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Biomedical subjects

A Schmidt

Publications and source records attributed to A Schmidt.

At least 109 records · Page 6Linked to original sources

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↗

A comparison of quantitative computed tomography and dual X-ray absorptiometry for evaluation of bone mineral density in patients on chronic hemodialysis.

Chronic renal failure leads to a reduction of bone mineral density (BMD). Therefore, noninvasive methods to evaluate BMD are also used regularly in this patient population. In this study, we compared the results of two widely used methods, quantitative computed tomography (QCT) of the lumbar spine and dual x-ray absorptiometry (DXA) at different sites in 90 patients on chronic hemodialysis. Additionally, we also determined various clinical and biochemical data to assess their relationship to BMD at the different measurement sites. A total of 75% of our patients was found to have reduced BMD, and 25% had an average z-score below -2. Z-scores obtained by the different methods and at the different measurement sites within an individual patient varied considerably from completely normal to severely reduced values. Multivariate analyses using clinical and biochemical parameters showed lower values of BMD at all measurement sites after transplantation and marginally higher values after parathyroidectomy, which was seen only in DXA measurement at the femoral neck. We conclude from our study that determination of BMD in chronic hemodialysis patients yields highly variable results, depending on the technique used. As long as the exact clinical relevance of these results has not been determined, regular routine measurement of isolated sites of BMD cannot be advocated in this patient population.

Absorptiometry, Photon↗

Effects of blood viscosity on proximal flow convergence calculations of regurgitant flow rate and jet dimensions as evaluated by color Doppler flow mapping: an in vitro study.

There are limited data on the potential influence of blood viscosity on the quantification of valvular regurgitation by color Doppler in the clinical setting. This study was designed to evaluate the effects of blood viscosity on jet dimensions and the proximal flow convergence (proximal isovelocity surface area, PISA) method of estimating valvular insufficiency severity. We used an in vitro flow model filled with human blood at varying hematocrits (15%, 35%, and 55%) and blood viscosity (blood/water viscosity: 2.6, 4.8, 9.1) in which jets were driven through a known orifice (16 mm(2)) into a 110-mL compliant receiving chamber (compliance: 2.2 mL/mm Hg) by a power injection pump. Blood injections (2 and 4 mL) at flow rates of 4, 6, 8, 10, and 12 mL/s were performed. Proximal flow convergence and spatial distribution of jets were imaged by a 3.5-MHz transducer. Pressure and volume in the flow model were kept constant before each injection. Ultrasound settings were the same for all experiments. Jet area decreased significantly with increasing blood viscosity, but the difference in jet dimensions was much larger for lower than for higher flow rates and for highest blood viscosity. Estimation of flow rate by the PISA method was not significantly influenced by blood viscosity. Blood viscosity has a major influence in jet area, especially for lower flow rates, but did not change significantly the grading of regurgitation by the PISA method. Thus this factor should be considered for determining the method of choice when quantification of valvular regurgitation is performed in patients with anemia or polycythemia.

Blood Viscosity↗

Antihypertensive effects of valsartan/hydrochlorothiazide combination in essential hypertension.

Fixed-dose combination therapy has received increased interest since publication of JNC-VI report and WHO/ISH guidelines 1999. We compared in a randomized, double-blind study the efficacy and tolerability of valsartan 80 mg combined with hydrochlorothiazide (HCTZ) 12.5 mg to monotherapy with either HCTZ 12.5 mg or 25 mg in patients with essential hypertension inadequately controlled by previous HCTZ 12.5 mg monotherapy. Two hundred and seventeen patients whose blood pressure (BP) control remained poor (95 mmHg < or = sitting diastolic BP < 115 mmHg) after a 4-week single-blind period with HCTZ 12.5 mg were randomized to receive either combination therapy with valsartan 80 mg plus HCTZ 12.5 mg (V/HCTZ) or monotherapy with HCTZ 12.5 mg or HCTZ 25 mg for 8 weeks. Reduction of sitting trough diastolic BP between baseline and week 8 as well as tolerability was evaluated. Reduction in trough diastolic BP was most pronounced in the V/HCTZ group (-11.3 mmHg) and significantly greater than in the HCTZ 12.5 mg group (-2.9 mmHg, p < 0.001) and the HCTZ 25 mg group (-5.7 mmHg, p < 0.001). Tolerability of study medication was comparable between all three groups. In conclusion, switching to V/HCTZ combination therapy provides an additional lowering of BP compared to dosage increase of the thiazide in patients with BP insufficiently controlled by HCTZ 12.5 mg monotherapy.

