During seasonal acclimation, Djungarian hamsters spontaneously exhibit a reduction in food intake, body mass and body fat stores, which is externally cued by shortening of day length in autumn and controlled by a sliding set-point. We investigated the function of the leptin adipostatic feedback system in the photoperiodic control of seasonal acclimation. In response to mouse recombinant leptin injections for 10 days, long day photoperiod (LD) and short day photoperiod (SD)-acclimated hamsters decreased food intake and body mass. The reduction of body mass was due to the depletion of body fat, as revealed by carcass composition analysis. In SD hamsters, leptin caused a larger reduction of body fat mass than observed under LD conditions, whereas the anorectic effect was similar in both photoperiods. The serum leptin concentration was 9.3 +/- 1.2 ng/ml in LD-acclimated hamsters and decreased significantly to 4.2 +/- 0.8 ng/ml and 2.1 +/- 0.6 ng/ml in hamsters exposed to SD for 66 days and 116 days, respectively (P < 0.001). A strong positive correlation between total body fat mass and serum leptin concentration was found (rS = 0.935, P < 0.0001, n = 70). Despite the anorectic action of exogenous leptin, higher endogenous leptin levels in LD hamsters were paralleled by higher food intake in LD hamsters as compared to SD hamsters. This paradoxical finding further supports the increased leptin sensitivity in SD hamsters as judged from leptin treatment experiments. We tested the functional significance of leptin for the controlled down-regulation of food intake and body mass induced by short photoperiod. Food restriction for 10 days during the transition phase decreased body mass below the desired sliding set-point, which was recovered in control hamsters following ad libitum refeeding. Treatment with mouse recombinant leptin during ad libitum refeeding inhibited the recovery of body mass and blunted the increase of food intake observed in controls, indicating that the sliding set-point utilizes leptin as a signal for the adjustment of the appropriate body mass level.

BackgroundNitroxoline, a hydroxychinoline derivate, has been used for many years to treat urinary tract infections (UTI). Many uncontrolled, but only few controlled clinical studies have been published. Four so far unpublished, controlled clinical studies were meta-analysed.MethodsA narrative literature review was performed. In addition the individual patient data (IPD) of 466 females with uncomplicated UTI of four prospective, single blind, randomized, clinical studies with similar protocols using nitroxoline (250 mg tid) versus cotrimoxazole (960 mg bid) or norfloxacin (400 mg bid) as controls for 5 days (sporadic UTI) or 10 days (recurrent UTI) were meta-analysed. The primary aim was eradication of bacteriuria 7–13 days after end of therapy (test of cure). Clinical efficacy was determined by elimination of symptoms and safety by adverse events and laboratory tests.ResultsReviewing a total of 26 uncontrolled, 2 controlled and one postmarketing studies including more than 11,000 patients, good efficacy and safety of nitroxoline could be confirmed. In the four unpublished controlled studies a total of 234 patients were treated orally with nitroxoline and 232 with controls. The safety of nitroxoline was very good and comparable to the controls (adverse events 9.4% vs 7.8%; p = 0.360). In the mMITT set (at least one outcome result), in the PP set (test of cure outcome) and in the modified PP set (missing test of cure rated failure) more than 90% of the patients showed eradication of bacteriuria with nitroxoline, which also met statistical non-inferiority compared to the controls (10% non-inferiority margin) in all three evaluation sets. The clinical efficacy was similar between the two treatment groups.ConclusionThe IPD meta-analysis using objective parameters (elimination of bacteriuria) demonstrated equivalent efficacy (non-inferiority) of nitroxoline with the controls tested (cotrimoxazole, norfloxacin) in the treatment of uncomplicated UTI. Considering the good safety and efficacy of nitroxoline as also shown in many uncontrolled and observational studies and the world wide increase of resistance of uropathogens against cotrimoxazole and fluoroquinolones, but not against nitroxoline within the last 20 years, nitroxoline should be reconsidered as one of the first line antibiotics for the treatment of uncomplicated UTI.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0628-7) contains supplementary material, which is available to authorized users.

In the present retrospective analysis of 643 patients with primary soft issue sarcomas of the extremities, surgical margins could be identified as independent predictors of local recurrence-free, disease-specific, and metastasis-free survival. Given the diminished outcome of patients left with positive margins, surgical efforts should aim to achieve microscopically negative margins whenever feasible. It is noteworthy that only the quality of surgical margins, but not the negative margin width attained, had an influence on the prognosis. Our findings suggest that surgical margins can be close as long as the resected tumor has no ink on it.

