Biomedical subjects

Otto Busse

Publications and source records attributed to Otto Busse.

12 recordsLinked to original sources

PubMed2006

Familial cervical artery dissections: clinical, morphologic, and genetic studies.

BACKGROUND AND PURPOSE: Genetic risk factors are thought to play a role in the etiology of spontaneous cervical artery dissections (CAD). However, familial CAD is extremely rare. In this study we analyzed patients with familial CAD and asked the question whether familial CAD has particular features. METHODS: Seven families with 15 CAD patients were recruited. All patients were carefully investigated by a neurologist, a neuroradiologist, and a dermatologist for clinical characteristics. From 11 patients a skin biopsy was performed to study the morphology of the connective tissue and to analyze the coding sequences of COL3A1, COL5A1, COL5A2, and part of COL1A1. RESULTS: The mean age of the patients (n=15, 9 women) at their first dissection was 36.2 years (median age 32 years, range 18 to 59). Two patients had bilateral CAD. One patient had a right and a left internal carotid artery dissection in successive weeks, another patient had 5 dissections over a period of 8 years. A high intrafamilial correlation was found between the affected vessels (ie, the carotid and the vertebral arteries) and between ages at the first dissection. In 1 patient we found clear and reproducible ultrastructural abnormalities in the skin biopsy, but the second patient from the family was not studied, because he died as a result of CAD before this study. The dermal connective tissue aberrations in the examined patient were similar to mild findings in patients with vascular Ehlers-Danlos syndrome (EDS type IV), but might be iatrogenic and related to long-term corticosteroid inhalation therapy. All other analyzed patients showed normal connective tissue morphology. In patients from 6 families we analyzed the whole coding sequence of COL3A1, COL5A1, and COL5A2, and from part of COL1A1. A missense mutation in the COL3A1 gene (leading to a G157S substitution in type III procollagen) was detected in both patients from 1e family. Two patients from another family carried a rare nonsynonymous coding polymorphism in COL5A1 (D192N); 1 of them carried also a rare variant in COL5A2 (T12337). CONCLUSIONS: Familial CAD patients are young and probably are at high risk for recurrent or multiple CAD. Ultrastructural alterations of the dermal connective tissue might not be an important risk factor for familial CAD. However, the finding of a COL3A1 mutation revealed the presence of an inherited connective tissue disorder in 1 family.

Adolescent↗

PubMed2006

Development and implementation of evidence-based indicators for measuring quality of acute stroke care: the Quality Indicator Board of the German Stroke Registers Study Group (ADSR).

BACKGROUND AND PURPOSE: There is no consensus about indicators for measuring quality of acute stroke care in Germany. Therefore, a standardized process was initiated recently to develop and implement evidence-based indicators for the measurement of quality of acute hospital stroke care. METHODS: Quality indicators were developed by a multidisciplinary board between November 2003 and December 2005. The process was initiated by the German Stroke Registers Study Group in cooperation with the German Stroke Society, the German Society of Neurology, the German Stroke Foundation, Regional Offices for Quality Assurance and other experts proven in the field. National and international recommendations were considered during the development process. The process was based on a systematic literature review, an independent external evaluation of the process and its results, and a prospective pilot study to evaluate the defined indicators in clinical practice. RESULTS: Overall a set of 24 indicators was developed to measure performance of acute care hospitals in the 3 health care dimensions structure, process and outcome as well as in 3 treatment phases prehospital, in-hospital/acute and postacute. Practicability of the derived indicators was tested in a prospective pilot study. During a 2-month period, 1006 patients in 13 hospitals were documented. Application of the new indicator set was found to be feasible by participating physicians and hospitals. Median time to document the required information for 1 patient was 5 minutes. Nationwide implementation of the new indicator set within regional registers in Germany started since April 2006. CONCLUSIONS: The development of indicators to measure hospital performance in stroke care is an important step toward improving stroke care on a national level. The chosen standardized evidence-based approach ensures maximal transparency, acceptance and sustainability of the developed indicators in Germany.

Acute Disease↗

PubMed2006

Genetic analysis of familial connective tissue alterations associated with cervical artery dissections suggests locus heterogeneity.

