Neurostimulation for Parkinson's disease with early motor complications.

BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS: In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS: For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS: Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

Plasma levels of mannan-binding lectin (MBL)-associated serine proteases (MASPs) and MBL-associated protein in cardio- and cerebrovascular diseases.

Growing evidence suggests a prominent role of the complement system in the pathogenesis of cardio- and cerebrovascular diseases (CVD). Mannan-binding lectin-associated serine proteases (MASPs) MASP-1 and MASP-2 of the complement lectin pathway contribute to clot formation and may represent an important link between inflammation and thrombosis. MBL-associated protein MAp44 has shown cardioprotective effects in murine models. However, MAp44 has never been measured in patients with CVD and data on MASP levels in CVD are scarce. Our aim was to investigate for the first time plasma levels of MAp44 and MASP-1, -2, -3 concomitantly in patients with CVD. We performed a pilot study in 50 healthy volunteers, in stable coronary artery disease (CAD) patients with one-vessel (n = 51) or three-vessel disease (n = 53) and age-matched controls with normal coronary arteries (n = 53), 49 patients after myocardial infarction (MI) and 66 patients with acute ischaemic stroke. We measured MAp44 and MASP-1 levels by in-house time-resolved immunofluorometric assays. MASP-2 and MASP-3 levels were measured using commercial enzyme-linked immunosorbent assay kits. MASP-1 levels were highest in subacute MI patients and lowest in acute stroke patients. MASP-2 levels were lower in MI and stroke patients compared with controls and CAD patients. MASP-3 and MAp44 levels did not differ between groups. MASP or MAp44 levels were not associated with severity of disease. MASP and MAp44 levels were associated with cardiovascular risk factors including dyslipidaemia, obesity and hypertension. Our results suggest that MASP levels may be altered in vascular diseases. Larger studies are needed to confirm our results and elucidate the underlying mechanisms.

Pulmonary nocardiosis in Western Europe-Clinical evaluation of 43 patients and population-based estimates of hospitalization rates.

BACKGROUND: Pulmonary nocardiosis (PN) is an uncommon but potentially life-threatening infection. Most of our knowledge on PN is derived from case reports and small case series. Increasing incidence rates of PN have been reported recently. The aim of this study was to describe the clinical course of and risk factors for PN in four Western European countries and to estimate population-based annual hospitalization rates. METHODS: This was a retrospective evaluation (1995-2011) of the clinical course of and risk factors for PN in patients at 11 hospitals in four European countries (Germany, Austria, Switzerland, and the Netherlands). Population-based estimates of hospitalization rates for PN in Germany (2005 to 2011) were calculated using official German nationwide diagnosis-related groups (DRG) hospital statistics. RESULTS: Forty-three patients fulfilled stringent criteria for proven (n=8) and probable (n=35) PN; seven had extrapulmonary dissemination. For these 43 patients, the major risk factors for PN were immunocompromising (83.7%) and/or pulmonary (58.1%; as only comorbidity in 27.9%) comorbidities. The median duration of PN targeted therapy was 12 weeks. Distinctive patterns of resistance were observed (imipenem susceptibility: Nocardia farcinica 33.3%; Nocardia asteroides 66.7%). The overall mortality rate was 18.9% (50% in disseminated PN). Over time, annual PN hospitalization rates remained unchanged at around 0.04/100000, with the highest rate among men aged 75-84 years (0.24/100000). CONCLUSIONS: PN is a rare, but potentially life-threatening disease, and mainly affects immunocompromised elderly males. Overall, annual hospitalization rates remained stable between 2005 and 2011.

Age-dependent differences in demographics, risk factors, co-morbidity, etiology, management, and clinical outcome of acute ischemic stroke.

