Biomedical subjects

H Reuter

Publications and source records attributed to H Reuter.

At least 19 recordsLinked to original sources

PubMed2006

The increased angiotensin II (type 1) receptor density in myocardium of type 2 diabetic patients is prevented by blockade of the renin-angiotensin system.

AIMS/HYPOTHESIS: The angiotensin II (type 1) (AT1) receptor mediates many biological effects of the renin-angiotensin system (RAS), leading to remodelling of cardiac tissue. The present study was designed to analyse changes in the function and expression of the AT1 receptor as principal effector of the RAS in myocardium from type 2 diabetic patients compared with non-diabetic myocardium as control. In addition, we determined the effect of treatment with ACE inhibitors or AT1 receptor blockers on expression levels of the receptor in diabetic patients. METHODS: Gene expression of the AT1 receptor was analysed by quantitative RT-PCR and protein expression was determined by immunoblot analysis in human right atrial myocardium. We investigated functional coupling of the receptors by measuring contractility in isolated trabeculae stimulated with increasing concentrations of angiotensin II. RESULTS: Diabetic myocardium showed a significant increase in protein expression (170 +/- 16% of control) and median mRNA expression (186% of control) of the AT1 receptor. The additional receptors were functionally coupled, resulting in a stronger inotropic response upon stimulation with angiotensin II (89 +/- 5.5% vs 29 +/- 1.6% in controls), whereas receptor affinity was similar in both groups. However, myocardium from diabetic patients treated with ACE inhibitors or AT1 receptor blockers showed no increase in AT1 receptor expression. CONCLUSIONS/INTERPRETATION: AT1 receptor expression in myocardium of type 2 diabetic patients is dynamic, depending on the level of glycaemic control and the activity of the RAS. These findings could at least in part explain the strong therapeutic benefit of RAS inhibition in diabetic patients.

Aged↗

PubMed2006

[DNA-chips in the diagnosis of hematological malignancies].

In hematological malignancies, gene expression profiling using DNA-microarrays led to the discovery of novel lymphoma and leukemia subgroups. The heterogeneous entity of diffuse large B-cell lymphoma could be subdivided into the germinal center B-cell-like and the activated B-cell-like subtype which differ in pathogenesis and clinical behavior. In leukemia, existing entities defined by morphological, cytogenetic, molecular and immunophenotypic criteria were confirmed on the global gene expression level; in addition, new important molecular subgroups could be identified. In retrospective clinical lymphoma and leukemia studies, robust gene expression signatures were discovered that predict the clinical course at the time of diagnosis. Given the huge potential of the DNA-microarray technology, application in the routine diagnostic setting appears possible.

Biomarkers, Tumor↗

PubMed2006

Diagnosing tuberculous pericarditis.

BACKGROUND: Definitive diagnosis of tuberculous pericarditis requires isolation of the tubercle bacillus from pericardial fluid, but isolating the organism is often difficult. AIM: To improve diagnostic efficiency for tuberculous pericarditis, using available tests. DESIGN: Prospective observational study. METHODS: Consecutive patients (n = 233) presenting with pericardial effusions underwent a predetermined diagnostic work-up. This included (i) clinical examination; (ii) pericardial fluid tests: biochemistry, microbiology, cytology, differential white blood cell (WBC) count, gamma interferon (IFN-gamma), adenosine deaminase (ADA) levels, polymerase chain reaction testing for Mycobacterium tuberculosis; (iii) HIV; (iv) sputum smear and culture; (v) blood biochemistry; and (vi) differential WBC count. A model was developed using 'classification and regression tree' analysis. The cut-off for the total diagnostic index (DI) was optimized using receiver operating characteristic (ROC) curves. RESULTS: Fever, night sweats, weight loss, serum globulin (>40 g/l) and peripheral blood leukocyte count (<10 x 10(9)/l) were independently predictive. The derived prediction model had 86% sensitivity and 84% specificity when applied to the study population. Pericardial fluid IFN-gamma >or=50 pg/ml, concentration had 92% sensitivity, 100% specificity and a positive predictive value (PPV) of 100% for the diagnosis of tuberculous pericarditis; pericardial fluid ADA >or=40 U/l had 87% sensitivity and 89% specificity. A diagnostic model including pericardial ADA, lymphocyte/neutrophil ratio, peripheral leukocyte count and HIV status had 96% sensitivity and 97% specificity; substituting pericardial IFN-gamma for ADA yielded 98% sensitivity and 100% specificity. DISCUSSION: Basic clinical and laboratory features can aid the diagnosis of tuberculous pericarditis. If available, pericardial IFN-gamma is the most useful diagnostic test. Otherwise we propose a prediction model that incorporates pericardial ADA and differential WBC counts.

