Asymmetry in The Lancet meta-analysis.
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Attitude of Health Personnel↗
Biomedical subjects
E Schuster
Publications and source records attributed to E Schuster.
Effect of a pocket-size tablet-dispensing device on glycaemic control in Type 2 diabetic patients.
AIM: To evaluate whether a pocket-size tablet-dispensing device would improve adherence to therapy as judged by reduction of HbA(1c) levels in a large population of Type 2 diabetic patients. METHODS: The study design was prospective, randomized, open label with two parallel groups. Patients (2296) were recruited from general practitioners and internists and randomized to either receive a tablet dispenser (TD) or no intervention (control group, CO). Patients' characteristics and current oral therapy (including dosage) were recorded at baseline. HbA(1c) was compared between groups at baseline and after 6 months' intervention. RESULTS: Data were available in 2081 patients. Baseline characterisitcs, including age, body mass index (BMI), blood pressure and gender distribution were comparable between the two groups, as was HbA(1c)[7.9 (7.9-8.0), TD vs. 8.0 (7.9-8.0)%, CO, means (95% CI)]. After 6 months, HbA(1c) improved in both groups, but improvement was significantly greater in TD than in controls [-0.74 (0.67-0.80) vs. -0.53 (0.47-0.59)%, P < 0.0001]. Possession of a dispenser remained an independent predictor of improved control in a multiple regression model. In the subgroup analysis, the effect was significantly more pronounced (i) in patients receiving more medications and (ii) more diabetes medications per day (iii) in younger patients. CONCLUSION: In this large study population in a 'realistic' setting, a simple tablet-dispensing device led to a significant and clinically relevant improvement in HbA(1c) levels. Because patients with a more complex therapy regimen benefited more, we suggest that TD might have improved adherence to therapy.
Administration, Oral↗
Increased power of microarray analysis by use of an algorithm based on a multivariate procedure.
MOTIVATION: The power of microarray analyses to detect differential gene expression strongly depends on the statistical and bioinformatical approaches used for data analysis. Moreover, the simultaneous testing of tens of thousands of genes for differential expression raises the 'multiple testing problem', increasing the probability of obtaining false positive test results. To achieve more reliable results, it is, therefore, necessary to apply adjustment procedures to restrict the family-wise type I error rate (FWE) or the false discovery rate. However, for the biologist the statistical power of such procedures often remains abstract, unless validated by an alternative experimental approach. RESULTS: In the present study, we discuss a multiplicity adjustment procedure applied to classical univariate as well as to recently proposed multivariate gene-expression scores. All procedures strictly control the FWE. We demonstrate that the use of multivariate scores leads to a more efficient identification of differentially expressed genes than the widely used MAS5 approach provided by the Affymetrix software tools (Affymetrix Microarray Suite 5 or GeneChip Operating Software). The practical importance of this finding is successfully validated using real time quantitative PCR and data from spike-in experiments. AVAILABILITY: The R-code of the statistical routines can be obtained from the corresponding author. CONTACT: Schuster@imise.uni-leipzig.de
Algorithms↗
Serum resistin levels of obese and lean children and adolescents: biochemical analysis and clinical relevance.
OBJECTIVE: It was hypothesized that resistin links obesity with diabetes, but this has not been studied in children and adolescents to date. PATIENTS: We determined serum resistin levels of 135 obese (body mass index, 32.0 +/- 6.2 kg/m2; age, 12.6 +/- 3.4 yr) and 201 lean children (body mass index, 18.7 +/- 2.4 kg/m2; age, 12.5 +/- 2.5 yr) by a newly developed and extensively evaluated in-house immunoassay. These results were controlled for their association with markers of puberty, obesity, and insulin sensitivity. RESULTS: The analytical evaluation of our assay revealed different resistin isoforms with major peaks of higher than 660 and 55 kDa in the size exclusion chromatography. Using this assay system we found no difference in the resistin levels of obese compared with lean subjects (P = 0.48). However, resistin was significantly higher in girls than in boys (6.74 +/- 2.42 vs. 5.79 +/- 2.45; P < 0.001). Interestingly, in both obese and lean children, resistin correlated with age (P < 0.01), Tanner stage, and testosterone and estradiol levels (P < 0.05). In contrast, no significant correlation was found with parameters of insulin resistance such as homeostasis model assessment, insulin sensitivity index, or insulin, proinsulin, and glucose concentrations in obese subjects. CONCLUSIONS: Resistin appears to be not the main link between obesity and insulin resistance in children and adolescents but because of its association with Tanner stage, it may be related to the maturation of children during pubertal development. Additionally, we have demonstrated the presence of different molecular isoforms of resistin in human blood, and this may raise problems in comparing data from diverse assay systems.
