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Biomedical subjects

L Binder

Publications and source records attributed to L Binder.

At least 19 recordsLinked to original sources
PubMed2006

Mediterranean diet has no effect on markers of inflammation and metabolic risk factors in patients with coronary artery disease.

OBJECTIVE: Mediterranean diet is associated with decreased levels of inflammatory markers and metabolic risk factors in epidemiologic studies and recent trials on patients with metabolic syndrome. Given the recent improvements in medical treatments, it is unclear if such beneficial effects are also present in patients with coronary artery disease (CAD). We therefore investigated the effect of Mediterranean diet on markers of inflammation and metabolic risk factors in patients with treated CAD. DESIGN: Randomized, controlled trial. SUBJECTS: A total of 101 patients (59.4+/-8.6 years, 23% female) with established and treated CAD (80% statins). INTERVENTIONS: Participants were assigned to a Mediterranean diet group (MG; n=48) with a 1-year program of 100 h of education, or to a written advice-only group (AG; n=53). Before and after intervention, we measured serum high-sensitivity C-reactive protein (hs-CRP), fibrinogen, fasting insulin, homocysteine, serum lipids and plasma fatty acids. RESULTS: The Mediterranean diet program increased the intakes of fish, fruits/vegetables and moderately of canola/olive oil and increased plasma concentrations of long-chain n-3 polyunsaturated fatty acids in the MG. Median hs-CRP and mean fibrinogen, homocysteine, fasting insulin, triglycerides and serum cholesterols remained unchanged in both groups. CONCLUSIONS: Adoption of a Mediterranean diet by patients with medically treated CAD has no effect on markers of inflammation and metabolic risk factors. SPONSORSHIP: Alfried Krupp Foundation, Essen, Germany.

Biomarkers↗
PubMed2005

Galanin plasticity in the cholinergic basal forebrain in Alzheimer's disease and transgenic mice.

Galanin (GAL) is a biologically active 29 amino acid (30 in humans) which participates in the modulation of several ascending neurotransmitter systems including cholinergic basal forebrain (CBF) neurons, which undergo extensive degeneration in Alzheimer's disease (AD). GAL immunoreactive fibers within the CBF display hypertrophy and hyperinnervate surviving CBF neurons in late AD. Over the years, this unique neuronal plasticity response has been an active area of research for our group. We have examined tissue from a clinically well characterized cohort of retired elderly clergy to determine whether people with mild cognitive impairment display GAL hyperinnervation upon CBF neurons. We found that GAL hyperinnervation is a late stage event and that CBF neuron reduction is not correlated with GAL over expression during prodromal AD. Interestingly, findings from our laboratory using tau immunohistochemistry and single cell gene array technologies suggest that GAL remodeling may influence neurofibrillary tangle formation by altering tau phosphorylation events in CBF neurons in AD. Studies using GAL-tg mice suggest that GAL over expression reduces the cholinergic phenotype but does not produce a frank loss of CBF cells. This phenotypic down regulation of ChAT is reminiscent of the lack of a frank CBF neuron loss in prodromal AD. Moreover, studies using mice transgenic for both the amyloid precursor protein (APP) and presenilin-1 (PS1) bearing AD-related mutations (APPswe/PS1delta9) displayed increased GAL immunoreactive fibers, neurities and plaques in cortex and hippocampus. These fin'dings provide evidence for a mechanistic relationship between amyloidosis and GAL over expression in AD. Understanding GALs role in the clinical and pathological features of AD, may lead to novel drug treatments for this disease.

Acetylcholine↗
PubMed2004

Elevated concentrations of serum relaxin are associated with metastatic disease in breast cancer patients.

