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"text": "\n114563\nOfficial Positions for FRAX(®) clinical regarding glucocorticoids: the impact of the use of glucocorticoids on the estimate by FRAX(®) of the 10 year risk of fracture from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX(®).\n\nLeib, ES\n\nSaag, KG\n\nAdachi, JD\n\nGeusens, PP\n\nBinkley, N\n\nMcCloskey, EV\n\nHans, DB\n\nFRAX(®) Position Development Conference Members\n\nBeiträge in Fachzeitschriften\nISI:000293989900007\n21810527.0\n10.1016/j.jocd.2011.05.014\nNone\nGiven the significant impact the use of glucocorticoids can have on fracture risk independent of bone density, their use has been incorporated as one of the clinical risk factors for calculating the 10-year fracture risk in the World Health Organization's Fracture Risk Assessment Tool (FRAX(®)). Like the other clinical risk factors, the use of glucocorticoids is included as a dichotomous variable with use of steroids defined as past or present exposure of 3 months or more of use of a daily dose of 5 mg or more of prednisolone or equivalent. The purpose of this report is to give clinicians guidance on adjustments which should be made to the 10-year risk based on the dose, duration of use and mode of delivery of glucocorticoids preparations. A subcommittee of the International Society for Clinical Densitometry and International Osteoporosis Foundation joint Position Development Conference presented its findings to an expert panel and the following recommendations were selected. 1) There is a dose relationship between glucocorticoid use of greater than 3 months and fracture risk. The average dose exposure captured within FRAX(®) is likely to be a prednisone dose of 2.5-7.5 mg/day or its equivalent. Fracture probability is under-estimated when prednisone dose is greater than 7.5 mg/day and is over-estimated when the prednisone dose is less than 2.5 mg/day. 2) Frequent intermittent use of higher doses of glucocorticoids increases fracture risk. Because of the variability in dose and dosing schedule, quantification of this risk is not possible. 3) High dose inhaled glucocorticoids may be a risk factor for fracture. FRAX(®) may underestimate fracture probability in users of high dose inhaled glucocorticoids. 4) Appropriate glucocorticoid replacement in individuals with adrenal insufficiency has not been found to increase fracture risk. In such patients, use of glucocorticoids should not be included in FRAX(®) calculations.\n\nDimai, Hans\n\n\n"
},
{
"text": "\n138544\nAssessing the effectiveness of 3 months day and night home closed-loop insulin delivery in adults with suboptimally controlled type 1 diabetes: a randomised crossover study protocol.\n\nLeelarathna, L\n\nDellweg, S\n\nMader, JK\n\nBarnard, K\n\nBenesch, C\n\nEllmerer, M\n\nHeinemann, L\n\nKojzar, H\n\nThabit, H\n\nWilinska, ME\n\nWysocki, T\n\nPieber, TR\n\nArnolds, S\n\nEvans, ML\n\nHovorka, R\n\nAP@home consortium\n\nBeiträge in Fachzeitschriften\nISI:000341640400027\n25186158.0\n10.1136/bmjopen-2014-006075\nPMC4158197\nDespite therapeutic advances, many people with type 1 diabetes are still unable to achieve optimal glycaemic control, limited by the occurrence of hypoglycaemia. The objective of the present study is to determine the effectiveness of day and night home closed-loop over the medium term compared with sensor-augmented pump therapy in adults with type 1 diabetes and suboptimal glycaemic control.\n The study will adopt an open label, three-centre, multinational, randomised, two-period crossover study design comparing automated closed-loop glucose control with sensor augmented insulin pump therapy. The study will aim for 30 completed participants. Eligible participants will be adults (≥18 years) with type 1 diabetes treated with insulin pump therapy and suboptimal glycaemic control (glycated haemoglobin (HbA1c)≥7.5% (58 mmol/mmol) and ≤10% (86 mmol/mmol)). Following a 4-week optimisation period, participants will undergo a 3-month use of automated closed-loop insulin delivery and sensor-augmented pump therapy, with a 4-6 week washout period in between. The order of the interventions will be random. All analysis will be conducted on an intention to treat basis. The primary outcome is the time spent in the target glucose range from 3.9 to 10.0 mmol/L based on continuous glucose monitoring levels during the 3 months free living phase. Secondary outcomes include HbA1c changes; mean glucose and time spent above and below target glucose levels. Further, participants will be invited at baseline, midpoint and study end to participate in semistructured interviews and complete questionnaires to explore usability and acceptance of the technology, impact on quality of life and fear of hypoglycaemia.\n Ethical approval has been obtained at all sites. Before screening, all participants will be provided with oral and written information about the trial. The study will be disseminated by peer-review publications and conference presentations.\n NCT01961622 (ClinicalTrials.gov).\n Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.\n\nKojzar, Harald\n\nMader, Julia\n\nPieber, Thomas\n\n\n"
},
{
"text": "\n144670\nTwo-stage revision of prosthetic hip joint infections using antibiotic-loaded cement spacers: When is the best time to perform the second stage?\n\nVielgut, I\n\nSadoghi, P\n\nWolf, M\n\nHolzer, L\n\nLeithner, A\n\nSchwantzer, G\n\nPoolman, R\n\nFrankl, B\n\nGlehr, M\n\nBeiträge in Fachzeitschriften\nISI:000360436200010\n25870167.0\n10.1007/s00264-015-2751-5\nNone\nManaging periprosthetic joint infections remains a challenging task, and adequate treatment strategies seem to be mandatory to avoid irreversible damage of the affected joint and/or systemic complications. Two-stage revision arthroplasty includes removing all implants and subsequent implantation of an antibiotic-loaded cement spacer, followed by revision arthroplasty as the second stage. Although this procedure is well described in the literature, results remain unpredictable due to various clinical findings and the absence of prospective randomised trials. We analysed (1) mortality and (2) reinfection rates in a series of patients who underwent two-stage revision surgery for periprosthetic hip joint infections with antibiotic-augmented joint spacers. We maintained a special focus on the spacer retention period and its influence on outcome in order to determine the best time for second-stage surgery.\n A consecutive series of 76 patients with native and periprosthetic hip joint infections and who underwent two-stage revision surgery with antibiotic-loaded cement spacers were studied between 2005 and 2010. The second-stage operation was performed when it was assumed that infection was eradicated. The further operative procedure depended upon intra-operative findings (frozen section, local status).