Female↗

PubMed2006

The role of histopathology in establishing the diagnosis of tuberculous pericardial effusions in the presence of HIV.

AIMS: To establish the influence of human immunodeficiency virus (HIV) infection on the histopathological features of patients presenting with tuberculous pericarditis. METHODS AND RESULTS: A prospective study was carried out at Tygerberg Academic Hospital, South Africa; 36 patients with large pericardial effusions had open pericardial biopsies under general anaesthesia and were included in the study. Patients underwent pericardiocentesis, followed by daily intermittent catheter drainage; a comprehensive diagnostic work-up (including histopathology of the pericardial tissue) was also performed. Histological tuberculous pericarditis was diagnosed according to predetermined criteria. Tuberculous pericarditis was identified in 25 patients, five of whom were HIV+. The presence of granulomatous inflammation (with or without necrosis) and/or Ziehl-Neelsen positivity yielded the best test results (sensitivity 64%, specificity 100% and diagnostic efficiency 75%). CONCLUSIONS: Co-infection with HIV impacts on the histopathological features of pericardial tuberculosis and leads to a decrease in the sensitivity of the test. In areas which have a high prevalence of tuberculosis, the combination of a sensitive test such as adenosine deaminase, chest X-ray and clinical features has a higher diagnostic efficiency than pericardial biopsy in diagnosing tuberculous pericarditis.

AIDS-Related Opportunistic Infections↗

PubMed2005

Epidemiology of pericardial effusions at a large academic hospital in South Africa.

The aim was to establish the prevalence of large pericardial effusions in the Western Cape Province of South Africa, and to determine the incidence of various types of effusions. A total of 233 patients presented with large pericardial effusions. Each patient underwent tests for HIV, sputum smear and culture, blood culture, blood biochemistry and serological testing. Tuberculous pericardial effusions were diagnosed according to pre-determined criteria. Eighty-four patients (36.1%) were found to be HIV positive; 81 of these (96.4 %) had tuberculous pericarditis. More than 65% of the study population was aged between 15 and 39 years. The prevalence of HIV amongst unemployed individuals was 49.0% compared to 30.0% amongst employed individuals. Tuberculous pericarditis was the most common cause of pericardial effusions (69.5%, n=162). It was concluded that tuberculosis (TB) is a leading cause of pericarditis in this province of South Africa. The prevalence of TB confounded by HIV co-infection is steadily increasing, burdening the health-care facilities.

Adolescent↗

PubMed2005

Determinants of unprotected sex among HIV-positive patients in South Africa.

