HTTP 200 OK
Allow: GET, HEAD, OPTIONS
Content-Type: application/json
Vary: Accept
{
"count": 127182,
"next": "https://api-test.medunigraz.at/v1/research/search/publication/?format=api&limit=20&offset=126180",
"previous": "https://api-test.medunigraz.at/v1/research/search/publication/?format=api&limit=20&offset=126140",
"results": [
{
"text": "\n1297\nIncomplete renal tubular acidosis in 'primary' osteoporosis.\n\nWeger, M\n\nDeutschmann, H\n\nWeger, W\n\nKotanko, P\n\nSkrabal, F\n\nBeiträge in Fachzeitschriften\nISI:000083340200012\n10692983.0\n10.1007%2Fs001980050235\nNone\nChronic metabolic acidosis may increase alkali mobilization from bone and thus promote the development of osteoporosis. While it is undisputed that overt metabolic acidosis is associated with metabolic bone disease, renal acidification in patients with idiopathic osteoporosis has not been studied systematically. The purpose of this study was to investigate the prevalence of renal acidification defects in patients with 'primary' osteoporosis. Thirty-two women (including 10 premenopausal women) and 16 men who were referred to our department for investigation of osteoporosis were enrolled in this study. Patients with obvious or possible secondary osteoporosis were excluded. None of the patients had overt metabolic acidosis. In random urine samples 12 of the 48 patients had pH levels below 5.5 and were therefore considered to have normal renal acidification. The remaining 36 patients underwent further testing by a short-course oral ammonium chloride load. In this test nine of these 36 patients (7 men and 2 premenopausal women) failed to lower urinary pH below 5.5 despite the induction of systemic metabolic acidosis. In these patients, therefore, the diagnosis of incomplete distal renal tubular acidosis was made (RTA I). Patients with incomplete RTA I had significantly lower spontaneous plasma pH (7.38 +/- 0.0081 vs 7.41 +/- 0.004, mean +/- SEM, p = 0.002), a lower serum bicarbonate concentration (21.9 +/- 0.49 mmol/l vs 23.1 +/- 0.24 mmol/l, p = 0.034), a lower base excess (-2.33 +/- 0.42 mmol/l vs -0.55 +/- 0.21 mmol/l, p = 0.001) and lower Z-scores in bone densitometry (-2.18 +/- 0.27 vs -1.40 +/- 0.15, p = 0.028) than patients with normal renal acidification. In conclusion, a high prevalence of incomplete RTA I (in 44% of the male patients, 20% of the premenopausal female patients and 6% of all female patients) was found in patients with osteoporosis who, without testing, would have been diagnosed as having 'primary' osteoporosis. The mild metabolic acidosis observed in these patients may have contributed to loss of bone mass by a compensatory mobilization of alkali and calcium from bone. Because of possible therapeutic consequences (e.g., administration of alkali salts and high doses of vitamin D) we propose that measurements of urinary pH and, if necessary, ammonium chloride testing should be included in the diagnostic investigation especially of male and of premenopausal female patients with osteoporosis. Since referral bias, although unlikely, cannot be excluded in our study, the prevalence of RTA I in unselected patients with osteoporosis needs to be determined at primary screening institutions.\n\nDeutschmann, Hannes\n\nWeger, Martin\n\nWeger, Wolfgang\n\n\n"
},
{
"text": "\n5566\nSpindle cell ductal carcinoma in situ. An unusual variant of ductal intra-epithelial neoplasia that simulates ductal hyperplasia or a myoepithelial proliferation.\n\nFarshid, G\n\nMoinfar, F\n\nMeredith, DJ\n\nPeiterse, S\n\nTavassoli, FA\n\nBeiträge in Fachzeitschriften\nISI:000170145700010\n11499843.0\n10.1007%2Fs004280100446\nNone\nSeventeen examples of a variant of ductal carcinoma in situ (DCIS) composed exclusively or predominantly of spindle cells arranged in fascicles, whorls, and solid sheets are described. The fascicular arrangement of the spindle cells simulates the "streaming" phenomenon associated with ordinary intraductal epithelial hyperplasia (IDH). This process also resembles the myoid, solid form of intraductal myoepithelial proliferation. The women ranged in age from 38 years to 79 years with a mean age of 59.3 years. Five patients presented with a palpable mass. The remaining tumors were discovered using mammography. The radiological appearances of the lesions raised concern for carcinoma, but there were no distinctive mammographic findings to suggest an unusual variant of DCIS. Cytological preparations were suspicious for malignancy in two patients and were reported as malignant in another case. Sixteen patients were treated with wide local excision, and one woman had a partial mastectomy. The tumors measured from 3 mm to 15 mm (mean 8.65 mm). In three cases, minute foci of stromal invasion were associated with the spindle cell DCIS. In another specimen, a 2.7-cm invasive ductal carcinoma of no special type was identified in an area away from the foci of the spindle cell DCIS. None of the patients has experienced recurrence or metastasis during the relatively short mean follow-up period of 16.2 months (range 4-77 months). Spindle cell DCIS is distinguished from the streaming pattern of ordinary IDH by its solid growth pattern, lack of secondary spaces or peripheral fenestrations, uniformity of appearance and distribution of nuclei, cytological atypia in the range of low to intermediate-grade DCIS, and negative immunoreaction with CK-34betaE12 (HMW-CK903). When fenestrations are present, they are evident in areas of cribriform DCIS that merge with the solid, spindle cell areas in hybrid ducts harboring both patterns. This admixture, with conventional cribriform DCIS, and the association with foci of invasive ductal carcinoma in some cases further help recognition and confirmation of this lesion as in situ carcinoma. When there is no transition from the spindle cells to recognizable cribriform DCIS, distinction from intraductal myoepithelial hyperplasia (myoepitheliosis) requires immunostains for actin and S-100 protein. Recognition of this pattern of DCIS is important in order to avoid its frequent misclassification as a benign lesion.\n\nMoinfar, Farid\n\n\n"
},
{