BACKGROUND: Comparisons between younger and older stroke patients including comorbidities are limited. METHODS: Prospective data of consecutive patients with first ever acute ischemic stroke were compared between younger (< or = 45 years) and older patients (> 45 years). RESULTS: Among 1004 patients, 137 (14 %) were < or = 45 years. Younger patients were more commonly female (57 % versus 34 %; p < 0.0001), had a lower frequency of diabetes (1 % versus 15 %; p < 0.0001), hypercholesterolemia (26 % versus 56 %; p < 0.0001), hypertension (19 % versus 65 %; p < 0.0001), coronary heart disease (14 % versus 40 %; p < 0.0001), and a lower mean Charlson co-morbidity index (CCI), (0.18 versus 0.84; p < 0.0001). Tobacco use was more prevalent in the young (39 % versus 26 %; P < 0.0001). Large artery disease (2 % versus 21 %; p < 0.0001), small artery disease (3 % versus 12 %; p = 0.0019) and atrial fibrillation (1 % versus 17 %; p = 0.001) were less common in young patients, while other etiologies (31 % versus 9 %; p < 0.0001), patent foramen ovale or atrial septal defect (44 % versus 26 %; p < 0.0001), and cervical artery dissection (26 % versus 7 %; p < 0.0001) were more frequent. A favorable outcome (mRS 0 or 1) was more common (57.4 % versus 46.9 %; p = 0.023), and mortality (5.1 % versus 12 %; p = 0.009) was lower in the young. After regression analysis, there was no independent association between age and outcome (p = 0.206) or mortality (p = 0.073). Baseline NIHSS score (p < 0.0001), diabetes (p = 0.041), and CCI (p = 0.002) independently predicted an unfavorable outcome. CONCLUSIONS: Younger patients were more likely to be female, had different risk factors and etiologies and fewer co-morbidities. There was no independent association between age and clinical outcome or mortality.

Carnitine status in early-treated children, adolescents and young adults with phenylketonuria on low phenylalanine diets.

BACKGROUND: In patients with phenylketonuria (PKU), the carnitine status may be impaired for metabolic or dietary reasons, including low carnitine intake, a deficient synthesis and acylcarnitine production from phenylalanine (Phe) metabolites. METHODS: Free carnitine and acylcarnitine status was assessed in 30 PKU patients, aged 0.5-36 years, mean age 13.8 years. Our cohort was divided into 2 groups according to the preparations of Phe-free amino acids (AA) prescribed, with or without carnitine supplementation. Daily Phe intake, dosage of AA mixtures and body weight were recorded along with measurements of acylcarnitines in blood spots (by tandem mass spectrometry) and serum AA. Control data were obtained from 50 healthy volunteers (aged 0.2-39 years, mean age 14.2. years). Statistical analysis comprised the t test, ANOVA and Pearson's correlation. RESULTS: PKU patients had lower free carnitine (C0) concentrations than controls (25.82 +/- 7.38 vs. 31.28 +/- 6.17 micromol/l; p < 0.001) and lower octanoyl- and decanoylcarnitine. Mean C0 and acylcarnitine concentrations did not differ between PKU patients taking the various protein substitutes with or without carnitine; mean C0 levels in PKU patients receiving AA enriched with carnitine were still lower compared with controls (p < 0.05). CONCLUSIONS: Actual dietary regimens can not completely normalize the carnitine status; therefore, carnitine levels should be given careful consideration in subjects with PKU.

Whn and mHa3 are components of the genetic hierarchy controlling hair follicle differentiation.

The molecular basis of the characteristic hair growth disorder in nude mice that carry a defective Whn transcription factor gene is unknown. A comparison of mRNA populations from wild-type and nude mice back skin by representational difference analysis revealed the absence of acidic hair keratin gene 3 (mHa3) mRNA in mutant mice. Whn and acidic hair keratin genes are co-expressed in hair follicles, nail forming regions and filiform papillae of the tongue: expression of the mHa3 gene is generally detectable about 1 day after Whn mRNA and rapidly ceases in its absence. Whn is strongly expressed during the anagen (growth) phase of the hair cycle in matrix, cortex and outer root sheath; its expression rapidly declines during catagen and is undetectable in telogen phases. In nude mice, low levels of mHa3 expression are maintained in nails and whisker follicles, whereas expression is completely absent in pelage hair follicles and filiform papillae. Thus, the nude phenotype represents the first example of an inherited skin disorder that is associated with the loss of expression rather than structural mutation of keratin genes. The distinct molecular difference between pelage and whisker follicles correlates with the improved mechanical stability of vibrissae in nude mice, implicating mHa3 as an important structural component of the hair shaft.

xPIPE--Reception of DICOM Data from any Sender via the Internet.

PURPOSE: Various technologies have been established for DICOM data exchange in radiology. In addition to the patient CD, online transfers via VPN (virtual private network) or DICOM email are common practice. However, dedicated network solutions are generally not appropriate for data exchange with occasional and spontaneous partners due to missing infrastructure at the partner institutions and/or complex setup procedures. The purpose was to develop a practical solution to complement the established technologies to allow users worldwide to transfer images without registration. MATERIALS AND METHODS: The development of the xPIPE system is based on Java and various software libraries. A client hosted on a website enables sending DICOM data to a receiving system of the hospital. RESULTS: The new xPIPE system creates a gateway to a receiving hospital which is accessible from any point worldwide, giving other hospitals, clinics and patients a simple and secure method to transmit DICOM data without intermediate storage on external servers. CONCLUSION: The system was deployed at the University Hospital Münster and subsequently widely used even without information events and training. Data protection during transfer is ensured by the use of signatures and encryption. From the user's perspective the system has only minor technical requirements and can be used with minimal setup effort.