BACKGROUND AND PURPOSE: Cervical artery dissections (CAD) can be associated with connective tissue aberrations in skin biopsies. The analysis of healthy relatives of patients suggested that the connective tissue phenotype is familial with an autosomal dominant inheritance. METHODS: We performed genetic linkage studies in 3 families of patients with CAD. Connective tissue phenotypes for the patients and all family members were assessed by electron microscopic study of skin biopsies. A genome-wide linkage analysis of 1 family (1 patient with 8 healthy relatives) indicated 2 candidate loci. Three genes were subsequently studied by sequence analysis. Part of the genome was also studied by linkage analysis in 2 further families. RESULTS: The genome-wide scan in a single family suggested linkage between the hypothetical mutation causing the connective tissue phenotype and informative genetic markers on chromosome 15q24 (logarithm of the odds score: Z= +2.1). A second possible candidate locus (Z=+1.9) was found on chromosome 10q26. Sequence analysis of 3 candidate genes in the suggestive locus (chondroitin sulfate proteoglycan4 [CSPG4], lysyl oxidase-like1 [LOXL1] and fibroblast growth factor receptor2 [FGFR2]) did not lead to the identification of a mutation responsible for connective tissue alterations. In 2 additional smaller families the loci on chromosome 15q24 and 10q26 were excluded by linkage analysis. CONCLUSIONS: Linkage analysis of a large family with CAD-associated connective tissue alterations suggested the presence of a candidate locus on chromosome 15q2 or on chromosome 10q26. Sequence analysis did not lead to the identification of a mutated candidate gene in 1 of these loci. The study of 2 additional pedigrees indicated locus heterogeneity for the connective tissue phenotype of CAD patients.

Adult↗

PubMed2004

Different types of connective tissue alterations associated with cervical artery dissections.

This study describes the technical handling and the diagnostic evaluation of skin biopsies in order to standardize the assessment of the delicate morphologic abnormalities that are found in patients with spontaneous cervical artery dissections (sCAD). Skin biopsies from 126 patients with sCAD and from 29 healthy relatives were analyzed. The morphology of the connective tissue was normal in 54 patients with sCAD (43%) and aberrant in 72 patients with sCAD (57%). These latter patients were classified into three groups: in 43 patients, we repeatedly observed composite collagen fibrils and elastic fibers with fragmentation and minicalcifications. In 13 further patients, the dermis was significantly thinner than in healthy subjects. The collagen fibers contained fibrils with highly variable diameters. In a third group of 16 sCAD patients, the abnormalities were restricted to the elastic fibers (with fragmentation and minicalcifications) without significant alterations in the morphology of the collagen fibrils. The finding of different morphologic classes of aberrations among patients suggests that the connective tissue defects are genetically heterogeneous. The segregation of the connective tissue phenotype in three families suggested an autosomal dominant pattern of inheritance.

Biopsy↗

PubMed2003

Management patterns and health care use after intracerebral hemorrhage. a cost-of-illness study from a societal perspective in Germany.

BACKGROUND: The German cost-of-illness study of stroke is a multicenter study in 6 departments of internal medicine, 9 departments of general neurology and 15 departments of neurology with an acute stroke unit. The aims of this study are to describe the management patterns, cost of treatment and overall resource utilization after intracerebral hemorrhage (ICH) as well as the major differences to ischemic stroke (IS). METHODS: During a 12-month period, 30 participating centers with a special interest in stroke prospectively included 586 patients with ICH which were collected in a joint data bank. About 75% of all patients could be centrally followed up via structured telephone interviews after 3 and 12 months to assess further acute hospital and rehabilitation stays, outpatient resource utilization, functional outcome and quality of life. RESULTS: Mortality after 3 months (33.5%) was markedly higher than in patients with IS from the same hospitals. Accordingly, only 30.9% of patients had regained independent functional status after 3 months. Cumulative cost of treatment amounted to 5301 EUR for inpatient stay in the documenting hospital and 8920 EUR for the overall hospital stay including rehabilitation. Mean direct cost after discharge during the first year amounted to 4598 EUR and the loss of work force was equivalent to 5537 EUR in all surviving patients. CONCLUSION: This study provides a comprehensive overview of patient characteristics, treatment strategies and health care cost of ICH from a societal perspective in Germany.

Adult↗

PubMed2003

Stroke units and stroke services in Germany.

BACKGROUND/OBJECTIVES: The German stroke units are sub-intensive units with the possibility of continuous monitoring of vital parameters. This is the main difference to Scandinavian and British non-intensive combined acute and rehabilitation stroke units. Germany has 56 regional and 50 local stroke units, and standards differ between them. Nearly 30% of all strokes in Germany are treated in these units. The German stroke units are cost intensive and unfortunately their effectiveness has not been proven yet.

