by three orders of magnitude and TA accelerated six times without impact on the shimming performances or quality of the resulting spectra. CONCLUSION: Multidimensional pulses can be used to minimize the RF energy and time spent for automated shimming using projection mapping at high field. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

Human papilloma virus type and recurrence rate after surgical clearance of anal condylomata acuminata.

BACKGROUND: Anal condylomata acuminata (ACA) are caused by human papilloma virus (HPV) infection which is transmitted by close physical and sexual contact. The result of surgical treatment of ACA has an overall success rate of 71% to 93%, with a recurrence rate between 4% and 29%. The aim of this study was to assess a possible association between HPV type and ACA recurrence after surgical treatment. METHODS: We performed a retrospective analysis of 140 consecutive patients who underwent surgery for ACA from January 1990 to December 2005 at our tertiary University Hospital. We confirmed ACA by histopathological analysis and determined the HPV typing using the polymerase chain reaction. Patients gave consent for HPV testing and completed a questionnaire. We looked at the association of ACA, HPV typing, and HIV disease. We used chi, the Monte Carlo simulation, and Wilcoxon tests for statistical analysis. RESULTS: Among the 140 patients (123 M/17 F), HPV 6 and 11 were the most frequently encountered viruses (51% and 28%, respectively). Recurrence occurred in 35 (25%) patients. HPV 11 was present in 19 (41%) of these recurrences, which is statistically significant, when compared with other HPVs. There was no significant difference between recurrence rates in the 33 (24%) HIV-positive and the HIV-negative patients. CONCLUSIONS: HPV 11 is associated with higher recurrence rate of ACA. This makes routine clinical HPV typing questionable. Follow-up is required to identify recurrence and to treat it early, especially if HPV 11 has been identified.

Effect of low-dose chest irradiation before chemotherapy on the rate of local failure in small-cell lung cancer.

PURPOSE: To evaluate the rate of tumor recurrence within the irradiated volume after initial low-dose irradiation of limited-stage small-cell lung cancer (SCLC), to assess the tolerance of a sequential combination of low-dose chest irradiation followed by chemotherapy, and to confirm the responsiveness of limited-stage SCLC to low-dose irradiation. METHODS AND MATERIALS: In this pilot study, 26 patients with limited-stage SCLC were treated by first-line 20-Gy thoracic irradiation followed 3 weeks later by chemotherapy (cisplatin, doxorubicin, and etoposide for six cycles). RESULTS: We present our final results with a median follow-up of surviving patients of 7 years. The response rate to this low-dose irradiation was 83%, with an overall response rate to radiochemotherapy of 96% and a median survival of 21 months. No unexpected early or late toxicity was observed. The rate of initial isolated local failure was 8%, which compares favorably with other published series using higher doses of radiochemotherapy. CONCLUSION: An initial chest irradiation of 20 Gy before chemotherapy could be sufficient to reduce the risk of local failure during the time of survival of patients with limited-stage SCLC. Potential advantages of this treatment may be the prevention of resistance mechanisms to radiotherapy induced by preliminary chemotherapy and a reduced radiation-induced toxicity.

Prevalence rate and reasons for refusals of influenza vaccine in the elderly

RESUME Peu d'informations sont disponibles concernant la prévalence et les motifs de refus de la vaccination contre la grippe dans la population âgée. Le but de notre recherche était d'investiguer les vrais motifs de refus de la vaccination (c'est-à-dire pas uniquement les raisons de non-vaccination parfois indépendantes du patient lui- même) chez les personnes âgées. Tous les patients ambulatoires de plus de 65 ans consultant la Policlinique Médicale Universitaire (PMU) de Lausanne ou leur médecin traitant durant les périodes de vaccination contre la grippe 1999-2000 et 2000-2001 ont été inclus. Chaque patient recevait une information sur la grippe et ses complications, de même que sur la nécessité de la vaccination, son efficacité et ses effets seconda ires éventuels. En l'absence de contre-indication, la vaccination était proposée. En cas de refus, les motifs étaient investigués par une question ouverte. Sur 1398 sujets inclus, 148 (12%) ont refusé la vaccination. Les raisons principales de refus étaient la perception d'être en bonne santé (16%), de ne pas être susceptible à la grippe (15%) ou le fait de ne jamais avoir été vacciné contre la grippe dans le passé (15%). On retrouvait également la mauvaise expérience personnelle ou d'un proche lors d'une vaccination (15%) et l'impression d'inutilité du vaccin (10%). 17% des personnes interrogées ont donné des motifs autres et 12% n'ont pas explicité leur non-acceptation. Les refus de vaccination contre la grippe dans la population âgée sont essentiellement liés aux convictions intimes du patient quant à son état de santé et à sa susceptibilité à la grippe, de même qu'à l'efficacité supposée de la vaccination. La résistance au changement semble être un obstacle majeur à l'introduction de la vaccination chez les personnes de plus de 65 ans. SUMMARY More knowledge on the reasons for refusal of the influenza vaccine in elderly patients is essential to target groups for additional information, and hence improve coverage rate. The objective of the present study was to describe precisely the true motives for refusal. All patients aged over 64 who attended the Medical Outpatient Clinic, University of Lausanne, or their private practitioner's office during the 1999 and 2000 vaccination periods were included. Each patient was informed on influenza and its complications, as well as on the need for vaccination, its efficacy and adverse events. The vaccination was then proposed. In case of refusal, the reasons were investigated with an open question. Out of 1398 patients, 148 (12%) refused the vaccination. The main reasons for refusal were the perception of being in good health (16%), of not being susceptible to influenza (15%), of not having had the influenza vaccine in the past (15%), of having had a bad experience either personally or a relative (15%), and the uselessness of the vaccine (10%). Seventeen percent gave miscellaneous reasons and 12% no reason at all for refusal. Little epidemiological knowledge and resistance to change appear to be the major obstacles for wide acceptance of the vaccine by the elderly.

