Demographic situation in operative medicine in Switzerland - time to react?

Objective: The decreasing proportion of physicians of Swiss origin and the increasing number of part-time jobs in operative medicine might lead to a shortage of physicians in operative disciplines in Switzerland. The objective of the present study was to analyze the current demographic situation in operative medicine in Switzerland. Methods: During the summer of 2011, a 19-item anonymous electronic questionnaire was mailed to all directors of departments in operative medicine in Switzerland. The questionnaire was designed to gather data about the characteristics of the participating departments, the demographics (including the appointment (consultant, attending or resident), the proportion of female and foreign physicians, the latter’s origin, and the number of part-time jobs with a working time between 20 and 90%), and the proportion of vacant posts. Results: Of 775 questionnaires mailed to all directors of departments in operative medicine in Switzerland, 183 (24%) were returned. Overall, 40% were female, and 42% foreign physicians. The proportion of part-time jobs amounted to 17%. Vacant posts were found in 2%. Conclusions: An expansion of study places at the medical universities and of the incentives for the incumbents in operative medicine is necessary to avert a shortage of physicians in Switzerland.

Climatic drivers of hourly to yearly tree radius variations along a 6°C natural warming gradient

Climate affects the timing, rate and dynamics of tree growth, over time scales ranging from seconds to centuries. Monitoring how a tree's stem radius varies over these time scales can provide insight into intra-annual stem dynamics and improve our understanding of climate impacts on tree physiology and growth processes. Here, we quantify the response of radial conifer stem size to environmental fluctuations via a novel assessment of tree circadian cycles. We analyze four years of sub-hourly data collected from 56 larch and spruce trees growing along a natural temperature gradient of ∼6 °C in the central Swiss Alps. During the growing season, tree stem diameters were greatest at mid-morning and smallest in the late evening, reflecting the daily cycle of water uptake and loss. Along the gradient, amplitudes calculated from the stem radius cycle were ∼50% smaller at the upper site (∼2200 m a.s.l.) relative to the lower site (∼800 m a.s.l.). We show changes in precipitation, temperature and cloud cover have a substantial effect on typical growing season diurnal cycles; amplitudes were nine times smaller on rainy days (>10 mm), and daily amplitudes are approximately 40% larger when the mean daily temperature is 15–20 °C than when it is 5–10 °C. We find that over the growing season in the sub-alpine forests, spruce show greater daily stem water movement than larch. However, under projected future warming, larch could experience up to 50% greater stem water use, which may severely affect future growth on already dry sites. Our data further indicate that because of the confounding influences of radial growth and short-term water dynamics on stem size, conventional methodology probably overstates the effect of water-linked meteorological variables (i.e. precipitation and relative humidity) on intra-annual tree growth. We suggest future studies use intra-seasonal measurements of cell development and consider whether climatic factors produce reversible changes in stem diameter. These study design elements may help researchers more accurately quantify and attribute changes in forest productivity in response to future warming.

A patient presenting with metabolic acidosis despite severe vomiting—correct diagnosis by use of the physical-chemical approac

We describe the case of a 28-year-old otherwise healthy woman who presents to our emergency department with nausea for 2 days and severe vomiting for 1 day. She has no history of travel, and her medical history is unremarkable. The physical examination shows a soft and nontender abdomen. Laboratory examinations reveal the presence of significant metabolic alkalosis despite the severe vomiting of the patient. Hypochloremic alkalosis would be expected to be present in this patient. We explain how to correctly identify the rare cause of metabolic acidosis present in this patient using the physicochemical approach (Stewarts approach) for the analysis of human acid-base disorders.

Ach, analog, digital - Quanten! Blitzkurs für alle Feinde des Digitalen und Technologieverächter

Die Natur integriert digitale und analoge Systeme umstandslos, man muss nur auf die Welt der Quantenmechanik schauen. Warum also diese Dauerproduktion gesellschaftlicher und kultureller Endzeitszenarien? Warum die Dauerbeschwörung der digitalen Bedrohung? Warum lassen wir uns nicht einfach auf das ein, was unsere physikalische Existenz grundlegend determiniert — die Koexistenz.