Relaxin (RLX) is known to induce remodeling of benign stromal tissues through upregulation of matrix metalloproteases (MMPs). Recently, we could show that RLX also induces MMPs in breast cancer cells and enhances in vitro invasiveness. To investigate its potential role for progression of breast cancer in vivo, RLX serum concentrations were determined in 160 breast cancer patients during post-surgical follow-up. RLX concentrations in cancer patients were significantly higher than in a control population of healthy blood donors and patients with various other diseases (0.47 versus 0.29 ng/ml, p < 0.0001). There was a significant difference between patients with metastases (0.62 ng/ml) and those without (0.38 ng/ml, p < 0.0001). Overall survival was shorter in RLX-positive ( > 0.4 ng/ml) than in RLX-negative patients (p = 0.016). Cox regression analysis showed that RLX was not an independent variable, in contrast to metastatic disease and primary lymph node involvement. Taken together, the detection of elevated RLX concentrations especially in patients with metastases supports the assumption that there is a role for RLX in tissue remodeling during breast cancer progression.

Adult↗
PubMed2003

Procalcitonin: a useful discriminator between febrile conditions of different origin in hemato-oncological patients?

Plasma concentrations of procalcitonin (PCT) have been shown to be elevated in bacterial and fungal infections. In contrast to C-reactive protein (CRP), PCT is not elevated in inflammations of noninfectious origin. Febrile inflammatory conditions are frequent in patients with hemato-oncological diseases. A reliable marker to discriminate infectious inflammations from drug-related and tumor-associated fever is still lacking. To evaluate the impact of PCT in this setting, PCT and CRP were prospectively measured in 95 febrile hemato-oncological patients. Infections could be identified in 40 of 95 patients: 38 of 95 had fever of unknown origin (FUO), 9 patients were suspected to suffer from drug-related fever, and 8 patients from tumor-associated fever. In the noninfection group (drug-related and tumor-associated fever), PCT levels were significantly lower than in patients with infections (P<0.001) or FUO (P<0.001). Differences were still highly significant comparing patients with suspected drug-related or tumor-associated fever alone with the infection or the FUO cohort. All eight patients with tumor-associated fever as well as eight of the nine patients with drug-related fever had PCT levels within the normal range (<0.5 micro g/l). CRP values only partially allowed discrimination between the various subgroups. Differences were significant between patients with drug-related fever and the infection (P=0.001) or FUO group (P=0.004). However, as CRP levels were far above the normal range also in the patients with drug-related fever, the significance of individual values was rather limited. In conclusion, PCT may provide useful additional information to assess the clinical significance of febrile conditions. PCT may facilitate the decision on when to initiate antimicrobial or cytotoxic therapy.

Adolescent↗
PubMed2001

Reduction of severe ischemia/reperfusion injury in rat kidney grafts by a soluble P-selectin glycoprotein ligand.

BACKGROUND: Inflammatory leukocyte-endothelium interactions, mediated by selectins, contribute to renal ischemia/reperfusion (I/R) injury. We examined the influence of the soluble P-selectin glycoprotein ligand 1 (sPSGL) on early I/R-induced changes in a rat kidney transplantation model with long cold ischemia. METHODS: After 24 hr of cold storage, syngeneic kidneys were grafted into bilaterally nephrectomized rats. Before transplantation, recipients received either 1 mg/kg of sPSGL or vehicle (n=8 per group). Six hours after reperfusion, grafts were removed for light microscopy and immunohistochemistry. Capillary blood flow was measured under a fluorescence microscope by using the concentric-circles method. RESULTS: A greater proportion, 74.7+/-7.2% (sPSGL) vs. 28+/-7.4% (controls), of all dye-labeled outer medullary capillaries appeared in the 12-microm radius (P<0.01), indicating dense blood flow, whereas 7.6+/-2.9% vs. 43.3+/-9.7%, respectively, appeared in the 60-microm radius (P<0.05), indicating rarefied blood flow. In the sPSGL-treated group, the extent of severe tubular damage within the inner stripe of the outer medulla was lower compared with controls (37.5+/-8.3% vs. 78.4+/-3.5%, P<0.01). Outer medullary heat shock protein 72 expression was 14.5+/-1.6% in the sPSGL-treated group compared with 9.6+/-1.4% in controls (P<0.05). The number of infiltrating polymorphonuclear leukocytes was similar in both groups. Treatment with sPSGL had no influence on the serum creatinine level. CONCLUSIONS: Our data suggest that impairment of outer medullary blood flow is crucial in I/R injury of kidney grafts with prolonged cold storage. Reduction of capillary blood flow perturbations by sPSGL protects tubular cells from severe structural damage. Blocking early selectin-mediated leukocyte adhesion may have therapeutic implications in improving the prognosis of renal transplants with severe I/R injury.