\n Mean implant-free period with the antibiotic-loaded spacer in situ was 12.6 weeks. Spacer re-implantation was necessary in 13 cases due to positive signs of acute infection in the frozen section and suspect intra-operative findings. Eight patients were not operated for a second time in the investigated time period due to poor general condition. In 40 patients, the spacer retention period was four to 11 weeks: <four weeks for five and >11 weeks for 23. We observed a significantly higher proportion of women free from reinfection in the four to 11-week group than in patients with the shorter or longer period.\n According to our findings, the optimal timing for second-stage surgery as a second-stage procedure is between four and 11 weeks. A significantly optimal reinfection rate was seen in patients undergoing revision arthroplasty within that time frame, and 90% of those patients remained infection free until final follow-up.\n\nGlehr, Mathias\n\nHolzer, Lukas\n\nLeithner, Andreas\n\nSadoghi, Patrick\n\nSchwantzer, Gerold\n\nVielgut, Ines\n\n\n"
},
{
"text": "\n176652\nMendelian Randomization Analysis Reveals a Causal Influence of Circulating Sclerostin Levels on Bone Mineral Density and Fractures.\n\nZheng, J\n\nMaerz, W\n\nGergei, I\n\nKleber, M\n\nDrechsler, C\n\nWanner, C\n\nBrandenburg, V\n\nReppe, S\n\nGautvik, KM\n\nMedina-Gomez, C\n\nShevroja, E\n\nGilly, A\n\nPark, YC\n\nDedoussis, G\n\nZeggini, E\n\nLorentzon, M\n\nHenning, P\n\nLerner, UH\n\nNilsson, KH\n\nMovérare-Skrtic, S\n\nBaird, D\n\nElsworth, B\n\nFalk, L\n\nGroom, A\n\nCapellini, TD\n\nGrundberg, E\n\nNethander, M\n\nOhlsson, C\n\nDavey Smith, G\n\nTobias, JH\n\nBeiträge in Fachzeitschriften\nISI:000479995200001\n31170332.0\n10.1002/jbmr.3803\nPMC6899787\nIn bone, sclerostin is mainly osteocyte-derived and plays an important local role in adaptive responses to mechanical loading. Whether circulating levels of sclerostin also play a functional role is currently unclear, which we aimed to examine by two-sample Mendelian randomization (MR). A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10, 84 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32, 44) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426, 24) and fracture risk (n = 426, 95) in UK Biobank. Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ). B4GALNT3 is an N-acetyl-galactosaminyltransferase, adding a terminal LacdiNAc disaccharide to target glycocoproteins, found to be predominantly expressed in kidney, whereas GALNT1 is an enzyme causing mucin-type O-linked glycosylation. Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21). Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%). Our findings suggest that higher sclerostin levels are causally related to lower BMD and greater fracture risk. Hence, strategies for reducing circulating sclerostin, for example by targeting glycosylation enzymes as suggested by our GWAS results, may prove valuable in treating osteoporosis. © 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.\n © 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n128861\nValidation of novel 3-dimensional electrocardiographic mapping of atrial tachycardias by invasive mapping and ablation: a multicenter study.\n\nShah, AJ\n\nHocini, M\n\nXhaet, O\n\nPascale, P\n\nRoten, L\n\nWilton, SB\n\nLinton, N\n\nScherr, D\n\nMiyazaki, S\n\nJadidi, AS\n\nLiu, X\n\nForclaz, A\n\nNault, I\n\nRivard, L\n\nPedersen, ME\n\nDerval, N\n\nSacher, F\n\nKnecht, S\n\nJais, P\n\nDubois, R\n\nEliautou, S\n\nBokan, R\n\nStrom, M\n\nRamanathan, C\n\nCakulev, I\n\nSahadevan, J\n\nLindsay, B\n\nWaldo, AL\n\nHaissaguerre, M\n\nBeiträge in Fachzeitschriften\nISI:000323900300007\n23727090.0\n10.1016/j.jacc.2013.03.082\nNone\nThis study prospectively evaluated the role of a novel 3-dimensional, noninvasive, beat-by-beat mapping system, Electrocardiographic Mapping (ECM), in facilitating the diagnosis of atrial tachycardias (AT).\n Conventional 12-lead electrocardiogram, a widely used noninvasive tool in clinical arrhythmia practice, has diagnostic limitations.\n Various AT (de novo and post-atrial fibrillation ablation) were mapped using ECM followed by standard-of-care electrophysiological mapping and ablation in 52 patients. The ECM consisted of recording body surface electrograms from a 252-electrode-vest placed on the torso combined with computed tomography-scan-based biatrial anatomy (CardioInsight Inc., Cleveland, Ohio). We evaluated the feasibility of this system in defining the mechanism of AT-macro-re-entrant (perimitral, cavotricuspid isthmus-dependent, and roof-dependent circuits) versus centrifugal (focal-source) activation-and the location of arrhythmia in centrifugal AT. The accuracy of the noninvasive diagnosis and detection of ablation targets was evaluated vis-à-vis subsequent invasive mapping and successful ablation.\n Comparison between ECM and electrophysiological diagnosis could be accomplished in 48 patients (48 AT) but was not possible in 4 patients where the AT mechanism changed to another AT (n = 1), atrial fibrillation (n = 1), or sinus rhythm (n = 2) during the electrophysiological procedure. ECM correctly diagnosed AT mechanisms in 44 of 48 (92%) AT: macro-re-entry in 23 of 27; and focal-onset with centrifugal activation in 21 of 21. The region of interest for focal AT perfectly matched in 21 of 21 (100%) AT. The 2:1 ventricular conduction and low-amplitude P waves challenged the diagnosis of 4 of 27 macro-re-entrant (perimitral) AT that can be overcome by injecting atrioventricular node blockers and signal averaging, respectively.\n This prospective multicenter series shows a high success rate of ECM in accurately diagnosing the mechanism of AT and the location of focal arrhythmia. Intraprocedural use of the system and its application to atrial fibrillation mapping is under way.\n Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.\n\nScherr, Daniel\n\n\n"
},
{