Aged↗

Virtual reality monitoring: phenomenal characteristics of real, virtual, and false memories.

This study explored virtual-reality (VR) monitoring, the decision process by which people discriminate memories of real and virtual events. In a study phase, subjects touched 10 real objects with their real finger and touched 10 virtual objects (visual only, no tactile feedback) with their cyberfinger in VR. One week later they took a real versus virtual versus new source identification test. After the source identification test, subjects rated phenomenal qualities associated with each memory, using a Virtual-Real Memory Characteristics Questionnaire (VRMCQ). For old items, results from the VRMCQ are consistent with the idea that VR monitoring draws on differences in qualitative characteristics of memories for perceived and virtual events/objects (consistent with Johnson and Raye). However, subjects also reported similar qualities associated with their false memories for new items, suggesting that they sometimes infer/reconstruct the qualities a memory should have, based on their decision of its source of origin. Furthermore, VR monitoring might prove useful as a sort of Turing test of how convincing the virtual world is, and the VRMCQ can identify which qualities of the virtual experience (e.g., color) require improvement. Examples of applications are discussed.

Decision Making↗

The effect of ACE inhibitor and angiotensin II receptor antagonist therapy on serum uric acid levels and potassium homeostasis in hypertensive renal transplant recipients treated with CsA.

BACKGROUND: The angiotensin II (AT II) type I receptor antagonist losartan has been reported to increase urinary uric acid and potassium excretion. These effects might be beneficial in cyclosporin (CsA)-treated renal transplant recipients, who frequently suffer from hyperuricaemia and hyperkalaemia. METHODS: In this prospective, open, randomized, two-way cross-over study we included 13 hypertensive CsA-treated patients after renal transplantation and administered either the angiotensin-converting enzyme (ACE) inhibitors enalapril or losartan. Laboratory parameters, 24-h urinary protein excretion, and mean 24-h arterial blood pressure (MAP) were checked after 3 weeks treatment with enalapril, after a wash-out period of 2 weeks, and before and after a 3-week treatment course with losartan. RESULTS: Both drugs slightly reduced MAP (losartan from 97+/-6 to 94+/-9 and enalapril to 93+/-8 mmHg). Serum potassium levels significantly increased during enalapril therapy (from 4.3+/-0.5 to 4.8+/-0.4 mmol/l, P<0.05), as did, although not significantly, uric acid concentrations (from 7.8+/-1.9 to 8.2+/-1.8 mg/dl, P=0.5). Losartan, on the contrary, only mildly affected serum potassium (4.3+/-0.5 vs 4.5+/-0.5 mmol/l, P=0.25) and serum uric acid decreased (from 7.8+/-2.4 to 7.3+/-1.8 mg/dl, P=0.6). Serum aldosterone and urinary aldosterone excretion were significantly reduced only during ACE inhibitor treatment, which might explain the variable effects on potassium homeostasis. CONCLUSION: Losartan may be a useful agent to reduce blood pressure and serum uric acid levels in renal transplant recipients treated with CSA: Furthermore, in this high-risk population, the effects on serum potassium levels are less marked with losartan than with enalapril.

Aged↗

Cloning and characterization of a hydroxycinnamoyl-CoA:tyramine N-(hydroxycinnamoyl)transferase induced in response to UV-C and wounding from Capsicum annuum.

Hydroxycinnamoyl-CoA : tyramine N-(hydroxycinnamoyl) transferase (THT) is a pivotal enzyme in the synthesis of N-(hydroxycinnamoyl)-amines, which are associated with cell wall fortification in plants. The cDNA encoding THT was cloned from the leaves of UV-C treated Capsicum annuum (hot pepper) using a differential screening strategy. The predicted protein encoded by the THT cDNA is 250 amino acids in length and has a relative molecular mass of 28,221. The protein sequence derived from the cDNA shares 76% and 67% identity with the potato and tobacco THT protein sequences, respectively. The recombinant pepper THT enzyme was purified using a bacterial overexpression system. The purified enzyme has a broad substrate specificity including acyl donors such as cinnamoyl-, sinapoyl-, feruloyl-, caffeoyl-, and 4-coumaroyl-CoA and acceptors such as tyramine and octopamine. In UV-C treated plants, the THT mRNA was strongly induced in leaves, and the elevated level of expression was stable for up to 36 h. THT mRNA also increased in leaves that were detached from the plant but not treated with UV-C. THT expression was measured in different plant tissues, and was constitutive at a similar level in leaf, root, stem, flower and fruit. Induction of THT mRNA was correlated with an increase in THT protein.

