The surprising Crab pulsar and its nebula: a review.

The Crab nebula and its pulsar (referred to together as 'the Crab') have historically played a central role in astrophysics. True to this legacy, several unique discoveries have been made recently. The Crab was found to emit gamma-ray pulsations up to energies of 400 GeV, beyond what was previously expected from pulsars. Strong gamma-ray flares, of durations of a few days, were discovered from within the nebula, while the source was previously expected to be stable in flux on these time scales. Here we review these intriguing and suggestive developments. In this context we give an overview of the observational properties of the Crab and our current understanding of pulsars and their nebulae.

Management and outcome of CSF-JC virus PCR-negative PML in a natalizumab-treated patient with MS.

OBJECTIVE: To describe the diagnosis and management of a 49-year-old woman with multiple sclerosis (MS) developing a progressive hemiparesis and expanding MRI lesion suspicious of progressive multifocal leukoencephalopathy (PML) 19 months after starting natalizumab. RESULTS: Polyomavirus JC (JCV)-specific qPCR in CSF was repeatedly negative, but JCV-specific antibodies indicated intrathecal production. Brain biopsy tissue taken 17 weeks after natalizumab discontinuation and plasmapheresis was positive for JCV DNA with characteristic rearrangements of the noncoding control region, but histology and immunohistochemistry were not informative except for pathologic features compatible with immune reconstitution inflammatory syndrome. A total of 22 months later, the clinical status had returned close to baseline level paralleled by marked improvement of neuroradiologic abnormalities. CONCLUSIONS: This case illustrates diagnostic challenges in the context of incomplete suppression of immune surveillance and the potential of recovery of PML associated with efficient immune function restitution.

Long-term outcome of acute encephalitis of unknown aetiology in adults.

Encephalitis is caused by a variety of conditions, including infections of the brain by a wide range of pathogens. A substantial number of cases of encephalitis defy all attempts at identifying a specific cause. Little is known about the long-term prognosis in patients with encephalitis of unknown aetiology, which complicates their management during the acute illness. To learn more about the prognosis of patients with encephalitis of unknown aetiology, patients in whom no aetiology could be identified were examined in a large, single-centre encephalitis cohort. In addition to analysing the clinical data of the acute illness, surviving patients were assessed by telephone interview a minimum of 2 years after the acute illness by applying a standardized test battery. Of the patients with encephalitis who qualified for inclusion (n = 203), 39 patients (19.2%) had encephalitis of unknown aetiology. The case fatality in these patients was 12.8%. Among the survivors, 53% suffered from various neurological sequelae, most often attention and sensory deficits. Among the features at presentation that were associated with adverse outcome were older age, increased C-reactive protein, coma and a high percentage of polymorphonuclear cells in the cerebrospinal fluid. In conclusion, the outcome in an unselected cohort of patients with encephalitis of unknown aetiology was marked by substantial case fatality and by long-term neurological deficits in approximately one-half of the surviving patients. Certain features on admission predicted an unfavourable outcome.

[Requests for online consultations on the operative reconstruction of the hymen--data from the university hospital Zurich and the children's hospital Zurich]. / Anfragen an Online-Arzte über die Möglichkeit einer operativen Rekonstruktion des Hymens: Datenerhebung am Universitäts- und am Kinderspital Zürich.

The "reconstruction of the hymen"consists in a surgical suture of the seam of a hymen that has been fissured due to vaginal intercourse or other causes. This intervention aims at triggering bleeding on the occasion of the next intercourse, a phenomenon often required as proof of virginity within certain traditions. Valid data regarding this ethically and medically controversial and predominantly tabooissue is scarce. In an effort to further explore this practice, we have collected information about hymenorrhaphy from the databases of two anonymous, medical, online counselling services provided by the University Hospital Zürich, and explicitly for teenagers by the Children's Hospital Zürich. We found a sample of 22 questions from women seeking advice, and the results vividly illustrate the psycho-social dilemma these women face, prompting us to suggest that further ethical discussion, collection of empirical data and broad public education on issues related to sexuality are necessary.

[Online medical consulting service at the University Hospital Zürich before and after introduction of a service fee]. / Medizinische Online-Beratung im Universitätsspital Zürich vor und nach Einführung einer Bearbeitungsgebühr.