"text": "\n136613\nThe flow rate significantly influences the leukocyte depletion rate during prestorage in-line filtration of platelet concentrates.\n\nJanetzko, K\n\nSchlenke, P\n\nKlüter, H\n\nBeiträge in Fachzeitschriften\nISI:000084306100005\n10747520.0\n10.1016/S0955-3886(99)00083-1\nNone\nBackground: White cell reduction of blood products minimizes the risks of alloimmunization against HLA-antigens, the transmission of viral diseases and the incidence of platelet transfusion reactions. One modern strategy is leukocyte depletion with an integrated filter system immediately after preparation and prior to storage. Study design and methods: We evaluated the efficiency of a never in-line filter system Sepacell(R) PLX-5 BPS for leukocyte reduction of platelet concentrates (PC) from pooled huffy-coats. A total of 44 PCs were investigated with regard to different filtration flow rates (25-110 ml/min) and leukocyte depletion and thrombocyte recovery rates were analysed. Furthermore, we studied the influence of filtration on PCs over a storage period of 6 days (n = 12) by investigation of pH, lactate and glucose. Platelet function was determined by means of hypotonic shock response, external shape change and expression of CD62p. Results: The mean leukocyte depletion rate was >log 5. After filtration the mean leukocyte count was 0.12 +/- 0.21 x 10(6). In 60% of the PCs the leukocyte count lay below the detection level of the Nageotte chamber, which is <0.3 x 10(5). The flow rate correlates significantly with the leukocyte count in the PCs (r = 0.325; p = 0.033) and therefore with the leukocyte depletion rate (r = -0.422; p = 0.01). Flow rates under 40 ml lead to a significantly lower leukocyte contamination. Only in one PC, at a flow rate of 84 ml/min, was the leukocyte threshold of 1 x 10(6) exceeded. We did not find a significant correlation between filtration flow rate and thrombocyte recovery (r = 0.315; p = 0.069). The mean platelet count in the PC was 2.88 +/- 0.47 x 10(11). Compared with the thrombocyte count in the pooled buffy coat, the recovery was 68.6%. We observed a decrease of pH, glucose, external shape change and hypotonic shock response over the storage period while lactate and the expression of CD62p increased. Conclusion: The filter system Sepacell(R) PLX-5 BPS proved to be suitable for in-line filtration of platelet concentrates prior to storage. Filtration flow rates of up to 40 ml/min allowed efficient leukocyte depletion without significant loss in the quality of the platelet concentrates and the platelet function in vitro. (C) 1999 Elsevier Science Ltd. All rights reserved.\n\nSchlenke, Peter\n\n\n"
},
{
"text": "\n139522\nCross-sectional study of 168 patients with hepatorenal tyrosinaemia and implications for clinical practice.\n\nMayorandan, S\n\nMeyer, U\n\nGokcay, G\n\nSegarra, NG\n\nde Baulny, HO\n\nvan Spronsen, F\n\nZeman, J\n\nde Laet, C\n\nSpiekerkoetter, U\n\nThimm, E\n\nMaiorana, A\n\nDionisi-Vici, C\n\nMoeslinger, D\n\nBrunner-Krainz, M\n\nLotz-Havla, AS\n\nCocho de Juan, JA\n\nCouce Pico, ML\n\nSanter, R\n\nScholl-Bürgi, S\n\nMandel, H\n\nBliksrud, YT\n\nFreisinger, P\n\nAldamiz-Echevarria, LJ\n\nHochuli, M\n\nGautschi, M\n\nEndig, J\n\nJordan, J\n\nMcKiernan, P\n\nErnst, S\n\nMorlot, S\n\nVogel, A\n\nSander, J\n\nDas, AM\n\nBeiträge in Fachzeitschriften\nISI:000341033000001\n25081276.0\n10.1186/s13023-014-0107-7\nPMC4347563\nHepatorenal tyrosinaemia (Tyr 1) is a rare inborn error of tyrosine metabolism. Without treatment, patients are at high risk of developing acute liver failure, renal dysfunction and in the long run hepatocellular carcinoma. The aim of our study was to collect cross-sectional data.\n Via questionnaires we collected retrospective data of 168 patients with Tyr 1 from 21 centres (Europe, Turkey and Israel) about diagnosis, treatment, monitoring and outcome. In a subsequent consensus workshop, we discussed data and clinical implications.\n Early treatment by NTBC accompanied by diet is essential to prevent serious complications such as liver failure, hepatocellular carcinoma and renal disease. As patients may remain initially asymptomatic or develop uncharacteristic clinical symptoms in the first months of life newborn mass screening using succinylacetone (SA) as a screening parameter in dried blood is mandatory for early diagnosis. NTBC-treatment has to be combined with natural protein restriction supplemented with essential amino acids. NTBC dosage should be reduced to the minimal dose allowing metabolic control, once daily dosing may be an option in older children and adults in order to increase compliance. Metabolic control is judged by SA (below detection limit) in dried blood or urine, plasma tyrosine (<400 μM) and NTBC-levels in the therapeutic range (20-40 μM). Side effects of NTBC are mild and often transient. Indications for liver transplantation are hepatocellular carcinoma or failure to respond to NTBC. Follow-up procedures should include liver and kidney function tests, tumor markers and imaging, ophthalmological examination, blood count, psychomotor and intelligence testing as well as therapeutic monitoring (SA, tyrosine, NTBC in blood).\n Based on the data from 21 centres treating 168 patients we were able to characterize current practice and clinical experience in Tyr 1. This information could form the basis for clinical practice recommendations, however further prospective data are required to underpin some of the recommendations.\n\nBrunner-Krainz, Michaela\n\n\n"
},
{
"text": "\n166097\nComprehensive genotyping and clinical characterisation reveal 27 novel NKX2-1 mutations and expand the phenotypic spectrum.\n\nThorwarth, A\n\nSchnittert-Hübener, S\n\nSchrumpf, P\n\nMüller, I\n\nJyrch, S\n\nDame, C\n\nBiebermann, H\n\nKleinau, G\n\nKatchanov, J\n\nSchuelke, M\n\nEbert, G\n\nSteininger, A\n\nBönnemann, C\n\nBrockmann, K\n\nChristen, HJ\n\nCrock, P\n\ndeZegher, F\n\nGriese, M\n\nHewitt, J\n\nIvarsson, S\n\nHübner, C\n\nKapelari, K\n\nPlecko, B\n\nRating, D\n\nStoeva, I\n\nRopers, HH\n\nGrüters, A\n\nUllmann, R\n\nKrude, H\n\nBeiträge in Fachzeitschriften\nISI:000336841300003\n24714694.0\n10.1136/jmedgenet-2013-102248\nPMC5240655\nNKX2-1 encodes a transcription factor with large impact on the development of brain, lung and thyroid. Germline mutations of NKX2-1 can lead to dysfunction and malformations of these organs. Starting from the largest coherent collection of patients with a suspected phenotype to date, we systematically evaluated frequency, quality and spectrum of phenotypic consequences of NKX2-1 mutations.\n After identifying mutations by Sanger sequencing and array CGH, we comprehensively reanalysed the phenotype of affected patients and their relatives. We employed electrophoretic mobility shift assay (EMSA) to detect alterations of NKX2-1 DNA binding. Gene expression was monitored by means of in situ hybridisation and compared with the expression level of MBIP, a candidate gene presumably involved in the disorders and closely located in close genomic proximity to NKX2-1.\n Within 101 index patients, we detected 17 point mutations and 10 deletions. Neurological symptoms were the most consistent finding (100%), followed by lung affection (78%) and thyroidal dysfunction (75%). Novel symptoms associated with NKX2-1 mutations comprise abnormal height, bouts of fever and cardiac septum defects. In contrast to previous reports, our data suggest that missense mutations in the homeodomain of NKX2-1 not necessarily modify its DNA binding capacity and that this specific type of mutations may be associated with mild pulmonary phenotypes such as asthma. Two deletions did not include NKX2-1, but MBIP, whose expression spatially and temporarily coincides with NKX2-1 in early murine development.\n The high incidence of NKX2-1 mutations strongly recommends the routine screen for mutations in patients with corresponding symptoms. However, this analysis should not be confined to the exonic sequence alone, but should take advantage of affordable NGS technology to expand the target to adjacent regulatory sequences and the NKX2-1 interactome in order to maximise the yield of this diagnostic effort.\n Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.\n\nPlecko, Barbara\n\n\n"