Adolescent↗
[Tracheobronchial ruptures: classification and management].
BACKGROUND: Tracheobronchial ruptures are rare surgical emergencies with significant mortality. We present management and outcome of such ruptures treated at the University of Leipzig in Germany and propose a novel therapeutic algorithm-a new classification system for stratifying treatment of patients with tracheobronchial ruptures. METHODS: We retrospectively studied 24 patients 19 to 88 years old who were treated in our institution for tracheobronchial injury. RESULTS: Eighty-seven percent of the injuries were caused iatrogenically. Fifty-four percent were type I injuries (isolated tracheal lesions), 38% type II (involvement of carina or main stem bronchi), and 8% type III (distal lesions of lobar or segmental bronchi). Seventy-five percent of the patients were operated via right-sided dorsolateral thoracotomy. In four (22%), insufficiency of the tracheal closure occurred, with mediastinitis possibly being a significant risk factor for this event (P<0.001). In surgically treated patients, rupture-related and overall mortality were 5.5% and 28%, respectively, whereas in medically treated patients, mortality was 33%. CONCLUSION: The proposed classification of tracheobronchial injuries enables stratifying the treatment of patients with tracheobronchial ruptures. Type I lesions can be surgically closed either by a right-sided thoracotomy or transcervical-transtracheal approach. In contrast, surgical management of type II and III injuries always requires thoracotomy.
Adult↗
[Surgical management, prognostic factors, and outcome in hepatic trauma].
Hepatic trauma is a rare surgical emergency with significant morbidity and mortality. Extensive experience in liver surgery is a prerequisite for the management of these injuries. The medical records of 68 consecutive patients with hepatic trauma were retrospectively reviewed for the severity of liver injury, management, morbidity, mortality, and risk factors. Of the patients, 14 were treated conservatively and 52 surgically (24 suture/fibrin glue, 16 perihepatic packing, 11 resections, 1 liver transplantation). Two patients died just before emergency surgery could be performed. Overall mortality was 21% (14/68), and 13, 14, 6, 27, and 50% for types I, II, III, IV, and V injuries, respectively. Only nine deaths (all type IV and V) were liver related, while four were caused by extrahepatic injuries and one by concomitant liver cirrhosis. With respect to treatment, conservative management, suture, and resection had a low mortality of 0, 4, and 9%, respectively. In contrast, mortality was 47% in patients in whom only packing was performed (in severe injuries). Stepwise multivariate regression analysis proved prothrombin values <40%, ISS scores >30, and transfusion requirements of more than 10 red packed cells to be significant risk factors for post-traumatic death. Type I-III hepatic injuries can safely be treated by conservative or simple surgical means. However, complex hepatic injuries (types IV and V) carry a significant mortality and may require hepatic surgery, including liver resection or even transplantation. Therefore, patients with severe hepatic injuries should be treated in a specialized institution.
Adolescent↗
Adjunctive homeopathic treatment in patients with severe sepsis: a randomized, double-blind, placebo-controlled trial in an intensive care unit.