OBJECTIVE: The University Hospital of Zürich has been providing an anonymous online consultation service since 1999. In January 2008 a service fee of CHF 20.- was introduced. The present investigation evaluated the impact of the service fee on the use of the medical online consulting service. METHODOLOGY: All 8269 requests between January 2007 and December 2008 were analysed using the following criteria: number, complexity and subjects (ICD-10) of the requests, personal statements of the users and evaluation of the online answers. RESULTS: The number of requests decreased by 69 % (6298 vs.1971) and the age of the users rose from 36 +/- 16 to 40 +/- 17 years. The text length of the requests increased (characters: 677 +/- 463 vs. 801 +/- 539), as did the length of the answers (characters: 1397 +/- 3224 vs. 2391 +/- 4327). In 2008 the assistance of specialists at the University Hospital Zürich were called upon more frequently (11.1 % vs. 15.9 %). Regarding the assessments of the quality of the answers, there were differences in the range of positive evaluations ("good": 38 % vs. 41 %, "excellent" 43 % vs. 36 %). DISCUSSION: The introduction of a new service fee resulted in a decrease in requests. At the same time, a greater number of older people used the service, and they asked questions that are more complex. Apparently, persons that probably have more medical problems have greater appreciation for the opportunity to ask questions and, in comparison to younger persons, are more willing to pay for the service. The continued positive evaluation given to the medical answers shows that an Internet service involving a fee can also be a useful supplement to the conventional physician/patient relationship.

Detection of gamma rays from a starburst galaxy.

Starburst galaxies exhibit in their central regions a highly increased rate of supernovae, the remnants of which are thought to accelerate energetic cosmic rays up to energies of approximately 10(15) electron volts. We report the detection of gamma rays--tracers of such cosmic rays--from the starburst galaxy NGC 253 using the High Energy Stereoscopic System (H.E.S.S.) array of imaging atmospheric Cherenkov telescopes. The gamma-ray flux above 220 billion electron volts is F = (5.5 +/- 1.0(stat) +/- 2.8(sys)) x 10(-13) cm(-2) s(-1), implying a cosmic-ray density about three orders of magnitude larger than that in the center of the Milky Way. The fraction of cosmic-ray energy channeled into gamma rays in this starburst environment is five times as large as that in our Galaxy.

Limits on an energy dependence of the speed of light from a flare of the active galaxy PKS 2155-304.

In the past few decades, several models have predicted an energy dependence of the speed of light in the context of quantum gravity. For cosmological sources such as active galaxies, this minuscule effect can add up to measurable photon-energy dependent time lags. In this Letter a search for such time lags during the High Energy Stereoscopic System observations of the exceptional very high energy flare of the active galaxy PKS 2155-304 on 28 July 2006 is presented. Since no significant time lag is found, lower limits on the energy scale of speed of light modifications are derived.

Acute partial transverse myelitis: risk factors for conversion to multiple sclerosis.

Acute partial transverse myelitis (APTM) may be the first clinical manifestation of multiple sclerosis (MS), of relapsing myelitis, or remain a monophasic event. Identification of risk factors associated with relapse or conversion to MS is important, as prognostic information might help to guide management. The objective of this study was to define clinical, laboratory and neuroimaging factors in patients with first-ever APTM that predict relapses or conversion to MS. We identified 73 patients with a first-ever APTM admitted to our institution from January 1999 to June 2005. The follow-up time ranged from 12 to 90 months (mean follow-up 46 months). Patient demographics, clinical impairment at onset and after 3 months, ancillary tests including cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), evoked potentials, recurrent and new symptoms and signs during follow-up were analysed. APTM remained a monophasic event in 35 patients (47.9%), conversion to MS occurred in 32 (43.8%) and recurred as relapsing myelitis in six patients (8.2%). According to univariate analysis, a family history of MS (P = 0.02), higher expanded disability status scale (EDSS) at onset (P = 0.03) and lesions on brain MRI (P = 0.03) were predictive factors for conversion to MS. CSF-specific oligoclonal bands (P = 0.04) or abnormal IgG-index (P = 0.04) were associated with increased risk for MS as well. In patients with a first-ever APTM, a family history of MS, high EDSS at presentation, lesions on brain MRI, CSF-specific oligoclonal bands or abnormal IgG-index may indicate an increased risk for conversion to MS.