},
{
"text": "\n1264\nImmunohistochemical characterization of a crypt cell-specific plasma membrane protein in rat small intestine epithelium using a monoclonal antibody.\n\nSchiechl, H\n\nBeiträge in Fachzeitschriften\nISI:A1991FT14600011\n1865113.0\n10.1177/39.7.1865113\nNone\nProteins of the basolateral membrane (BLM) of small intestine epithelial cells of adult rats, in the MW ranges of 50-65 KD, 85-100 KD, and over 100 KD, were obtained as follows. After isolation of the BLM and subsequent SDS-PAGE and transblotting of the proteins on nitrocellulose sheets, the bands in these MW ranges were cut out of the nitrocellulose sheet and extracted. Balb/C mice were immunized with these protein fractions and a monoclonal antibody (MAb) was then produced. MAb SI/CC1 obtained via immunization with the 50-65 KD protein fraction shows specificity for the crypt epithelium of the small intestine. It can be used to characterize, by light and electron microscopic immunohistochemical methods, a crypt cell protein (SI/CC1-Ag) with a very specific localization. Fluorescence labeling shows that the SI/CC1-Ag can be found only in the epithelium of small intestine crypts (except for the granules in eosinophilic granulocytes). The epithelium of the colon, as well as the epithelia of other organs, could not be labeled. In the small intestine crypts, SI/CC1-Ag is found only in the Paneth cells located in the basal crypt section, and in the undifferentiated cells in the middle crypt section; it is lacking in the cells of the upper crypt section. Gold labeling shows that SI/CC1-Ag in the undifferentiated cells is localized exclusively in the basolateral PM domain. On the Paneth cells, the content of the secretory granules is labeled, along with the basolateral PM domain; the labeling sometimes present on their luminal part is probably due to passively absorbed secretion from these cells. The SI/CC1-Ag in the BLM of undifferentiated and Paneth cells is found only on Days 21-23 post partum, whereas the Paneth cell granules could be labeled as early as the Day 16 post partum. With immunodetection with SI/CC1, one band at about 55 KD is specifically labeled in the protein pattern of the isolated small intestine cell BLM. In the protein pattern of the isolated crypt cells two bands were labeled, again one at 55 KD and one at about 120 KD. These findings indicate that SI/CC1-Ag is a 55 KD protein that appears on Days 21-23 post partum in the BLM of undifferentiated cells and of Paneth cells.\n\n\n"
},
{
"text": "\n12576\nImpact of age-related cerebral white matter changes on the transition to disability -- the LADIS study: rationale, design and methodology.\n\nPantoni, L\n\nBasile, AM\n\nPracucci, G\n\nAsplund, K\n\nBogousslavsky, J\n\nChabriat, H\n\nErkinjuntti, T\n\nFazekas, F\n\nFerro, JM\n\nHennerici, M\n\nO'brien, J\n\nScheltens, P\n\nVisser, MC\n\nWahlund, LO\n\nWaldemar, G\n\nWallin, A\n\nInzitari, D\n\nBeiträge in Fachzeitschriften\nISI:000226021500009\n15459510.0\n10.1159/000081050\nNone\nAge-related white matter changes (ARWMC) on brain MRI have been associated with cognitive, motor, mood and urinary disturbances. These factors are known to contribute to disability in elderly people, but the impact of ARWMC and of their progression on the transition to disability is not determined. The LADIS (Leukoaraiosis and Disability in the Elderly) study aims at assessing the role of ARWMC as an independent predictor of the transition to disability in initially nondisabled elderly (65-84 years). Subjects who are not impaired or impaired on only 1 item of the Instrumental Activity of Daily Living (IADL) scale, presenting with different grades of ARWMC severity, were enrolled. Eleven European centers are involved. All the patients were assessed at baseline using an extensive set of clinical and functional tests including global functioning, cognitive, motor, psychiatric and quality of life measures. MRI studies were performed at baseline and will be repeated at the end of the follow-up period to evaluate changes of ARWMC and other lesions. ARWMC were categorized into mild, moderate or severe using the scale of Fazekas et al. For each ARWMC severity class, the primary study outcome is the transition to disability defined as an impairment on 2 or more IADL scale items. Secondary outcomes are the occurrence of dementia, depression, vascular events or death. Six-hundred and thirty-nine subjects (mean age 74.13 +/- 5.0 years, M/F: 288/351) were enrolled in a hospital-based setting and are being followed up for up to 3 years. The large and comprehensive set of measures in LADIS enables a comprehensive description of their functional and clinical features to be examined in relation to different morphological patterns and severity of ARWMC. The longitudinal design will give insight into the possible role of ARWMC and their progression as an independent contributor to disability in the elderly, eventually helping to develop preventive strategies to reduce the burden of disability in late life. The study results may also help to standardize, on an international basis, tools and criteria to identify early stages of disability.\n\nFazekas, Franz\n\n\n"
},
{