BACKGROUND: Mortality in patients with severe sepsis remains high despite the development of several therapeutic strategies. The aim of this randomized, double-blind, placebo-controlled trial was to evaluate whether homeopathy is able to influence long-term outcome in critically ill patients suffering from severe sepsis. METHODS: Seventy patients with severe sepsis received homeopathic treatment (n = 35) or placebo (n = 35). Five globules in a potency of 200c were given at 12h interval during the stay at the intensive care unit. Survival after a 30 and 180 days was recorded. RESULTS: Three patients (2 homeopathy, 1 placebo) were excluded from the analyses because of incomplete data. All these patients survived. Baseline characteristics including age, sex, BMI, prior conditions, APACHE II score, signs of sepsis, number of organ failures, need for mechanical ventilation, need for vasopressors or veno-venous hemofiltration, and laboratory parameters were not significantly different between groups. On day 30, there was non-statistically significantly trend of survival in favour of homeopathy (verum 81.8%, placebo 67.7%, P= 0.19). On day 180, survival was statistically significantly higher with verum homeopathy (75.8% vs 50.0%, P = 0.043). No adverse effects were observed. CONCLUSIONS: Our data suggest that homeopathic treatment may be a useful additional therapeutic measure with a long-term benefit for severely septic patients admitted to the intensive care unit. A constraint to wider application of this method is the limited number of trained homeopaths.
APACHE↗
[Wound infection and infection-promoting factors in breast cancer surgery -- a prospective multicenter study on quality control].
INTRODUCTION: The quality of treatment of cancer of the female breast is reflected not only in such parameters as local recurrence rate and survival times, but also in the development of surgical complications. Within the framework of a study investigating the performance and quality assurance in surgical treatment of breast cancer, therefore, the wound infection rate (WIR) and factors influencing it were analysed in a large patient population. METHODS: In the period between 1.1.2000 and 31.12.2000, 84 surgical departments participated in a prospective multicenter study to investigate primary surgery for breast cancer. A total of 1 416 patients were recruited to the study, the organization and conduction of which was in the hands of the former surgical department 1 of the University of Leipzig under the patronage of the East German Working Group for Performance and Quality Control in Surgery in cooperation with the An Institute for Quality Control in Operative Medicine of the Otto-von-Guericke University in Magdeburg. In addition to parameters characterizing patients, tumors and diagnostic work-up, we also analysed the surgical treatment and its possible complications with the aid of a questionnaire. The definition of wound infection was based on the criteria of the "Hospital Infection Control Practice Advisory Committee". RESULTS: The overall WIR was 4.5 % (n = 65). 21 (32 %) of the wound infections (WI) were diagnosed exclusively on a clinical basis without establishing the responsible pathogens. In 44 (68 %) of the WI, a search for the pathogen was undertaken which in 3 cases (7 %) was negative, and in 41 cases (93 %) positive. 118 (8.3 %) of the patients received perioperative antibiotic cover. The following parameters were found to have a significant influence on WIR: local drainage, blood transfusion, the time lapse between biopsy and definitive surgery, and the size of the primary tumor. DISCUSSION: Some of the above factors (transfusion, time lapse, drainage) can be influenced by the therapist. The wound infection rate is a marker for treatment quality.
Adult↗
Bias in the trial and reporting of trials of homeopathy: a fundamental breakdown in peer review and standards?
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Homeopathy↗
Distribution of prostate carcinoma foci within the peripheral zone: analysis of 8,062 prostate biopsy cores.
The aim of this study was to evaluate the distribution of prostate cancer within the peripheral zone by prostate biopsies excluding the influence of the transition zone. A prospective, multicenter study was carried out using a consecutive series of men who underwent transrectal ultrasound guided prostate biopsies using different biopsy techniques at six institutions. Biopsies were directed strictly within the peripheral zone or strictly within the transition zone. A model of the peripheral zone with 18 sectors of similar volume was established and the biopsy cores obtained were associated with these sectors and analysed with respect to prostate cancer detection rate. A total of 904 men (mean age 66.8 years, range 42-86) with a median serum PSA of 8.1 ng/ml (2.2-940 ng/ml) entered the study. A total of 8,062 biopsy cores (mean 8.92/patient) were obtained. Each of the peripheral zone sectors tested by biopsies yielded a similar percentage of prostate cancer ( P=0.6). There was no increase in the incidence of cancer toward the lateral sectors compared to midline sectors ( P=0.53) of the peripheral zone. Biopsy sampling of the peripheral zone from the apex to the base yielded a similar percentage of prostate cancer ( P=0.47). Our data suggest that the distribution of cancer foci detected by biopsies in the peripheral zone of the prostate is homogeneous.
Adult↗
[Prospective multicenter study for quality management of breast cancer surgery].
