Serum procalcitonin as a marker of post-cardiac arrest syndrome and long-term neurological recovery, but not of early-onset infections, in comatose post-anoxic patients treated with therapeutic hypothermia.

OBJECTIVE: To examine the relationship of early serum procalcitonin (PCT) levels with the severity of post-cardiac arrest syndrome (PCAS), long-term neurological recovery and the risk of early-onset infections in patients with coma after cardiac arrest (CA) treated with therapeutic hypothermia (TH). METHODS: A prospective cohort of adult comatose CA patients treated with TH (33°C, for 24h) admitted to the medical/surgical intensive care unit, Lausanne University Hospital, was studied. Serum PCT was measured early after CA, at two time-points (days 1 and 2). The SOFA score was used to quantify the severity of PCAS. Diagnosis of early-onset infections (within the first 7 days of ICU stay) was made after review of clinical, radiological and microbiological data. Neurological recovery at 3 months was assessed with Cerebral Performance Categories (CPC), and was dichotomized as favorable (CPC 1-2) vs. unfavorable (CPC 3-5). RESULTS: From December 2009 to April 2012, 100 patients (median age 64 [interquartile range 55-73] years, median time from collapse to ROSC 20 [11-30]min) were studied. Peak PCT correlated with SOFA score at day 1 (Spearman's R=0.44, p<0.0001) and was associated with neurological recovery at 3 months (peak PCT 1.08 [0.35-4.45]ng/ml in patients with CPC 1-2 vs. 3.07 [0.89-9.99] ng/ml in those with CPC 3-5, p=0.01). Peak PCT did not differ significantly between patients with early-onset vs. no infections (2.14 [0.49-6.74] vs. 1.53 [0.46-5.38]ng/ml, p=0.49). CONCLUSIONS: Early elevations of serum PCT levels correlate with the severity of PCAS and are associated with worse neurological recovery after CA and TH. In contrast, elevated serum PCT did not correlate with early-onset infections in this setting.

Esotropie précoce: résultats à long terme d'une série de 82 cas opérés par myopexie rétro-équatoriale et recul simultané des deux muscles droits médiaux avant l'âge de 24 mois [Early-onset esotropia operated before the age of 24 months: long-term results of Cüpper's retropexy combined with simultaneous recession of both medial recti]

BACKGROUND: When and how to operate an early-onset esotropia (onset before 6 months of age) is still controversial. We conducted a retrospective study of such patients operated before the age of 24 months. PATIENTS AND METHODS: 82 patients were operated by one surgeon (GK) and followed by the same team. At 5 years post-operation, evaluation criteria included the residual angle of deviation, visual acuity (Birkhäuser Nr 505, 5 m) and binocularity (Lang stereotest I, Bagolini glasses). RESULTS: At 5 years, the residual angle was excellent (0 degrees to + 5 degrees ) in 67 % good, (>+5 degrees to +10 degrees or 0 to -5 degrees ) in 23 %, and poor (>+10 degrees or <-5 degrees ) in 10 %. During the 5 years of follow-up the rate of reoperation was 9.7 %. Isoacuity was obtained in 62 %, slight amblyopia (2 lines of interocular difference) was present in 32 %, and average amblyopia (> 3 lines of interocular difference) was noted in 6 %. Simultaneous perception was present in 53 %, whereas one eye was suppressed or results were undetermined in 47 %. No patient demonstrated stereoscopy using the Lang's stereotest I. CONCLUSION: The results from our study demonstrate that early surgery of early-onset esotropia has a favourable outcome on both visual acuity and the residual angle of strabismus. Simultaneous perception was achieved in 53 %. These figures are comparable to the results of the ELISSS multicentric study.

Examining non-response bias in substance use research-Are late respondents proxies for non-respondents?