"text": "\n108227\nSurgical occlusion of cerebrospinal fistulas of the anterior skull base using intrathecal sodium fluorescein].\n\nStammberger, H\n\nGreistorfer, K\n\nWolf, G\n\nLuxenberger, W\n\nBeiträge in Fachzeitschriften\nISI:A1997YE39800005\n9445526.0\n10.1055/s-2007-997487\nNone\nFor more than 25 years, intrathecal 5% sodium fluorescein has been routinely used at the University ENT Hospital at Graz during surgical closures of CSF leaks of the anterior skull base. Especially with endoscopic approaches, this technique has been of significant help in identifying and localizing dural defects. No fluorescein-related complications occurred in the series reported.\n In a retrospective study, indications, techniques, and results of surgical closures of CSF leaks of the anterior skull base are reviewed. During 5 1/2 years from 1990-1995, 72 patients with CSF-rhinorrhea were operated on at our department, 69 of whom had sodium fluorescein applied intrathecally. In 41 patients strictly endoscopic techniques were applied, in 22 patients an external approach was chosen and in 9 cases combined approaches were used. Defects in the roof of the ethmoid, the lamina cribrosa, and in the sphenoid sinus almost exclusively were approached endoscopically. Defects in the posterior table of the frontal sinus, especially when located laterally, were approached from externally or via combined endonasal and external routes. The causes of the CSF leaks, their localization, and the surgical approaches chosen are analysed and the surgical techniques described in detail.\n The direct coronal CT of the paranasal sinuses/anterior skull base proved to be significantly better in detecting lesions compared to axial CT images (82% vs. 53%). In all cases intrathecal fluorescein allowed for a precise localization of the defect(s). There were no fluorescein related complications in this series. In one patient with massive frontobasal chip fractures and substantial dural defect, a rhinosurgical closure was not successful. Two patients developed recurrent fistulae after several months and years respectively. One of these patients had to be operated 3 times until permanent closure was achieved. Two patients had to be revised because of mucoceles of the frontal sinuses, in both cases the initial closure of the dural defect proved to be tight.\n Our results demonstrate that with exception of defects of the posterior lateral table of the frontal sinus, CSF leaks of the rhinobasis can be closed safely endoscopically. After a follow-up from 19-65 months, the overall success rate for 72 CSF leaks was at 94.5%. When applied correctly, the fluorescein technique proves to be an extremely helpful technique for diagnosis and surgery of CSF leaks.\n\nLuxenberger, Wolfgang\n\n\n"
},
{
"text": "\n109833\nExpression of cell cycle proteins in male breast carcinoma.\n\nKanthan, R\n\nFried, I\n\nRueckl, T\n\nSenger, JL\n\nKanthan, SC\n\nBeiträge in Fachzeitschriften\nISI:000275096700001\n20152033.0\n10.1186/1477-7819-8-10\nPMC2829567\nMale breast cancer (MBC) is a rare, yet potentially aggressive disease. Although literature regarding female breast cancer (FBC) is extensive, little is known about the etiopathogenesis of male breast cancer. Studies from our laboratory show that MBCs have a distinct immunophenotypic profile, suggesting that the etiopathogenesis of MBC is different from FBCs. The aim of this study was to evaluate and correlate the immunohistochemical expression of cell cycle proteins in male breast carcinoma to significant clinico-biological endpoints.\n 75 cases of MBC were identified using the records of the Saskatchewan Cancer Agency over 26 years (1970-1996). Cases were reviewed and analyzed for the immunohistochemical expression of PCNA, Ki67, p27, p16, p57, p21, cyclin-D1 and c-myc and correlated to clinico-biological endpoints of tumor size, node status, stage of the disease, and disease free survival (DFS).\n Decreased DFS was observed in the majority of tumors that overexpressed PCNA (98%, p = 0.004). The overexpression of PCNA was inversely correlated to the expression of Ki67 which was predominantly negative (78.3%). Cyclin D1 was overexpressed in 83.7% of cases. Cyclin D1 positive tumors were smaller than 2 cm (55.6%, p = 0.005), had a low incidence of lymph node metastasis (38.2%, p = 0.04) and were associated with increased DFS of >150 months (p = 0.04). Overexpression of c-myc (90%) was linked with a higher incidence of node negativity (58.3%, p = 0.006) and increased DFS (p = 0.04). p27 over expression was associated with decreased lymph node metastasis (p = 0.04). P21 and p57 positive tumors were related to decreased DFS (p = 0.04). Though p16 was overexpressed in 76.6%, this did not reach statistical significance with DFS (p = 0.06) or nodal status (p = 0.07).\n Aberrant cell cycle protein expression supports our view that these are important pathways involved in the etiopathogenesis of MBC. Tumors with overexpression of Cyclin D1 and c-myc had better outcomes, in contrast to tumors with overexpression of p21, p57, and PCNA with significantly worse outcomes. P27 appears to be a predictive marker for lymph nodal status. Such observation strongly suggests that dysregulation of cell cycle proteins may play a unique role in the initiation and progression of disease in male breast cancer. Such findings open up new avenues for the treatment of MBC as a suitable candidate for novel CDK-based anticancer therapies in the future.\n\nFried, Isabella\n\n\n"
},
{
"text": "\n113057\nMeta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque.\n\nBis, JC\n\nKavousi, M\n\nFranceschini, N\n\nIsaacs, A\n\nAbecasis, GR\n\nSchminke, U\n\nPost, WS\n\nSmith, AV\n\nCupples, LA\n\nMarkus, HS\n\nSchmidt, R\n\nHuffman, JE\n\nLehtimäki, T\n\nBaumert, J\n\nMünzel, T\n\nHeckbert, SR\n\nDehghan, A\n\nNorth, K\n\nOostra, B\n\nBevan, S\n\nStoegerer, EM\n\nHayward, C\n\nRaitakari, O\n\nMeisinger, C\n\nSchillert, A\n\nSanna, S\n\nVölzke, H\n\nCheng, YC\n\nThorsson, B\n\nFox, CS\n\nRice, K\n\nRivadeneira, F\n\nNambi, V\n\nHalperin, E\n\nPetrovic, KE\n\nPeltonen, L\n\nWichmann, HE\n\nSchnabel, RB\n\nDörr, M\n\nParsa, A\n\nAspelund, T\n\nDemissie, S\n\nKathiresan, S\n\nReilly, MP\n\nTaylor, K\n\nUitterlinden, A\n\nCouper, DJ\n\nSitzer, M\n\nKähönen, M\n\nIllig, T\n\nWild, PS\n\nOrru, M\n\nLüdemann, J\n\nShuldiner, AR\n\nEiriksdottir, G\n\nWhite, CC\n\nRotter, JI\n\nHofman, A\n\nSeissler, J\n\nZeller, T\n\nUsala, G\n\nErnst, F\n\nLauner, LJ\n\nD'Agostino, RB\n\nO'Leary, DH\n\nBallantyne, C\n\nThiery, J\n\nZiegler, A\n\nLakatta, EG\n\nChilukoti, RK\n\nHarris, TB\n\nWolf, PA\n\nPsaty, BM\n\nPolak, JF\n\nLi, X\n\nRathmann, W\n\nUda, M\n\nBoerwinkle, E\n\nKlopp, N\n\nSchmidt, H\n\nWilson, JF\n\nViikari, J\n\nKoenig, W\n\nBlankenberg, S\n\nNewman, AB\n\nWitteman, J\n\nHeiss, G\n\nDuijn, Cv\n\nScuteri, A\n\nHomuth, G\n\nMitchell, BD\n\nGudnason, V\n\nO'Donnell, CJ\n\nCARDIoGRAM Consortium\n\nBeiträge in Fachzeitschriften\nISI:000295316200007\n21909108.0\n10.1038/ng.920\nPMC3257519\nCarotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31, 11 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11, 73 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10(-8)). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events.\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\nStögerer-Oberschmid, Eva Maria\n\n\n"
},
{