Over the last 10 years a dramatic decrease became apparent in primary treatment of breast cancer in general surgical departments. A prospective 1-year observational study involving 84 surgical departments was carried out to describe the current therapeutic situation. A total of 1,416 patients undergoing primary surgical treatment for mammary carcinoma were recorded, and their data evaluated. 68.9% of the carcinomas were treated in departments with an annual case load for this disease of more than 20 operations, with 50% of them being operated on in 8 departments with a case load of 40-100 procedures per year. 94.4% of the carcinomas were confirmed histologically, and in 91% of the patients surgery was performed in curative intention. The rate of breast-preserving procedures was 40%, and breast amputations accounted for 60%. An analysis of the data allowed an evaluation of this specific patient group in the surgical departments. Deficits in terms of management quality are identified.
Adult↗
On the safety of Aspergillus niger--a review.
Aspergillus niger is one of the most important microorganisms used in biotechnology. It has been in use already for many decades to produce extracellular (food) enzymes and citric acid. In fact, citric acid and many A. niger enzymes are considered GRAS by the United States Food and Drug Administration. In addition, A. niger is used for biotransformations and waste treatment. In the last two decades, A. niger has been developed as an important transformation host to over-express food enzymes. Being pre-dated by older names, the name A. niger has been conserved for economical and information retrieval reasons and there is a taxonomical consensus based on molecular data that the only other common species closely related to A. niger in the Aspergillus series Nigri is A. tubingensis. A. niger, like other filamentous fungi, should be treated carefully to avoid the formation of spore dust. However, compared with other filamentous fungi, it does not stand out as a particular problem concerning allergy or mycopathology. A few medical cases, e.g. lung infections, have been reported, but always in severely immunocompromised patients. In tropical areas, ear infections (otomycosis) do occur due to A. niger invasion of the outer ear canal but this may be caused by mechanical damage of the skin barrier. A. niger strains produce a series of secondary metabolites, but it is only ochratoxin A that can be regarded as a mycotoxin in the strict sense of the word. Only 3-10% of the strains examined for ochratoxin A production have tested positive under favourable conditions. New and unknown isolates should be checked for ochratoxin A production before they are developed as production organisms. It is concluded, with these restrictions, that A. niger is a safe production organism.
Aspergillosis↗
PAI-I 4G/5G polymorphism and sudden cardiac death in patients with coronary artery disease.
UNLABELLED: The 4G/5G polymorphism of the plasminogen activator inhibitor type I (PAI-I) gene is involved in coronary artery disease (CAD), with the highest risk in 4G/4G homozygotes. The role of PAI-I polymorphism in patients suffering from CAD and history of sudden cardiac death (SCD) has not been addressed yet. We studied the frequency distribution of the PAI-I gene to test the hypothesis that the 4G/4G genotype favors myocardial ischemia and, even in the absence of acute infarction, promotes SCD in patients with CAD. METHODS: The PAI-I 4G/5G genotypes and PAI-I antigen plasma levels were determined in 97 patients with CAD and a history of SCD treated with an implantable cardioverter defibrillator (ICD) (defibrillator group) comparing to 113 patients with CAD but no history of SCD (control group). RESULTS: The defibrillator group consisted of significantly more 4G/4G homozygotes and higher PAI-I levels than the control group (44% vs. 24%, 173+/-41 vs. 144+/-49 ng/ml; P<.01). The carriers of 4G allele had a significantly higher risk for SCD (odds ratio (OR) 1.9) with the highest risk in the 4G/4G genotype (OR 3.6, P<.01). CONCLUSION: These results suggest that the PAI-I 4G/4G genotype is associated with SCD in patients suffering from CAD.
Aged↗
Differential effects of growth hormone therapy in malnourished hemodialysis patients.
