First negative ion beam measurement by the Short-Time Retractable Instrumented Kalorimeter Experiment (STRIKE).

The Source for Production of Ion of Deuterium Extracted from Rf plasma (SPIDER) test facility is under construction in Padova to optimise the operation of the beam source of ITER neutral beam injectors. The SPIDER beam will be characterised by the instrumented calorimeter STRIKE, whose main components are one-directional carbon-fibre-carbon-composite tiles. A small-scale version of the entire system has been employed in the BAvarian Test MAchine for Negative ions (BATMAN) testbed by arranging two prototype tiles in the vertical direction. The paper presents a description of the mini-STRIKE system and of the data analysis procedures, as well as some results concerning the BATMAN beam under varying operating conditions.

3D numerical simulations of negative hydrogen ion extraction using realistic plasma parameters, geometry of the extraction aperture and full 3D magnetic field map.

Decreasing the co-extracted electron current while simultaneously keeping negative ion (NI) current sufficiently high is a crucial issue on the development plasma source system for ITER Neutral Beam Injector. To support finding the best extraction conditions the 3D Particle-in-Cell Monte Carlo Collision electrostatic code ONIX (Orsay Negative Ion eXtraction) has been developed. Close collaboration with experiments and other numerical models allows performing realistic simulations with relevant input parameters: plasma properties, geometry of the extraction aperture, full 3D magnetic field map, etc. For the first time ONIX has been benchmarked with commercial positive ions tracing code KOBRA3D. A very good agreement in terms of the meniscus position and depth has been found. Simulation of NI extraction with different e/NI ratio in bulk plasma shows high relevance of the direct negative ion extraction from the surface produced NI in order to obtain extracted NI current as in the experimental results from BATMAN testbed.

Treatment of severe, nonfulminant acute hepatitis B with lamivudine vs placebo: a prospective randomized double-blinded multicentre trial.

Acute hepatitis B virus (aHBV) infection can lead to fulminant liver failure, which likely is prevented by early lamivudine therapy. Even nonfulminant but severe acute hepatitis B can lead to significant morbidity and impaired quality of life. Therefore, lamivudine was evaluated in patients with severe aHBV in a placebo-controlled trial. Patients with severe aHBV infection (ALT >10× ULN, bilirubin >85 µm, prothrombin time >50%) were prospectively treated with lamivudine 100 mg/day or with placebo within 8 days after the diagnosis. The primary end point was time to bilirubin <34.2 µm. Secondary end points were time to clear HBsAg and HBV-DNA, development of anti-HBs and normalization of ALT. Eighteen cases were randomized to lamivudine, 17 to placebo. 94% of patients were hospitalized. No individual progressed to hepatic failure; all but one patient achieved the primary end point. Due to smaller than expected patient numbers, all study end points did not become statistically significant between treatment arms. Median time end points [in days] were bilirubin <34.2 µm (26.5 vs 32), ALT normalization (35 vs 48) and HBsAg clearance (48 vs 67) referring to earlier recovery under lamivudine, in contrast to loss of HBV-DNA (62 vs 54) and development of anti-HBs (119 vs 109). In all but two patients (one in every group), HBsAg clearance was reached in the study. Adverse events occurred more frequently during lamivudine therapy, but did not reach statistical significance. Lamivudine may ameliorate severe aHBV infection, but limited patient numbers prevented definite conclusions.

[Musculoskeletal infections in the era of multiresistant pathogens]. / Muskuloskelettale Infektionen im Zeitalter multiresistenter Erreger.

The burden of musculoskeletal infections is permanently growing. A probable explanation for this development could be the increasing number of elderly people undergoing extensive surgery using implants and prosthetic devices while having more significant comorbidities (e.g. cardiovascular, metabolic and malignant). However, a relative reduction of acute (hematogenous) osteomyelitis compared to the occurrence of much more complex situations, such as diabetic foot syndrome or chronic osteitis and prosthetic implant infections is being observed. This poses new challenges for the clinician in managing these patients. Furthermore, there is the evolving threat of antimicrobial resistance as well as the increasing amount of infections with Gram-negative pathogens. Several aspects have to be considered for successful management of musculoskeletal infections: the site of infection and feasibility of local surgical treatment, the effectiveness of antimicrobial treatment, the inclusion of comorbidities and their specific treatment in an advanced therapeutic concept as well as the interdisciplinary approach led by surgeons and infectious disease specialists.

Abnormal prefrontal activity subserving attentional control of emotion in remitted depressed patients during a working memory task with emotional distracters.