Radiometrical, hormonal and biological correlates of skeletal growth in the female rat from birth to senescence

OBJECTIVE We investigated the skeletal growth profile of female rats from birth to senescence (100weeks) on the basis of sequential radiometrical, hormonal and biochemical parameters. DESIGN Weaning rats entered the study which was divided into two sections: a) sequential measurements of vertebral and tibial growths and bone mineral density (BMD), estimation of mineral content of the entire skeleton (BMC) and chemical analysis of vertebral Ca; and b) determination of basal and pulsatile growth hormone (rGH), insulin-like growth hormone (IGF-I), estradiol (E2), parathyroid hormone (PTH), osteocalcin (OC) and urinary d-pyridinoline (dp) throughout the experimental period. RESULTS Vertebral and tibial growths ceased at week 25 whereas BMD and BMC as well as total vertebral Ca exhibited a peak bone mass at week 40. rGH pulsatile profiles were significantly higher in younger animals coinciding with the period of active growth and IGF-I peaked at 7weeks, slowly declining thereafter and stabilizing after week 60. OC and dp closely paralleled IGF-I coinciding with the period of enhanced skeletal growth, remaining thereafter in the low range indicative of reduced bone turnover. E2 increased during reproductive life but the lower values subsequently recorded were still in the physiological range, strongly suggesting a protective role of this steroid on bone remodeling. PTH followed a similar profile to E2, but the significance of this after completion of growth remains unclear. CONCLUSIONS Mechanisms governing skeletal growth in the female rat appear similar to those in humans. Bone progression and attainment of peak bone mass are under simultaneous control of rGH, IGF-I and calciotropic hormones and are modulated by E2. This steroid seems to protect the skeleton from resorption before senescence whereas the role of PTH in this context remains uncertain.

Oxygen isotope ratios (18O/16O) of hemicellulose-derived sugar biomarkers in plants, soils and sediments as paleoclimate proxy II: insight from a climate transect study

The oxygen isotopic composition of precipitation (δ18Oprec) is well known to be a valuable (paleo-)climate proxy. Paleosols and sediments and hemicelluloses therein have the potential to serve as archives recording the isotopic composition of paleoprecipitation. In a companion paper (Zech et al., 2014) we investigated δ18Ohemicellulose values of plants grown under different climatic conditions in a climate chamber experiment. Here we present results of compound-specific δ18O analyses of arabinose, fucose and xylose extracted from modern topsoils (n = 56) along a large humid-arid climate transect in Argentina in order to answer the question whether hemicellulose biomarkers in soils reflect δ18Oprec. The results from the field replications indicate that the homogeneity of topsoils with regard to δ18Ohemicellulose is very high for most of the 20 sampling sites. Standard deviations for the field replications are 1.5‰, 2.2‰ and 1.7‰, for arabinose, fucose and xylose, respectively. Furthermore, all three hemicellulose biomarkers reveal systematic and similar trends along the climate gradient. However, the δ18Ohemicellulose values (mean of the three sugars) do not correlate positively with δ18Oprec (r = −0.54, p < 0.014, n = 20). By using a Péclet-modified Craig-Gordon (PMCG) model it can be shown that the δ18Ohemicellulose values correlate highly significantly with modeled δ18Oleaf water values (r = 0.81, p < 0.001, n = 20). This finding suggests that hemicellulose biomarkers in (paleo-)soils do not simply reflect δ18Oprec but rather δ18Oprec altered by evaporative 18O enrichment of leaf water due to evapotranspiration. According to the modeling results, evaporative 18O enrichment of leaf water is relatively low (∼10‰) in the humid northern part of the Argentinian transect and much higher (up to 19‰) in the arid middle and southern part of the transect. Model sensitivity tests corroborate that changes in relative air humidity exert a dominant control on evaporative 18O enrichment of leaf water and thus δ18Ohemicellulose, whereas the effect of temperature changes is of minor importance. While oxygen exchange and degradation effects seem to be negligible, further factors needing consideration when interpreting δ18Ohemicellulose values obtained from (paleo-)soils are evaporative 18O enrichment of soil water, seasonality effects, wind effects and in case of abundant stem/root-derived organic matter input a partial loss of the evaporative 18O enrichment of leaf water. Overall, our results prove that compound-specific δ18O analyses of hemicellulose biomarkers in soils and sediments are a promising tool for paleoclimate research. However, disentangling the two major factors influencing δ18Ohemicellulose, namely δ18Oprec and relative air humidity controlled evaporative 18O enrichment of leaf water, is challenging based on δ18O analyses alone.

Levels of matrix metalloproteinase-9 within cerebrospinal fluid in a rabbit model of coccidioidal meningitis and vasculitis.