"text": "\n119045\nShould dermal scald burns in children be covered with autologous skin grafts or with allogeneic cultivated keratinocytes?--"The Viennese concept".\n\nRab, M\n\nKoller, R\n\nRuzicka, M\n\nBurda, G\n\nKamolz, LP\n\nBierochs, B\n\nMeissl, G\n\nFrey, M\n\nBeiträge in Fachzeitschriften\nISI:000230717600007\n15993303.0\n10.1016/j.burns.2005.01.001\nNone\nThe treatment of scald burns in children is still under discussion. The aim of the present study was to evaluate an optimised treatment regime for scald burns in children. Between 1997 and 2002, 124 children underwent surgical intervention due to burn injuries. Thirty-six out of these 124 children were enrolled into the evaluation of our recent treatment protocol. Twenty-two children with scald burns covering an average body surface area (TBSA) of 18.5% were treated by early excision and coverage with allogeneic keratinocytes in case of partial thickness lesions (keratinocyte group). Fourteen children with a TBSA of 17.2% were treated with autologous skin grafts alone (skin graft group). Both groups were comparable according to age, burn depth and affected TBSA. The complete clinical follow-up examination of at least 17 months was performed in 12 out of 22 children of the keratinocyte group and in 9 out of 14 patients of the comparative group. Visible scar formations were classified according to the Vancouver Scar Scale (VSS) in each patient. The use of allogeneic keratinocytes led to complete epithelialisation within 12 days in 20 of the 22 cases. No secondary skin grafting procedures had to be done. Skin take rate at the sixth postoperative day was 100% in the skin graft group. Blood transfusions were administered intraoperatively according to the clinical need of the patients by the responsible anaesthesiologist. The mean volume of blood, which had to be transfused was 63.9 ml in the keratinocyte group and significantly lower than the volume of 151.4 ml, which was administered in the skin graft group (p=0.04). At follow up the VSS observed in areas covered by keratinocytes was 2.33 on the average and therefore, significantly lower than the VSS of 5.22 in skin grafted areas of the comparative group (p=0.04). In children the use of cultivated keratinocytes in partial thickness scald burns is a procedure, which renders constantly reliable results. It minimizes the areas of autologous skin harvesting and reduces the amount of blood transfusions. The fact that less scarring is observed after keratinocyte grafting leads to the conclusion that skin grafting in children should be restricted to scalded areas, which have to be excised to the subcutaneous fat tissue.\n\nKamolz, Lars-Peter\n\n\n"
},
{
"text": "\n121043\nApplying the National Institute for Clinical Excellence criteria to patients treated with the Genous™ Bio-engineered R stent™: a sub-study of the e-HEALING (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth) worldwide registry.\n\nKlomp, M\n\nDamman, P\n\nBeijk, MA\n\nSilber, S\n\nGrisold, M\n\nRibeiro, EE\n\nSuryapranata, H\n\nWòjcik, J\n\nSim, KH\n\nTijssen, JG\n\nde Winter, RJ\n\ne-HEALING investigators\n\nBeiträge in Fachzeitschriften\nISI:000306428000004\n21725668.0\n10.1007/s00380-011-0167-8\nNone\nThe National Institute for Clinical Excellence (NICE) guidelines recommend the use of bare-metal stents (BMS) in non-complex lesions with a low risk of restenosis (diameter ≥3 mm and lesion length ≤15 mm) and the use of drug-eluting stents (DES) in more complex lesions with a high risk of restenosis (diameter <3.0 mm or lesion length >15 mm). However, the guidelines were created based on studies evaluating BMS and DES only. We performed an analysis of patients undergoing non-urgent percutaneous coronary intervention with the novel endothelial cell capturing stent (ECS). The ECS is coated with CD34(+) antibodies that attract circulating endothelial progenitor cells to the stent surface, thereby accelerating the endothelialization of the stented area. We analyzed all patients enrolled in the worldwide e-HEALING registry that met the NICE criteria for either low-risk or high-risk lesions and were treated with ≥1 ECS. The main study outcome was target vessel failure (TVF) at 12-month follow-up, defined as the composite of cardiac death or MI and target vessel revascularization (TVR). A total of 4, 41 patients were assessed in the current analysis. At 12-month follow-up, TVF occurred in 7.0% of the patients with low-risk lesions and in 8.8% of the patients with high-risk lesions (p = 0.045). When evaluating the diabetic patients versus the non-diabetic patients per risk group, no significant differences were found in TVF, MI or TVR in either risk group. The ECS shows good clinical outcomes in lesions carrying either a high or a low risk of restenosis according to the NICE guidelines with comparable rates of cardiac death, myocardial infarction, and stent thrombosis. The TVF rate with ECS was slightly higher in patients with high-risk lesions, driven by higher clinically driven TLR. The risk of restenosis with ECS in patients carrying high-risk lesions needs to be carefully considered relative to other risks associated with DES. Furthermore, the presence of diabetes mellitus did not influence the incidence of TVF in either risk group.\n\n\n"
},
{
"text": "\n168876\nFatigue - a symptom in endometriosis.\n\nRamin-Wright, A\n\nSchwartz, ASK\n\nGeraedts, K\n\nRauchfuss, M\n\nWölfler, MM\n\nHaeberlin, F\n\nvon Orelli, S\n\nEberhard, M\n\nImthurn, B\n\nImesch, P\n\nFink, D\n\nLeeners, B\n\nBeiträge in Fachzeitschriften\nISI:000440947500011\n29947766.0\n10.1093/humrep/dey115\nNone\nIs fatigue a frequent symptom of endometriosis?\n Fatigue is an underestimated symptom of endometriosis as it affects the majority of women with endometriosis, but it is not widely discussed in literature.\n Fatigue can be a symptom of endometriosis causing major distress impacting the daily activities and quality of life of women with endometriosis. However, few studies with large sample sizes have investigated fatigue as a symptom of endometriosis.\n The study was designed as a multi-center matched case-control study. Recruitment took place at hospitals and private practices in Switzerland, Germany and Austria between 2010 and 2016. Data was collected from 1120 women, 560 of them with endometriosis. The women with endometriosis were matched to 560 control women in regard to age ±3 years and ethnic background.\n Diagnosis of women with endometriosis had to be surgically and histologically confirmed. Surgical exclusion or absence of any endometriosis-identifying symptoms was required for control subjects. Materials included surgical and histological reports as well as data retrieved from a self-administered questionnaire. This study focused on the symptom fatigue in endometriosis. Relationships of variables were established by regression analysis and associations were quantified as odds ratios.\n Frequent fatigue was experienced by a majority of women diagnosed with endometriosis (50.7% versus 22.4% in control women, P < 0.001). Fatigue in endometriosis was associated with insomnia (OR: 7.31, CI: 4.62-11.56, P < 0.001), depression (OR: 4.45, CI: 2.76-7.19, P < 0.001), pain (OR: 2.22, CI: 1.52-3.23, P < 0.001), and occupational stress (OR: 1.45, CI: 1.02-2.07, P = 0.037), but was independent of age, time since first diagnosis and stage of the disease.\n Women with asymptomatic endometriosis cannot be excluded in the control group which would lead to underestimation of our results. The study's design allows no evaluation of causal effects.\n As fatigue is experienced by numerous women with endometriosis, it needs to be addressed in the discussion of management and treatment of the disease. In addition to treating endometriosis, it would be beneficial to reduce insomnia, depression, pain and occupational stress in order to better manage fatigue.\n There was no additional funding received for this study and no conflict of interest.\n ClinicalTrials.gov, NCT02511626.\n © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.\n\nWölfler, Monika Martina\n\n\n"