Germany↗

PubMed2003

Adherence to secondary stroke prevention strategies--results from the German Stroke Data Bank.

Only very limited data are available concerning patient adherence to antithrombotic medication intended to prevent a recurrent stroke. Reduced adherence and compliance could significantly influence the effects of any stroke prevention strategies. This study from a large stroke data bank provides representative data concerning the rate of stroke victims adhering to their recommended preventive medication. During a 2-year period beginning January 1, 1998, all patients with acute stroke or TIA in 23 neurological departments with an acute stroke unit were included in the German Stroke Data Bank. Data were collected prospectively, reviewed, validated and processed in a central data management unit. Only 12 centers with a follow-up rate of 80% or higher were included in this evaluation. 3,420 patients were followed up after 3 months, and 2,640 patients were followed up one year after their stroke. After one year, 96% of all patients reported still adhere to at least one medical stroke prevention strategy. Of the patients receiving aspirin at discharge, 92.6% reported to use that medication after 3 months and 84% after one year, while 81.6 and 61.6% were the respective figures for clopidogrel, and 85.2 and 77.4% for oral anticoagulation. Most patients who changed medication switched from aspirin to clopidogrel. Under the conditions of this observational study, adherence to stroke prevention strategies is excellent. The highest adherence rate is noticed for aspirin and oral anticoagulation. After one year, very few patients stopped taking stroke preventive medication.

Administration, Oral↗

PubMed2003

Etiology and long-term prognosis of unilateral paramedian pontine infarction with progressive symptoms.

Progressive pure motor hemiparesis is a common feature in paramedian pontine infarction. To assess the etiology, clinical course and long-term prognosis of this stroke subtype, we identified 26 patients with progressive symptoms in a retrospective study, treated in our hospital between 1993 and 1998. All patients had more than one stroke risk factor, and in 20, basilar branch disease, an atherosclerotic occlusion of basilar perforating arteries, was causative. Most patients developed severe hemiparesis after a mean time of 3 days, nearly 50% showed deterioration in connection with a fall in systolic blood pressure. The patients were followed up for 4-9 years: 4 patients had further strokes, 5 died, and 17 patients were independent, which may be interpreted as a good long-term prognosis.

Aged↗

PubMed2002

Treatment of acute ischaemic stroke with the low-affinity, use-dependent NMDA antagonist AR-R15896AR. A safety and tolerability study.

BACKGROUND AND PURPOSE: A low-affinity, use-dependent N-Methyl-D-Aspartate (NMDA) antagonist AR-R15896AR has neuroprotective properties in animal models of ischaemic stroke. The aim of the present study was to examine the safety and tolerability of a new and higher dosage regimen that would enable acute stroke patients to achieve and maintain neuroprotective plasma concentrations. METHODS: A randomised, multi-centre, double-blind, placebo-controlled, parallel group study was carried out at 19 centres in France, Germany and the Netherlands in patients with a clinical diagnosis of acute ischaemic stroke, and onset of symptoms within 12 hours before start of study drug administration. Two loading doses of 3.5 mg/kg of AR-R15896AR over 60 minutes, followed by a 2.5 mg/kg infusion over the next 120 minutes were given. Eight hours after the start of the loading dose infusion, the first maintenance dose (120 mg) was administered over 60 minutes. Eight further maintenance infusions were administered at intervals of 8 hours over a total treatment period of 3 days. Main variables were safety, tolerability and pharmacokinetics. Follow-up assessments also included the Barthel Index (BI) and the NIH Stroke Scale (NIHSS) at 4-7 days after the end of the last infusion and at 30 days after the onset of stroke. RESULTS: 103 patients with acute ischaemic stroke were randomised to either treatment with AR-R15896AR (70 patients) or placebo (33 patients). Mortality was not significantly different in the AR-R15896AR group compared with the placebo group (10 % vs. 6 %). Serious adverse events during treatment due to psychiatric conditions were associated with AR-R15896AR (3 vs. 0). Other side effects were more common in the group treated with AR-R15896AR: vomiting (29 % vs. 9 %), nausea (23 % vs. 12 %), fever (17 % vs. 12 %), agitation (7 % vs. 3 %), dizziness (7 % vs. 0 %), and hallucinations (6 % vs. 0 %). No significant difference between the two groups (with respect to the proportions of patients with favourable outcome) was detected in either the analysis of the BI or the NIHSS. Pharmacokinetic data showed that plasma concentrations of AR-R15896AR were in the expected neuroprotective range. CONCLUSION: In most of the patients with acute stroke receiving AR-R15896AR the intended high plasma levels were reached within a short time period. However, active treatment produced more side effects than placebo, thus indicating safety concerns and tolerability issues for use in high doses in an acute stroke population.