HESS observations of the galactic center region and their possible dark matter interpretation.

The detection of gamma rays from the source HESS J1745-290 in the Galactic Center (GC) region with the High Energy Spectroscopic System (HESS) array of Cherenkov telescopes in 2004 is presented. After subtraction of the diffuse gamma-ray emission from the GC ridge, the source is compatible with a point source with spatial extent less than 1.2;{'}(stat) (95% C.L.). The measured energy spectrum above 160 GeV is compatible with a power law with photon index of 2.25+/-0.04(stat)+/-0.10(syst) and no significant flux variation is detected. It is finally found that the bulk of the very high energy emission must have non-dark-matter origin.

Fast variability of tera-electron volt gamma rays from the radio galaxy M87.

The detection of fast variations of the tera-electron volt (TeV) (10(12) eV) gamma-ray flux, on time scales of days, from the nearby radio galaxy M87 is reported. These variations are about 10 times as fast as those observed in any other wave band and imply a very compact emission region with a dimension similar to the Schwarzschild radius of the central black hole. We thus can exclude several other sites and processes of the gamma-ray production. The observations confirm that TeV gamma rays are emitted by extragalactic sources other than blazars, where jets are not relativistically beamed toward the observer.

Quantification of central motor conduction deficits in multiple sclerosis patients before and after treatment of acute exacerbation by methylprednisolone.

OBJECTIVE: To compare the effects of intravenous methylprednisolone (IVMP) in patients with relapsing-remitting (RR-MS), secondary progressive (SP-MS), and primary progressive multiple sclerosis (PP-MS). METHODS: Clinical and neurophysiological follow up was undertaken in 24 RR-MS, eight SP-MS, and nine PP-MS patients receiving Solu-Medrol 500 mg/d over five days for exacerbations involving the motor system. Motor evoked potentials (MEPs) were used to measure central motor conduction time (CMCT) and the triple stimulation technique (TST) was applied to assess conduction deficits. The TST allows accurate quantification of the number of conducting central motor neurones, expressed by the TST amplitude ratio. RESULTS: There was a significant increase in TST amplitude ratio in RR-MS (p<0.001) and SP-MS patients (p<0.02) at day 5, paralleling an increase in muscle force. TST amplitude ratio and muscle force remained stable at two months. In PP-MS, TST amplitude ratio and muscle force did not change. CMCT did not change significantly in any of the three groups. CONCLUSIONS: In RR-MS and SP-MS, IVMP is followed by a prompt increase in conducting central motor neurones paralleled by improvement in muscle force, which most probably reflects partial resolution of central conduction block. The lack of similar clinical and neurophysiological changes in PP-MS corroborates previous clinical reports on limited IVMP efficacy in this patient group and points to pathophysiological differences underlying exacerbations in PP-MS.

[The online-consultation of the University Hospital Zurich]. / Medizinische Beratung via Internet: Erfahrungen aus dem Universitätsspital Zürich.

Since August 1999 free medical Internet consultations are offered by the University Hospital Zurich. Overall 13,984 inquiries have been answered until December 2003. As of today an average of about 10 questions has been received per day. The users are predominantly between 20 and 50 years old and most of them show normal characteristics in terms of weight and size. The incoming questions refer to a wide variety of medical subjects and 53% of them have been asked by women. Frequently asked questions refer to topics like HIV, nutrition, vaccination as well as contraceptive methods. Intimate questions concerning e.g. sexual dysfunction disorder as well as changes on male genitals are also overrepresented. Therefore medical Internet consultation is characterised by low thresholds and is particularly well suited for the consultation of intimate and sensitive topics.