},
{
"text": "\n174114\nDistinct Clinicopathological and Prognostic Features of Thin Nodular Primary Melanomas: An International Study from 17 Centers.\n\nDessinioti, C\n\nDimou, N\n\nGeller, AC\n\nStergiopoulou, A\n\nLo, S\n\nKeim, U\n\nGershenwald, JE\n\nHaydu, LE\n\nRibero, S\n\nQuaglino, P\n\nPuig, S\n\nMalvehy, J\n\nKandolf-Sekulovic, L\n\nRadevic, T\n\nKaufmann, R\n\nMeister, L\n\nNagore, E\n\nTraves, V\n\nChampsas, GG\n\nPlaka, M\n\nDreno, B\n\nVarey, E\n\nRamirez, DM\n\nDummer, R\n\nMangana, J\n\nHauschild, A\n\nEgberts, F\n\nPeris, K\n\nDel Regno, L\n\nForsea, AM\n\nZurac, SA\n\nVieira, R\n\nBrinca, A\n\nZalaudek, I\n\nDeinlein, T\n\nLinos, E\n\nEvangelou, E\n\nThompson, JF\n\nScolyer, RA\n\nGarbe, C\n\nStratigos, AJ\n\nBeiträge in Fachzeitschriften\nISI:000509549100009\n30863861.0\n10.1093/jnci/djz034\nPMC6910161\nNodular melanoma (NM) is more likely to be fatal compared with other melanoma subtypes, an effect attributed to its greater Breslow thickness.\n Clinicopathological features of NM and superficial spreading melanoma (SSM) diagnosed in 17 centers in Europe (n = 15), the United States, and Australia between 2006 and 2015, were analyzed by multivariable logistic regression analysis, with emphasis on thin (T1 ≤ 1.0 mm) melanomas. Cox analysis assessed melanoma-specific survival. All statistical tests were two sided.\n In all, 20 132 melanomas (NM: 5062, SSM: 15 070) were included. Compared with T1 SSM, T1 NM was less likely to have regression (odds ratio [OR] = 0.46, 95% confidence interval [CI] = 0.29 to 0.72) or nevus remnants histologically (OR = 0.60, 95% CI = 0.42 to 0.85), and more likely to have mitoses (OR = 1.97, 95% CI = 1.33 to 2.93) and regional metastasis (OR = 1.77, 95% CI = 1.02 to 3.05). T1 NM had a higher mitotic rate than T1 SSM (adjusted geometric mean = 2.2, 95% CI = 1.9 to 2.5 vs 1.6, 95% CI = 1.5 to 1.7 per mm2, P < .001). Cox multivariable analysis showed a higher risk for melanoma-specific death for NM compared with SSM for T1 (HR = 2.10, 95% CI = 1.24 to 3.56) and T2 melanomas (HR = 1.30, 95% CI = 1.01 to 1.68), and after accounting for center heterogeneity, the difference was statistically significant only for T1 (HR = 2.20, 95% CI = 1.28 to 3.78). The NM subtype did not confer increased risk within each stratum (among localized tumors or cases with regional metastasis).\n T1 NM (compared with T1 SSM) was associated with a constellation of aggressive characteristics that may confer a worse prognosis. Our results indicate NM is a high-risk melanoma subtype that should be considered for inclusion in future prognostic classifications of melanoma.\n © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.\n\nDeinlein, Teresa Maria\n\nZalaudek, Iris\n\n\n"
},
{
"text": "\n181635\nAn international update of the EORTC questionnaire for assessing quality of life in breast cancer patients: EORTC QLQ-BR45.\n\nBjelic-Radisic, V\n\nCardoso, F\n\nCameron, D\n\nBrain, E\n\nKuljanic, K\n\nda Costa, RA\n\nConroy, T\n\nInwald, EC\n\nSerpentini, S\n\nPinto, M\n\nWeis, J\n\nMorag, O\n\nLindviksmoen Astrup, G\n\nTomaszweksi, KA\n\nPogoda, K\n\nSinai, P\n\nSprangers, M\n\nAaronson, N\n\nVelikova, G\n\nGreimel, E\n\nArraras, J\n\nBottomley, A\n\nEORTC Quality of Life Group and Breast Cancer Group\n\nBeiträge in Fachzeitschriften\nISI:000516712400016\n31959345.0\n10.1016/j.annonc.2019.10.027\nNone\nThe European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR23 was one of the first disease-specific questionnaires developed in 1996 to assess quality of life (QoL) in patients with breast cancer (BC). However, since 1996 major changes in BC treatment have occurred, requiring an update of the EORTC BC module. This study presents the results of the phase I-III update of the QLQ-BR23 questionnaire.\n The update of the EORTC QLQ-BR23 module followed standard EORTC guidelines. A systematic literature review revealed 83 potential relevant QoL issues during phases I and II. After shortening the issues list and following interviews with patients and health care providers, 15 relevant issues were transformed into 27 items. The preliminary module was pretested in an international, multicentre phase III study to identify and solve potential problems with wording comprehensibility and acceptability of the items. Descriptive statistics are provided. Analyses were qualitative and quantitative. We provide a psychometric structure of the items.\n The phase I and II results indicated the need to supplement the original QLQ-BR23 with additional items related to newer therapeutic options. The phase III study recruited a total of 250 patients (from 12 countries). The final updated phase III module contains a total of 45 items: 23 items from the QLQ-BR23 and 22 new items. The new items contain two multi-item scales: a target symptom scale and a satisfaction scale. The target symptom scale can be divided into three subscales: endocrine therapy, endocrine sexual and skin/mucosa scale.\n Our work has led to the development of a new EORTC QLQ-BR45 module that provides a more accurate and comprehensive assessment of the impact of new and scalable treatments on patients' QoL. The final version of the EORTC QLQ-BR45 is currently available for use in clinical practice. The final phase IV study is underway to confirm psychometric properties of the module.\n Copyright © 2019 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.\n\nBjelic-Radisic, Vesna\n\nGreimel, Elfriede Renate\n\n\n"
},
{
"text": "\n182623\nVascular function and cardiovascular risk in a HIV infected and HIV free cohort of African ancestry: baseline profile, rationale and methods of the longitudinal EndoAfrica-NWU study.\n\nFourie, CMT\n\nBotha-Le Roux, S\n\nSmith, W\n\nSchutte, AE\n\nBreet, Y\n\nMels, CMC\n\nGafane-Matemane, LF\n\nLammertyn, L\n\nUys, L\n\nBurger, A\n\nJoseph, JS\n\nGoswami, N\n\nDe Boever, P\n\nStrijdom, H\n\nBeiträge in Fachzeitschriften\nISI:000548783800001\n32620082.0\n10.1186/s12879-020-05173-6\nPMC7333423\nPeople living with the Human Immunodeficiency Virus (PLHIV) have an increased susceptibility to develop non-communicable diseases such as cardiovascular disease (CVD). Infection with HIV contributes to the development of CVD independent of traditional risk factors, with endothelial dysfunction being the central physiological mechanism. While HIV-related mortality is declining due to antiretroviral treatment (ART), the number of deaths due to CVD is rising in South Africa - the country with the highest number of PLHIV and the world's largest ART programme. The EndoAfrica study was developed to determine whether HIV infection and ART are associated with cardiovascular risk markers and changes in vascular structure and function over 18 months in adults from different provinces of South Africa. This paper describes the rationale, methodology and baseline cohort profile of the EndoAfrica study conducted in the North West Province, South Africa.