BACKGROUND: Patients with major depressive disorder (MDD) show deficits in processing of facial emotions that persist beyond recovery and cessation of treatment. Abnormalities in neural areas supporting attentional control and emotion processing in remitted depressed (rMDD) patients suggests that there may be enduring, trait-like abnormalities in key neural circuits at the interface of cognition and emotion, but this issue has not been studied systematically. METHOD: Nineteen euthymic, medication-free rMDD patients (mean age 33.6 years; mean duration of illness 34 months) and 20 age- and gender-matched healthy controls (HC; mean age 35.8 years) performed the Emotional Face N-Back (EFNBACK) task, a working memory task with emotional distracter stimuli. We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to measure neural activity in the dorsolateral (DLPFC) and ventrolateral prefrontal cortex (VLPFC), orbitofrontal cortex (OFC), ventral striatum and amygdala, using a region of interest (ROI) approach in SPM2. RESULTS: rMDD patients exhibited significantly greater activity relative to HC in the left DLPFC [Brodmann area (BA) 9/46] in response to negative emotional distracters during high working memory load. By contrast, rMDD patients exhibited significantly lower activity in the right DLPFC and left VLPFC compared to HC in response to positive emotional distracters during high working memory load. These effects occurred during accurate task performance. CONCLUSIONS: Remitted depressed patients may continue to exhibit attentional biases toward negative emotional information, reflected by greater recruitment of prefrontal regions implicated in attentional control in the context of negative emotional information.

Lack of evidence for systemic cytomegalovirus reactivation in maintenance hemodialysis patients.

The risk of cytomegalovirus (CMV) reactivation among hemodialysis (HD) patients is unknown. In 52 HD patients from a single center, CMV serology and quantitative PCR were performed. The detection limit of PCR was 20 copies/ml. Here, PCR ruled out CMV viremia, despite CMV-IgM seropositivity in 15.4% patients.

The 5-HT1B receptor: a novel target for the pathophysiology of depression.

The serotonergic (5-HT) system has been widely implicated in the pathophysiology of Major Depressive Disorder (MDD). Although the 5-HT system is a popular target for drug therapy in MDD the role that serotonin plays in MDD is not clearly understood. An abundance of research suggests that several 5-HT receptor subtypes may be dysfunctional in patients with MDD including the 5-HT(1B) receptor. Evidence implicating 5-HT(1B) receptors in the pathophysiology of depression comes from a number of converging lines of research. Two common genetic polymorphisms of 5-HT(1B) receptors, G861C and C129T, have been implicated in affective disorders. Rats predisposed to learned helplessness have exhibited downregulation of 5-HT(1B) receptor messenger ribonucleic acid (mRNA) in dorsal raphe nucleus (DRN). Pharmacological studies have demonstrated augmentation of extracellular 5-HT levels and antidepressant effects following administration of selective serotonin reuptake inhibitors (SSRIs) in the absence or blockade of 5-HT(1B) receptors. 5-HT(1B) receptor agonists administered alone or with antidepressants have been shown to be effective in preclinical models of depression. Recent interest has focused on p11, an s100 EF-hand protein family protein which colocalizes with 5-HT(1B) receptors. P11 plays a central role in the modulation of 5-HT(1B) receptor function and is dysregulated in preclinical models of depression and postmortem MDD samples. A review of the literature provides strong evidence that 5-HT(1B) receptors and related factors such as p11 are involved in the pathophysiology of depression. The following explores possible factors which may render the 5-HT(1B) receptor dysfunctional, resulting in susceptibility to depression. Implications of using the 5-HT(1B) receptor as a biomarker for vulnerability to MDD are discussed.

Reducing the burden of influenza-associated complications with antiviral therapy.

INTRODUCTION: Influenza imposes an annual burden on individuals, society, and healthcare systems. This burden is increased by the development of complications that are often more severe than the primary infection. Here, we examine the main complications associated with influenza and review the effectiveness of antiviral therapy in reducing the incidence of such events. MATERIAL AND METHODS: The content of this review is taken from the study of the authors' extensive collection of reference materials, examination of the bibliographical content of relevant papers, and the results of Medline searches. RESULTS: The most commonly encountered complications in adults are sinusitis, pharyngitis, bronchitis, and, particularly in the elderly, bacterial pneumonia. Such complications may exacerbate pulmonary complaints. Children are particularly prone to post-influenza croup and otitis media. Complications involving the central nervous system, heart, or skeletal muscle also occur in influenza patients. Influenza-associated complications impose sizeable healthcare costs in terms of outpatient contacts, hospitalizations, and antibiotic use. Vaccination is the primary prevention strategy for influenza and its complications, but has limitations. Neuraminidase inhibitors have demonstrated efficacy in reducing the incidence of influenza-associated complications in populations with different ages and risks. CONCLUSIONS: Influenza complications place a large burden on healthcare providers and society. Neuraminidase inhibitors can reduce the incidence of such complications, particularly in high-risk groups.

[Polyuria]. / Polyurie--Pathogenese, Diagnostik und Therapie.