Acute Disease↗

PubMed2002

Complications following acute ischemic stroke.

The objective of this study was to assess typical early-onset complications following ischemic stroke in a large, hospital-based cohort to provide clinical data for future randomized trials and quality standards in clinical routine. 3,866 patients with acute ischemic stroke were prospectively documented in 14 Neurology Departments with an acute stroke unit. Within the first week after admission, increased intracranial pressure (7.6%) and recurrent cerebral ischemia (5.1%) were the most frequent neurological complications. Fever >38 degrees C (13.2%), severe arterial hypertension (7.5%) and pneumonia (7.4%) were the most frequent medical complications. Multivariate regression analysis yielded brain stem infarction and large-artery atherosclerosis as independent predictors for early recurrent ischemic stroke. This study provides representative data on onset and severity of early neurological and medical complications as well as possible predictors for early recurrent cerebral ischemia following acute ischemic stroke.

Aged↗

PubMed2002

Assessment of functioning and disability after ischemic stroke.

BACKGROUND AND PURPOSE: Functioning and disability after ischemic stroke are clinically meaningful and of major relevance to patients. Despite many instruments available to assess these outcomes, little is known about their interrelation and predictive factors. METHODS: We prospectively identified 4264 patients with acute ischemic stroke from 30 hospitals in Germany during a 1-year period between 1998 and 1999 and registered them in a common data bank. The patients were centrally followed up via telephone interview after 100 days and 1 year to assess various scales such as the Barthel Index (BI), modified Rankin Scale (MRS), extended Barthel Index (EBI), Short Form-36 Physical Functioning (SF-36 PF), and Center for Epidemiologic Studies-Depression short form (CES-D). RESULTS: Outcome status could be assessed in 67.2% of patients 100 days after hospital admission. Of these, 13.9% had died, 53.7% had regained functional independence (BI <95), 46.3% had no or mild residual symptoms (MRS < or =1), and 44.6% had no higher cognitive deficits on the EBI. Of the patients who personally answered the follow-up questions, 67% had no major physical disability (SF-36 PF <60), and 32.9% reported symptoms classified as depression (CES-D > or =10). The high percentage of patients reaching the maximum score (ceiling effect) in the BI was less pronounced in the MRS and SF-36 PF. The predictive factors for dichotomized outcomes on each scale were similar for adverse functioning and disability but varied considerably for depression. CONCLUSIONS: To avoid ceiling effects in outcome distribution of patients treated in specialized stroke centers, the MRS and SF-36 PF instruments are preferable to the BI. Parametric use of the SF-36 PF could further improve outcome measurement by considering individual treatment effects.

Aged↗

PubMed2002

Ultrastructural connective tissue aberrations in patients with intracranial aneurysms.

BACKGROUND AND PURPOSE: An unknown connective tissue defect might predispose for the development and rupture of intracranial aneurysms in some patients. This study of connective tissue samples of a series of patients with intracranial aneurysms investigates the morphology of the extracellular matrix with methods that are currently used in the routine diagnosis of inherited connective tissue disorders. METHODS: Skin biopsies from 21 patients with intracranial aneurysms, many with multiple aneurysms, were studied by electron microscopy. None of the patients included in this study showed clinical signs of a known connective tissue disorder. RESULTS: In 7 patients (33%), we observed repetitive aberrations in the morphology of collagen fibrils and elastic fibers of the reticular dermis. The observed ultrastructural findings were somewhat similar to those typically observed in patients with Ehlers-Danlos syndrome (EDS) and in a subgroup of patients with spontaneous cervical artery dissections. The patterns of abnormalities fell into 2 classes: 4 patients displayed abnormalities that resembled those found in patients with EDS type III, and the electron microscopic findings in the skin biopsies from 3 patients resembled those of EDS type IV patients. The sequence of the COL3A1 gene from the patients with EDS type IV-like alterations of the connective tissue morphology was analyzed. No mutation was detected. CONCLUSIONS: Connective tissue alterations were found in skin biopsies from a minority of patients with intracranial aneurysms. Electron microscopic investigation of skin biopsies from patients and their relatives might become valuable for clinical diagnostics, identification of persons at risk, and basic studies of the pathogenesis of this vascular disease.

Adult↗