\n In this case-control study, conducted between August 2017 and June 2018, 382 volunteers of African descent (276 women; 106 men), comprising of 278 HIV infected and 104 HIV free individuals were included. We measured health behaviours, a detailed cardiovascular profile, and performed biomarker analyses. We compared baseline characteristics, blood pressure, vascular function and biochemical markers between those infected and HIV free.\n At baseline, the HIV infected participants were older (43 vs 39 years), less were employed (21% vs 40%), less had a tertiary education (7% vs 16%) and their body mass index was lower (26 vs 29 kg/m2) than that of the HIV free participants. While the cardiovascular profile, flow-mediated dilation and pulse wave velocity did not differ, glycated haemoglobin was lower (p = 0.017) and total cholesterol, high density lipoprotein cholesterol, triglycerides, gamma-glutamyltransferase and tobacco use were higher (all p < 0.047) in PLHIV.\n Despite PLHIV being older, preliminary cross-sectional analysis suggests that PLHIV being treated with ART do not have poorer endothelial or vascular function compared to the HIV free participants. More detailed analyses on the baseline and follow-up data will provide further clarity regarding the cardiovascular profile of South Africans living with HIV.\n\nGoswami, Nandu\n\n\n"
},
{
"text": "\n183938\nAssociation between kidney function, nutritional status and anthropometric measures in older people : The Screening for CKD among Older People across Europe (SCOPE) study.\n\nGuligowska, A\n\nCorsonello, A\n\nPigłowska, M\n\nRoller-Wirnsberger, R\n\nWirnsberger, G\n\nÄrnlöv, J\n\nCarlsson, AC\n\nTap, L\n\nMattace-Raso, F\n\nFormiga, F\n\nMoreno-Gonzalez, R\n\nFreiberger, E\n\nSieber, C\n\nGregorio, PG\n\nMartínez, SL\n\nArtzi-Medvedik, R\n\nYehoshua, I\n\nFabbietti, P\n\nLattanzio, F\n\nKostka, T\n\nSCOPE investigators\n\nBeiträge in Fachzeitschriften\nISI:000576901000003\n33008315.0\n10.1186/s12877-020-01699-1\nPMC7531088\nDifferent mechanisms connect the nutritional status with the occurrence and the course of chronic kidney disease (CKD). The end-stage renal disease is complicated by catabolic inflammatory reactions and cachexia which leads to malnutrition (undernutrition). On the other hand, obesity is an important risk factor for the development and acceleration of CKD.\n In the SCOPE study, community-dwelling persons aged 75 years and over, from 6 European countries and Israel were examined at the baseline phase. We assessed the relationship between anthropometric measures (Body Mass Index (BMI), circumferences of arm (AC), waist (WC), hip (HC), and calf (CC), waist-to-hip ratio - WHR, waist-to-height ratio - WHtR, risk of malnutrition (Mini Nutritional Assessment - MNA), serum albumin) and estimated glomerular filtration rate (eGFR) calculated by Berlin Initiative Study (BIS) equation.\n We studied 2151 subjects (932 men and 1219 women) with a mean age of 79.5 ± 5.9 years. A total of 1333 (62%) participants had CKD (GRF < 60 ml/min/1.73 m2). Negative correlations between eGFR and weight, AC, WC, HC, CC, BMI, WHtR were observed. Positive correlation occurred between eGFR and MNA score (Spearman's rho = 0.11) and albumin concentration (rho = 0.09). Higher weight, AC, WC, HC, CC, BMI and WHtR increased the odds ratio of CKD; higher MNA (OR = 0.98, 95% CI 0.94-1.0) and higher serum albumin (OR = 0.73, 95% CI 0.53-1.0) were weakly associated with reduced odds. The risk of malnutrition was the highest with eGFR < 30 as compared to eGFR > 60 (OR = 2.95, 95%CI = 1.77-4.94 for MNA < 24; OR = 5.54, 95%CI = 1.66-18.5 for hypoalbuminemia < 3.5 g/dL).\n The population of community dwelling people aged 75+ with CKD shows general features of overweight and obesity with a small prevalence of malnutrition. For anthropometric measures, the strongest association with eGFR and the highest odds of CKD were identified using WC, HC, CC and WHtR. Albumin level and MNA, but not MNA Short Form, indicated an increased odds of malnutrition with a decrease in eGFR.\n\nRoller-Wirnsberger, Regina\n\nWirnsberger, Gerhard\n\n\n"
},
{
"text": "\n187953\nTherapeutic options for CTLA-4 Insufficiency.\n\nEgg, D\n\nRump, IC\n\nMitsuiki, N\n\nRojas-Restrepo, J\n\nMaccari, ME\n\nSchwab, C\n\nGabrysch, A\n\nWarnatz, K\n\nGoldacker, S\n\nPatiño, V\n\nWolff, D\n\nOkada, S\n\nHayakawa, S\n\nShikama, Y\n\nKanda, K\n\nImai, K\n\nSotomatsu, M\n\nKuwashima, M\n\nKamiya, T\n\nMorio, T\n\nMatsumoto, K\n\nMori, T\n\nYoshimoto, Y\n\nDybedal, I\n\nKanariou, M\n\nKucuk, ZY\n\nChapdelaine, H\n\nPetruzelkova, L\n\nLorenz, HM\n\nSullivan, KE\n\nHeimall, J\n\nMoutschen, M\n\nLitzman, J\n\nRecher, M\n\nAlbert, MH\n\nHauck, F\n\nSeneviratne, S\n\nSchmid, JP\n\nKolios, A\n\nUnglik, G\n\nKlemann, C\n\nSnapper, S\n\nGiulino-Roth, L\n\nSvaton, M\n\nPlatt, CD\n\nHambleton, S\n\nNeth, O\n\nGosse, G\n\nReinsch, S\n\nHolzinger, D\n\nKim, YJ\n\nBakhtiar, S\n\nAtschekzei, F\n\nSchmidt, R\n\nSogkas, G\n\nChandrakasan, S\n\nRae, W\n\nDerfalvi, B\n\nMarquart, HV\n\nOzen, A\n\nKiykim, A\n\nKarakoc-Aydiner, E\n\nKrálíčková, P\n\nde Bree, G\n\nKiritsi, D\n\nSeidel, MG\n\nKobbe, R\n\nDantzer, J\n\nAlsina, L\n\nArmangue, T\n\nLougaris, V\n\nAgyeman, P\n\nNyström, S\n\nBuchbinder, D\n\nArkwright, PD\n\nGrimbacher, B\n\nBeiträge in Fachzeitschriften\nNone\n34111452.0\n10.1016/j.jaci.2021.04.039\nNone\nHeterozygous germline mutations in cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) impair the immunomodulatory function of regulatory T cells. Affected individuals are prone to life-threatening autoimmune and lymphoproliferative complications. A number of therapeutic options are currently used with variable effectiveness.\n To characterize the responsiveness of patients with CTLA-4 insufficiency to specific therapies and provide recommendations for the diagnostic work-up and therapy at an organ-specific level.\n Clinical features, laboratory findings, and response to treatment were reviewed retrospectively in an international cohort of 173 CTLA4 mutation carriers. Patients were followed between 2014 and 2020 for a total of 2, 24 months from diagnosis. Clinical manifestations were grouped based on organ-specific involvement. Medication use and response were recorded and evaluated.\n Among the 173 CTLA4 mutation carriers, 123 (71%) had been treated for immune complications. Abatacept, rituximab, sirolimus, and corticosteroids ameliorated disease severity especially in case of cytopenias and lymphocytic organ-infiltration of the gut, lungs and central nervous system. Immunoglobulin replacement was effective in infection prevention. Only four (25%) of 16 patients with cytopenia who were splenectomized had a sustained clinical response. Cure was achieved with stem cell transplantation in 13 (72%) of 18 patients. As a result of the above, organ-specific treatment pathways were developed.\n Systemic immunosuppressants and abatacept may provide partial control but require ongoing administration. Allogeneic hematopoietic stem cell transplantation offers a possible cure for patients with CTLA-4 insufficiency.\n The benefits and risks of symptomatic and curative therapies need to be considered when deciding on the best treatment for patients with CTLA-4 insufficiency.\n Copyright © 2021. Published by Elsevier Inc.\n\nSeidel, Markus\n\n\n"