The importance of individual nucleotides for the structure and function of rRNA molecules in E. coli. A mutagenesis study.

Methods of in vitro mutagenesis were employed to determine the importance of individual nucleotides within the ribosomal RNAs for the structure and function of E. coli ribosomes. A series of defined nucleotides in the genes for the 5 S and 16 S RNA were altered by transition and transversion mutations using either oligonucleotide-directed or bisulfite-catalyzed mutation procedures. Plasmids harbouring the mutated rRNA genes were expressed and the ribosomes containing such altered RNAs were investigated for impairments in RNA-protein interaction assembly and mRNA-coded tRNA binding.

Texture analysis of direct magnification radiographs of vertebral specimens: correlation with bone mineral density and biomechanical properties.

RATIONALE AND OBJECTIVES: The authors used direct magnification radiographs, combines with texture analysis, to investigate the trabecular structure of human vertebral specimens and compared these techniques with measurement of bone mineral density (BMD) by using quantitative computed tomography to predict bone strength. METHODS: Direct magnification radiographs and BMD measurements were obtained from 38 motion segments from the thoracolumbar spines of 11 female human cadavers. Maximum compressive strength (MCS) was determined with a materials testing machine. Morphologic parameters, digital skeletons, and fractal dimension were obtained from the radiographs in three different regions of interest. RESULTS: Correlations between BMD and MCS were statistically significant (r = .81, P < .01). With morphologic parameters, correlation coefficients of up to .64 (P < .01) were obtained. Use of multivariate regression analysis with one morphologic parameter (the width of the black pixels, or thicknessB) in addition to BMD improved correlations versus MCS (P < .01). CONCLUSION: In an experimental setting, BMD showed statistically significant correlation with bone strength, whereas the structural parameters demonstrated only modest correlations. BMD together with one of these measures (thicknessB), however, showed the highest correlation.

[The texture-analysis of high-resolution computed tomograms as an additional procedure in osteoporosis diagnosis: in-vitro studies on vertebral segments]. / Strukturanalyse hochauflösender Computertomogramme als ergänzendes Verfahren in der Osteoporosediagnostik: in-vitro-Untersuchungen an Wirbelsäulensegmenten.

PURPOSE: The purpose of this study was to perform texture analysis of high-resolution CT images obtained from human vertebral specimens and to correlate these parameters with the biomechanical stability of the specimens. In addition, structure data were compared with bone mineral density (BMD) assessed by quantitative CT (QCT). MATERIAL AND METHODS: High-resolution CT images and standard QCT sections were obtained in 36 vertebral motion segments, each consisting of two vertebrae with intact ligaments and intervertebral disc. The trabecular structure in the CT images was assessed using three texture analysis techniques: Trabecular threshold area ratio (TTAR), fractal dimension without thresholding (OTS) and fractal dimension with thresholding (ITS). Finally, the maximum compressive strength (MCS) was determined using a biomechanical testing device. RESULTS: A correlation of r = 0.76 (p < 0.01) was obtained for TTAR versus MCS, of r = 0.83 (p < 0.01) for ITS versus MCS, and of r = 0.35 (p > 0.01) for OTS versus MCS, while r = 0.76 (p < 0.01) was found for BMD versus MCS. Best results were obtained by combining structure measures and BMD (r = 0.85, p < 0.01). CONCLUSIONS: This in vitro study showed a significant correlation between structure measures and biomechanical strength, which was comparable to BMD and strength. However, best correlations were obtained by combining both measures. Using both BMD and structure measures therefore may improve the prediction of biomechanically determined bone strength.

[Dose reduction of radiographs of the pediatric pelvis for diagnosing hip dysplasia using a digital flat-panel detector system]. / Dosisreduktion bei Röntgenaufnahmen des kindlichen Beckenskelettes zur Diagnostik der Hüftgelenksdysplasie unter Verwendung eines digitalen Flachdetektorsystems.