Beyond polyuria following psychogenic polydipsia, in a more narrow sense, this condition may be classified into impaired water re-absorption (i) due to tubular injury or (ii) relative or absolute loss of function of antidiuretic hormone (ADH). Tubular injury may be caused by different toxins affecting the ascending Henle loop as hypercalciuria, drugs and antibiotics as tubular necrosis. ADH deficiency, either absolute or relative, occurs with central or peripheral diabetes insipidus, which is based on synthesis failure or loss of peripheral efficacy of ADH due to receptor malfunction. Diagnosis of polyuria rests upon a thirst challenge in conjunction with laboratory studies of osmolality in serum and urine, which discloses the non-function of the hypothalamic-renal axis. Administration of ADH may differentiate between central and peripheral diabetes insipidus.

Antiviral treatment and prophylaxis of influenza in primary care: German recommendations.

Antiviral drugs are a valuable supplementation to vaccines for the control and prevention of influenza. In Germany, for treating influenza amantadine, oseltamivir and zanamivir are approved. Amantadine and oseltamivir are also licensed for prophylactic use. On behalf of the Paul-Ehrlich-Society of Germany and the German Association for the Control of Virus Diseases, as two independent scientific societies, the first consensus Conference on the Antiviral Treatment and Prophylaxis of Influenza was held in June 2002. Based on the available data of clinical studies an expert group developed the following recommendations for the appropriate clinical use of the antiviral drugs: (1) since oseltamivir (orally administered) and zanamivir (administered by inhalation) have apparently similar clinical efficacy both drugs can be used alternatively for treatment. (2) Amantadine is not an alternative to the neuraminidase (NA) inhibitors because it is not effective against influenza B viruses, it frequently selects resistant virus mutants and it can cause adverse events. (3) When influenza is prevalent in the community patients with the clinical diagnosis of influenza should be treated with neuraminidase inhibitors if the symptoms are lasting not longer than 48 h. (4) Immunocompetent patients with a non-febrile illness and patients with a symptom history of more than 2 days should not be treated with antiviral drugs. (5) Although there are no data from clinical trials immunocompromised patients should also be treated when influenza has been diagnosed. (6) The prophylactic use of antiviral drugs can be recommended for persons with close contact to acutely ill persons and no recent vaccination against influenza. (7) The use of anti-influenza drugs have to be considered for prophylaxis in pandemics. A precondition for the adequate use of anti-influenza drugs in the primary medical care is the timely information on the local influenza situation delivered by surveillance systems.

Open, randomized study to compare the immunogenicity and reactogenicity of an influenza split vaccine with an MF59-adjuvanted subunit vaccine and a virosome-based subunit vaccine in elderly.

BACKGROUND: An open, randomized, multicenter study was carried out in elderly to compare the immunogenicity and reactogenicity of a conventional influenza split vaccine (SpV) with an MF59-adjuvanted subunit vaccine (aSuV) and a virosome-based subunit vaccine (vSuV) since earlier studies reported better immunogenicity for adjuvanted and virosome-based vaccines. PATIENTS AND METHODS: A total of 840 subjects, aged 60 years or more, who had not been vaccinated or diagnosed with influenza in the preceding season were investigated. Hemagglutination-inhibition antibody titers were measured, and signs and symptoms recorded. RESULTS: The three vaccines exceeded EU efficacy requirements for subjects aged older than 60 years and seroprotective levels (titers > 1:40) were equally maintained with the three vaccines during 8 months post vaccination. SpV was as immunogenic as aSuV for the A/H3N2 strain (p < 0.0001) and significantly more immunogenic than aSuV for A/H1N1 strain (p = 0.0006). SpV was as immunogenic as vSuV for all three strains and significantly more immunogenic than vSuV for the A/H1N1 strain (p < 0.0001). In terms of reactogenicity, aSuV showed a higher rate of solicited local signs and symptoms than SpV (p = 0.021) and vSuV (p = 0.046), respectively. Incidence of solicited general symptoms was comparable on all treatments. No serious adverse event related to vaccination was reported. CONCLUSION: These findings suggest that all three vaccines are highly immunogenic with an acceptable reactogenicity profile and that they are appropriate for use in elderly.

[Toxic hepatitis and liver failure under therapy with flutamide]. / Ikterus und schwere Leberfunktionsstörung bei der hormonablativen Behandlung des Prostatakarzinoms.

Flutamide is an antiandrogen and frequently used for the treatment of prostatic cancer. Severe hepatotoxicity occurs in few patients but may be fatal. We report on two patients with prostatic cancer who received a therapy with flutamide. They showed different degrees of liver damage. One patient recovered completely after withdrawal of Flutamide under medication with steroids. Clinical symptoms and laboratory findings returned to normal within four weeks. Despite immediate withdrawal of Flutamide, the other patient showed a severe course with progressive liver dysfunction and hepatorenal syndrome. He finally died under the clinical picture of fulminant hepatic coma. This case represents the first death associated with flutamide in Germany. The literature concerning the metabolism of flutamide and the published cases of hepatotoxicity of this drug are reviewed.

