Cenozoic evolution of the steppe-desert biome in Central Asia.

The origins and development of the arid and highly seasonal steppe-desert biome in Central Asia, the largest of its kind in the world, remain largely unconstrained by existing records. It is unclear how Cenozoic climatic, geological, and biological forces, acting at diverse spatial and temporal scales, shaped Central Asian ecosystems through time. Our synthesis shows that the Central Asian steppe-desert has existed since at least Eocene times but experienced no less than two regime shifts, one at the Eocene-Oligocene Transition and one in the mid-Miocene. These shifts separated three successive "stable states," each characterized by unique floral and faunal structures. Past responses to disturbance in the Asian steppe-desert imply that modern ecosystems are unlikely to recover their present structures and diversity if forced into a new regime. This is of concern for Asian steppes today, which are being modified for human use and lost to desertification at unprecedented rates.

Resilience of the Asian atmospheric circulation shown by Paleogene dust provenance.

The onset of modern central Asian atmospheric circulation is traditionally linked to the interplay of surface uplift of the Mongolian and Tibetan-Himalayan orogens, retreat of the Paratethys sea from central Asia and Cenozoic global cooling. Although the role of these players has not yet been unravelled, the vast dust deposits of central China support the presence of arid conditions and modern atmospheric pathways for the last 25 million years (Myr). Here, we present provenance data from older (42-33 Myr) dust deposits, at a time when the Tibetan Plateau was less developed, the Paratethys sea still present in central Asia and atmospheric pCO2 much higher. Our results show that dust sources and near-surface atmospheric circulation have changed little since at least 42 Myr. Our findings indicate that the locus of central Asian high pressures and concurrent aridity is a resilient feature only modulated by mountain building, global cooling and sea retreat.

Asian monsoons in a late Eocene greenhouse world.

The strong present-day Asian monsoons are thought to have originated between 25 and 22 million years (Myr) ago, driven by Tibetan-Himalayan uplift. However, the existence of older Asian monsoons and their response to enhanced greenhouse conditions such as those in the Eocene period (55-34 Myr ago) are unknown because of the paucity of well-dated records. Here we show late Eocene climate records revealing marked monsoon-like patterns in rainfall and wind south and north of the Tibetan-Himalayan orogen. This is indicated by low oxygen isotope values with strong seasonality in gastropod shells and mammal teeth from Myanmar, and by aeolian dust deposition in northwest China. Our climate simulations support modern-like Eocene monsoonal rainfall and show that a reinforced hydrological cycle responding to enhanced greenhouse conditions counterbalanced the negative effect of lower Tibetan relief on precipitation. These strong monsoons later weakened with the global shift to icehouse conditions 34 Myr ago.

Switching of ± 360° domain wall states in a nanoring by an azimuthal Oersted field.

We demonstrate magnetic switching between two 360° domain wall vortex states in cobalt nanorings, which are candidate magnetic states for robust and low power magnetoresistive random access memory (MRAM) devices. These 360° domain wall (DW) or 'twisted onion' states can have clockwise or counterclockwise circulation, the two states for data storage. Reliable switching between the states is necessary for any realistic device. We accomplish this switching by applying a circular Oersted field created by passing current through a metal atomic force microscope tip placed at the center of the ring. After initializing in an onion state, we rotate the DWs to one side of the ring by passing a current through the center, and can switch between the two twisted states by reversing the current, causing the DWs to split and meet again on the opposite side of the ring. A larger current will annihilate the DWs and create a perfect vortex state in the rings.

Evaluation of critical incidents in general surgery.

BACKGROUND: The analysis of adverse events is a central step in critical incident reporting, but has not been described in a surgical setting. The aim of this study was to develop an evaluation protocol and assess its feasibility. METHODS: All incidents were analysed by a multidisciplinary team. A coding system based on three published theories was used to assess all incidents and their underlying causes. A risk analysis was also conducted. RESULTS: Between July 2004 and December 2005, 9785 inpatients were treated and 139 critical incidents reported. Classification of active errors revealed 47.7 per cent to be execution failures and 45.9 per cent knowledge-based errors. The distribution of medical errors was 12.9 per cent diagnostic, 46.0 per cent treatment, 17.3 per cent preventive and 23.7 per cent other. Some 282 latent failures were identified among the 139 incidents. Risk analysis revealed a severe incident rate of 21.6 per cent. CONCLUSION: This study has shown the feasibility of an evaluation protocol based on a combination of three classification systems and a risk analysis. It allows a thorough assessment of critical incidents, identification of priorities and tailored countermeasures.

