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Insa Feinkohl,1,* Gunnar Lachmann,2,* Wolf-Rüdiger Brockhaus,2 Friedrich Borchers,2 Sophie K Piper,3 Thomas H Ottens,4 Hendrik M Nathoe,5 Anne-Mette Sauer,4 Jan M Dieleman,4 Finn M Radtke,6 Diederik van Dijk,7 Tobias Pischon,1,8,9,* Claudia Spies2,* 1Molecular Epidemiology Research Group, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin-Buch, Germany; 2Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 3Institute of Biometry and Clinical Epidemiology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 4Department of Anesthesiology, University Medical Center Utrecht, Utrecht, the Netherlands; 5Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands; 6Department of Anesthesiology, Naestved Hospital, Naestved, Denmark; 7Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, the Netherlands; 8Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 9MDC/BIH Biobank, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), and Berlin Institute of Health (BIH), Berlin, Germany *These authors contributed equally to this work Background: Age-related cognitive impairment is rising in prevalence but is not yet fully characterized in terms of its epidemiology. Here, we aimed to elucidate the role of obesity, diabetes and hypertension as candidate risk factors. Methods: Original baseline data from 3 studies (OCTOPUS, DECS, SuDoCo) were obtained for secondary analysis of cross-sectional associations of diabetes, hypertension, blood pressure, obesity (body mass index [BMI] ≥30 kg/m²) and BMI with presence of cognitive impairment in log-binomial regression analyses. Cognitive impairment was defined as scoring more than 2 standard deviations below controls on at least one of 5–11 cognitive tests. Underweight participants (BMI

Severely deficient activity of the von Willebrand Factor (VWF) cleaving metalloprotease, ADAMTS13, is associated with thrombotic thrombocytopenic purpura (TTP). The mutation spectrum ofADAMTS13 is rather heterogeneous, and numerous mutations spread across the gene have been described in association with congenital TTP. The 4143insA mutation is unusual with respect to its geographic concentration. Following the initial report from Germany in which the 4143insA mutation was detected in four apparently unrelated families, we have now identified this mutation in a further eleven patients from Norway, Sweden, Poland, Germany, the Czech Republic and Australia. Confirmation that the Australian patient is of German ancestry, together with the Northern and Central European origin of most of the other patients, suggests that the 4143insA mutation has a common genetic background. We established ADAMTS13 haplotypes by analyzing 17 polymorphic intragenic markers. The haplotypes linked to 4143insA were identical in all informative families. Three novel candidate mutations, C347S, P671L and R1060W, as well as the known mutation R507Q, were also identified during the course of the study. We conclude that 4143insA has a common genetic background and is frequent among patients with hereditary ADAMTS13 deficiency in Northern and Central European countries.

Patients and Methods: Of all patients who died of HIV infection within 10 years (1. 1. 1988 to 31. 12. 1997) at the Klinikum Nürnberg 58 autopsy cases were reviewed at the Institute of Pathology of the above mentioned hospital., Results: The male:female ratio was 2.1:1, the mean age being 40.5 years. Most of the patients showed an advanced stage of lymphadenopathy at the moment of death. Non-Hodgkin's lymphoma and Kaposi's sarcoma, both HIV-related malignant diseases, were diagnosed in 6/58 cases, 10.3% each. HIV-related myelodysplastic changes existed in 28/58 patients (48.3%). Twelve patients showed an HIV-associated encephalopathy (20.7%). Opportunistic infections (pneumocystis carinii, cytomegaly, toxoplasmosis, atypical mycobacteriosis) were found in 28/58 patients (48.3%). A mycosis was diagnosed in 9/58 cases (15.5%). Tuberculosis was identified in 4/58 patients (6.9%). Cirrhosis of the liver was ascertained in 8/58 patients (13.8%). 24/58 patients (41.4%) died of respiratory disorder., Conclusion: In the acquired immunodeficiency syndrome numerous morphological findings will be helpful in diagnosis and therapy.

Our aim was to establish the frequency and the longitudinal pattern of MAC culture positivity in late stage HIV-infected patients. Two other aims were to analyse risk factors for progression from localized to systemic disease and the value of PCR diagnosis using blood specimens. A total of 107 patients were recruited to be followed for 32 weeks. Prior MAC treatment and CD4 > 100/microliters were exclusion criteria. A total of 56 patients showed M. avium in at least 1 culture. 10/37 patients with MAC detected by culture first in 'non-sterile' specimens (stool, sputum) and urine progressed to systemic disease as determined by positive blood culture. Risk factors associated with this progression were a high symptom score at baseline, lymphadenopathy, anaemia, and low platelets. PCR was less sensitive than culture in detection of M. avium in blood specimens: Only 7/29 patients with positive blood cultures had a positive PCR at the same time. We conclude that symptomatic patients with advanced HIV-infection have a high frequency of MAC detection. Progression from localized to systemic culture positivity is associated with risk factors. Early 'pre-emptive' therapy is discussed.

In a randomized open controlled study the clinical effects and tolerability of prostaglandin E1 (PGE1) and the stable prostacyclin (PGI2) analogue, iloprost in the management of diabetic and non-diabetic patients with advanced peripheral arterial occlusive disease (PAOD Fontaine stage IV) were compared. 267 patients were enrolled in this multicentre study and treated for 21-28 days, either by daily infusions of 6 h with iloprost or 2 x 2 h with PGE1. At the end of treatment patients were assessed for evidence of improvement of trophic lesions, relief of rest pain and change of global clinical status. 228 patients were considered as evaluable for efficacy analysis, which revealed 52.7% responders in the iloprost group and 43.1% for PGE1 (p = 0.148). Whereas iloprost showed similar effects in diabetics and non-diabetics (53.3% and 51.4% response rates, respectively), the diabetics treated with PGE1 had a considerably poorer outcome (36.6% versus 53.3%). At 6 months follow-up 62.2% of patients in both groups were alive with a viable limb. Slightly more iloprost patients underwent major amputation (32.1% versus 27.2%), but the number of deaths was reduced by 50% in the iloprost group compared to the PGE1 group (7.5% versus 14.6%, p = 0.10). Side-effects such as headache, flushing and gastrointestinal symptoms were significantly more common in the iloprost group (73.9%) than in the PGE1 group (31.0%), particularly during the first 3 days of dose titration. No specific toxic or unexpected reactions were reported in either group.