[Sporadic acute hepatitis E in Germany: an underdiagnosed phenomenon?]. / Sporadische akute Hepatitis E in Deutschland: eine zu selten erkannte Erkrankung?

Hepatitis E virus infection is the leading cause of enterically transmitted hepatitis worldwide. Case reports of hepatitis E in individuals in Germany so far related to travel to endemic areas. A 33-year-old man presented with painless jaundice. By serology and liver biopsy, no cause of hepatitis could be identified. After discharge transaminases were persistently elevated. Serology (IgG and IgM) confirmed acute hepatitis E. The transaminases declined to normal values within six months. Detailed anamnestic questioning revealed no travel to an endemic region or contact with individuals who had visited such areas. In addition to our patient, a total of 34 cases of acute hepatitis E were reported to the Robert-Koch-Institute (German center of disease control) in 2001. In five of them, the disease had obviously been acquired in Germany. These data indicate that community acquired hepatitis E virus infection may occur sporadically in Germany and should be considered as a cause of seronegative (non-A-non-B-non-C) hepatitis.

[Colonisation of the airways with ureaplasma urealyticum as a risk factor for bronchopulmonary dysplasia in VLBW infants?]. / Chronische Atemstörung sehr kleiner Frühgeborener: Besiedlung mit Ureaplasma urealyticum als ätiologischer Faktor?

BACKGROUND: Chronic inflammatory processes contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). We hypothesized colonisation with Ureaplasma urealyticum (Uu) as a possible reason for an increased risk of developing prolonged oxygen dependency > 28 days in very low birth weight (VLBW) infants. PATIENTS AND METHODS: From January 1998 to November 1999 pharyngeal swabs were prospectively obtained and tested for Uu at birth and then weekly in VLBW infants. The following variables were compared between Uu-positive and Uu-negative infants: prenatal corticosteroids, maternal infections, mode of delivery, gestational age, birth weight, gender distribution, RDS, surfactant therapy, maximum inspiratory oxygen concentration during the first 24 and 48 hours, duration of oxygen supplementation beyond day 28, PDA, and weight differences during the first week of life. RESULTS: Of a total of 74 infants, 17 were found to be Uu-positive. The latter group showed a lower mean gestational age (29; 25 - 37 vs. 28; 24 - 34 WOG; p = 0.02) and a longer duration of oxygen supplementation after day 28 (0; 0 - 121 vs. 5; 0 - 134 d; p = 0.02). All other variables did not differ significantly between both groups. Multivariate analyses identified the variables birth weight and colonisation with Uu as risk factors for a longer period of oxygen dependency after day 28 (p < 0.01; p = 0.05). CONCLUSION: These data indicate a correlation between the colonisation with Uu and prolonged oxygen dependency > 28 days.

Effectiveness of twice-weekly pyrimethamine-sulfadoxine as primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis in patients with advanced HIV infection.

The safety and efficacy of a fixed 25 mg pyrimethamine-500 mg sulfadoxine combination supplemented with 15 mg folinic acid twice a week as primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis was evaluated in 106 patients infected with the human immunodeficiency virus. All patients had a CD4+ T-lymphocyte count of less than 100 cells/microl at study entry. Efficacy in this single-arm open-label prospective study was analyzed on an as-treated basis. No patient received highly active antiretroviral treatment, including protease inhibitors or non-nucleoside reverse transcriptase inhibitors, while on study medication. PCP developed in four patients, one of whom had been noncompliant. No PCP episode occurred in the first year. Probabilities of freedom from PCP were 0.97 (95%CI, 0.92-1) after 24 months and 0.93 (95%CI, 0.84-1) after 36 months. Of 74 (69.8%) patients positive for anti-toxoplasma IgG antibodies, one noncompliant patient developed toxoplasmic encephalitis after 24 months. Allergic reactions were observed in 18 (17%) patients and resulted in permanent discontinuation in 7 (6.6%) patients. One (0.9%) patient who had continued prophylaxis despite progressive hypersensitivity reactions developed a serious adverse reaction (Stevens-Johnson syndrome). The median survival of study participants was 29 months, with relentless progression of AIDS accounting for most deaths. The prophylaxis regimen studied appeared safe and effective for primary prophylaxis of PCP and toxoplasmic encephalitis. Severe adverse events can likely be prevented by discontinuation of prophylaxis at the time allergic reactions are noted. Rechallenge frequently results in tolerance. Efficacy and safety compare favorably with previously studied regimens. This simple prophylactic regimen may provide a convenient alternative for patients failing or intolerant to approved regimens.