Computerised tomography for the detection of pulmonary emboli in intensive care patients--a retrospective cohort study.

Pulmonary emboli are frequently considered as a cause for respiratory deterioration in intensive care unit (ICU) patients, however empirical observation suggests that computerised tomographic (CT) angiography is infrequently positive after the first 24 hours. This study aimed to determine the rate and risk factors for detection of pulmonary emboli by CT angiography in ICU patients. All patients undergoing CT angiography > 24 hours after ICU admission for respiratory deterioration from April 2000 until January 2004 were included. The positivity rate for pulmonary emboli was determined and risk factors analysed. Seven (6%) out of 113 CT angiograms were positive for pulmonary emboli. All were found in trauma patients. Comparing positive to negative scans, predefined risk factors including head injury (5/7 positive scans, 71% vs. 23/106 negative scans, 22%, P = 0.005), spine injury with neurological impairment (4/7, 57% vs. 9/106, 8%, P = 0.002) and lower limb injury (3/7, 43% vs. 12/106, 9%, P = 0.039) were significantly more frequent in patients with positive scans. Deep vein thrombosis prophylaxis was employed less frequently prior to a positive scan (in 3/7, 43% patients with positive scans vs. 91/106, 86% patients with negative scans P = 0.015). Only the predefined risk factors were independently associated with positive CT angiography on limited logistic regression (OR 24.7 per risk factor, 95% CI 2.38 to 255.1, P = 0.007). Pulmonary emboli were infrequently diagnosed using CT angiography in ICU patients admitted for more than 24 hours and found only in patients with recognised risk factors.

[Sepsis after pharyngitis]. / Sepsis nach einer Pharyngitis.

We report about a 36-year-old patient, who developped 4 days after a pharyngitis a sepsis with high temperature und recurrent vomiting. The chest radiograph showed multiple pulmonary abcesses and in the computed tomography additionally a thrombosis was detected in a communicans vein between the right jugularis anterior and the jugularis interna. This disease is commonly known as Lemierre Syndrom. The most common pathogen is the Fusobacterium necrophorum, but other bacteria of the normal oropharyngeal flora can also be the causative organisms. Given an adequate antibiotic therapy and supportive care, the prognosis is favourable.

Does skin prick test correlate with basophil-associated mite-specific IgE in atopic children?

Skin prick test (SPT), as the standard diagnostic tool for immediate hypersensitivity to aeroallergens, is an expression of IgE-dependent mediator release from dermal mast cells. Though probably involved in the late-phase response, peripheral blood basophils (PBB) don't seem to participate in the immediate hypersensitivity response in the skin. We aimed to assess a possible correlation between the SPT to mites and levels of basophil-associated mite-specific IgE. We sequentially enrolled 15 children with allergic rhinitis and documented class > II mite sensitization, mean age 13 years (range 9.5-18), 11 males, 4 females. Symptoms score was determined using a validated questioner. SPT area under the curve (AUC) for 10 common respiratory allergens was measured in all patients. Heparinized blood after basophil enrichment, was lysed with CHAPS. Determination of allergen-specific and total IgE in serum and cell lysate supernatant was performed using standard commercial kits. Basophil-associated, mite-specific IgE could be reliably determined only in 10 patients with a skin reaction greater than 70 mm2, OR 36 (95% CI 1.8-732, p = 0.02). We found a strong linear correlation (R2 = 0.74, p = 0.001) between mite-specific basophil-associated IgE density (IgE molecules per cell) and the SPT AUC. This finding suggests that skin mast cell precursors and basophil both bind specific IgE at a common site prior to the arrival of mast cells to the skin.

Effects of perioperative recombinant human IFN-gamma (rHuIFN-gamma) application in vivo on T cell response.