Clinical growth rate of acoustic schwannomas: correlation with the growth fraction as defined by the monoclonal antibody ki-67.

The growth rate of acoustic tumors, although slow, varies widely. There may be a continuous spectrum or distinct groups of tumor growth rates. Clinical, audiologic, and conventional histologic tests have failed to shed any light on this problem. Modern immunohistochemical methods may stand a better chance. The Ki-67 monoclonal antibody stains proliferating cells and is used in this study to investigate the growth fraction of 13 skull base schwannomas. The acoustic tumors can be divided into two different growth groups, one with a rate five times the other. The literature is reviewed to see if this differentiation is borne out by the radiologic studies. Distinct growth rates have been reported: one very slow, taking 50 years to reach 1 cm in diameter, a second rate with a diameter increase of 0.2 cm/year, and a third rate five times the second, with a 1.0 cm increase in diameter per year. A fourth group growing at 2.5 cm/year is postulated, but these tumors cannot be followed for long radiologically, since symptoms demand surgical intervention. The clinical implications of these separate growth rates are discussed.

Treatment of genital mycoplasma in colonized pregnant women in late pregnancy is associated with a lower rate of premature labour and neonatal complications.

Mycoplasma hominis and Ureaplasma spp. may colonize the human genital tract and have been associated with adverse pregnancy outcomes such as preterm labour and preterm premature rupture of membranes. However, as these bacteria can reside in the normal vaginal flora, there are controversies regarding their true role during pregnancy and so the need to treat these organisms. We therefore conducted a retrospective analysis to evaluate the treatment of genital mycoplasma in 5377 pregnant patients showing symptoms of potential obstetric complications at 25-37 weeks of gestation. Women presenting with symptoms were routinely screened by culture for the presence of these bacteria and treated with clindamycin when positive. Compared with uninfected untreated patients, women treated for genital mycoplasma demonstrated lower rates of premature labour. Indeed preterm birth rates were, respectively, 40.9% and 37.7% in women colonized with Ureaplasma spp. and M. hominis, compared with 44.1% in uncolonized women (Ureaplasma spp., p 0.024; M. hominis, p 0.001). Moreover, a reduction of neonatal complications rates was observed, with 10.9% of newborns developing respiratory diseases in case of Ureaplasma spp. colonization and 5.9% in the presence of M. hominis, compared with 12.8% in the absence of those bacteria (Ureaplasma spp., p 0.050; M. hominis, p <0.001). Microbiological screening of Ureaplasma spp. and/or M. hominis and pre-emptive antibiotic therapy of symptomatic pregnant women in late pregnancy might represent a beneficial strategy to reduce premature labour and neonatal complications.

Deficit in memory consolidation (abnormal forgetting rate) in childhood temporal lobe epilepsy. Pre and postoperative long-term observation.

Deficits in memory consolidation have been reported in adult patients with epilepsy but, not to our knowledge, in children. We report the long-term follow-up (9 y. o. to 18 y. o.) of a boy who suffered from temporal lobe epilepsy and underwent a left temporal lobectomy with amygdalo-hippocampal resection at the age of 10. He showed an abnormal forgetting rate when trying to encode new information and a significant deficit for retrieving remote episodic memories (when compared with his twin brother), both consistent with a consolidation disorder. His memory condition slightly improved after cessation of the epilepsy, nevertheless did not normalize. No standard memory assessment could pinpoint his memory problem, hence an adapted methodology was needed. We discuss the nature of the memory deficit, its possible causes and its clinical implications.