This study examined the prevalence of unprotected sex, other sexual risk behaviours, and factors associated with unprotected sex among men and women recently diagnosed with HIV in South Africa. One hundred and forty-nine outpatients (44 males and 105 females) were assessed, of whom 101 were sexually active at least 6 months prior to study entry. Subjects were asked about sexual risk behaviours with reference to their most recent sexual encounter. Logistic regression analysis was employed to determine the predictors of condom use, with independent variables selected from five general categories: (1) sociodemographic characteristics; (2) situational characteristics regarding sexual intercourse (i.e. alcohol or drugs used before intercourse); (3) clinical diagnoses; (4) negative life events; and (5) coping styles. Fifty-five patients (19 males and 36 females), representing 54.4% of those sexually active in the 6 months preceding the study, had not used a condom during the most recent intercourse. Compared with those who used condoms, participants who did not significantly reported shorter duration of HIV infection (t = -2.7, p < 0.001), have a current partner (chi2 = 3.98, p = 0.005), and lack knowledge of their partner's HIV status (chi2 = 4.78, p = 0.004). Also they were significantly more likely to engage in denial (t = 3.2, p < 0.002) and to use substances (t = 1.98, p < 0.05) as a means of coping. Logistic regression showed that shorter duration of illness (odds ratio (OR) = 1.2, 95% confidence interval (CI) = 1.01-1.41) and coping styles characterized by denial (OR = 0.6, 95% CI = 0.45-0.96) were significantly associated with unprotected sex. These data suggest the need for interventions to further reduce sexual risk behaviours in HIV-positive patients in South Africa.

Adult↗

PubMed2005

Large pericardial effusions due to systemic lupus erythematosus: a report of eight cases.

The aim of this study was to describe the clinical, echocardiographic and laboratory characteristics of large pericardial effusions and cardiac tamponade secondary to systemic lupus erythematosus (SLE). An ongoing prospective study was conducted at Tygerberg Academic Hospital, South Africa between 1996 and 2002. All patients older than 13 years presenting with large pericardial effusions (> 10 mm) requiring pericardiocentesis were included. Eight cases (out of 258) were diagnosed with SLE. The mean (SD) age was 29.5 (10.7) years. Common clinical features were Raynaud's phenomenon, arthralgia and lupus nephritis class III/IV. Echocardiography showed Libman-Sacks endocarditis (LSE) in all the mitral valves. Two patients developed transient left ventricular dysfunction; both these patients had pancarditis. Typical serological findings included antinuclear antibodies, anti-double stranded DNA antibodies, low complement C4 levels and low C3 levels. CRP was elevated in six cases. Treatment consisted of oral steroids and complete drainage of the pericardial effusions. No repeat pericardial effusions or constrictive pericarditis developed amongst the survivors (3.1 years follow up). This study concludes that large pericardial effusions due to SLE are rare, and associated with nephritis, LSE and myocardial dysfunction. Treatment with steroids and complete drainage is associated with a good cardiac outcome.

Adolescent↗

PubMed2003

[Establishing a quality management system according to DIN EN ISO 9001:2000 in an academic radiological department].

PURPOSE: Establishing a quality management (QM) system according the guidelines of DIN EN ISO 9001:2000 in an academic radiological department. MATERIALS AND METHODS: To fulfill the requirements of an academic radiological department a quality management system according the guidelines of DIN EN ISO 9001 : 2000 has been established within one year. All important educational, research and patient care issues have been discussed in plenary sessions of all employees of the department twice a week. All core processes of the department have been documented as process instructions and standard operation procedures. RESULTS: Supported by the staff unit "quality assurance" of the university hospital, the QM system has been established during one year. Assisted by all parties of the department, obliging regulations have been established which are well accepted in the daily routine clinical work but also in research and education. The implementation of the QM system caused an additional work load. However, spreading the work load by a consequent responsibility assignment, it could be reduced effectively. CONCLUSION: The implementation of a QM system within the daily routine work of an academic radiological department is feasible. It allows the installation of generally accepted rules which regulate the principal tasks of research and education, and patient care.

Diagnostic Imaging↗

PubMed2003

Infective endocarditis in the Western Cape Province of South Africa: a three-year prospective study.