},
{
"text": "\n2639\n[Preclinical blood gas analysis. 1. The value of preclinical blood gas analysis].\n\nPrause, G\n\nHetz, H\n\nDoppler, R\n\nBeiträge in Fachzeitschriften\nISI:000074072000007\n9645280.0\n10.1007/s001010050576\nNone\nPrehospital blood gas analysis is a new method in out-of-hospital emergency care. In a prospective pilot study we evaluated the feasibility of prehospital compensation of severe acidosis relying on different monitoring systems to evaluate patients oxygen, carbon dioxide or acid-base status, respectively.\n With the help of arterial blood gas checks taken at the site of the emergency, the acid base status of patients undergoing out of hospital cardiopulmonary resuscitation was analysed. The values derived from the first arterial puncture were used to determine the presence and the type of acidosis. The data of the arterial blood gas checks were set into relation with the time elapsed since the beginning of resuscitation and they were compared with end-tidal CO2.\n During the observation period 26 blood gas analyses from patients who had out-of-hospital resuscitation because of cardiac arrest were done. Twenty three patients had severe acidosis (pH range < 6.9 to 7.31), one had alkalosis (pH 7.51). Only two had an arterial pH within normal range. The pCO2 was variable (range: 24 to 97 mm Hg). The correlation of pH with time from the beginning of resuscitation to arterial puncture was poor (r = 0.407, p < 0.05). There was no correlation between pH and BE (r = 0.267) or pH and pCO2, (r = 0.016) respectively. Prehospital capnometry had a poor correlation with arterial pCO2 in most emergency patients. Only patients with respiratory disturbances of extrapulmonary origin showed a good correlation between end-tidal CO2 and the arterial pCO2. In severely ill patients the arterio-alveolar CO2-difference was unexpectedly high (> 15 mm Hg). In four patients resuscitation was not successful until compensation of an unexpectedly severe acidosis based upon the findings from blood-gas analysis had been performed.\n Arterial blood gas analysis proved to be helpful in the optimal management of out of hospital cardiac arrest. The incidence of severe acidosis in patients undergoing cardiopulmonary resuscitation was 80%. The probability of developing acidosis was found to increase slightly depending on the time elapsed since the beginning of CPR. The application of a calculated buffering of acidosis with sodium bicarbonate showed a good outcome in selected cases. In emergency patients alternative methods fail to detect severe disturbances of the patients oxygen and/or carbon dioxide status and the acid-base balance. Management of prehospital cardiac arrest could be optimized by the routine use of blood gas analysis.\n\nPrause, Gerhard\n\n\n"
},
{
"text": "\n84882\nRisk management of coronary heart disease-prevention\n\nDorner, T\n\nRieder, A\n\nBeiträge in Fachzeitschriften\nNone\n15287702.0\nNone\nNone\nCardiovascular disease is one of the leading causes of death worldwide and is responsible for 45% of deaths in the western world and 24.5% of deaths in the developing countries. In the 21st century these diseases will continue to dominate the disease spectrum and death statistics in both the industrialised and developing worlds. Since 1975 mortality from cardiovascular disease has decreased by about 24 to 28% in most countries. About 45% of this reduction can be attributed to an improvement in treatment of coronary heart disease and around 55% are attributable to a reduction in risk factors, in particular, stopping smoking and control of hypertension. However, especially in the case of ischaemic heart disease, it is not clear whether the reduction in mortality reflects a reduction in incidence of this disease. Due to the aging population and the reduction in age-related mortality, it is expected that the absolute number of people with heart disease will increase. Furthermore, the increase in prevalence of obesity, metabolic syndrome, type II diabetes as well as the higher prevalence of female smokers compared with thirty years ago could result in an increase in mortality over the next years and decades. It has been shown that prevention strategies, such as education campaigns aimed at the general public, can potentially greatly contribute to a reduction in incidence of cardiovascular disease at every stage. In order for such campaigns to be effective, it is necessary to understand and reduce the risk factors for cardiovascular disease. A large proportion of these risk factors are associated with lifestyle and are therefore modifiable. These modifiable risk factors include smoking, hypertension, poor diet, dyslipidemia, lack of exercise, overweight, adiposity and diabetes mellitus and optimisation of these should be a key aim for all adults. Gender differences also play a role in the incidence and prevention of cardiovascular disease. Incidence of myocardial infarction in women increases significantly after the menopause, and mortality through coronary heart disease is higher amongst women than men. Hormonal status, use of oral contraceptives and pregnancy all influence risk for cardiovascular disease in women. Due to the enormity of the problem that cardiovascular disease presents to society and the great potential for management of risk factors for cardiovascular disease through preventive medicine, a number of health promotion and prevention programmes have been initiated by various national and global organisations. This paper presents an analysis of modifiable risk factors for cardiovascular disease together with a review of targeted prevention programmes aiming at reducing these risks.\n\n\n"
},
{
"text": "\n86680\nHeterogeneity of white matter hyperintensities in Alzheimer's disease: post-mortem quantitative MRI and neuropathology.\n\nGouw, AA\n\nSeewann, A\n\nVrenken, H\n\nvan der Flier, WM\n\nRozemuller, JM\n\nBarkhof, F\n\nScheltens, P\n\nGeurts, JJ\n\nBeiträge in Fachzeitschriften\nISI:000261996700020\n18927145.0\n10.1093/brain/awn265\nNone\nWhite matter hyperintensities (WMH) are frequently seen on T(2)-weighted MRI scans of elderly subjects with and without Alzheimer's disease. WMH are only weakly and inconsistently associated with cognitive decline, which may be explained by heterogeneity of the underlying neuropathological substrates. The use of quantitative MRI could increase specificity for these neuropathological changes. We assessed whether post-mortem quantitative MRI is able to reflect differences in neuropathological correlates of WMH in tissue samples obtained post-mortem from Alzheimer's disease patients and from non-demented elderly. Thirty-three formalin-fixed, coronal brain slices from 11 Alzheimer's disease patients (mean age: 83 +/- 10 years, eight females) and 15 slices from seven non-demented controls (mean age: 78 +/- 10 years, four females) with WMH were scanned at 1.5 T using qualitative (fluid-attenuated inversion recovery, FLAIR) and quantitative MRI [diffusion tensor imaging (DTI) including estimation