"text": "\n127840\nDermoscopic Evaluation of Nodular Melanoma.\n\nMenzies, SW\n\nMoloney, FJ\n\nByth, K\n\nAvramidis, M\n\nArgenziano, G\n\nZalaudek, I\n\nBraun, RP\n\nMalvehy, J\n\nPuig, S\n\nRabinovitz, HS\n\nOliviero, M\n\nCabo, H\n\nBono, R\n\nPizzichetta, MA\n\nClaeson, M\n\nGaffney, DC\n\nSoyer, HP\n\nStanganelli, I\n\nScolyer, RA\n\nGuitera, P\n\nKelly, J\n\nMcCurdy, O\n\nLlambrich, A\n\nMarghoob, AA\n\nZaballos, P\n\nKirchesch, HM\n\nPiccolo, D\n\nBowling, J\n\nThomas, L\n\nTerstappen, K\n\nTanaka, M\n\nPellacani, G\n\nPagnanelli, G\n\nGhigliotti, G\n\nOrtega, BC\n\nCrafter, G\n\nOrtiz, AM\n\nTromme, I\n\nKaraarslan, IK\n\nOzdemir, F\n\nTam, A\n\nLandi, C\n\nNorton, P\n\nKaçar, N\n\nRudnicka, L\n\nSlowinska, M\n\nSimionescu, O\n\nDi Stefani, A\n\nCoates, E\n\nKreusch, J\n\nBeiträge in Fachzeitschriften\nISI:000320857700008\n23553375.0\n10.1001/jamadermatol.2013.2466\nNone\nImportance: Nodular melanoma (NM) is a rapidly progressing potentially lethal skin tumor for which early diagnosis is critical.\nObjective: To determine the dermoscopy features of NM.\nDesign: Eighty-three cases of NM, 134 of invasive non-NM, 115 of nodular benign melanocytic tumors, and 135 of nodular nonmelanocytic tumors were scored for dermoscopy features using modified and previously described methods. Lesions were separated into amelanotic/hypomelanotic or pigmented to assess outcomes.\nSetting: Predominantly hospital-based clinics from 5 continents.\nMain Outcome Measures: Sensitivity, specificity, and odds ratios for features/models for the diagnosis of melanoma.\nResults: Nodular melanoma occurred more frequently as amelanotic/hypomelanotic (37.3%) than did invasive non-NM (7.5%). Pigmented NM had a more frequent (compared with invasive non-NM; in descending order of odds ratio) symmetrical pigmentation pattern (5.8% vs 0.8%), large-diameter vessels, areas of homogeneous blue pigmentation, symmetrical shape, predominant peripheral vessels, blue-white veil, pink color, black color, and milky red/pink areas. Pigmented NM less frequently displayed an atypical broadened network, pigment network or pseudonetwork, multiple blue-gray dots, scarlike depigmentation, irregularly distributed and sized brown dots and globules, tan color, irregularly shaped depigmentation, and irregularly distributed and sized dots and globules of any color. The most important positive correlating features of pigmented NM vs nodular non-melanoma were peripheral black dots/globules, multiple brown dots, irregular black dots/globules, blue-white veil, homogeneous blue pigmentation, 5 to 6 colors, and black color. A model to classify a lesion as melanocytic gave a high sensitivity (ANDgt;98.0%) for both nodular pigmented and nonnodular pigmented melanoma but a lower sensitivity for amelanotic/hypomelanotic NM (84%). A method for diagnosing amelanotic/ hypomelanotic malignant lesions (including basal cell carcinoma) gave a 93% sensitivity and 70% specificity for NM.\nConclusions and Relevance: When a progressively growing, symmetrically patterned melanocytic nodule is identified, NM needs to be excluded.\n\nZalaudek, Iris\n\n\n"
},
{
"text": "\n140670\nUltrasound composite scores for the assessment of inflammatory and structural pathologies in Psoriatic Arthritis (PsASon-Score).\n\nFicjan, A\n\nHusic, R\n\nGretler, J\n\nLackner, A\n\nGraninger, WB\n\nGutierrez, M\n\nDuftner, C\n\nHermann, J\n\nDejaco, C\n\nBeiträge in Fachzeitschriften\nISI:000349885900053\n25361855.0\n10.1186/s13075-014-0476-2\nPMC4247751\nThis study was performed to develop ultrasound composite scores for the assessment of inflammatory and structural lesions in Psoriatic Arthritis (PsA).\n We performed a prospective study on 83 PsA patients undergoing two study visits scheduled 6 months apart. B-mode and Power Doppler (PD) findings were semi-quantitatively scored at 68 joints (evaluating synovia, perisynovial tissue, tendons and bone) and 14 entheses. We constructed bilateral and unilateral (focusing the dominant site) ultrasound composite scores selecting relevant sites by a hierarchical approach. We tested convergent construct validity, reliability and feasibility of inflammatory and structural elements of the scores as well as sensitivity to change for inflammatory items.\n The bilateral score (termed PsASon22) included 22 joints (6 metacarpophalangeal joints (MCPs), 4 proximal interphalangeal joints (PIPs) of hands (H-PIPs), 2 metatarsophalangeal joints (MTPs), 4 distal interphalangeal joints (DIPs) of hands (H-DIPs), 2 DIPs of feet (F-DIPs), 4 large joints) and 4 entheses (bilateral assessment of lateral epicondyle and distal patellar tendon). The unilateral score (PsASon13) compromised 13 joints (2 MCPs, 3 H-PIPs, 1 PIP of feet (F-PIP), 2 MTPs, 1 H-DIP and 2 F-DIPs and 2 large joints) and 2 entheses (unilateral lateral epicondyle and distal patellar tendon). Both composite scores revealed a moderate to high sensitivity (bilateral composite score 43% to 100%, unilateral 36% to 100%) to detect inflammatory and structural lesions compared to the 68-joint/14-entheses score. The inflammatory and structural components of the composite scores correlated weakly with clinical markers of disease activity (corrcoeffs 0 to 0.40) and the health assessment questionnaire (HAQ, corrcoeffs 0 to 0.39), respectively. Patients with active disease achieving remission at follow-up yielded greater reductions of ultrasound inflammatory scores than those with stable clinical activity (Cohen's d effect size ranging from 0 to 0.79). Inter-rater reliability of bi- and unilateral composite scores was moderate to good with ICCs ranging from 0.42 to 0.96 and from 0.36 to 0.71, respectively for inflammatory and structural sub-scores. The PsASon22 and PsASon13 required 16 to 26 and 9 to 13 minutes, respectively to be completed.\n Both new PsA ultrasound composite scores (PsASon22 and PsASon13) revealed sufficient convergent construct validity, sensitivity to change, reliability and feasibility.\n\nDejaco, Christian\n\nGraninger, Winfried\n\nHermann, Josef\n\nHusic, Rusmir\n\nLackner, Angelika\n\n\n"
},
{