PURPOSE: To evaluate a possible dose reduction in pediatric pelvic radiographs in congenital hip dysplasia using a digital flat-panel system instead of a phosphor-storage system. MATERIALS AND METHODS: During a six-month period, all pediatric patients referred for pelvic radiography for the evaluation of congenital hip dysplasia were randomly assigned to be examined by either a phosphor-storage system or a digital flat-panel system, whereby the latter system was operated with half the radiation dose. Thirty pairs of radiographs were assessed for the visibility of 16 anatomic details and for 5 orthopedic-radiographic measurements (5-point scale with 1 = excellent; three independent observers). The projection indices of Ball and Kommenda and of Tönnis and Brunken were calculated for all radiographs. The Student's t-test was used to compare the flat-panel and the phosphor-storage radiographs for observers' assessments, patients' age and projection indices. RESULTS: In a total of 7560 observations, the scores for the visibility of anatomic details and orthopedic-radiographic measurements were respectively 2.72 and 2.64 for the flat-panel system and 2.93 and 2.79 for the phosphor-storage system. No significant differences were found between both systems (p > 0.05) and between patient age and projection indices (p > 0.05). CONCLUSION: Pediatric pelvic radiographs can be obtained with a digital flat-panel system using half the radiation dose instead of a phosphor-storage system without sacrificing relevant information in the diagnosis of congenital hip dysplasia.

[An extended CT scale technique for evaluating periprosthetic bone lesions - an in vitro study]. / Extended-field CT-Technik zur Evaluation von periprothetischen Knochenläsionen--In-vitro-Untersuchung.

PURPOSE: In the present study the reduction of artifacts using an extended CT scale technique was examined in 5 vitallium and 5 titanium-aluminium-vanadium tumor prostheses. METHODS: 5 titanium-aluminium-vanadium and 5 vitallium distal femur Mutars(R) tumor prostheses (Mutars(R) - Modular Universal Tumor And Revision System) were implanted in 10 human femur specimens. 110 artifical drill hole lesions of 1 mm, 2 mm, 3 mm, 5 mm and 8 mm diameter were placed in the bone around the hexagonal stem of the tumor prosthesis and furthermore in the proximal part of the femur. All specimens were examined using conventional CT and an extended CT scale technique in a slice thickness of 3 mm. RESULTS: In the proximal part of the femur all drill holes could be detected using 3 mm slices, no artefacts were observed. Along the hexagonal stem smooth lines arising from each hexagonal plane could be observed. This made it impossible to detect a 1 mm drill in 1 vitallium and in 1 titanium-aluminium-vanadium stem. There was no difference between the extended CT scale and conventional CT. CONCLUSION: The extended CT scale did not significantly (p > 0.05, t-test) improve the imaging of artificial drill hole lesions along the hexagonal Mutras(R) stem.

Joint accumulations of FDG in whole body PET scans.

PURPOSE: To retrospectively evaluate FDG accumulations in major joints in a large series of non-absorption corrected partial body and whole body FDG-PET scans, and to determine the frequency and intensity of accumulation. MATERIALS AND METHODS: 354 consecutive PET partial- and whole body non-transmission corrected scans of patients obtained for tumor staging were examined with respect to FDG accumulations in the acromio-clavicular (AC)-, gleno-humeral-, hip-, knee- and talo-tibial joints. FDG-uptake was graded using a semi-quantitative scale from 0 (no accumulation) to 4 (very strong accumulation comparable to brain uptake). RESULTS: Joint activity of grade 1-2 was noted frequently, while grade 3 was rare, occurring only in the knee and shoulder joints, and grade 4 was inexistent. The 43 patients with grade 3 accumulations or with at least 4 joints showing grade 2 uptake were interviewed, but all denied pain specifically referred to a joint. Joint accumulations were seen in 50% of the acromio-clavicular-, 80% in the glenohumeral-, 50% in the hip-, 90% in the knee and 80% in the talo-tibial joints. The intensities of joint accumulations correlated positively and significantly with patient age, ranging from r = 0.7 and p < 0.05 in the knee to r = 0.96 and p < 0.0001 in the AC joint. CONCLUSIONS: FDG accumulations in the joints in whole body FDG-PET scans are frequent and are very likely not related to symptoms. As there is a strong age correlation, and FDG is known to accumulate in inflammatory lesions, the findings are most likely a result of sub-clinical inflammatory synovial proliferation or other chronic inflammatory processes occurring in aging joints.

Are collimated low-dose digital radiographs valid for performing Delaire's architectural analysis?