Matrix metalloproteinase (MMP)-9 is produced by the central nervous system and inflammatory cells in a variety of inflammatory conditions in both animals and humans. MMP-9 promotes inflammation, breakdown of the blood-brain barrier, and vasculitis. Because vasculitis is seen frequently in patients with coccidioidal meningitis (CM), this study evaluated the presence of MMP-9 within the cerebrospinal fluid (CSF) of rabbits infected intracisternally with Coccidioides immitis arthroconidia. Infected rabbits demonstrated systemic and neurological sequelae to infection, including CSF pleocytosis. Levels of MMP-9 within CSF were assayed by use of zymography and compared with MMP-2 levels, which served as an internal control. Elevated levels of MMP-9 were detectable by day 3, continued to increase through day 10, and declined by day 15 after infection. MMP-9 may contribute to inflammation and vasculitis in this animal model. Future work can focus on evaluation of MMP inhibitors, to gain a better perspective of the role of this MMP in CM.

[Meningitis (I)--differential diagnosis; aseptic and chronic meningitis].

Meningitis is the most common serious manifestation of infection of the central nervous system. Inflammatory involvement of the subarachnoid space with meningeal irritation leads to the classical triad of headache, fever, and meningism, and to a pleocytosis of the cerebrospinal fluid (CSF). Meningitis is clinically categorized into an acute and chronic disease based on the acuity of symptoms. Acute meningitis develops over hours to days, while in chronic meningitis symptoms evolve over days or even weeks. Aseptic meningitis, in which no bacterial pathogen can be isolated by routine cultures, can mimic bacterial meningitis, but the disease has a much more favorable prognosis. Many cases of aseptic meningitis are caused by viruses, primarily enteroviruses, but bacteria and noninfectious etiologies also cause meningitis with negative cultures. Symptoms of meningeal inflammation with CSF pleocytosis that persist for more than 4 weeks define the chronic meningitis syndrome. The diagnosis is based on the patient history, clinical evidence of meningitis, CSF examination, and often imaging studies. The differential diagnosis is broad, and the predominant CSF cell type can provide clues as to the underlying disease. Empiric therapy is primarily based on the age of the patient, with modifications if there are positive findings on CSF gram stain or if the patient presents with special risk factors. In patients with chronic meningitis, a definite diagnosis is often not available or delayed for days, in which case empiric therapy may have to be initiated. It is important to cover the treatable causes of meningitis, for which the outcome is poor if treatment is delayed.

Microbial-immune cross-talk and regulation of the immune system

We are all born germ-free. Following birth we enter into a lifelong relationship with microbes residing on our body's surfaces. The lower intestine is home to the highest microbial density in our body, which is also the highest microbial density known on Earth (up to 10(12) /g of luminal contents). With our indigenous microbial cells outnumbering our human cells by an order of magnitude our body is more microbial than human. Numerous immune adaptations confine these microbes within the mucosa, enabling most of us to live in peaceful homeostasis with our intestinal symbionts. Intestinal epithelial cells not only form a physical barrier between the bacteria-laden lumen and the rest of the body but also function as multi-tasking immune cells that sense the prevailing microbial (apical) and immune (basolateral) milieus, instruct the underlying immune cells, and adapt functionally. In the constant effort to ensure intestinal homeostasis, the immune system becomes educated to respond appropriately and in turn immune status can shape the microbial consortia. Here we review how the dynamic immune-microbial dialogue underlies maturation and regulation of the immune system and discuss recent findings on the impact of diet on both microbial ecology and immune function.

Hypertrophy of infected Peyer’s patches arises from global, interferon-receptor, and CD69-independent shutdown of lymphocyte egress

Lymphoid organ hypertrophy is a hallmark of localized infection. During the inflammatory response, massive changes in lymphocyte recirculation and turnover boost lymphoid organ cellularity. Intriguingly, the exact nature of these changes remains undefined to date. Here, we report that hypertrophy of Salmonella-infected Peyer's patches (PPs) ensues from a global "shutdown" of lymphocyte egress, which traps recirculating lymphocytes in PPs. Surprisingly, infection-induced lymphocyte sequestration did not require previously proposed mediators of lymphoid organ shutdown including type I interferon receptor and CD69. In contrast, following T-cell receptor-mediated priming, CD69 was essential to selectively block CD4+ effector T-cell egress. Our findings segregate two distinct lymphocyte sequestration mechanisms, which differentially rely on intrinsic modulation of lymphocyte egress capacity and inflammation-induced changes in the lymphoid organ environment.