BACKGROUND: The last 50 years have seen major changes in the epidemiology of infective endocarditis (IE). AIM: To evaluate local patient characteristics, risk factors, clinical sequelae, microbiology, morbidity and mortality in patients with definite IE. DESIGN: Prospective observational study. METHODS: Over a three-year period, patients referred with probable IE were prospectively enrolled. All received a standardized diagnostic evaluation. Epidemiological data were documented; underlying risk factors for IE were sought. Initial evaluation and follow-up (to 6 months) included the documentation of vascular or immunological phenomena, morbidity and mortality. RESULTS: Of 92 patients referred with probable IE, 47 had definite IE. These patients had a mean age of 37.7 years with a male predominance (1.6:1). Rheumatic heart disease was present in 36 (76.6%). Eight had prosthetic valves. Three had congenital heart disease, mitral valve prolapse or multiple central intravascular catheters, respectively. All denied the use of intravenous recreational drugs and only one tested seropositive for HIV. Renal involvement (59.6%) and clubbing (29.8%) were commonly observed. The 6-month mortality rate was 35.6%, while 44.7% needed valvular replacement. An aetiological diagnosis was made in 21, with viridans streptococci the most common isolate. DISCUSSION: Infective endocarditis in the Western Cape of South Africa is a disease of younger adults, with a male predominance. Rheumatic heart disease is the major predisposing factor. Degenerative heart disease and intravenous drug abuse are not important risk factors. Our data do not support the notion that HIV infection is an independent risk factor for IE. Local mortality rates are much higher than recent international figures, as is the proportion of 'culture-negative' IE.

Adult↗

PubMed2003

RIONET: a water quality management tool for river basins.

The water quality management tool RIONET for river basins has been developed with regard to the EU Water Framework Directive. The management tool can simulate the water quality in catchment basins not only in the dimension of a single river but in whole river networks. A submodel of the IWA River Water Quality Model No. 1 is used in RIONET. The river model is based on the assumption that self purification processes in the river takes place both in the benthic biofilm and the bulk water phase. Laboratory experiments with sediment cores underline the major role of the benthic biofilm. The input parameters of the management tool such as volumetric flow rates from waste water treatment plants and flow velocities and discharge in the main river and its tributaries can be loaded directly from geographic information systems (GIS). The subcatchment basin of the river Bode in Saxon Anhalt was used for test runs of RIONET.

Biofilms↗

PubMed2002

Effects of the Ca2+ sensitizers EMD 57033 and CGP 48506 on myocardial contractility and Ca2+ transients in human ventricular and atrial myocardium.

Ca2+ sensitizers like EMD 57033 (EMD) and CGP 48506 (CGP) may be advantageous for the treatment of human heart failure, as they increase force of contraction without increasing the intracellular Ca2+ transients or energy consumption. However, whether or not Ca2+ sensitizers differ in their mode of action in human myocardium is not fully understood. The present study investigates the influence of EMD and CGP on force of contraction (FOC) and the intracellular Ca2+ transient (fura-2 ratio method) in left ventricular papillary muscle strips from left ventricular failing human myocardium (DCM, n = 28) as well as in right atrial trabeculae (RA, n = 21) obtained from patients undergoing cardiac bypass surgery. In isolated trabeculae of DCM, FOC was more efficacious and potently increased after application of EMD (EC50 EMD: 4.7 +/- 1.0 mumol/l, max. PIE EMD: + 12.0 +/- 2.0 mN/mm2) than CGP (EC50: 16.9 +/- 7.6 mumol/l, max. PIE: +6.4 +/- 2.8 mN/mm2). Similar results were obtained in RA. Application of carbachol (100 mumol/l) had no effect on the positive inotropic effect of EMD or CGP. Both Ca2+ sensitizers significantly increased time to half peak relaxation as well as diastolic tension in DCM. EMD (10 mumol/l) and CGP (30 mumol/l) did not affect the Ca2+ transients in RA. The Ca2+ sensitizers EMD and CGP increase cAMP and Ca2+ independently from the force of contraction in the human myocardium. However, their therapeutic use in human heart failure may be limited as they impair relaxation.

Azocines↗

PubMed2002

Cytokine production in patients with tuberculous pericarditis.