of apparent diffusion coefficient (ADC) and fractional anisotropy (FA), and T(1)-relaxation time mapping based on flip-angle array). A total of 104 regions of interest were defined on FLAIR images in WMH and normal appearing white matter (NAWM). Neuropathological examination included (semi-)quantitative assessment of axonal density (Bodian), myelin density (LFB), astrogliosis (GFAP) and microglial activation (HLA-DR). Patient groups (Alzheimer's disease versus controls) and tissue types (WMH versus NAWM) were compared with respect to QMRI and neuropathological measures. Overall, Alzheimer's disease patients had significantly lower FA (P < 0.01) and higher T(1)-values than controls (P = 0.04). WMH showed lower FA (P < 0.01) and higher T(1)-values (P < 0.001) than NAWM in both patient groups. A significant interaction between patient group and tissue type was found for the T(1) measurements, indicating that the difference in T(1)-relaxation time between NAWM and WMH was larger in Alzheimer's disease patients than in non-demented controls. All neuropathological measures showed differences between WMH and NAWM, although the difference in microglial activation was specific for Alzheimer's disease. Multivariate regression models revealed that in Alzheimer's disease, axonal density was an independent determinant of FA, whereas T(1) was independently determined by axonal and myelin density and microglial activation. Quantitative MRI techniques reveal differences in WMH between Alzheimer's disease and non-demented elderly, and are able to reflect the severity of the neuropathological changes involved.\n\n\n"
},
{
"text": "\n125415\nSelf-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data.\n\nHeneghan, C\n\nWard, A\n\nPerera, R\n\nSelf-Monitoring Trialist Collaboration\n\nBankhead, C\n\nFuller, A\n\nStevens, R\n\nBradford, K\n\nTyndel, S\n\nAlonso-Coello, P\n\nAnsell, J\n\nBeyth, R\n\nBernardo, A\n\nChristensen, TD\n\nCromheecke, ME\n\nEdson, RG\n\nFitzmaurice, D\n\nGadisseur, AP\n\nGarcia-Alamino, JM\n\nGardiner, C\n\nHasenkam, JM\n\nJacobson, A\n\nKaatz, S\n\nKamali, F\n\nKhan, TI\n\nKnight, E\n\nKörtke, H\n\nLevi, M\n\nMatchar, D\n\nMenéndez-Jándula, B\n\nRakovac, I\n\nSchaefer, C\n\nSiebenhofer, A\n\nSouto, JC\n\nSunderji, R\n\nGin, K\n\nShalansky, K\n\nVöller, H\n\nWagner, O\n\nZittermann, A\n\nBeiträge in Fachzeitschriften\nISI:000300047300039\n22137798.0\n10.1016/S0140-6736(11)61294-4\nNone\nBackground Uptake of self-testing and self-management of oral coagulation has remained inconsistent, despite good evidence of their effectiveness. To clarify the value of self-monitoring of oral anticoagulation, we did a meta-analysis of individual patient data addressing several important gaps in the evidence, including an estimate of the effect on time to death, first major haemorrhage, and thromboembolism. Methods We searched Ovid versions of Embase (1980-2009) and Medline (1966-2009), limiting searches to randomised trials with a maximally sensitive strategy. We approached all authors of included trials and requested individual patient data: primary outcomes were time to death, first major haemorrhage, and first thromboembolic event. We did prespecified subgroup analyses according to age, type of control-group care (anticoagulation-clinic care vs primary care), self-testing alone versus self-management, and sex. We analysed patients with mechanical heart valves or atrial fibrillation separately. We used a random-effect model method to calculate pooled hazard ratios and did tests for interaction and heterogeneity, and calculated a time-specific number needed to treat. Findings Of 1357 abstracts, we included 11 trials with data for 6417 participants and 12 800 person-years of follow-up. We reported a significant reduction in thromboembolic events in the self-monitoring group (hazard ratio 0.51; 95% CI 0.31-0.85) but not for major haemorrhagic events (0.88, 0.74-1.06) or death (0.82, 0.62-1.09). Participants younger than 55 years showed a striking reduction in thrombotic events (hazard ratio 0.33, 95% CI 0.17-0.66), as did participants with mechanical heart valve (0.52, 0.35-0.77). Analysis of major outcomes in the very elderly (age >= 85 years, n=99) showed no significant adverse effects of the intervention for all outcomes. Interpretation Our analysis showed that self-monitoring and self-management of oral coagulation is a safe option for suitable patients of all ages. Patients should also be offered the option to self-manage their disease with suitable health-care support as back-up.\n\nSiebenhofer-Kroitzsch, Andrea\n\n\n"
},
{
"text": "\n176382\nIvabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial.\n\nFox, K\n\nFord, I\n\nSteg, PG\n\nTendera, M\n\nFerrari, R\n\nBEAUTIFUL Investigators\n\nBeiträge in Fachzeitschriften\nISI:000259124900023\n18757088.0\n10.1016/S0140-6736(08)61170-8\nNone\nIvabradine specifically inhibits the I(f) current in the sinoatrial node to lower heart rate, without affecting other aspects of cardiac function. We aimed to test whether lowering the heart rate with ivabradine reduces cardiovascular death and morbidity in patients with coronary artery disease and left-ventricular systolic dysfunction.\n Between December, 2004, and December, 2006, we screened 12 473 patients at 781 centres in 33 countries. We enrolled 10 917 eligible patients who had coronary artery disease and a left-ventricular ejection fraction of less than 40% in a randomised, double-blind, placebo-controlled, parallel-group trial. 5479 patients received 5 mg ivabradine, with the intention of increasing to the target dose of 7.5 mg twice a day, and 5438 received matched placebo in addition to appropriate cardiovascular medication. The primary endpoint was a composite of cardiovascular death, admission to hospital for acute myocardial infarction, and admission to hospital for new onset or worsening heart failure. We analysed patients by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00143507.\n Mean heart rate at baseline was 71.6 (SD 9.9) beats per minute (bpm). Median follow-up was 19 months (IQR 16-24). Ivabradine reduced heart rate by 6 bpm (SE 0.2) at 12 months, corrected for placebo. Most (87%) patients were receiving beta blockers in addition to study drugs, and no safety concerns were identified. Ivabradine did not affect the primary composite endpoint (hazard ratio 1.00, 95% CI 0.91-1.1, p=0.94). 1233 (22.5%) patients in the ivabradine group had serious adverse events, compared with 1239 (22.8%) controls (p=0.70). In a prespecified subgroup of patients with heart rate of 70 bpm or greater, ivabradine treatment did not affect the primary composite outcome (hazard ratio 0.91, 95% CI 0.81-1.04, p=0.17), cardiovascular death, or admission to hospital for new-onset or worsening heart failure. However, it did reduce secondary endpoints: admission to hospital for fatal and non-fatal myocardial infarction (0.64, 95% CI 0.49-0.84, p=0.001) and coronary revascularisation (0.70, 95% CI 0.52-0.93, p=0.016).\n Reduction in heart rate with ivabradine does not improve cardiac outcomes in all patients with stable coronary artery disease and left-ventricular systolic dysfunction, but could be used to reduce the incidence of coronary artery disease outcomes in a subgroup of patients who have heart rates of 70 bpm or greater.\n\nEber, Ernst\n\n\n"