Efficacy and Safety of Natalizumab in Crohn’s Disease Patients Treated at 6 Boston Academic Hospitals

BACKGROUND: Despite trials demonstrating its efficacy, many physicians harbor concerns regarding the use of natalizumab in the treatment of patients with refractory Crohn's disease (CD). The purpose of this study was to perform a descriptive analysis of a series of CD patients not currently enrolled in a clinical trial. METHODS: A retrospective case review of patients treated with natalizumab at 6 sites in Massachusetts: Boston Medical Center, Beth Israel Deaconess Medical Center, Brigham & Women's Hospital, Lahey Clinic, Massachusetts General Hospital, and UMass Medical Center. RESULTS: Data on 69 CD patients on natalizumab were collected. At the start of treatment, patients' disease duration was 12 years. A high proportion of patients were women (68%), presented with perianal disease (65%) and upper gastrointestinal tract involvement (14%). Prior nonbiologic therapies were steroids (96%), thiopurines (94%), antibiotics (74%), methotrexate (58%), and at least two anti-tumor necrosis factor agent failures (81%). Sixty-nine percent (44 of 64 patients) with available medical evaluation had a partial or complete clinical response. Loss of response was 13% after an average of 1 year of treatment. Adverse events were infusion reactions, headaches, fever, and infections. No case of progressive multifocal leukoencephalopathy was observed. CONCLUSIONS: In our clinical experience outside the context of a clinical trial, natalizumab is largely reserved for CD patients with extensive ileocolonic disease who have failed conventional immunosuppressants and of at least 2 anti-tumor necrosis factor agents. This drug is, however, well tolerated and offers significant clinical improvement for more than a year in one-third of these difficult-to-treat CD patients.

Elektive Splenektomie bei Erwachsenen – Vorbereitung, Durchführung und Nachbetreuung

Elective splenectomy in adults is often performed after failure of conservative treatment in patients with hematologic, neoplastic, or autoimmune disorders. The indication to perform a splenectomy should be discussed in an interdisciplinary team and the surgeon should not make the decision on his own. Laparoscopic splenectomy is nowadays established as the gold-standard treatment due to low morbidity and mortality and - compared to open surgery - lower postoperative pain, less intraoperative blood loss and shorter hospital stay. Every patient with planned splenectomy must undergo vaccination against pneumococci and meningococci at least two weeks prior to the operation, which helps reducing the risk of the "overwhelming post-splenectomy infection" (OPSI). Beside re-vaccination against pneumococci and meningococci during follow-up, every patient should be informed about the increased risk of infection, receive a personal post-splenectomy pass and emergency antibiotics in case of infection

Apolipoprotein E genotypes and cognitive functions in healthy elderly persons

Objectives- We investigated whether apoE genotypes correlate with cognitive functions in clinically healthy persons. Methods - In 1993 and 1995, we measured information processing speed, delayed free recall and semantic aspects of long-term memory in 227 men and 105 women aged 65 and over, a randomly selected subsample of the prospective Basel Study. Cardiovascular risk factors and education were assessed. Results -E2 were more prevalent in old-old (>75 years, 23.5% vs 15%) compared to E4 than in young-old (<75 years, 19.3% vs 23.5%). Taking into account age and education, subjects with ɛ3/ɛ4 or ɛ4/ɛ4 alleles (E4) performed lowest in all 3 tests compared to those homozygous for ɛ3 (E3) or carriers of one or two ɛ2 alleles (E2) (reaction time P=0.009, free recall P=0.05, WAIS-R vocabulary P<0.05). In old-old there was a significant difference between E2 and E4 for reaction time (P=0.02) and free recall (P<0.02) but not for vocabulary (P=0.086). In all 3 groups there were no significant changes after 2 years. The subgroup with the genotype ɛ2/ɛ4 performed consistently best in the cognitive tests. Cholesterol was significantly increased in the E4 and E3 group compared to the E2 group. Conclusion - ApoE genotype correlates with cognitive performance. The increased prevalence of E2 in the old-old and the significantly lower plasma cholesterol levels suggest differential morbidity and mortality as important factors influencing the prevalence of cognitive disorders in late life.

Forschung: Die allermeisten packen das (Interview)

Pasqualina Perrig-Chiello über Chancen und ­Risiken in der Lebensmitte. Und warum Männer mehr von Nebenwirkungen betroffen sind.