Animals↗
PubMed2001

Enterovirus infection--a possible trigger for Graves' disease?

Viruses are potential environmental factors in autoimmune disease. Some evidence suggests a relationship between enteroviral infection (especially Coxsackie B virus) and autoimmunity. We investigated 21 individuals with recent onset of Graves' hyperthyroidism in regard of (subclinical) enterovirus infection. Thyrotoxic symptoms had started about two months before blood sample collection. The patients were from Upper Austria and mainly female (17/21). Their mean free thyroxin levels in blood were twice the maximum normal value and the majority achieved a euthyroid state 1 1/2 years later, after antithyroid medication. We employed a nested PCR reaction with primers of the enterovirus genome on blood samples. All were negative for RNA of the enterovirus group. Coxsackie and related viruses were not identified as a trigger factor in autoimmune thyrotoxic disease.

Adult↗
PubMed2000

Cardiac troponin I elevation in acute pulmonary embolism is associated with right ventricular dysfunction.

OBJECTIVES: The purpose of this study was to evaluate the prevalence and diagnostic utility of cardiac troponin I to identify patients with right ventricular (RV) dysfunction in pulmonary embolism. BACKGROUND: Right ventricular overload resulting from elevated pulmonary resistance is a common finding in major pulmonary embolism. However, biochemical markers to assess the degree of RV dysfunction have not been evaluated so far. METHODS: In this prospective, double-blind study we included 36 study patients diagnosed as having acute pulmonary embolism. RESULTS: Among the whole study population, 14 patients (39%) had positive troponin I tests. Ten of 16 patients (62.5%) with RV dilatation had increased serum troponin I levels, while only 4 of 14 patients (28.6%) with elevated troponin I values had a normal RV diameter as assessed by echocardiography, indicating that positive troponin I tests were significantly associated with RV dilatation (p = 0.009). Patients with positive troponin I tests had significantly more segmental defects in ventilation/perfusion lung scans than patients with normal serum troponin I (p = 0.0002). CONCLUSIONS: Our data demonstrate that more than one-third of patients clinically diagnosed as having pulmonary embolism presented with elevated serum troponin I concentrations. Troponin I tests helped to identify patients with RV dilatation who had significantly more segmental defects in lung scans. Thus, troponin I assays are useful to detect minor myocardial damage in pulmonary embolism.

Acute Disease↗
PubMed2000

Epstein-Barr virus infection in peripheral blood mononuclear cells, synovial fluid cells, and synovial membranes of patients with rheumatoid arthritis.

OBJECTIVE: Different infectious agents have been proposed to be involved in the pathogenesis of rheumatoid arthritis (RA). We investigated the role of latent Epstein-Barr virus (EBV) infection in patients with RA. METHODS: Sera of 55 patients with RA and 60 age and sex matched healthy controls were examined for antibodies against EBV encoded antigens (EBNA-1, VCA, and EA) by ELISA. The presence of viral DNA was analyzed by polymerase chain amplification of DNA isolated from peripheral blood mononuclear cells (PBMC) of these samples and from cells of synovial fluid (SF) specimens. Paraffin sections of synovial membranes from 25 patients were subjected to in situ hybridization analysis for the EBV encoded small RNA EBER1 and EBER2. RESULTS: Two-fold increased values of IgG antibodies against EBNA-1 were found in patients with RA in comparison to healthy controls (p = 0.029). No statistically significant difference could be observed for antibody levels against EBV-VCA. Fourteen (24.1%) of 55 patients with RA had serological evidence of reactivated EBV infection in comparison to none of the control group (p = 0.028). In PBMC, EBV DNA was detected in a significantly higher proportion in the patient group (50.9 vs. 30%; p = 0.02). In addition, SF cells harbored the viral DNA in 30% of RA cases compared to 16.6% of control cases (p = 0.02). However, EBER1/2 transcripts could only be found within synovial membranes of 2 (8%) of 25 patients with RA. CONCLUSION: These findings support the hypothesis that EBV infection may be involved in the pathogenesis of RA. Further studies may define the precise pathogenetic mechanisms of viral infection for the development of inflammatory arthritis.