BACKGROUND: Malnutrition is common in chronic hemodialysis patients and is associated with increased morbidity and mortality. Several factors such as metabolic acidosis, hyperparathyroidism, and insulin as well as growth hormone (GH) resistance may lead to enhanced protein catabolism. Recombinant human growth hormone (rhGH) has been proposed as treatment of malnutrition because of its anabolic effects. METHODS: In the present placebo-controlled, double blind study, the effects of three months of rhGH therapy on nutritional and anthropometric parameters, on bone metabolism and bone mineral density (BMD), as well as on polymorphonuclear leukocyte (PMNL) function and quality of life (QoL) were evaluated in 19 malnourished hemodialysis patients (10 females and 9 males) with a mean age of 59.3 +/- 13.4 years. RhGH (0.125 IU/kg) was given three times a week during the first four weeks and 0.25 IU/kg thereafter three times a week after each dialysis session. RESULTS: Insulin-like growth factor I (IGF-I) concentration rose significantly from 169.2 +/- 95.6 ng/mL to 262.9 +/- 144.4 ng/mL (p< 0.01) in the group receiving rhGH. Albumin, prealbumin, transferrin, cholesterol, high-density lipoprotein (HDL) cholesterol, cholinesterase, predialytic creatinine, and blood urea nitrogen showed no significant changes during the three months in both groups. Total body fat (%TBF) was slightly reduced after three months (P = NS) in the patients receiving GH, whereas lean body mass (LBM) remained stable during therapy. Procollagen I carboxy terminal peptide (PICP), a marker of bone formation, increased significantly after three months from 250.1 +/- 112.6 to 478.5 +/- 235.2 microg/L (P < 0.01) in the GH-treated patients, whereas parameters of bone resorption like telopeptide ICTP showed only a slight increase (50.3 +/- 18.5 vs. 70.0 +/- 39.5 microg/L, P = NS). BMD at the lumbar spine decreased significantly after three months in the treatment group (0.8 +/- 0.17 vs. 0.77 +/- 0.16 g/cm2, P < 0.01), whereas BMD at the femoral neck remained stable in both groups. Phagocytic activity of PMNLs increased significantly after three months of therapy with rhGH, whereas other parameters of PMNL function were not affected by GH. QoL was slightly improved in the GH treated group, but decreased markedly in the placebo group. CONCLUSIONS: Three months of treatment with rhGH in malnourished patients on chronic hemodialysis causes a significant increase in IGF-I levels without significant changes in nutritional and anthropometric parameters. In contrast, bone turnover was enhanced with an initial decrease in BMD at the lumbar spine, and phagocytic activity of PMNLs was increased.
Adult↗
Informational contribution of noninvasive screening tests for coronary artery disease in patients on chronic renal replacement therapy.
The prevalence of coronary artery disease (CAD) is high in patients on renal replacement therapy; therefore, reliable noninvasive screening tests are needed. We retrospectively determined the sensitivity, specificity, and positive and negative likelihood ratios (LRs) for a history of chest pain, resting and exercise electrocardiography (ECG), thallium dipyridamole scintigraphy, and echocardiography in 42 patients undergoing chronic hemodialysis and 42 patients after renal transplantation who also underwent coronary angiography. In addition, the prognostic power of each test for the occurrence of a cardiovascular event after angiography (therapeutic intervention, myocardial infarction, or cardiovascular death) was evaluated during a follow-up of 37 months. Forty-three patients had significant CAD on angiography. Angina pectoris had a sensitivity of 65% and specificity of 66%, corresponding to a positive LR of 1.9 and a negative LR of 0.5. A variable number of patients underwent noninvasive tests before angiography. Results were similar in patients undergoing hemodialysis and after renal transplantation and in patients with or without angina pectoris. Exercise ECG could not be performed in the majority of patients, and resting ECG (sensitivity, 67%; specificity, 52%; corresponding to a positive LR of 1.4 and negative LR of 0.6) and scintigraphy (sensitivity, 80%; specificity, 37%; positive LR, 1.3; negative LR, 0.5) in patients on renal replacement therapy were not useful for the diagnosis of CAD. Angina also markedly increased the relative odds for the occurrence of a cardiovascular event during follow-up (relative odds, 4.6) compared with other noninvasive tests. Angina pectoris had the best informational and prognostic value of noninvasive screening methods, but angiography seems to be the only method to clearly document CAD in patients on renal replacement therapy.
Aged↗
Occurrence of matrix metalloproteinases and tissue inhibitors of metalloproteinases in tuberculous pleuritis.