"text": "\n148537\nThe Consolidated Framework for Implementation Research (CFIR): a useful theoretical framework for guiding and evaluating a guideline implementation process in a hospital-based nursing practice.\n\nBreimaier, HE\n\nHeckemann, B\n\nHalfens, RJ\n\nLohrmann, C\n\nBeiträge in Fachzeitschriften\nNone\n26269693.0\n10.1186/s12912-015-0088-4\nPMC4533946\nImplementing clinical practice guidelines (CPGs) in healthcare settings is a complex intervention involving both independent and interdependent components. Although the Consolidated Framework for Implementation Research (CFIR) has never been evaluated in a practical context, it appeared to be a suitable theoretical framework to guide an implementation process. The aim of this study was to evaluate the comprehensiveness, applicability and usefulness of the CFIR in the implementation of a fall-prevention CPG in nursing practice to improve patient care in an Austrian university teaching hospital setting.\n The evaluation of the CFIR was based on (1) team-meeting minutes, (2) the main investigator's research diary, containing a record of a before-and-after, mixed-methods study design embedded in a participatory action research (PAR) approach for guideline implementation, and (3) an analysis of qualitative and quantitative data collected from graduate and assistant nurses in two Austrian university teaching hospital departments. The CFIR was used to organise data per and across time point(s) and assess their influence on the implementation process, resulting in implementation and service outcomes.\n Overall, the CFIR could be demonstrated to be a comprehensive framework for the implementation of a guideline into a hospital-based nursing practice. However, the CFIR did not account for some crucial factors during the planning phase of an implementation process, such as consideration of stakeholder aims and wishes/needs when implementing an innovation, pre-established measures related to the intended innovation and pre-established strategies for implementing an innovation. For the CFIR constructs reflecting & evaluating and engaging, a more specific definition is recommended. The framework and its supplements could easily be used by researchers, and their scope was appropriate for the complexity of a prospective CPG-implementation project. The CFIR facilitated qualitative data analysis and provided a structure that allowed project results to be organised and viewed in a broader context to explain the main findings.\n The CFIR was a valuable and helpful framework for (1) the assessment of the baseline, process and final state of the implementation process and influential factors, (2) the content analysis of qualitative data collected throughout the implementation process, and (3) explaining the main findings.\n\nLohrmann, Christa\n\n\n"
},
{
"text": "\n178106\nObeticholic acid may increase the risk of gallstone formation in susceptible patients.\n\nAl-Dury, S\n\nWahlström, A\n\nPanzitt, K\n\nThorell, A\n\nStåhlman, M\n\nTrauner, M\n\nFickert, P\n\nBäckhed, F\n\nFändriks, L\n\nWagner, M\n\nMarschall, HU\n\nBeiträge in Fachzeitschriften\nISI:000490139600018\n31254596.0\n10.1016/j.jhep.2019.06.011\nNone\nThe nuclear farnesoid X receptor (FXR) agonist obeticholic acid (OCA) has been developed for the treatment of liver diseases. We aimed to determine whether OCA treatment increases the risk of gallstone formation.\n Twenty patients awaiting laparoscopic cholecystectomy were randomized to treatment with OCA (25 mg/day) or placebo for 3 weeks until the day before surgery. Serum bile acids (BAs), the BA synthesis marker C4 (7α-hydroxy-4-cholesten-3-one), and fibroblast growth factor 19 (FGF19) were measured before and after treatment. During surgery, biopsies from the liver and the whole bile-filled gallbladder were collected for analyses of gene expression, biliary lipids and FGF19.\n In serum, OCA increased FGF19 (from 95.0 ± 8.5 to 234.4 ± 35.6 ng/L) and decreased C4 (from 31.4 ± 22.8 to 2.8 ± 4.0 nmol/L) and endogenous BAs (from 1, 12.2 ± 236.2 to 517.7 ± 178.9 nmol/L; all p <0.05). At surgery, BAs in gallbladder bile were lower in patients that received OCA than in controls (OCA, 77.9 ± 53.6 mmol/L; placebo, 196.4 ± 99.3 mmol/L; p <0.01), resulting in a higher cholesterol saturation index (OCA, 2.8 ± 1.1; placebo, 1.8 ± 0.8; p <0.05). In addition, hydrophobic OCA conjugates accounted for 13.6 ± 5.0% of gallbladder BAs after OCA treatment, resulting in a higher hydrophobicity index (OCA, 0.43 ± 0.09; placebo, 0.34 ± 0.07, p <0.05). Gallbladder FGF19 levels were 3-fold higher in OCA patients than in controls (OCA, 40.3 ± 16.5 ng/L; placebo, 13.5 ± 13.1 ng/ml; p <0.005). Gene expression analysis indicated that FGF19 mainly originated from the gallbladder epithelium.\n Our results show for the first time an enrichment of FGF19 in human bile after OCA treatment. In accordance with its murine homolog FGF15, FGF19 might trigger relaxation and filling of the gallbladder which, in combination with increased cholesterol saturation and BA hydrophobicity, would enhance the risk of gallstone development.\n Obeticholic acid increased human gallbladder cholesterol saturation and bile acid hydrophobicity, both decreasing cholesterol solubility in bile. Together with increased hepatobiliary levels of fibroblast growth factor 19, our findings suggest that pharmacological activation of the farnesoid X receptor increases the risk of gallstone formation. Clinical trial number: NCT01625026.\n Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.\n\nFickert, Peter\n\nPanzitt, Katrin\n\nWagner, Martin\n\n\n"
},
{
"text": "\n2402\nSpecific cutaneous infiltrates of B-cell chronic lymphocytic leukemia: a clinicopathologic and prognostic study of 42 patients.\n\nCerroni, L\n\nZenahlik, P\n\nHöfler, G\n\nKaddu, S\n\nSmolle, J\n\nKerl, H\n\nBeiträge in Fachzeitschriften\nISI:A1996UZ12600009\n8712287.0\n10.1097%2F00000478-199608000-00009\nNone\nThe clinical and histopathologic features of specific skin infiltrates in patients with B-cell chronic lymphocytic leukemia (B-CLL) have rarely been reported in detail. In this study we analyzed the clinical, histopathologic, immunophenotypic, and molecular features of 84 skin lesions from 42 patients (M:F = 1.3:1; mean age, 66.0 years; range, 42-83 years) with specific cutaneous manifestations of B-CLL. The duration of B-CLL before skin manifestations varied from 0 to 142 months (mean, 39 months). In seven patients (16.7%), skin lesions represented the first sign of disease. Clinical presentations included localized or generalized erythematous papules, plaques, nodules, and large tumors. Ulceration was uncommon. In six patients lesions were confined at the sites of scars from previous herpes zoster (four patients) or herpes simplex (two patients) eruptions. Histologically, three main patterns were recognized: (a) patchy perivascular and periadnexal, (b) nodular-diffuse, and (c) band-like. Cytomorphologically, small monomorphous lymphocytes predominated. Proliferation centers were observed in only four specimens. In two patients presenting with tumors, a high content of large cells with feature of centroblasts and immunoblasts was found (Richter's syndrome). Immunohistologic analyses were performed on paraffin-embedded specimens in 40 biopsies from 20 patients and on cryostat sections in 17 biopsies from 11 