[Availability of mechanical thrombectomy for acute stroke : Analysis of the health care reality in Germany]. / Verfügbarkeit der mechanischen Thrombektomie bei akutem Hirninfarkt : Analyse der Versorgungsrealität in Deutschland.

BACKGROUND: Mechanical thrombectomy (MT) has become an evidence-based therapy for stroke patients with proximal vessel occlusion of the anterior cerebral circulation. Nationwide availability of MT for all eligible patients within the shortest possible time window is a major challenge. AIM OF THE STUDY: Nationwide analysis of the rates of systemic thrombolysis (STL) and MT in Germany according to region and hospital-based evaluation. METHODS: The evaluation involved data analysis of the diagnosis-related groups (DRG) statistics and structured quality reports of hospitals for 2010 and 2014. The rates and changes of STL and MT were evaluated in the 413 German districts with reference to the corresponding case number of patients with acute ischemic stroke. RESULTS: Nationwide recanalization treatment rates increased from 2010 to 2014 both for STL (from 8.0% to 11.6%) and MT (from 0.7% to 2.3%). High variations were observed depending on the patient's place of residence (STL = 3.4-36.7%, MT = 0-7.4%). In 2014 a total of 5526 MT were coded in a total of 244,757 ischemic strokes. A total of 134 hospitals with more than 2 MT per year were identified; however, 21% of the nationwide MTs were performed in only 7 hospitals with more than 100 MT/year. In 308 (75%) of the 413 districts, not a single MT was performed. CONCLUSION: Due to a narrow net of certified stroke units with nationwide availability of STL, excellent structural conditions for treatment of acute stroke patients are already established in Germany. With regard to the nationwide availability of MT, there is still a need for optimization. Despite the increasing number of hospitals providing MT as an emergency procedure, a trend toward large intervention centers with supraregional catchment areas can be observed.

[Treatment reality of internal carotid artery stenosis in Germany : requirement and reality in international comparison and in light of the current S3 guidelines]. / Versorgungsrealität von Karotisstenosen in Deutschland : Forderung und Wirklichkeit im internationalen Vergleich und im Lichte der aktuellen S3-Leitlinie.

BACKGROUND: Severe atherosclerotic extracranial carotid artery stenosis accounts for 5-10 % of all ischemic strokes. Currently, therapeutic recommendations are undergoing changes, particularly regarding the treatment of asymptomatic stenosis. Consolidated knowledge on the indications, nationwide distribution and numbers of cases are not available. Moreover, the impact and grade of implementation of the recently published national S3 guidelines on the reality of medical treatment remain unclear. METHODS: Analysis of administrative hospital data involving the diagnosis-related groups (DRG) statistics and structured quality reports for 2010 and 2013 to evaluate the procedural therapy trends concerning operative and interventional approaches for symptomatic and asymptomatic carotid artery stenoses. RESULTS: In Germany approximately 37,000 carotid endarterectomies (CEA) and approximately 5,000 carotid angioplasties with stenting (CAS) are carried out per year. Approximately 94 % of CEA and 62 % of CAS are performed in centers with more than 25 procedures per year. Only 33 % of CEA and 39 % of CAS are related to symptomatic stenosis. CONCLUSION: Mathematically, an undertreatment of symptomatic and an overtreatment of asymptomatic carotid artery stenoses become apparent. Efforts should be made to achieve inpatient medical treatment conforming to the national S3 guidelines, in particular to adequately reduce the risk of stroke recurrence in patients with atherosclerotic symptomatic carotid artery stenosis.

[Pseudotumor cerebri: quantitative in-vivo measurements of markers of intracranial hypertension]. / Pseudotumor cerebri: Quantitative Normalwerte anatomischer Kennstrukturen im kraniellen MRT.

PURPOSE: Intracranial hypertension can change the morphology of anatomical structures that are critical in the evaluation of pseudotumor syndromes. The purpose of our study was to establish the normal range of such markers of intracranial hypertension and to consider a dependency on sex, age and body-mass index (BMI). MATERIALS AND METHODS: 123 persons without signs or symptoms of intracranial hypertension (63 females, 60 males, 18- 86-years-old, mean 49.5 SD17.8 years, mean BMI 25.3 SD42) were prospectively enrolled and MRI was performed at 3T. A STIR sequence in the coronal plane was used to measure the width of the optic nerve, the perioptic fluid rim and the total optic nerve sheath diameter in 4 different locations behind the eyeball. The height and width of the pituitary and Meckel's cave were also measured and the area was calculated. RESULTS: The mean width of the optic nerve sheath narrows significantly from anterior (mean 5.3 SD 0.6 mm) to posterior (mean 4.1 SD 0.4 mm), as does the perioptic fluid rim (mean 1.4 SD 0.3 mm vs. mean 1.0 SD 0.2 mm) and--to a lesser extent--the optic nerve itself (mean 2.4 SD 0.4 mm vs. mean 2 SD 0.3 mm, p=0.000 for all). There was no statistically relevant correlation of the width of the optic nerve sheath with age. The coronal area of Meckel's cave was independent of sex, age or BMI (mean 39 SD 9.3 mm2). The height of the pituitary differed little in women (mean 4.4 SD 0.9 mm) and men (mean 4.2 SD 0.8 mm), but we found a significant negative correlation with age in women only (r = -0.38, p = 0.01). CONCLUSION: The presented typical values and their deviations serve as a basis for the evaluation of pathologies in patients suspected of having pseudotumor syndrome.