BACKGROUND: Non-response is a major concern among substance use epidemiologists. When differences exist between respondents and non-respondents, survey estimates may be biased. Therefore, researchers have developed time-consuming strategies to convert non-respondents to respondents. The present study examines whether late respondents (converted former non-participants) differ from early respondents, non-consenters or silent refusers (consent givers but non-participants) in a cohort study, and whether non-response bias can be reduced by converting former non-respondents. METHODS: 6099 French- and 5720 German-speaking Swiss 20-year-old males (more than 94% of the source population) completed a short questionnaire on substance use outcomes and socio-demographics, independent of any further participation in a cohort study. Early respondents were those participating in the cohort study after standard recruitment procedures. Late respondents were non-respondents that were converted through individual encouraging telephone contact. Early respondents, non-consenters and silent refusers were compared to late respondents using logistic regressions. Relative non-response biases for early respondents only, for respondents only (early and late) and for consenters (respondents and silent refusers) were also computed. RESULTS: Late respondents showed generally higher patterns of substance use than did early respondents, but lower patterns than did non-consenters and silent refusers. Converting initial non-respondents to respondents reduced the non-response bias, which might be further reduced if silent refusers were converted to respondents. CONCLUSION: Efforts to convert refusers are effective in reducing non-response bias. However, converted late respondents cannot be seen as proxies of non-respondents, and are at best only indicative of existing response bias due to persistent non-respondents.

The Effect of Amifostine on Acute and Late Radiation Side Effects in Head and Neck Cancer Patients

Objective: We aimed to investigate the effect of amifostine on acute and late side effects, and its tolerability in head and neck cancer patients treated with radiotherapy (RT). Material and Methods: The study included 87 patients with primary head and neck cancers and cervical lymph node metastases from unknown primary cancers treated with RT alone or combined with chemotherapy (CT). Forty-one patients (47%) received amifostine combined with RT (ART group) and 46 patients (52%) received RT without amifostine (RT group). The patients were evaluated every week during the treatment and at month 1 and 2 after the completion of RT for acute side effects and month 3, 6, 9, 12, and 24 after the treatment for late side effects according to SOMA/LENT scale. Amifostine was administered prior to RT, along with anti-emetic prophylaxis. The two groups were compared with the Student's t and Mann-Whitney U and Chi-square tests. Results: The ART group had significantly less toxicity (grade! 1 mucositis, grade 2 fibrosis) than patients in the RT group (p=0.001, p=0.03, respectively). At week 3 of RT grade 2 mucositis developed in two patients (5%) in the ART group and 10 patients (22%) in the RT group (p=0.02). The protective effect of amifostine on skin reactions developed at week 4 of RT (p=0.05). Grade 3 xerostomia at 9, 12, and 15 months of follow-up (p=0.02, p=0.02, and p=0.02, respectively), grade 2 xerostomia at 18 and 24 months (p=0.02 and p=0.01, respectively) and fibrosis at 15, 18 and 24 months (p=0.05, p=0.02 and p=0.02, respectively) decreased markedly in the ART group compared with the RT group. Emesis was the most common adverse effect of amifostine. Conclusion: Daily administration of amifostine during RT was effective in avoiding late grade 2-3 xerostomia, as well as grade 2 fibrosis.

Non-invasive diagnostic biomarkers for estimating the onset time of permanent cerebral ischemia.

The treatments for ischemic stroke can only be administered in a narrow time-window. However, the ischemia onset time is unknown in ~30% of stroke patients (wake-up strokes). The objective of this study was to determine whether MR spectra of ischemic brains might allow the precise estimation of cerebral ischemia onset time. We modeled ischemic stroke in male ICR-CD1 mice using a permanent middle cerebral artery filament occlusion model with laser Doppler control of the regional cerebral blood flow. Mice were then subjected to repeated MRS measurements of ipsilateral striatum at 14.1 T. A striking initial increase in γ-aminobutyric acid (GABA) and no increase in glutamine were observed. A steady decline was observed for taurine (Tau), N-acetyl-aspartate (NAA) and similarly for the sum of NAA+Tau+glutamate that mimicked an exponential function. The estimation of the time of onset of permanent ischemia within 6 hours in a blinded experiment with mice showed an accuracy of 33±10 minutes. A plot of GABA, Tau, and neuronal marker concentrations against the ratio of acetate/NAA allowed precise separation of mice whose ischemia onset lay within arbitrarily chosen time-windows. We conclude that (1)H-MRS has the potential to detect the clinically relevant time of onset of ischemic stroke.