OBJECTIVE: Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) have been found in high concentrations in pleural effusions. Because MMP and TIMP may play a part in the causation of the fibrosis seen in tuberculous (TB) pleuritis their occurrence was examined. DESIGN: Pleural effusion fluid and plasma concentrations of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, TIMP-1 and TIMP-2 were determined by ELISA in 21 patients with TB pleuritis. To adjust for the total protein content, respective ratios were calculated. Activities of MMP-2 and MMP-9 were measured by gelatine zymography and the MMP-9/MMP-2 ratios calculated. Pleural effusions and plasma of 15 patients with congestive heat failure (CHF) and plasma of 15 healthy persons (CON) served as controls. RESULTS: Immunoreactive pleural fluid concentrations of MMP-1, MMP-2, MMP-8, and MMP-9 were higher in TB compared to CHF, but plasma concentrations were not different between the groups. TB pleural fluid concentrations of MMP-1, MMP-2, TIMP-1, and TIMP-2 were higher compared to TB plasma. MMP-3 was found in trace amounts only. The MMP-9/total protein ratios in pleural fluid were higher in TB compared to CHF (0.4492+/-0.1633 vs 0.0364+/-0.0145, P<0.005) but the TIMP-1 ratios were lower (139.0+/-28.7 vs 517.8+/-183.7, P<0.0005). In TB pleural fluid vs TB plasma, the respective MMP-1, MMP-2, TIMP-1, and TIMP-2 ratios were increased (0.46+/-0.10 vs 0.17+/-0.02; 25.2+/-2.8 vs 4.2+/-0.9; 139.0+/-28.7 vs 27.8+/-8.2; 0.67+/-0.13 vs 0.18+/-0.04, P<0.0005 each). Gelatine zymography demonstrated MMP-2 and MMP-9 bands of different brightness in TB effusions but in CHF effusions the MMP-9 band was barely visible. The MMP-9/MMP-2 effusion ratios were therefore higher in TB compared to CHF (0.46+/-0.15 vs 0.05+/-0.04, P<0.0005). CONCLUSION: Compartmentalized MMP-1, MMP-2, TIMP-1, and TIMP-2 and, compared to CHF, a surplus of MMP-1, MMP-2, MMP-8, and MMP-9 in the pleural space obviously contribute to the fibrotic reactions in TB pleuritis.
Adult↗
Immunogenetic markers and seropositivity predict radiological progression in early rheumatoid arthritis independent of disease activity.
OBJECTIVE: A prospective clinical study of patients with recent onset rheumatoid arthritis (RA) to examine the relationship between inflammatory disease activity and joint destruction in a 4 year followup, and to evaluate prognostic markers for severe joint erosions early in the disease. METHODS: Eighty-seven patients with RA according to the American College of Rheumatology criteria and a disease duration < 2 years were followed for an observation time of 2 to 4 years (mean 3.1 yrs). Variables of clinical and laboratory disease activity were monitored, and HLA-DRB1 alleles were determined. Hand and foot radiographs were taken every 6 months. RESULTS: Multivariate analysis of independent contributions of covariates to progression of joint destruction resulted in a mixed effect regression model with significant influences for the presence of a shared epitope (SE) positive DR4 allele (SE+ DR4+; p = 0.007), rheumatoid factor (RF) IgA (p = 0.01), and sex (p = 0.059), but not for clinical variables or acute phase reactants. The odds ratio to reach a Larsen score above 32 during the observation period of 4 years was increased in patients positive for RF IgM (OR 2.7, p = 0.019), for the shared epitope on a DR4 allele (OR 8.6, p < 0.005), and in patients with erosions already at study entry (OR 11.9, p = 0.001). The highest sensitivity and specificity for the prediction of severe bone destruction (84% and 79%) were found when the presence of either a SE+ DR4 allele or of early erosions was used as a prognostic marker (OR 20.4, p < 0.0001). CONCLUSION: Our results show the pace of joint destruction in RA to be influenced by the presence of SE+ DR4 alleles, RF production, and sex and by the presence of erosive disease at presentation. Those prognostic markers exert their influence independently from the inflammatory disease activity.
Adult↗
Loss of heterozygosity (LOH) at p53 is correlated with LOH at BRCA1 and BRCA2 in various human malignant tumors.
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BRCA2 Protein↗