[Off-label use in dermatological practice. The conflict between professional duty and legal requirements]. / Off-Label-Use in der Dermatologie. Im Dilemma zwischen ärztlicher Verpflichtung und rechtlichen Voraussetzungen.

When making therapeutic decisions, doctors often find themselves faced with a dilemma regarding ethical, professional, legal liability, social and service aspects of their duties. These conflicts may be enhanced when medications have to be prescribed for non-approved usages, known as off-label prescribing, because existing therapy options have been exhausted. This option become considerably more difficult since the German Federal Social Court decision of March 2002 which limited off-label use to a number of very strictly defined circumstances. In order to clarify the basis for taking decisions in a given situation, an oncology expert commission has been formed under the coordination of the Department of Health and Social Security. However, this is no solution for the great variety of uncommon dermatological diseases which often require off-label medication usage.

[HIV/AIDS competence network research group presents first results]. / Kompetenznetz HIV/AIDS Forschungsverbund präsentiert erste Ergebnisse.

Germany's clinical HIV research efforts are underrepresented on an international level. This deficit is primarily due to a lack of clinical studies involving patients from across the country and the fact that no national patient cohort system exists in Germany which could provide a basis for such clinical studies. The competence network HIV/AIDS is filling this shortcoming by serving as a comprehensive, nationwide research alliance. The establishment of a patient cohort is linked to 20 projects. The success of this new structure is becoming visible.

[HIV/AIDS Competence Network. An example for research networking in Germany]. / Kompetenznetz HIV/AIDS. Ein Beispiel für vernetzte Forschung in Deutschland.

Thanks to a nationwide network of specialized, clinic-associated outpatient facilities and competent registered physicians, the quality of care for HIV-infected patients in Germany is high. Although basic HIV research is also well advanced in several centers, in contrast Germany's clinical HIV research is barely discemable on an international level. This deficit is primarily due to a lack of clinical studies involving patients from across the country and the fact that no national patient cohort system exists which could provide a basis for such clinical studies. The competence network HIV/AIDS aims to overcome this shortcoming by serving as a comprehensive, nationwide research alliance. The established patient cohort is linked to 13 projects. The infrastructure required for communications and data exchange will be based on a telematics platform. There will also be various service facilities established within the network, creating an organizational structure to promote the horizontal exchange of information between centers, as well as establish the vertical exchange of knowledge between physicians, patients, public health policy makers, and the general public.

[Screening and therapy of anal intraepithelial neoplasia (AIN) and anal carcinoma in patients with HIV-infection]. / Screening und Therapie der analen intraepithelialen Neoplasie (AIN) und des Analkarzinoms bei HIV-Infektion.

Anal intraepithelial neoplasia (AIN) is a potential precursor of invasive anal carcinoma. Introduction of highly active antiretroviral therapy (HAART) in the treatment of HIV infection substantially reduced the incidence of some diseases associated with opportunistic viral infections. However, the incidence of AIN is reported to increase and HAART seems to have only little impact on the regression or progression of AIN. Paradoxically, improvement of survival in the HAART era results in an increased risk of anal cancer. The incidence of anal carcinoma amongst homosexual men is substantially higher compared to the normal population (35/100.000). This incidence is similar to the incidence of cervical cancer before screening for CIN with cervical cytology. Recent data suggest that the incidence of AIN and anal cancer is even higher among HIV-infected individuals. Both cancer entities share biologic similarities, including the association with human papillomavirus infection (HPV). Screening for CIN with cervical cytology and early treatment has resulted in a significant decline in the incidence of cervical carcinoma. Like cervical cancer, anal carcinoma may be preventable through identification and treatment of its precursors. Future efforts should focus on a screening protocol, training of clinicians in the diagnosis and treatment of AIN and anal carcinoma, and novel approaches to treatment of these lesions. This screening protocol could help to reduce anal cancer in HIV-infection as well as save limited resources in health care system.