Personality traits, cognition and volumetric MRI changes in elderly patients with early-onset depression: A 2-year follow-up study.

Previous studies revealed personality changes in elderly patients with early-onset depression (EOD) that persist in euthymic stages. However, depression in older patients is a complex disorder that may affect not only personality, but also cognition and brain structure. To address this issue, a cross-sectional comparison and 2-year follow-up of 28 EOD elderly patients and 48 healthy controls included detailed neurocognitive assessment, estimates of brain volumes in limbic areas and white matter hyperintensities, as well as evaluation of the Five Factor Model of personality, in a remitted mood state. Results revealed that cognitive performances as well as brain volumes were preserved in EOD patients both at baseline and at follow-up. The increased Neuroticism factor and Anxiety facet scores as well as the decreased Warmth and Positive Emotions facet scores found at baseline reached the level of healthy controls after 2years. Only the Depression facet scores remained significantly higher in EOD patients compared to controls upon follow-up. Results were independent of depressive relapse since baseline (25% of patients). These findings suggest that both cognitive performances and brain volumes show long-term preservation in older EOD patients. In contrast, the depression-related personality facet might be a trait like marker that persists in the long-term evolution of this disorder.

Stable isotope compositions of mammoth teeth from Niederweningen, Switzerland: Implications for the Late Pleistocene climate, environment, and diet

Oxygen and carbon isotope compositions of well-preserved mammoth teeth from the Middle Wurmian (40-70 ka) peat layer of Niederweningen, the most important mammoth site in Switzerland, were analysed to reconstruct Late Pleistocene palaeoclimatic and palaeoenvironmental conditions. Drinking water (delta(18)O values of approximately -12.3 +/- 0.9 parts per thousand were calculated front oxygen isotope compositions of mammoth tooth enamel apatite using a species-specific calibration for modern elephants. These delta(18)O(H2O) values reflect the mean oxygen isotope composition of the palaeo-precipitation and are similar to those directly measured for fate Pleistocene groundwater from aquifers in northern Switzerland and southern Germany. Using a present-day delta(18)O(H2)o-precipitation-air temperature relation for Switzerland, a mean annual air temperature (MAT) of around 4.3 +/- 2.1 degrees C can be calculated for the Middle Wurmian at this site. This MAT is in good agreement with palaeotemperature estimates on the basis of Middle Wurmian groundwater recharge temperatures and beetle assemblages. Hence, the climatic conditions in this region were around 4 degrees C cooler during the Middle Wurmian interstadial phase, around 45-50ka BP, than they are today. During this period the mammoths from Niederweningen lived in an open tundra-like, C(3) plant-dominated environment as indicated by enamel (delta(13)C values of -11.5 +/- 0.3 parts per thousand and pollen and macroplant fossils found in the embedding peat. The low variability of enamel delta(13)C and delta(18)O values from different mammoth teeth reflects similar environmental conditions and supports a relatively small time frame for the fossil assemblage. (C) 2006 Elsevier Ltd and INQUA. All rights reserved.

Characterization of Human Late Outgrowth Endothelial Progenitor-Derived Cells under Various Flow Conditions.