Computed radiography (CR) provides the dynamic exposure range to reveal objects in film areas exposed by very low X-ray exposure. Conventional cephalometric radiographs are normally beam limited to the facial skeleton. The cranial vault and cervical vertebra are collimated and only exposed by extra-focal radiation and scatter. We hypothesize that, on conventional cephalometric radiographs obtained with CR, image data of collimated film areas can be enhanced for reliable performance of Delaire's cephalometric analysis of the entire skull. Therefore the aim of the present study was to compare the reproducibility of landmark placement on normal and underexposed film areas of CR images. Intra- and inter-observer reproducibility of landmark identification was evaluated on 200 randomly selected radiographs by calculating the error radius of repeated landmark placements. A paired-samples t-test revealed differences (P< 0.001) between intra- and inter-observer reproducibility. Intra-observer accuracy was influenced (P< 0.001) by variability of suture obliteration (bregma). Identification of landmarks in areas of extra-focal radiation showed no difference (P> 0.05) from that of landmarks inside the normally exposed area. CR offers the opportunity to perform of a full cranial analysis on a cephalometric radiograph collimated to the facial region.

First experience with a public domain computer-aided surgical system.

The outcome of complex craniofacial operations is critically dependent on careful and accurate preoperative planning. Recent advances in computer technology enable the surgeon to do surgical simulations directly on to a computer terminal. We describe the clinical application of a public domain-based computer-aided system in craniofacial surgery. Operation planning was based on clinical investigations and radiological images, with particular use of a virtual three-dimensional surgical simulation. Three patients with complex craniofacial malformations were admitted for orbital correction. Surgical simulation defined numerically the extent of bone movements and the extent of resection areas. Operations were guided by the virtual planning. The outcome was compared with the planning to assess the accuracy of the operative correction. Our first experience confirms that computer-assisted simulation is a reliable and useful tool that improves surgical planning and helps to evaluate the surgical outcome.

Evaluation of accuracy of insertion of dental implants and prosthetic treatment by computer-aided navigation in minipigs.

The survival of loaded implants is critically dependent on their biomechanical stability. We have used a computer-guided navigation technique to evaluate the accuracy of computer-assisted insertion for immediately-loaded implants in minipigs. On the basis of computed tomographical data, the Robodent system was used for preoperative planning and guidance of inserting the implant. An optical tracking system allowed positioning of the implant and immediate prosthetic rehabilitation by inserting it in a plaster model and during the operation. Postoperative computed tomograms (CT) showed that the implants were placed precisely in the preoperatively planned position. The accuracy achieved corresponded well with the spatial resolution of the CT used. Immediate placement of the prefabricated crowns resulted in favourable occlusal positioning. Histological cross-sections showed that the implants were biomechanically stable. The accuracy of insertion of oral implants illustrated here suggests that insertion and prosthetic modelling of implants may benefit from computer-assisted navigation.

Computer-aided automated landmarking of cephalograms.

The computer-aided method presented is able to interpret and measure radiological structures automatically and reproducibly on a large number of randomly selected lateral head films of different film quality. For example the hard and soft tissue expression of the profile is used to discuss method, application and disadvantages. The performance of the system depends on image quality. The algorithm cannot be influenced by opacifications due to metal structure. In 90% of all cases the contours are identified correctly. Even if the image quality is poor, the recognition rate is about 84%. The selected cephalometric landmarks are placed in the right way in 85% of all cases. The constraint mathematical conditions and the high reproducibility improve the quality process of the cephalometric analysis. Recognition rates of 84% to 90% justify even nowadays the routine use of semi-automatic systems in PC-based analysis. With advancing digital radiography and improved computer performance, image interpreting systems will certainly become established.

[Development and evaluation of a German version of the Tegner activity scale for measuring outcome after anterior cruciate ligament injury]. / Entwicklung und Evaluation einer deutschen Version der Tegner Aktivitätsskala zur Erfassung der Funktion nach einer Verletzung des vorderen Kreuzbands.