Prevalence of endocrine dysfunction in HIV-infected men.

OBJECTIVE: Endocrine dysfunction is a common problem in patients with human immunodeficiency virus infection (HIV). We therefore evaluated the endocrine function in 31 male homosexual HIV-1-infected men: mean age 37 +/- 7.2 years (range 24-52). METHODS AND MATERIALS: Blood was obtained for baseline T3, T4, TSH, LH, FSH, prolactin, testosterone, ACTH and cortisol values. Endocrine function tests were performed as TRH, CRH, ACTH, LH-RH and HCG tests. RESULTS: Thyroid function: There was a temporarily increased TSH in 3 of 17 patients but normal levels for T3, T4 and fT4 (without thyroid antibodies). One patient showed signs of latent hyperthyroidism (no response in TRH test). Adrenocortical function: Two patients had adrenal insufficiency. They showed a normal baseline cortisol level, an elevated ACTH level and no increase in cortisol levels after stimulation with CRH. All other patients revealed normal responses on the CRH/ACTH tests. Gonadal function: 9 patients had elevated FSH levels (tubular insufficiency), 4 patients additionally had increased LH levels (hypergonadotropic hypogonadism). 5 patients showed signs of tertiary hypogonadism (low LH and testosterone, increase of LH after stimulation with LH-RH). CONCLUSION: In disorders of thyroid and adrenocortical function of primary or tertiary origin, a substitution of hormones should be taken into consideration.

Influence of foscarnet on HIV-associated Kaposi's sarcoma derived cell lines.

Recent reports showed a positive therapeutic effect of foscarnet on Kaposi's sarcoma (KS) in HIV-positive patients. We investigated the therapeutic effect of foscarnet on KS-derived cell lines. Three KS spindle cell cultures of HIV-positive patients as well three fibroblast cell cultures of HIV-positive as HIV-negative patients were established. The influence of different foscarnet concentrations (50, 100, 200, 400, 600, 1000 microg/ml) on these cell lines were analysed. There was no significant change in fibroblast cell numbers suggesting that there is neither a proliferative nor an antiproliferative effect of foscarnet on these cell lines. Furthermore, incubation of the three KS-derived cell lines of HIV-positive patients with different foscarnet concentrations did not change KS-cell number significantly.

Effect of fusidic acid on the hepatic cytochrome P450 enzyme system.

OBJECTIVE: To investigate the effects of fusidic acid therapy on the hepatic cytochrome P450 (CYP450) enzyme system. METHODS: Thirty HIV-seropositive L-methadone-substituted i.v. drug abusers (stage CDC/WHO B2 - 3 with CD4+-counts ranging from 65 to 293/microl) were randomized into 3 groups (A - C). Ten patients were treated with fusidic acid 500 mg/day over a period of 14 (group A) or 28 days (group B), respectively. Patients in group C served as a control group and did not receive any medication apart from L-methadone. In order to investigate the hepatic monooxygenase system, pharmacokinetics were determined in all patients before initiation and 14 and 28 days after starting therapy with fusidic acid. The concentration of antipyrine and its 3 main metabolites (norantipyrine (NORA), 4-hydroxyantipyrine (OHA), 3-hydroxymethylantipyrine (HMA)) in plasma and urine were measured by high-performance liquid chromatography (HPLC). RESULTS: No effects on antipyrine pharmacokinetics and pharmacokinetics of antipyrine metabolites were found in group A after 14 days of fusidic acid intake and in the control group without therapy. However, in contrast an activation of the CYP450 enzyme system was observed in group B after 28 days of fusidic acid therapy with an increase of total antipyrine clearance (43.0 +/- 7.62 ml/min to 51.0 +/- 9.03 ml/min) as well as clearances to all metabolites (NORA 7.11 +/- 1.75 to 8.60 +/-2.10 ml/min, OHA 11.5 +/- 2.89 to 14.0 +/- 3.97 ml/min, HMA 4.05 +/- 0.99 to 4.94 +/- 1.27 ml/min). Antipyrine half-life was significantly reduced (12.3 +/- 2.8 h to 9.4 +/- 2.2 h) and some patients developed clinical signs of L-methadone underdosage. CONCLUSIONS: Our results suggest that fusidic acid has a time-dependent activating effect on the CYP450 enzyme system. Especially in treatment of patients who are frequently under multidrug regimens such as HIV-positive patients drug interactions should be taken into consideration.

Thymic selection of H-2-incompatible bone marrow cells in SCID mice. Differences in T help for induction of B cell IgG responses versus cytotoxic T cells.