patients. Neoplastic B lymphocytes in all cases showed an aberrant phenotype (paraffin sections: CD20+/CD5+/CD43+; cryostat sections: CD19+/CD5+; immunoglobulin light-chain restriction). Proliferation markers (Ki67, PCNA, MIB1) stained 5 to 80% of cells (mean, 25%; median, 20%). Polymerase chain reaction performed in nine cases on paraffin-embedded tissues using consensus primers for immunoglobulin heavy-chain genes showed a monoclonal population of B lymphocytes in all cases. Several discrete bands in addition to the prominent ones were noted in five cases, indicating the additional presence of B lymphocytes whose immunoglobulin genes were not monoclonally but oligoclonally rearranged. Follow-up data could be obtained from 31 patients. The two patients with Richter's syndrome died after 5 and 8 months, respectively. The 5-year survival of patients with small-cell cutaneous B-CLL was 66.6%. Our study indicates that cutaneous specific manifestations of B-CLL present with characteristic histologic, immunophenotypic, and molecular patterns. Prognosis in these patients is probably not affected by skin involvement.\n\nCerroni, Lorenzo\n\nHöfler, Gerald\n\nKaddu, Steven\n\nKerl, Helmut\n\nSmolle, Josef\n\n\n"
},
{
"text": "\n4412\nSerum elimination of HES in moderately reduced renal function\n\nSchimetta, W\n\nKröll, W\n\nPölz, W\n\nColombo, T\n\nGassmayr, SE\n\nSirtl, C\n\nList, WF\n\nBeiträge in Fachzeitschriften\nISI:000177645100005\n12165916.0\n10.1055/s-2002-33159\nNone\nObjective: If or at which conditions hydroxyethyl starch (HES) is administerable in presence of reduced renal function, is a question still to be answered. The aim of this study was to give hints, whether a moderately reduced renal function (creatinine concentrations around 2, mg/dl) induces clinically relevant changes in pharmacokinetics of HES 200/0.5. Methods: Each of 8 test persons with elevated serum creatinine concentration (1.6-2.9 mg/dl - group H) and 6 test persons with normal serum creatinine concentration (0.7 - 1.1 mg/dl - group N) were infused with 500 ml of 10% HES 200/0.5 within 30 minutes. Concentrations of creatinine and HES were measured before starting the infusion, immediately after the end of the infusion as well as 30 minutes, 60 minutes, 3 hours, 6 hours and 24 hours I ater. Additionally in group H also the mean values of the intravital molecular mass of HES (weight average molecular weight Mw and number average molecular weight Mn) were assessed. HES concentrations were quantified by the hexokinase method. HES molecular mass spectrum was analyzed by an HPLC method. The mean dwelling time served as an indicator for HES pharmacokinetics. Results: The serum creatinine concentrations remained stable within the observation period. The HES serum concentrations were comparable between the two groups at any examination. Immediately after the end of the infusion, the HES serum concentration reached a maximum of 17.5 mg/ml (group H) and 17.4 mg/ml (group N), 24 hours later HES serum concentration ranged between 1.4 and 2.0 mg/ml (group H) respectively between 1.1 and 2.8 mg/ml (group N). The calculation for the mean dwelling time resulted in 5.0 hours for group H and 4.5 hours for group N (median values) without significant difference between the groups (p = 0.147). At the end of the observation period, the mean values of the molecular weight Mw and Mn measured in group H - reached the closest convergence (Mw: 71, 00 Dalton; Mn: 58, 00 Dalton; Mw/Mn: 1.32 - median values). Conclusion: Compensated renal failure with serum creatinine concentrations up to 2.9 mg/dl does not significantly delay the serum elimination of HES 200/0.5. All findings support the opinion that a peri-operative volume substitution with HES 200/0.5 can be applied in patients suffering from moderately reduced renal function in the same way as in patients without any renal impairment.\n\nKröll, Wolfgang\n\n\n"
},
{
"text": "\n4495\nPost-methionine-load hyperhomocysteinemia and increased lipoprotein(a) are associated with renal metabolic dysfunction: a hypothesis.\n\nHerrmann, W\n\nStanger, O\n\nKnapp, JP\n\nSemmelrock, HJ\n\nLemmerer, M\n\nRigler, B\n\nBeiträge in Fachzeitschriften\nISI:000178587200003\n12370840.0\n10.1053%2Fmeta.2002.35179\nNone\nPrevious studies have shown that homocysteine influences the structure of lipoprotein(a) [Lp(a)] and its affinity to fibrin, and that there is an increased risk of vascular disease when both homocysteine and Lp(a) are elevated. The aim of this study was to determine whether there is a correlation between increased total homocysteine (tHCY) and high Lp(a) concentrations, and whether increased concentrations of tHCY affect the concentration of unbound serum apolipoprotein(a) [Apo(a)]. Forty-seven male subjects recruited from a primary prevention screening program with normal serum creatinine and Lp(a) concentrations above 30 mg/dL were included and underwent a standardized oral methionine-loading test to increase the plasma tHCY concentration. This increase might lead to a modification of the Apo(a) structure, thus possibly influencing the serum concentration of unbound Apo(a). Fasting blood samples were taken before the tests and after 6 hours. The median values of tHCY increased about 4-fold after the methionine-loading test. Fasting tHCY did not show an association with Apo(a) and a post-methionine load increase of unbound Apo(a) was not observed. Backward multiple linear regression analysis, however, revealed that only post-load tHCY was independently and significantly influenced by Lp(a). Furthermore, Lp(a) correlated significantly with post-load tHCY, but not with fasting tHCY. Subdividing the subjects according to the Lp(a) concentration showed a significantly higher median concentration of tHCY after methionine load in subjects with Lp(a) over 50 mg/dL compared to subjects with Lp(a) under 50 mg/dL (P =.009). A similar cut-off was seen for post-load Apo(a) at 7.3 mg/dL (P =.04). Factors such as age, C677T-methylene-tetrahydrofolate-reductase (MTHFR) mutation, folate, vitamin B(12), and creatinine showed no significant influence on post-load tHCY in the different subgroups. The reasons for our findings remain partially unclear. However, considering our results and the current knowledge on the association of tHCY and Lp(a) concentration with the renal function, we hypothesize that both parameters may be linked by commencing renal metabolic dysfunction. It should be stressed that our hypothesis is speculative and that further studies will be necessary to improve the understanding of the interrelation of tHCY and Lp(a) concentration.\n Copyright 2002, Elsevier Science (USA). All rights reserved.\n\nLemmerer, Martina\n\n\n"
}
]
}