In spite of the well-known immunoregulatory effects of recombinant human interferon-gamma (rHuIFN-gamma), in vitro clinical trials in trauma patients remain inconclusive. In vitro studies have shown that IFN-gamma has an effect on lymphocyte responses in addition to immunomodulatory effects on the monocyte/macrophage system. To investigate the in vivo effect of rHuIFN-gamma perioperatively on lymphocyte behavior in surgical patients, we studied 46 anergic patients undergoing major surgery. Treated patients (T, n = 24) received 100 microg rHuIFN-gamma subcutaneously (s.c.), and control patients (C, n = 22) received a placebo on preoperative days -7, -5, and -3 in a controlled, double-blinded placebo trial. Whole blood cultures were stimulated with mitogen on perioperative days, and cytokines were investigated in the supernatants. Interleukin-2 receptor (IL-2R) levels were significantly elevated in the treatment arm during the postoperative period (p < 0.05). The postoperative enhancement of IL-4 in C was completely attenuated in T (p < 0.05). IL-2 levels were elevated perioperatively in T but not in C. No significant effect of rHuIFN-gamma could be demonstrated on IL-10 or lymphocyte proliferation in vitro. From this pilot study, we conclude that preoperative in vivo immunomodulation of lymphocyte function with rHuIFN-gamma in anergic patients is effective. It improves immunoreactivity, as shown by elevated IL-2R levels. Elevated IL-2 and suppressed IL-4 levels indicate a shift toward a Th1-driven lymphocyte response.

Eosinophilic pneumonia after administration of fludarabine for the treatment of non-Hodgkin's lymphoma.

Fludarabine is a purine analogue which is effective in the treatment of patients with low-grade non-Hodgkin's lymphoma, including chronic lymphocytic leukemia. While pulmonary toxicity due to cytotoxic drugs is increasingly diagnosed, only few cases of interstitial pneumonitis have been described following fludarabine administration. Here we report the first case in the literature of an acute eosinophilic pneumonia associated with peripheral blood eosinophilia after the administration of fludarabine monotherapy for stage IV follicular lymphoma.

Laparoscopic enucleation of an insulinoma: advantages of using the curved laparoscopic coagulating shears.

Laparoscopic excision is a widely accepted and well-described approach to islet cell tumors of the pancreas. We report the case of a patient with biochemically proven insulinoma who underwent successful enucleation using the curved laparoscopic coagulating shears. We discuss the advantages of using laparoscopy to manage these tumors and the increased benefit of using the curved instrument for this type of procedure.

[Speech recognition in clinical routine, a pilot trial at the Zurich University Hospital]. / Spracherkennung im klinischen Alltag, ein Pilotversuch am Universitätsspital Zürich.

Two systems for continuous German speech recognition were evaluated in pilot installations in a Department of Medicine. Word recognition accuracies of 92-94% were achieved one month after implementation. For standardized text the performance increased to 97%. Speech recognition proved to be economical for physicians when producing short reports, whereas for comprehensive discharge summaries no significant time savings were observed. All reports could be made available much faster by using speech recognition. However, some particle difficulties may still limit the success of comprehensive installations in clinical settings. Adequate hardware, appropriate choice of areas of application, reasonably quiet working conditions and well motivated users are essential for successful implementations.

Protein oxidation and proteolysis in RAW264.7 macrophages: effects of PMA activation.

Macrophages are stimulable cells able to increase the production of reactive oxygen and nitrogen species dramatically for a short period of time. Free radicals and other oxidants are able to oxidize the intracellular protein pool. These oxidized proteins are selectively recognized and degraded by the intracellular proteasomal system. We used the mouse macrophage-like cell line RAW264.7 to test whether macrophagial cells are able to increase their protein turnover after oxidative stress and whether this is accompanied by an increased protein oxidation. Macrophagial cells are particularly susceptible to bolus additions of hydrogen peroxide and peroxynitrite. In further experiments we activated RAW264.7 cells with PMA to test whether the production of endogenous oxidants has analogous effects. A clear dependence of the protein turnover and protein oxidation on the oxidative burst could be measured. In further experiments the role of the proteasomal system in the selective removal of oxidized proteins could be revealed exploring the proteasome specific inhibitor lactacystin. Therefore, although oxidants are able to attack the intracellular protein pool in macrophages, these cells are able to remove oxidized proteins selectively and protect the intracellular protein pool from oxidation.

An IgE-dependent secretory response of mast cells can be induced by a glycosphingolipid-specific monoclonal antibody.

The signal transduction pathway of the type 1 Fcepsilon receptor (FcepsilonRI) has been proposed to be spatially constrained to plasma membrane microdomains enriched in glycosphingolipids and cholesterol. These domains are proposed to serve as platforms that enhance the efficiency of the antigen-receptor stimulus-response coupling process. Here we describe a monoclonal antibody (mAb) designated 2B5, raised by immunizing mice with rat mucosal-type mast cell (line RBL-2H3) membranes, which binds to glycosphingolipids and causes a dose-dependent secretory response of these cells. This secretory response to mAb 2B5 requires binding of IgE to the FcepsilonRI on these cells, although direct interactions between IgE and mAb 2B5 are excluded. The bound IgE- or FcepsilonRI-specific mAb did not affect binding of mAb 2B5 or its Fab fragments to the RBL-2H3 cells and only a limited interference with the binding of IgE to the FcepsilonRI by mAb 2B5 was observed. Binding of mAb 2B5 to the RBL-2H3 cells induced a distribution of fluorescently labeled IgE similar to that produced by antigen-induced aggregation of the IgE-FcepsilonRI. Thus we suggest that mAb 2B5 binds to cell surface glycosphingolipids that are probably associated with the FcepsilonRI-IgE complexes and causes their aggregation, thereby initiating the cascade leading to the cell's secretory response.