SETTING: An academic hospital in the Western Cape, South Africa. OBJECTIVE: To evaluate cytokine production (interferon-gamma [IFN-gamma], interleukin-1 [IL-1], interleukin-2 [IL-2], interleukin-6 [IL-6], interleukin-10 [IL-10], interleukin-4 [IL-4] and tumour necrosis factor-alpha [TNF-alpha]) in patients with tuberculous pericarditis. DESIGN: Subpopulation of a consecutive prospective case series. PATIENTS: Thirty patients presenting with pericardial effusions due to tuberculosis (n = 19), malignancy (n = 6) and non-tuberculous infections (n = 5), and five control subjects who had undergone open heart surgery. RESULTS: The concentration of IFN-gamma was significantly higher in tuberculous pericardial effusions than in the other diagnostic classes (P < 0.0005). The concentration of TNF-alpha was similar in both infective and tuberculous effusions, but was significantly higher than that of malignant effusions. IL-1 and IL-2 were undetectable in malignant effusions, but elevated in both infective and tuberculous pericardial effusions. The levels of IL-1 and IL-2 were furthermore significantly higher in pericardial effusions due to infective compared to tuberculous causes. The concentration of IL-6, while elevated in all diagnostic classes, was significantly higher in the malignant group. Elevated levels of IL-10 and undetectable levels of IL-4 were observed in all three diagnostic groups. CONCLUSION: These findings suggest that tuberculous pericardial effusions arise due to a hypersensitivity reaction that is orchestrated by the TH-1 lymphocytes.

Adult↗

PubMed2001

The total synthesis of C-glycosides with completely resolved seven-carbon backbone polyol stereochemistry: stereochemical correlations and access to L-configured and other rare carbohydrates.

The de novo synthesis of a full set of hydroxymethyl C-glycosides from only two precursors is described. The seven-carbon target molecules contain five stereocentres and bridge the stereochemical gap between natural D-configured and non-natural L-configured series of hexoses. Key steps include hydroxylation, differential protection, stereoselective reduction and desymmetrization of 8-oxabicyclo[3.2.1]oct-6-enes. C-Terminus differentiation and C-terminus excision of the seven-carbon polyol backbone lead to hexoses, including those of the L-series. A stereochemical and genetic classification of C-glycosides is presented.

Carbohydrate Conformation↗

PubMed2001

Molecular basis of calmodulin tethering and Ca2+-dependent inactivation of L-type Ca2+ channels.

Ca(2+)-dependent inactivation (CDI) of L-type Ca(2+) channels plays a critical role in controlling Ca(2+) entry and downstream signal transduction in excitable cells. Ca(2+)-insensitive forms of calmodulin (CaM) act as dominant negatives to prevent CDI, suggesting that CaM acts as a resident Ca(2+) sensor. However, it is not known how the Ca(2+) sensor is constitutively tethered. We have found that the tethering of Ca(2+)-insensitive CaM was localized to the C-terminal tail of alpha(1C), close to the CDI effector motif, and that it depended on nanomolar Ca(2+) concentrations, likely attained in quiescent cells. Two stretches of amino acids were found to support the tethering and to contain putative CaM-binding sequences close to or overlapping residues previously shown to affect CDI and Ca(2+)-independent inactivation. Synthetic peptides containing these sequences displayed differences in CaM-binding properties, both in affinity and Ca(2+) dependence, leading us to propose a novel mechanism for CDI. In contrast to a traditional disinhibitory scenario, we suggest that apoCaM is tethered at two sites and signals actively to slow inactivation. When the C-terminal lobe of CaM binds to the nearby CaM effector sequence (IQ motif), the braking effect is relieved, and CDI is accelerated.

Amino Acid Motifs↗

PubMed2001

The high-anti conformation of 8-aza-1,3-dideaza-2'-deoxyadenosine.