Background : Exercise-induced arterial hypertension (EIAH) leads to myocardial hypertrophy and is associated with a poor prognosis. EIAH might be related to the “cardiac fatigue” caused by endurance training. The goal of this study was to examine whether there is any relationship between EIAH and left ventricular hypertrophy in Ironman-triathletes. Methods: We used echocardiography and spiroergometry to determine the left ventricular mass (LVM), the aerobic/anaerobic thresholds and the steady-state blood pressure of 51 healthy male triathletes. The main inclusion criterion was the participation in at least one middle or long distance triathlon. Results: When comparing triathletes with LVM <220g  and athletes with LVM >220g there was a significant difference between blood pressure values (BP) at the anaerobic threshold (185.2± 21.5 mmHg vs. 198.8 ±22.3 mmHg, p=0.037). The spiroergometric results were: maximum oxygen uptake (relative VO 2max) 57.3 ±7.5ml/min/kg vs. 59.8±9.5ml/min/kg (p=ns). Cut-point analysis for the relationship of BP >170 mmHg at the aerobic threshold and the probability of LVM >220g showed a sensitivity of 95.8%, a specificity of 33.3%, with a positive predictive value of 56.8 %, a good negative predictive value of 90%. The probability of LVM >220g increased with higher BP during exercise (OR: 1.027, 95% CI 1.002-1.052, p= 0.034) or with higher training volume (OR: 1.23, 95% CI 1.04 -1.47, p = 0.019). Echocardiography showed predominantly concentric remodelling, followed by concentric hypertrophy. Conclusion: Significant left ventricular hypertrophy with LVM >220g is associated with higher arterial blood pressure at the aerobic or anaerobic threshold. The endurance athletes with EIAH may require a therapeutic intervention to at least prevent extensive stiffening of the heart muscle and exercise-induced cardiac fatigue.

The data from this study could not determine a prognostic significance of surgical margins suggesting that tumour characteristics other than margin status are important. Tumour biology reflected by the histologic grade dictates the final outcome.

Polymorphisms in several genes contribute to interindividual differences in the metabolism of xenobiotics, and may lead to toxicity and disease. The balance between activation and/or detoxification processes may influence an individual's susceptibility to disease. One postulated mechanism underlying multiple chemical sensitivity (MCS) is based on increased metabolism of xenobiotics. The aim of the present study was to determine such polymorphisms in cases with self-reported MCS (sMCS) and controls. sMCS cases (14 men, 45 women, mean age: 48 yr) and controls (14 men, 26 women, mean age: 44 yr) of the same anthroposphere were characterized using the MCS-questionnaire from Huppe and coworkers (2000) and a standardized questionnaire for living conditions and living factors. Allelic frequencies of genomic variations for 5HTT, NAT1, NAT2, PON1, PON2, and SOD2 were determined. The MCS questionnaire from Huppe et al. (2000) differentiated between cases and controls with 87.5% sensitivity and 90% specificity. Compared to controls the sMCS cases had lower exposures, especially to odorous factors, and worse social conditions. No significant differences of the allelic distribution of genetic polymorphisms in the genes for 5HTT, NAT1, NAT2, PON1, PON2, and SOD2 were found between cases and controls. The results are in contrast to the study of McKeown-Eyssen and coworkers (2004) but in accordance with the German MCS multicenter study. Although the MCS questionnaire from Huppe et al. (2000) allowed us to differentiate sMCS cases and controls, it was not strong enough for a discrimination based on sequence variations in genes for enzymes involved in xenobiotic metabolism. Therefore, further research needs to focus on a unique phenomenological characterization of MCS.

Data on prognostic factors and treatment outcomes for chest wall soft tissue sarcomas (STS) are sparse. Wide resections with negative margins are the mainstay of therapy, but the prognostic impact of surgical margins remains controversial. The purpose of the present study was to determine the significance of microscopic margins through a long-term follow-up. The associations between local recurrence-free survival (LRFS), overall survival (OS) and potential prognostic factors were retrospectively assessed in a consecutive series of 110 patients who were suitable for surgical treatment with curative intent. Potential prognostic factors were assessed using univariate and multivariate analyses. The median follow-up time following primary diagnosis was 9.6 years [95% confidence interval (CI), 7.2–10.5]. In the entire cohort, the 5-year estimates of the OS and LRFS rates were 66.0% (95% CI, 55.9–74.3) and 60.6% (95% CI, 50.3–69.4), respectively. A total of 27 patients (24.5%) developed distant metastases with a median survival time of 0.9 years following the diagnosis of metastasis. Surgical margins attained at the initial resection and eventual re-excisions significantly influenced OS in univariate analysis (5-year OS, R0 69.9% vs. R1/R2 38.5%; P=0.046), but this failed to reach statistical significance in the multivariate analysis. In the multivariate analysis, significant adverse prognostic features of LRFS included angiosarcoma subtype, G2 and G3 histology. For OS, the only independent significant predictors were age >50 years, tumor size >5 cm, angiosarcoma subtype and G3 histology. The results of the present study suggest that tumor biology, as reflected by the histological grade, influences the final outcome in patients with chest wall STS. Surgical margins failed to reach statistical significance in multivariate analysis as they demonstrated a dependency towards the independent predictors of OS. Subsequently, a positive margin status may be a result rather than a cause of biological aggressiveness, and it may not influence the outcome directly.

During the last ten years, data of urinary calculi was received in 4094 cases on the criterion of "recurrence", whereby the answer was "yes" in 1446 cases. The overall "adjusted relative recurrence rate" (ARRR) is therefore 35.3%. The importance of an exact physical analysis of urinary stones, involving a differentiation of the various Ca oxalates and Ca phosphates, becomes clear looking at the high recurrence rates for the monomineralic stones of the Ca stone class like brushite and weddellite (ARRR = 66.7% and 50.0%, respectively) compared to apatite and whewellite (ARRR = 36.5% and 29.2%, respectively). Dramatic changes in the composition of the recurrent stone were observed only in 12.7% of all cases. The highest ARRR was found in infection stones with a large content of struvite (about 75%), whereas the total recurrence rate of the infection stone class was about 38%. An assessment of the "danger" of a urinary stone taking into account the criteria of "composition" and "prevalence to recur" is given.