BACKGROUND: The aim of this study is to provide a valid and reliable German version of the Tegner activity scale (Tegner-G). The Tegner activity scale assesses on 11 levels the activity in sports (competitive and recreational) and work of patients with anterior cruciate ligament injuries. The English original version was elaborated in Sweden and contains sports that are unknown in German-speaking countries. METHODS: The translation and adaptation was conducted in several steps according to the guidelines in the literature. The validity (discriminative validity and content validity) and (absolute and relative) reliability were determined in 46 patients after reconstruction of the anterior cruciate ligament and in 20 healthy subjects. The patients were divided into an acute group (< 3 months after operation; 11 men; 30.9 ± 8.3 years) and a chronic group (3 - 12 months after operation; 18 men; 31.3 ± 11.6 years). All subjects filled in the scale two times within 3 - 7 days. For the additional determination of the relation between activity and function, they also filled in the German version of the Lysholm score (Lysholm-G). RESULTS: The three groups differed significantly from each other (Kruskal-Wallis test: χ2 = 27.95, p < 0.001; post hoc Mann-Whitney U tests: acute-chronic p < 0.001; acute-control p < 0.001; chronic-control p = 0.003). There was a floor effect in the acute patient group. The intraclass correlation coefficients indicated a high relative reliability (ICC2,1 > 0.9). The minimal detectable change was 1.4 points. The relation between activity (Tegner-G) and function (Lysholm-G) was stronger in the acute than in the chronic patient group (ρ = 0.77 and ρ = 0.60, respectively). CONCLUSION: The psychometric properties of the Tegner-G are comparable to those of the English original version. The Tegner-G is thus valid and reliable for the German-speaking part of Switzerland. The application in other German-speaking countries probably requires adaptations for some of the sports included. The relation between activity and function changes depending on time since operation. This confirms that a comprehensive assessment of the outcome after an anterior cruciate ligament injury requires the separate assessment of both parameters.

IV thrombolysis and statins.

OBJECTIVE: To examine whether prior statin use affects outcome and intracranial hemorrhage (ICH) rates in stroke patients receiving IV thrombolysis (IVT). METHODS: In a pooled observational study of 11 IVT databases, we compared outcomes between statin users and nonusers. Outcome measures were excellent 3-month outcome (modified Rankin scale 0-1) and ICH in 3 categories. We distinguished all ICHs (ICH(all)), symptomatic ICH based on the criteria of the ECASS-II trial (SICH(ECASS-II)), and symptomatic ICH based on the criteria of the National Institute of Neurological Disorders and Stroke (NINDS) trial (SICH(NINDS)). Unadjusted and adjusted odds ratios (OR) with 95% confidence intervals were calculated. RESULTS: Among 4,012 IVT-treated patients, 918 (22.9%) were statin users. They were older, more often male, and more frequently had hypertension, hypercholesterolemia, diabetes, coronary heart disease, and concomitant antithrombotic use compared with nonusers. Fewer statin users (35.5%) than nonusers (39.7%) reached an excellent 3-month outcome (OR(unadjusted) 0.84 [0.72-0.98], p = 0.02). After adjustment for age, gender, blood pressure, time to thrombolysis, and stroke severity, the association was no longer significant (0.89 [0.74-1.06], p = 0.20). ICH occurred by trend more often in statin users (ICH(all) 20.1% vs 17.4%; SICH(NINDS) 9.2% vs 7.5%; SICH(ECASS-II) 6.9% vs 5.1%). This difference was statistically significant only for SICH(ECASS-II) (OR = 1.38 [1.02-1.87]). After adjustment for age, gender, blood pressure, use of antithrombotics, and stroke severity, the OR(adjusted) for each category of ICH (ICH(all) 1.15 [0.93-1.41]; SICH(ECASS-II) 1.32 [0.94-1.85]; SICH(NINDS) 1.16 [0.87-1.56]) showed no difference between statin users and nonusers. CONCLUSION: In stroke patients receiving IVT, prior statin use was neither an independent predictor of functional outcome nor ICH. It may be considered as an indicator of baseline characteristics that are associated with a less favorable course.

Endocrine controls of primary adult human stem cell biology: thyroid hormones stimulate keratin 15 expression, apoptosis, and differentiation in human hair follicle epithelial stem cells in situ and in vitro.

Here we demonstrate that physiological concentrations of the thyroid hormones T3 and T4 enhance the KERATIN 15 promoter activity and expression in epithelial stem cells of adult human scalp hair follicles in situ and in vitro. Additionally, T3 and T4 stimulate expression of the immuno-inhibitory surface molecule CD200. Subsequently, T3 and T4 induce apoptosis and differentiation and inhibit clonal growth of these progenitor cells in vitro. These data suggest that human hair follicle bulge-derived epithelial stem cells underlie profound, previously unknown hormonal regulation by thyroid hormones, and show that primary human keratin 15-GFP+ progenitor cells can be exploited to further elucidate fundamental endocrine controls of human epithelial stem cells.