Background: Endothelial progenitor-derived cells (EPC) are a cell therapy tool in peripheral arterial disease and for re-endothelialization of bypasses and stents. Objective: To assess EPC behavior under flow conditions normally found in vivo. Results: EPC were isolated from human cord blood, cultured on compliant tubes and exposed in an in vitro flow system mimicking hemodynamic environments normally found in medium and large arteries. EPC exposed for 24 h to unidirectional (0.3 ± 0.1 or 6 ± 3 dynes/cm(2)) shear stress oriented along flow direction, while those exposed to bidirectional shear stress (0.3 ± 3 dynes/cm(2)) or static conditions had random orientation. Under bidirectional flow, tissue factor (TF) activity and mRNA expression were significantly increased (2.5- and 7.0-fold) compared to static conditions. Under low shear unidirectional flow TF mRNA increased 4.9 ± 0.5-fold. Similar flow-induced increases were observed for TF in mature umbilical vein-derived endothelial cells. Expression of tissue-type plasminogen activator (t-PA), urokinase (u-PA) and monocyte chemotactic protein 1 (MCP1) were reduced by 40-60% in late outgrowth endothelial progenitor-derived cells (LO-EPC) exposed to any flow environment, while MCP1, but not t-PA or u-PA, was decreased in HUVEC. Conclusions: Flow, in particular bidirectional, modifies the hemostatic balance in LO-EPC with increased TF and decreased plasminogen activator expression.

Late Pan-African magmatism in the Himalaya: new geochronological and geochemical data from the Ordovician Tso Morari metagranites (Ladakh, NW India)

Two granitic plutons, the Tso Morari gneiss and the Rupshu metagranite, crop out in the Tso Morari area. The Polokongka La granite, classically interpreted as a young intrusion in the Tso Morari gneiss, has been recognized as the undeformed facies of the latter. Conventional isotope dilution U-Pb zircon dating on single-grain and small multi-grain fractions yielded magmatic ages of 479 +/- 2 Ma for the Tso Morari gneiss and the Polokongka La granite, and 482.5 +/- 1 Ma for the Rupshu granite. There is a great difference in zircon morphology between the Tso Morari gneiss (peraluminous type) and the Rupshu granite (alkaline type). This difference is confirmed by whole-rock chemistry. The Tso Morari gneiss is a typical deformed S-type granite, resulting from crustal anatexis. On the other hand, the Rupshu granite is an essentially metaluminous alkali-calcic intrusion derived from a different source material. Data compilation from other Himalayan Cambro-Ordovician granites reveals huge and widespread magmatic activity all along and beyond the northern Indian plate between 570 and 450 Ma, with a peak at 500-480 Ma. A major, continental-scale tectonic event is required to generate such a large magmatic belt; it has been tentatively compared to the Variscan post-orogenic extensional regime of Western Europe, as a late evolution stage of a Pan-African orogenic event.

Subjective pubertal timing and health-compromising behaviours among Swiss adolescent girls reporting an on-time objective pubertal timing.

Aim:  The aim of this research is to assess the associations between subjective pubertal timing (SPT) and onset of health-compromising behaviours among girls reporting an on-time objective pubertal timing (OPT). Methods:  Data were drawn from the Swiss SMASH 2002 survey, a self-administered questionnaire study conducted among a nationally representative sample of 7548 adolescents aged 16-20 years. From the 3658 girls in the initial sample, we selected only those (n = 1003) who provided information about SPT and who reported the average age at menarche, namely 13, considering this as an on-time OPT. Bivariate and logistic analyses were conducted to compare the early, on-time and late SPT groups in terms of onset of health-compromising behaviours. Results:  A perception of pubertal precocity was associated with sexual intercourse before age 16 [adjusted odds ratio (AOR): 2.10 (1.30-3.37)] and early use of illegal drugs other than cannabis [AOR: 2.55 (1.30-5.02)]. Conversely, girls perceiving their puberty as late were less likely to report intercourse before age 16 [AOR: 0.30 (0.12-0.75)]. Conclusion:  Faced with an adolescent girl perceiving her puberty as early, the practitioner should investigate the existence of health-compromising behaviours even if her puberty is or was objectively on-time.