Mice with congenital severe combined immunodeficiency disease (SCID) failed to mount either a T cell-independent IgM or T cell-dependent IgG anti-vesicular stomatitis virus (VSV) Indiana (IND) response. They did not generate cytotoxic T cells against lymphocytic choriomeningitis virus (LCMV) or vaccinia virus, but exhibited NK cell-like activities. When SCID mice were given bone marrow from syngeneic BALB/c (H-2d) nu/nu mice, all immune responses were expressed at control levels. If SCID mice were reconstituted with allogeneic H-2b C57BL/6 nu/nu bone marrow, the following primary anti-viral immune responses were measured. T-independent IgM anti-VSV-IND were normal, but T-dependent IgG anti-VSV-IND responses were absent. Cytotoxic T cell responses to LCMV and vaccinia virus were within normal ranges, were donor cell mediated, and were specific exclusively for the recipient SCID H-2d type. Since antigen presentation by spleen cells was functional in these chimaeras, the presented results indicate that (a) thymic selection of T cell restriction is strict; and (b) the type of T help necessary for B cells depends upon H-2-restricted contact between T and B cells, whereas, such contact-dependent help is not mandatory for the induction of virus-specific cytotoxic T cells.

[Problems of standardization in electrically induced experimental thrombosis]. / Standardisierungsprobleme bei experimentellen elektrisch induzierten Thrombosen.

Electrically induced experimental thrombosis was investigated to the possibility of their standardization and reproduction and with respect with it for their qualification as model thrombosis. The lesions of the vessel wall by the electric field were recorded quantitatively by passive electrical behaviour of the arterial wall.

[Thrombocyte changes in electrically induced experimental thrombosis]. / Thrombozytenveränderungen bei experimentellen elektrisch induzierten Thrombosen.

The influence of the function of the thrombocytes after electrical thrombosis induction by means of anodic direct current was investigated in 39 mongrel dogs. The platelet factor 3, the rotation thromboelastography, and the collagen induced thrombocytes aggregation in the optical test by Born was examined. The platelet factor 3 adhering on the thrombocytes decreased from 95% to 49% in the course of the thrombosis induction. Its activity was provable by means of the rotation thrombelastogram in the plasma. Besides of it the electrical field caused an activation of the thrombocytes which corresponds to a contact activation on foreign body surfaces. The collagen induced aggregation ability of the thrombocytes remains unaffected after the passage of the electrical field.

[Significance of blood flow in electrically induced thrombosis]. / Zur Bedeutung des Blutflusses bei der elektrischen Thrombusinduktion.

The thrombosis in dependence on the stream velocity in the electrically induced thrombosis was investigated by blood flow measurements in the femoral artery in 16 mongrel dogs. Thromboses were shown histologically in all 16 animals. 8 of them did not obturate. Obturating thromboses were produced with the application of anodic direct current of 1 mA during 60 minutes only with a blood stream velocity between 0.0465 and 0.0928 m/s. Not any obturating thrombosis was visible outside of this range.

[Vascular injuries caused by electric direct current in experimental thrombosis models]. / Die Gefässwandschädigung durch elektrischen Gleichstrom bei experimentellen Modellthrombosen.

The eventual causes of the lesion of the vascular wall through electric direct current (D. C.) in experimental artificial thrombosis are discussed by means of microscopic investigations by electron microscope and light microscope in altogether 73 mongrel dogs and 14 mini pigs. No thermic lesions of the vascular wall were observed in the coronary thrombosis pattern on the closed thorax by means of 1 mA amperage and an induction time of 60 minutes. Secondary processes for cell lesions are to be made responsible in which the electrolysis on the cell membrane and the influence of functional ranges in the artery wall play an important part.

[Light and electron microscopy studies on experimental arterial thrombosis in dwarf swine]. / Licht- und elektronenmikroskopische Untersuchungen zur experimentellen arteriellen Thrombose am Zwergschwein.

In light and electron microscopic investigations on electrically induced thrombosis in the femoral artery of the minipig thrombi by deposition of platelets were found. Thrombosis was induced by means of an intravascular electrode with constant current intensity of 1 mA and different induction periods. Injury of the vascular wall was found in every case of thrombosis, ranging from minimal lesion of endothelium to almost total necrosis of the vascular wall. Aside from direct impact by the current on the vascular wall and the blood, mechanical, rheological and hypoxemic causes can not be excluded.

[Methods of induction of a coronary thrombosis by means of direct current in the closed dog and dwarf swine thorax]. / Zur Methodik der Induktion einer Koronarthrombose mittels elektrischem Gleichstrom am geschlossenen Thorax beim Hund und Zwergschwein.

Coronary thrombosis is a perilous disease. Animal experiments may contribute to investigate its pathogenesis and treatment. The development of an experimental model of coronary thrombosis on closed thorax is important. In this report the methodics of such model is entered into, pointing at its dangers and possible complications.