},
{
"text": "\n185702\nPROMISE international; a clinical post marketing trial investigating the percutaneous deep vein arterialization (LimFlow) in the treatment of no-option chronic limb ischemia patient.\n\nSchreve, MA\n\nLichtenberg, M\n\nÜnlü, Ç\n\nBranzan, D\n\nSchmidt, A\n\nvan den Heuvel, DAF\n\nBlessing, E\n\nBrodmann, M\n\nCabane, V\n\nLin, WTQ\n\nKum, S\n\nBeiträge in Fachzeitschriften\nNone\n32026120.0\n10.1186/s42155-019-0067-z\nPMC6966404\nCritical limb ischemia (CLI) is the clinical end stage of peripheral artery disease and is associated with high amputation, mortality rates and poor quality of life. For CLI patients with no revascularization options, venous arterialization could be an alternative technique for limb salvage. A systematic review and meta-analysis published in 2017 concluded that venous arterialization may be considered a viable alternative. A recent development, is the Percutaneous Deep Vein Arterialization (pDVA), that is CE-marked and currently under investigation of the FDA. This procedure, called LimFlow, is a novel, minimally invasive, endovascular approach to perform a venous arterialization procedure. The limited evidence for its use necessitates a scientific judgement of the pDVA. Therefore, we initiated a prospective clinical post market trial to investigate the outcome of the pDVA in no-option critical limb ischemia.\n The objective of this prospective study is to collect "real-life" clinical data among a population of patients treated with the pDVA in order to evaluate the clinical effectiveness and safety of the LimFlow System in patients with no-option critical limb ischemia. This study is a single-arm, open-label, prospective, post-market follow-up study to be conducted on up to fifty (50) eligible patients with a twelve-month follow-up period. The Primary endpoint is measured by amputation free survival. Secondary endpoints are complete wound healing, primary and secondary patency, limb salvage, renal function and technical and procedural success. Patients will be assessed at regular intervals during one year after the initial percutaneous deep vein arterialization procedure through clinical evaluation and self-completed questionnaires.\n The last decade several studies have been published with promising results and the number of treated patients has considerably grown. Venous arterialization could be a valuable treatment option in patients with often no other options than amputation of the affected limb. The first results in men are promising although more research and long term follow up is needed to establish the efficacy of this new treatment modality. With this prospective study, we evaluate the clinical effectiveness and safety in patients with no-option CLI treated with the pDVA (LimFlow System).\n NCT03321552 .\n\nBrodmann, Marianne\n\n\n"
},
{
"text": "\n61828\nChanges in specific airway resistance after powder inhalation of formoterol or salmeterol in moderate bronchial asthma\n\nSill, V\n\nBartuschka, B\n\nVilliger, B\n\nOrtland, C\n\nDomej, W\n\nBeiträge in Fachzeitschriften\nNone\n10091511.0\nNone\nNone\nFormoterol and salmeterol are two long acting beta 2 agonists available for the treatment of asthma which show differences in onset of action. In a multicentre parallel group study, patients with moderate asthma were investigated by measuring the specific airway resistance (sRaw), a more sensitive parameter than FEV1. A total of 99 patients were randomised for open treatment with either 12 micrograms formoterol delivered via Turbohaler or 50 micrograms salmeterol via Diskus. The patients were between 18 and 66 years of age, had a medium FEV1 of 68.8% (+/- 17.8%) predicted and showed a medium reversibility of 28.8% (+/- 16.5%). The patients response to one inhalation of the study drug was investigated by sRaw measurements 2, 5, 10, 20 and 60 minutes after inhalation of the formulation. Additionally, FEV1 was measured. The results show a significant decrease in specific airway resistance of 29% within the first two minutes in patients who had received 12 micrograms formoterol via Turbohaler. However, patients on salmeterol showed no change (sRaw +/- 1%). This difference is statistically highly significant (p < 0.0001). Furthermore, in 49% of the patients treated with salmeterol an increase in sRaw was seen immediately after inhalation of the drug. This increase was +16.4% in an average of 2 minutes after inhalation. One hour after inhalation the differences between the groups were small and not significant neither between formoterol and salmeterol-treated patients nor within the salmeterol group. In the following week patients were treated with 12 micrograms formoterol Turbohaler b.i.d. or 50 micrograms salmeterol Diskus b.i.d., respectively. A further sRaw measurement was performed 11 +/- 1 hours after the last inhalation of the drug. The results for sRaw and FEV1 show no differences between both study drugs indicating a similar duration of action for both formoterol Turbohaler and Salmeterol Diskus in moderate asthma. No serious adverse events were reported. The adverse event profile observed in both study groups was comparable. Thus, this study shows once again that formoterol delivered via Turbohaler has a more rapid onset of bronchodilating action compared with salmeterol Diskus. Furthermore the inhalation of salmeterol via Diskus in one-half of the patients led to an increase in specific airway resistance within the first minutes after inhalation. It is worth discussing whether an unspecific reaction to the relatively large lactose particles which are components of the salmeterol Diskus formulation are responsible for this observation.\n\nDomej, Wolfgang\n\n\n"
},
{
"text": "\n71372\nEFFECTS OF PRAVASTATIN IN PATIENTS WITH SERUM TOTAL CHOLESTEROL LEVELS FROM 5.2 TO 7.8 MMOL LITER (200 TO 300 MG DL) PLUS 2 ADDITIONAL ATHEROSCLEROTIC RISK-FACTORS\n\nBEHOUNEK, BD\n\nMARKOWITZ, JS\n\nBERGMAN, M\n\nMCGOVERN, ME\n\nKASSLERTAUB, KB\n\nVANHANEN, H\n\nELORANTA, M\n\nJUVONEN, J\n\nKANTOLA, I\n\nKEKKI, S\n\nKIVELA, H\n\nKNUTAR, F\n\nNISSEN, M\n\nSALMI, J\n\nSALONEN, R\n\nTARPILA, S\n\nTUNTURIHIHNALA, H\n\nAMANN, FW\n\nBERENDES, G\n\nBONNER, G\n\nDUBACH, UC\n\nEGGSTEIN, M\n\nFRANKENBERG, HV\n\nFROER, KL\n\nHOHL, H\n\nHOPPE, F\n\nKUMMER, H\n\nMARZ, W\n\nMOCCETTI, T\n\nNOSEDA, G\n\nREUTTER, FW\n\nSCHWENKE, R\n\nVOSSCHULTE, G\n\nWAMBACH, G\n\nWEIDMANN, P\n\nBONNIER, JJRM\n\nDEWEERD, P\n\nHUIGE, MC\n\nJANSEN, LJ\n\nTERIJDT, AJ\n\nTEVELDE, K\n\nOLSSON, AG\n\nLARSSON, H\n\nASPLUND, J\n\nDAHLQVIST, A\n\nLONNQVIST, F\n\nFRITHZ, G\n\nHOGLUND, C\n\nKJELLSTROM, T\n\nKUYLENSTIERNA, J\n\nMOLLER, B\n\nOSTERGREN, J\n\nCRAMB, R\n\nDAVIES, J\n\nIVERSON\n\nJOHNSTON, GD\n\nMUNRO, A\n\nPEACOCK, I\n\nRITCHIE, LD\n\nRITTER, J\n\nRYLANCE, PB\n\nSEVER, PS\n\nSIMMONS, RL\n\nBeiträge in Fachzeitschriften\nISI:A1993MD55900010\nNone\nNone\nNone\nThis