Adolescent↗
PubMed1999

Surgical treatment of cholangiocellular carcinoma.

Cholangiocarcinoma is a primary liver tumor arising from the small bile ducts within the liver. According to its different location, clinical features, frequency of metastases, treatment modalities and prognosis, intrahepatic cholangiocarcinoma should well be differentiated from proximal bile duct carcinoma. To date, there is no therapeutic measure with curative potential apart from surgical treatment. Partial hepatectomy is the treatment of choice. It is of overriding importance to achieve microscopically tumor-free margins. However, only few patients treated in an early stage have a prolonged recurrence-free survival or a chance for cure. Liver transplantation is not an alternative therapeutic option for unresectable cholangiocarcinoma, due to early tumor recurrence in almost all recipients. Liver transplantation has a place in preventing cholangiocarcinoma in primary sclerosing cholangitis, although the timing of replacement is still a matter of debate. Results of surgery need further improvement by adjuvant or neoadjuvant treatment protocols.

Bile Duct Neoplasms↗
PubMed1999

Nitrotyrosine formation with endotoxin-induced kidney injury detected by immunohistochemistry.

The presence of nitrotyrosine in the kidney has been associated with several pathological conditions. In the present study, we investigated nitrotyrosine formation in rat kidney after animals received endotoxin for 24 h. With lipopolysaccharide (LPS) treatment, immunohistochemical data demonstrated intense nitrotyrosine staining throughout the kidney. In spite of marked nitrotyrosine formation, the architectural appearance of tubules, glomeruli, and capillaries remained intact when examined by reticulin staining. Our data suggested that the marked staining of nitrotyrosine in proximal tubular epithelial cells was in the subapical compartment where the endocytic lysosomal apparatus is located. Thus a large portion of nitrotyrosine may come from the hydrolysis of nitrated proteins that are reabsorbed by the proximal tubule during the LPS treatment. We also found the colocalization of nitric oxide synthase (NOS-1) and nitrotyrosine within the macula densa of LPS-treated rats by using a double fluorescence staining method. In renal arterial vessels, vascular endothelial cells were more strongly stained for nitrotyrosine than vascular smooth muscle cells. Control animals without LPS treatment showed much less renal staining for nitrotyrosine. The general distribution of nitrotyrosine staining in control rat renal cortex is in the proximal and convoluted tubules, whereas the endothelial cells of vasa recta are major areas of nitrotyrosine staining in inner medulla. The renal distribution of nitrotyrosine in control and LPS-treated animals suggests that protein nitration may participate in renal regulation and injury in ways that are yet to be defined.

Animals↗
PubMed1998

BCG lymphadenitis in an HIV-infected child 9.5 years after vaccination.

Complications of Bacillus Calmette-Guerin (BCG) vaccination have been reported in immunocompetent as well as in immunocompromised individuals. Severe and/or late complications have been associated with impairment of cell-mediated immunity. A case of BCG lymphadenitis in a vertically infected HIV-positive boy 9.5 years after vaccination is presented. The vaccination was performed within the first week of life, the HIV status of the mother being unknown. When the boy was 2.5 years old, his HIV infection was diagnosed after his mother had died from AIDS. At that time his CD4 count was 739 cells/microL. In the course of the following years, his CD4 count declined steadily, until it reached a low of about 20 cells/microL at the age of 5.5 years. He was troubled with recurring respiratory infections and one incidence of severe pancreatitis. Apart from that, he was in stable condition and led a more or less normal life. At the age of 9.5 years he developed lymphadenitis in his left axilla. The node was examined via biopsy, and the appropriate tests showed an infection with Mycobacterium bovis BCG variety. The CD4 count at that time was 16 cells/microL, polymerase chain reaction showed 220,000 RNA copies/mL. There were no signs of dissemination. Antitubercular agents were administered, and an antiretroviral combination therapy was started. The patient was discharged from the hospital after approximately 2 months. After an uneventful period of 9 months, the boy, still on antitubercular medicine, exhibited a secreting fistula in his left axilla, again due to Mycobacterium bovis, BCG variety. The fistulous tissue was removed surgically, and the antitubercular treatment was given intravenously for almost 3 months before being changed to an oral application. In addition, the antiretroviral regimen was completely exchanged. The case presented illustrates that there is a risk of very late complications in HIV-infected individuals, even when they are vaccinated when they are asymptomatic newborns. Although the risk seems low, one has to be aware of the problem because timely treatment is probably essential to prevent dissemination of the infection. Late complications of BCG vaccinations are most likely to be detected in countries with high medical standards, where HIV-infected children are surviving for longer periods of time.