Hemispheric asymmetry in visuospatial attention assessed with transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) was used to study visuospatial attention processing in ten healthy volunteers. In a forced choice recognition task the subjects were confronted with two symbols simultaneously presented during 120 ms at random positions, one in the left and the other in the right visual field. The subject had to identify the presented pattern out of four possible combinations and to press the corresponding response key within 2 s. Double-pulse TMS (dTMS) with a 100-ms interstimulus interval (ISI) and an intensity of 80% of the stimulator output (corresponding to 110-120% of the motor threshold) was applied by a non-focal coil over the right or left posterior parietal cortex (PPC, corresponding to P3/P4 of the international 10-20 system) at different time intervals after onset of the visual stimulus (starting at 120 ms, 270 ms and 520 ms). Double-pulse TMS over the right PPC starting at 270 ms led to a significant increase in percentage of errors in the contralateral, left visual field (median: 23% with TMS vs 13% without TMS, P=0.0025). TMS applied earlier or later showed no effect. Furthermore, no significant increase in contra- or ipsilateral percentage of errors was found when the left parietal cortex was stimulated with the same timing. These data indicate that: (1) parietal influence on visuospatial attention is mainly controlled by the right lobe since the same stimulation over the left parietal cortex had no significant effect, and (2) there is a vulnerable time window to disturb this cortical process, since dTMS had a significant effect on the percentage of errors in the contralateral visual hemifield only when applied 270 ms after visual stimulus presentation.

The triple stimulation technique to study central motor conduction to the lower limbs.

OBJECTIVE: To quantify the percentage of motor units of a foot muscle that can be activated by transcranial magnetic stimulation (TMS) in normal subjects and patients. METHODS: We adapted the recently described triple stimulation technique (TST) for recordings from abductor hallucis (AH). Conventional motor evoked potentials (MEPs) of this muscle are usually small and variable in shape, because of an important temporal desynchronization of the TMS induced spinal motor neuron discharges. The TST allows 'resynchronization' of these discharges and thereby a quantification of the proportion of motor units activated by TMS. The lower limb (LL-) TST was applied to 33 sides of 18 normal subjects and 51 sides of 46 patients with multiple sclerosis, amyotrophic lateral sclerosis, or spinal cord disorders. RESULTS: In healthy subjects, the LL-TST demonstrated that TMS achieves activation of virtually all motor neurons supplying the AH. In 33 of 51 patient sides, abnormal LL-TST responses suggested corticospinal conduction failures of various degrees. The LL-TST was 2.54 times more sensitive to detect central conduction failures than the conventional LL-MEPs. Combining the LL-TST with TST of the upper limbs further increased the sensitivity to detect a conduction failure by 1.50 times. CONCLUSION: The LL-TST markedly improves the examination of corticospinal pathways.

Prevention of hyperacute rejection by removal of antibodies to HLA immediately before renal transplantation.

BACKGROUND: Many patients with circulating antibodies to human leucocyte antigens (anti-HLA) are highly sensitised against renal transplantation and are liable to immediate graft loss through hyperacute rejection. Our aim was to find out whether removal of anti-HLA immediately before renal transplantation prevented hyperacute graft rejection. METHODS: 13 highly sensitised patients underwent cadaveric renal transplants immediately after immunoadsorption (IA) treatment to remove anti-HLA. Before IA, 12 patients had a positive crossmatch against donor cells either by cytotoxic or flow-cytometric assay; results for one patient were equivocal. FINDINGS: Renal biopsy samples were obtained 20 min after removal of the vascular clamps in nine patients. There was no evidence of hyperacute rejection in six of the nine patients; the other three patients showed glomerular thrombosis but no other evidence of hyperacute rejection. Two of these three grafts were functioning at 31 months of follow-up. Six episodes of acute rejection occurred in five patients during the first month after transplantation and overall there were 13 rejection episodes in nine patients. At latest follow-up (median 26 months, range 9-42), 12 of 13 patients were alive and seven of 13 grafts were surviving with a median plasma creatinine concentration of 185 mumol/L (range 106-296) in the functioning grafts. No graft was lost as a result of classic hyperacute rejection. INTERPRETATION: Immediate pretransplant IA can prevent hyperacute rejection and provide an opportunity for successful transplantation in highly sensitised patients.

Effect of diabetes and peritonitis on the peritoneal equilibration test.