In the title compound, 4-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-1H-benzotriazole, C11H14N4O3, the conformation of the N-glycosidic bond is in the high-anti range [chi = -77.1 (4) degrees ] and the 2'-deoxyribofuranose moiety adopts a 2'-endo ((2)E) sugar puckering. The 5'-hydroxyl group is disordered and has conformations ap with gamma = 171.1 (3) degrees [occupation of 61.4 (3)%] and +sc with gamma = 52.4 (6) degrees [occupation of 38.6 (3)%]. The nucleobases are stacked in the crystal state.

Adenosine↗

PubMed2001

Synaptic and extrasynaptic gamma -aminobutyric acid type A receptor clusters in rat hippocampal cultures during development.

We have simultaneously measured the expression of postsynaptic gamma-aminobutyric acid type A (GABA(A)) receptor clusters and of presynaptic boutons in neonatal rat hippocampal cultures between days 1 and 30. GABA(A) receptors were labeled with antibodies recognizing the extracellular domains of beta2/3 and gamma2 subunits. Boutons were visualized by activity-dependent uptake of the styryl dye FM4-64, or by antibodies against the presynaptic vesicular protein SV2 or the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). GABA(A) receptor clusters could be seen in living neurons already 6 h after culturing, much before presynaptic markers could be identified in nerve terminals. The densities of receptor clusters that contained the beta2/3 subunits were constant between days 10 and 30 in culture, whereas gamma2 subunit-containing clusters fluctuated and reached a maximum on day 20. SV2 and GAD staining could be measured from day 2 onwards. Clustering of GAD in presynaptic terminals and FM4-64 uptake were observed only at day 5 and afterward. SV2 staining and FM4-64 uptake increased in parallel between days 5 and 20 and remained constant thereafter. GAD-stained boutons were fewer than those labeled with other, less specific, presynaptic stains. They reached a maximum on day 20 and fell again toward day 30. Double labeling of GABA(A) receptors and of presynaptic boutons in neurons during differentiation showed that, even after 30 days in culture, large fractions of GABA(A) receptor clusters containing beta2/3 and/or gamma2 subunits remained extrasynaptic.

Animals↗

PubMed2001

Force/shortening-frequency relationship in multicellular muscle strips and single cardiomyocytes of human failing and nonfailing hearts.

BACKGROUND: Force of contraction (FOC) frequency-dependently increases in multicellular muscle strip preparations of human nonfailing myocardium, whereas FOC declines in human failing myocardium with increasing stimulation frequency. We investigated whether these characteristics can be observed in single isolated myocytes. METHODS AND RESULTS: Isolated multicellular muscle strip preparations and single isolated cardiomyocytes of failing (heart transplants, dilative cardiomyopathy; n = 11) and nonfailing (donor hearts; n = 11) human hearts were studied. The changes in contraction amplitude (cell shortening in micrometers) at increasing frequency of stimulation (0.5-2 Hz) were continuously recorded with a 1-dimensional high-speed camera that detected the cell edges and measured their distance during contraction. The increase in stimulation frequency was associated with a significant decrease in FOC (2 v 0.5 Hz; 68% basal) and a decrease in cell shortening of human left ventricular cardiomyocytes from failing hearts (2 v 0.5 Hz; 65% basal). In contrast, in human nonfailing myocardium, contraction increased at increasing stimulation frequencies (2 v 0.5 Hz; FOC, 180% basal; cell shortening, 129% basal). CONCLUSIONS: The negative force-frequency relationship measured in multicellular preparations of failing human myocardium results from alterations at the single cell level.

Cardiomyopathy, Dilated↗

PubMed2001

Measurements of vesicle recycling in central neurons.

Neurotransmitter-containing vesicles in presynaptic nerve terminals are essential for synaptic transmission. The vesicles undergo a cycle that leads to transmitter release by exocytosis followed by endocytosis and refilling of the vesicles. Here we discuss new optical methods that have helped researchers study this cycle at functional and molecular levels, which is essential for our understanding of the regulation of synaptic transmission.

Animals↗