Antitubercular Agents↗
PubMed1998

Superiority of combined CK-MB and troponin I measurements for the early risk stratification of unselected patients presenting with acute chest pain.

BACKGROUND: Recent studies have suggested that positive troponin I tests are associated with an increased risk of cardiac death during short-term follow-up. However, it is unknown if troponin I tests alone or in addition to CK-MB measurements are superior to predict unfavorable outcome during long-term follow-up. PATIENTS AND METHODS: In a prospective, double-blind study we assessed the prevalence and prognostic value of combined troponin I and CK-MB tests in an unselected cohort of patients (n = 292) admitted to the emergency department for acute chest discomfort. Patients were grouped according to the diagnosis on discharge in those with acute myocardial infarction (1), unstable angina (2), and noncardiac chest pain (3). Six months after enrollment, death rates were obtained and follow-up interviews were performed with respect to survival, recurrence of chest pain, and myocardial infarction. RESULTS: In patients with evidence of coronary heart disease, the mortality rate for abnormal troponin I and normal CK-MB levels was 5.0%. Baseline troponin I and elevated CK-MB levels were associated with a mortality rate of 4.0%. However, the mortality rate was significantly higher (11.1%) in patients presenting with elevated troponin I and CK-MB values. In patients without myocardial infarction on admission, 10.5% with positive troponin I tests died compared to 1.6% with negative tests. The mortality rate in patients without myocardial infarction was 2.7% for patients with elevated CK-MB but normal troponin I values. In patients with both markers elevated a significantly higher mortality rate (16.7%) was found, representing a 6-fold increase in the death event rate. With the additional knowledge of troponin I values, it could be demonstrated that certain cases were misclassified as having noncardiac chest pain. At least some of the latter patients with above-normal values of troponin I were retrospectively to be reclassified as unstable angina. Acute non-Q-wave myocardial infarctions were occasionally misdiagnosed as either angina pectoris or nonischemic chest pain. CONCLUSIONS: Our data suggest the superiority of combined CK-MB and troponin I measurements in clinical practice for the early risk stratification of patients presenting with acute chest pain. In nonmyocardial infarctions, both CK-MB and troponin I convey independent prognostic information with regard to fatal outcome. Troponin I tests in addition to CK-MB measurements contribute to a lower rate of misdiagnoses.

Aged↗
PubMed1998

Clinical outcome and economic impact of aminoglycoside peak concentrations in febrile immunocompromised patients with hematologic malignancies.

The aim of this study was to investigate the clinical and economic significance of aminoglycoside peak concentrations in febrile neutropenic patients with hematologic malignancies. Sixty-one patients were treated according to protocol II of the Paul-Ehrlich-Gesellschaft: initial application of gentamicin or tobramycin in combination with a cephalosporin or ureidopenicillin and, after 3 days, a potential change of antibiosis to be decided in case of nonresponse. At the same time, samples were collected by an independent controller. We found a significant dependence of clinical outcome on aminoglycoside peak concentrations (P = 0.004). Twelve of 17 patients with peak concentrations > 4.8 mg/L, but only 13 of 44 patients with concentrations < or = 4.8 mg/L, responded to initial therapy. Average infection-related costs per patient with peak values > 4.8 mg/L were US$1429, $1790, and $1701 for nursing, diagnostics, and therapeutics, respectively (total $4920). Expenses for patients with peak concentrations < or = 4.8 mg/L were approximately 1.8-fold higher (average total $8718). If all 61 patients had achieved peaks > 4.8 mg/L, the potential savings would have totalled $167,112. We conclude that neutropenic patients form a target group for successful pharmacokinetic intervention and cost saving.