Peritoneal equilibration tests (PET) were performed on 47 patients (15 diabetics) who had been on CAPD for 1 to 112 months. Among new patients on CAPD (1 to 3 months) with no history of peritonitis, diabetics had higher D/PCr than non-diabetics (P < 0.02). However, after > or = 7 months of CAPD, in patients with < or = 2 episodes of peritonitis, glucose and creatinine transport rates were lower (P < 0.05) in diabetic than non-diabetic patients. Among patients on CAPD for > or = 7 months, creatinine (P < 0.05) and glucose transport (P < 0.01) were higher in patients with a history of > or = 3 episodes of peritonitis than in those with < or = 2 episodes. Drain volumes did not differ between any of the subgroups (all P > 0.05). The observations in patients newly established on CAPD were substantiated in a larger study of 55 non-diabetic and 35 non-insulin dependent diabetic patients. D/D0 glucose correlated with plasma glucose (r = 0.40, P < 0.02) in the diabetic group. Net ultrafiltration was reduced in hyperglycemic (P = 0.022) but not normoglycemic diabetics (non-diabetics 231 +/- 167 ml, hyperglycemic diabetics 127 +/- 177 ml, normoglycemic diabetics 238 +/- 159 ml). Creatinine clearance was higher in normoglycemic (P = 0.02) but not hyperglycemic diabetics (non-diabetics 6.8 +/- 0.9 ml/min, hyperglycemic diabetics 6.9 +/- 0.8 ml/min, normoglycemic diabetics 7.4 +/- 0.7 ml/min). These data show that diabetes and peritonitis incidence should be borne in mind when interpreting results of the PET.(ABSTRACT TRUNCATED AT 250 WORDS)

Sequential potassium binding at the extracellular side of the Na,K-pump.

Ion binding at the extracellular face of the Na,K-ATPase is electrogenic and can be monitored by the styryl dye RH 421 in membrane fragments containing a high density of the Na,K-pumps. The fluorescent probe is noncovalently bound to the membrane and responds to changes of the local electric field generated by binding or release of cations inside the protein. Due to the fact that K+ binding from the extracellular side is an electrogenic reaction, it is possible to detect the amount of ions bound to the pump as function of the aqueous concentration. The results are in contradiction to a second order reaction, i.e., a simultaneous binding of two K+ ions. A mathematical model is presented to discuss the nature of the two step binding process. On the basis of this model the data allow a quantitative distinction between binding of the first and the second K+ ion. The temperature dependence of ion binding has been investigated. At low temperatures the apparent dissociation constants differ significantly. In the temperature range above 20 degrees C the resulting apparent dissociation constants for both K+ ions merge and have values between 0.2 and 0.3 mM, which is consistent with previous experiments. The activation energy for the half saturating concentration of K+ is 22 kJ/mol. Additional analysis of the titration curve of K+ binding to the state P-E2 by the Hill equation yields a Hill coefficient, nHill, of 1.33, which is in agreement with previously published data.

Improved detection of proteolytically cleaved high molecular weight kininogen by immunoblotting using an antiserum against its reduced 47 kDa light chain.

Several ligand blotting or immunoblotting assays for the detection of single-chain and proteolytically cleaved two-chain high molecular weight kininogen (HK) in whole plasma have been described. Since they may suffer from poor sensitivity for the light chain species of cleaved HK on reduced blots, an antiserum against the reduced and alkylated 47 kDa light chain of HK was raised in rabbits allowing improved immunodetection of HK species on blots of reduced electropherograms. This immunoblotting method is highly specific and sensitive, permitting detection of 0.2 ng single-chain HK or the light chains of 2 ng proteolytically cleaved HK in whole plasma. Thus, this immunoblotting technique is at least 50-100 times more sensitive than ligand blotting with radiolabelled factor XI overlay. A similar cleavage pattern was observed following in vitro activation of normal human plasma by dextran sulphate and after plasma kallikrein-induced proteolysis of purified HK. However, bands of different molecular weights were generated after HK had been cleaved by purified leukocyte elastase. During acute attack in a patient with hereditary angioedema, high levels of in vivo cleaved HK were noticed, whereas concentration of cleaved HK in plasma samples and synovial fluids from patients suffering from various inflammatory conditions were not substantially higher than those in normal plasma. During in vitro cold activation of plasma samples of pregnant women concomitant HK cleavage and plasma kallikrein generation were observed.