Myeloma and severe cholestasis.

Amyloidosis is a frequent complication of multiple myeloma. Liver involvement is common in amyloidosis. Hepatic dysfunction and liver chemistry abnormalities are often mild or absent and obstructive jaundice is rare. We report on a 44-year-old patient with multiple myeloma and rapidly deteriorating liver involvement with severe intrahepatic cholestasis. Autopsy showed widespread amyloidosis primarily involving the liver. This unusual cholestatic manifestation of hepatic amyloidosis has an uniformly poor prognosis, with death occurring within a few months. We discuss the clinical and pathologic aspects.

Mast cell stimulation by co-clustering the type I Fc epsilon-receptors with mast cell function-associated antigens.

The secretory response of rat mucosal-type mast cells (line RBL 2H3) to stimuli produced by clustering or co-clustering two of its membranal components; the type I Fc epsilon receptor and the mast cell function associated antigen (MAFA) was investigated. The primary reagents employed for this purpose were Fab fragments of the monoclonal antibodies J17 and G63 specific to the above respective proteins. The Fabs were then aggregated by F(ab')2 fragments of mouse IgG specific goat antibodies. This reaction was assumed to yield predominantly three different bivalent clustering reagents. Namely, dimers of the Fc epsilon RI specific (J17-Fab)2; dimers of the MAFA specific, (G63-Fab)2 and bispecific (J17-Fab-G63-Fab) dimers. The observed cellular secretory response was analyzed by employing a model which accounts for the clustering and co-clustering of Fc epsilon RIs and MAFAs by the above protocols. Results of this analysis provided evidence that at least some of the MAFA molecules are physically associated with the Fc epsilon RI. As a consequence, clustering of MAFA and Fc epsilon RI by bispecific J17-Fab-G63-Fab dimers induces secretion at comparatively low concentrations of these reagents, though with a significantly lower maximal response than that caused by the respective monospecific reagent (J17-Fab)2. This result most likely reflects the inhibitory capacity of MAFA-Fc epsilon RI interaction.

Median cleft lip with associated midline sinuses.

Midline upper lip sinuses alone are rare entitities, with less than 25 cases reported previously. Midline upper lip sinuses with associated cleft lip are even more rare. A patient report of median cleft lip with associated upper lip sinuses in a 16-year-old boy is presented. Controversy exists as to whether these abnormalities are related. This report demonstrates the plausibility of a cause-and-effect relationship between midline clefts and sinuses.

Antibodies specific to membrane components of rat mast cells are cross-reacting with human basophils.

Murine monoclonal antibodies (mAbs) have previously been raised by us with specificity to the following plasma membrane components of rat mucosal mast cells (RBL-2H3 subline): (1) the alpha-subunit of the type I Fc epsilon receptor, (Fc epsilon RI); (2) a newly described membrane glycoprotein, distinct from any of the Fc epsilon RI subunits, yet affecting the cell's secretory response to Fc epsilon RI clustering and hence named mast cell functional antigen (MAFA), and (3) a glycolipid, GD1b present in the RBL-2H3 cell's plasma membrane. The cross-reactivity of these mAbs with human basophils (from both allergic and nonallergic children) was now examined by three different protocols: (1) by microscopy (light and dark field) of double stained basophils by toluidine blue and by fluorescein-labeled anti-mouse antibodies as secondary ligands binding to the mAbs; (2) by flow cytometry (using directly labeled mAbs), and (3) by monitoring the binding of the 125I-radiolabeled mAbs. In order to exclude the possibility of the (intact) mAbs binding to the Fc gamma receptors, also present on human basophils, Fab and (Fab')2 fragments derived from the above respective mAbs were employed wherever necessary. The results show that the above described murine mAbs fragments do bind specifically to basophils obtained from allergic and nonallergic children. These antibodies may thus also be employed as tools for studying the human basophils function.