placebo-controlled, multinational study evaluated the use of pravastatin in 1, 62 patients with hypercholesterolemia (serum total cholesterol concentrations of 5.2 to 7.8 mmol/liter [200 to 300 mg.dl] and greater-than-or-equal-to additional risk factors for atherosclerotic coronary artery disease. Efficacy and safety analyses were performed on the initial 26-week, randomized, double-blind, placebo-controlled period; further safety analyses were conducted on the subsequent 52 weeks, which included an additional 26-week double-blind phase permitting other lipid-lowering agents and a final 26-week open-label period. At 13 weeks, pravastatin at a dose of 20 mg once daily at bedtime significantly lowered serum low-density lipoprotein cholesterol 26% (4.7 to 3.5 mmol/liter [182 to 135 mg/dl]), total cholesterol 19% (6.8 to 5.6 mmol/liter [263 to 217 mg/dl]) and triglycerides 12% (1.8 to 1.6 mmol/liter [159 to 142 mg/dl]) (p < 0.001 compared with placebo) and significantly raised serum high-density lipoprotein cholesterol 7% (1.1 to 1.2 mmol/liter [43 to 46 mg/dl]) (p < 0.001 compared with placebo). Efficacy of pravastatin was maintained at 26 weeks, and during this initial period there were significantly more serious cardiovascular adverse events in the placebo group (13 events, 2.4%) than in the pravastatin group (1 event, 0.2%) (p < 0.001). Six myocardial infarctions, 5 cases of unstable angina and 1 sudden cardiac death occurred in the placebo group, compared with none of these events in the pravastatin group. In this study, pravastatin produced beneficial effects on serum lipids and was associated with a reduction in the incidence of serious cardiovascular adverse events.\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n117943\nInduction of differentiation of human mast cells from bone marrow and peripheral blood mononuclear cells by recombinant human stem cell factor/kit-ligand in long-term culture.\n\nValent, P\n\nSpanblöchl, E\n\nSperr, WR\n\nSillaber, C\n\nZsebo, KM\n\nAgis, H\n\nStrobl, H\n\nGeissler, K\n\nBettelheim, P\n\nLechner, K\n\nBeiträge in Fachzeitschriften\nISI:A1992JW43600012\n1384799.0\nNone\nNone\nIn the murine system, a number of cytokines (including interleukin-3 [IL-3], IL-4, and stem cell factor [SCF]) promote the growth of mast cells (MCs). However, so far little is known about factors controlling differentiation of human MCs. Recent data suggest that human MCs express receptors (R) for SCF. The aim of the present study was to investigate whether recombinant human (rh) SCF induces differentiation of human MCs from their precursor cells. For this purpose, bone marrow (BM; normal donors, n = 6) and peripheral blood (PB; normal donors, n = 11) mononuclear cells (MNC) were cultured in the presence of rhSCF, rhIL-3, rhIL-4, rhIL-9, recombinant human macrophage colony-stimulating factor (rhM-CSF), or control medium in long-term (8 weeks) suspension cultures. After 4 weeks, up to 5% of the MNC (BM and PB) cultured in the presence of rhSCF, but not in the presence of other cytokines, were found to exhibit the characteristics of MCs. These MCs expressed the YB5.B8-reactive domain of the SCF R as well as IgE R, as determined by combined toluidine blue/immunofluorescence staining. Myeloid antigens, likewise expressed on human basophils (ie, CD11b, CDw65, and Bsp-1), could not be detected on these cells. Furthermore, rhSCF, but not rhIL-3, rhIL-4, rhIL-9, or rhM-CSF, induced dose- and time-dependent increases in the formation of cellular tryptase (an MC-specific enzyme) (rhSCF [100 ng/mL], 1, 08 +/- 679 ng/mL v control medium, 18 +/- 6 ng/mL tryptase on day 35 of PB cell cultures), as well as an increase in cellular histamine. After 6 to 8 weeks, when other mature hematopoietic cells decreased, MCs still could be detected in culture, with up to 40% of all cells being MCs. To test whether rhSCF also activates tissue MCs, we performed histamine release experiments (dispersed tissue; lung, n = 3; uterus, n = 3). SCF was found to enhance (by up to 3.4-fold) the capacity of the MCs to release histamine upon cross-linkage of IgE R with anti-IgE. Together, these observations suggest that rhSCF induces in vitro differentiation of human MCs from their BM and PB precursor cells in long-term culture and upregulates MC releasability.\n\nStrobl, Herbert\n\n\n"
},
{
"text": "\n137528\nMechanisms of lidocaine's action on subtypes of spinal dorsal horn neurons subject to the diverse roles of Na(+) and K(+) channels in action potential generation.\n\nWolff, M\n\nSchnöbel-Ehehalt, R\n\nMühling, J\n\nWeigand, MA\n\nOlschewski, A\n\nBeiträge in Fachzeitschriften\nISI:000339455900030\n24892804.0\n10.1213/ANE.0000000000000280\nNone\nSuperficial dorsal horn neurons of the spinal cord receive sensory information from Aδ and C fibers. According to their response to sustained depolarization, these cells can be divided into 3 groups: tonic (TFN), adapting (AFN), and single spike firing (SSN) neurons. During spinal and systemic administration of lidocaine, these neurons are exposed to different concentrations of the local anesthetic lidocaine. In this study, we explored its effect on the excitability of sensory neurons.\n Whole-cell patch-clamp recordings from dorsal horn neurons of Wistar rats were used to study the action of lidocaine on firing properties. To estimate the impact of a blockade of voltage-gated potassium channels by lidocaine (100 μM) on the firing properties of different neurons, the sodium and potassium channel inhibition of lidocaine was investigated in the light of the effects of tetrodotoxin (TTX, 10 nM) and tetraethylammonium (10 mM). For statistical analysis, the Wilcoxon matched-pairs signed rank test was used throughout.\n All 3 types of neurons responded to lidocaine with changes in the shape of their action potentials. The peak amplitude of the single action potentials was decreased (P = 0.031, P = 0.013, and P = 0.014 for SSN, AFN, and TFN neurons, respectively), and the duration of the action potentials was increased (P = 0.016, P = 0.032, and P = 0.031 for SSN, AFN, and TFN neurons, respectively). The maximum positive slope (P = 0.016 and P = 0.0010 for SSN and AFN, respectively) and the negative slope (P = 0.016, P = 0.0025, and P = 0.020 for SSN, AFN, and TFN neurons, respectively) decreased after application of lidocaine. In tonically firing neurons, lidocaine reduced the repetitive firing (P = 0.0016), and this effect was mimicked by a combination of TTX and tetraethylammonium. In AFN, TTX mimicked the action of lidocaine.\n Lidocaine at low concentrations suppresses tonic firing neurons by interacting with voltage-gated potassium channels. The effects on adapting firing neurons can be explained by an interaction with voltage-gated sodium channels. In contrast, the firing pattern of SSN is not affected at the administered concentrations. This different sensitivity to low concentrations of sodium and particularly of potassium channel blockers might represent a novel approach for a differentiated blockade of different spinal dorsal horn neurons.\n\nOlschewski, Andrea\n\n\n"
}
]
}