Adult↗
PubMed1997

Influence of cycloheximide-mediated downregulation of glucose transport on TNF alpha-induced apoptosis.

Enhancement of cellular sensitivity to TNF alpha-induced apoptosis by cycloheximide (CX) has been attributed to its quality as an inhibitor of protein synthesis, presumably by prevention of the synthesis of short-lived death antagonists. CX is also known to interfere with glucose transport, which in turn influences cell death. Hexose uptake, expression of glucose transporter (Glut) mRNAs and proteins, and other related factors were therefore examined upon induction of apoptosis with TNF alpha and CX in breast cancer cell lines. In the early phase of apoptosis, a dramatic decrease in glucose transport was observed, preceded by stimulation of Glut 1 and 3 mRNAs. Transport downregulation was also detectable upon incubation with CX alone, albeit to a lesser extent. With the doses used, TNF alpha had no such effect. Protein synthesis was inhibited to the same degree in TNF alpha/CX-treated apoptotic cells compared to viable CX-treated cells. Diminished hexose uptake was associated with decreased Vmax, while Glut affinity remained unaffected. As there was no evidence for changes in total cellular Glut content or for Glut translocation from the plasma membrane, a diminished intrinsic activity of Gluts must be postulated. In conclusion, CX is proposed to contribute to TNF alpha-induced apoptosis predominantly by interference with glucose transport; the exact nature of this effect remains to be elucidated.

Adenosine Triphosphate↗
PubMed1997

A simple and reliable reverse-phase high-performance liquid chromatographic procedure for determination of paclitaxel (taxol) in human serum.

A simple, fast, and reliable isocratic (mobile phase: acetonitrile/methanol/water [48/11/41], reverse-phase (C18 column) high-performance liquid chromatography method for the determination of paclitaxel concentration in human serum is presented. The procedure uses a new and convenient one-step sample-purification procedure that requires only 400 microliters of sample and uses N-heptylbenzamide as an internal standard. Paclitaxel is detected by UV absorbance measurement at 227 nm. The method has a broad linear range (0.01 to 10 mg/l, or 0.012 to 11.7 mumol/l; r > 0.999), and the detection limit is 0.01 mg/l (0.012 mumol/l). The deviation from target value is < or = 1.5%, and coefficients of variation are < or = 13.8% within runs and < or = 15.3% between runs. Recovery paclitaxel is > or = 92.6%. No interferences were observed from endogenous compounds or from more than 30 drugs that may be administered with paclitaxel. Docetaxel, which is not concurrently administered, coeluted with paclitaxel. Compared with previously published high-performance liquid chromatography procedures for the determination of paclitaxel, the particular advantage of the method presented here is its simple and rapid single-step sample-purification procedure, which makes a high recovery of paclitaxel from serum samples possible and results in a pure extract, avoiding interferences from endogenous compounds. The method is suitable for pharmacological studies and routine analysis.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Antibiotic susceptibility of pneumococci isolated in Austria over a four-year period.

The antibiotic susceptibility of pneumococci isolated from clinical specimens from 1991 through 1994 was investigated. Of 305 strains tested by the agar dilution method, 16 (5.2%) were resistant to penicillin (MICs > or = 0.12 mg/l). Of the resistant strains, 0.3% showed high-level resistance (MIC > or = 2 mg/l). The rate of resistance to erythromycin (MIC > or = 4 mg/l) was 2.3%, to tetracycline (MIC > or = 8 mg/l) 8.5%, to chloramphenicol (MIC > or = 8 mg/l) 1.0%, and to trimethoprim sulfamethoxazole (MIC > or = 3.2/64 mg/l) 3.3%. Penicillin-resistant strains showed significantly higher resistance to the other antibiotics tested. Resistance to penicillin was higher in isolates from the respiratory tract than in those from blood and cerebrospinal fluid (6.2% vs. 2.4%, respectively). There was no increase in penicillin resistance from 1991 through 1994 (5.3% vs. 4.9%, respectively).

Anti-Bacterial Agents↗