Acyltransferases↗

Social phobia as a comorbid condition in sex offenders with paraphilia or impulse control disorder.

Studies on the prevalence of social anxiety in sex offenders show mixed results. This may be due to social anxiety being heightened only in diagnostic subgroups of sex offenders, namely in paraphiliacs. In study 1, 72 mentally disordered sexual delinquents and 30 controls were screened for social anxiety with the Social Interaction Anxiety Scale and the Social Phobia Scale by Mattick and Clarke (German versions). In study 2, 55 mentally disordered sexual delinquents were diagnosed with a structured clinical interview. In both studies, sex offenders were categorized as either paraphilic or impulse control disordered (without paraphilia) according to research criteria. Study 1 showed markedly heightened scores for social anxiety in paraphiliacs, particularly for social interaction anxiety. Study 2 found a high lifetime and point prevalence of social phobia in paraphiliacs for which corroborating evidence was again found in questionnaire results. Implications for further research, diagnostic procedures, and therapy are discussed.

Adult↗

Characterization of a maternal-fetal HIV transmission model using pregnant macaques infected with HIV-2(287).

To study mechanisms involved in mother-to-fetus transmission of human immunodeficiency virus (HIV) in utero, we have developed a chronically catheterized pregnant macaque model that permits simultaneous and sequential determination of virus in maternal and fetal blood and amniotic fluid during pregnancy. In this report, we have characterized this model using three groups of pregnant macaques designed to sample: (1) maternal blood, fetal blood, and amniotic fluid (n = 6); (2) maternal blood and amniotic fluid (n = 6); or (3) maternal blood only (n = 2). After inoculation with the highly pathogenic HIV-2(287), all pregnant macaques developed brief but intense viremias followed by precipitous CD4+ T-cell declines within 2-3 weeks. While all the infants born to dams of the three groups were HIV positive, the degree of infection and outcome of HIV infection varied. All infants were shown to be HIV-RNA-positive by reverse transcriptase-polymerase chain reaction (RT-PCR). However, HIV-infected cells were detected only in the blood of those born to dams enrolled in groups 1 and 2: most of these infants progressed to CD4+ T-cell depletion. The infants in group 3 exhibited HIV-RNA in plasma, although neither HIV-infected cells nor CD4+ T-cell depletion was detectable. However, all infants developed HIV-2-specific antibody at various levels by 2 months of age. Together, the data suggest that, while the degree of instrumentation may modulate intensity of virus transmission to fetus, the highly pathogenic HIV-2(287) exhibited a high frequency of virus transmission from the mother to fetus.

Amniotic Fluid↗

Lipopolysaccharide-induced activation of beta2-integrin function in macrophages requires Irak kinase activity, p38 mitogen- activated protein kinase, and the Rap1 GTPase.

Lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria, is a potent activator of macrophages. Besides inducing many transcriptional pathways, LPS also elicits rapid morphological changes such as cell spreading. Here we have investigated the signaling pathway that controls macrophage beta2-integrin-dependent spreading in response to LPS. We show that inhibition of the adapter protein MyD88, the interleukin-1 receptor-associated kinase Irak, the p38 mitogen-activated protein kinase, or the Ras-like GTPase Rap1 blocks LPS-induced spreading. In addition, Irak activates p38 and stimulates p38-dependent spreading. The activation of p38 by Irak requires Irak's kinase activity. We find that p38 controls spreading independently of its role in transcription but rather through activation of Rap1. Together, our results suggest that beta2-integrin-dependent spreading of macrophages in response to LPS is controlled by a linear signaling pathway via MyD88, Irak, p38, and Rap1.

Adaptor Proteins, Signal Transducing↗

Patients with acute coronary syndromes express enhanced CD40 ligand/CD154 on platelets.

OBJECTIVE: To investigate whether CD40L/CD154 on platelets and soluble CD40L/CD154 may play a role in the inflammatory process of acute coronary syndromes. DESIGN AND SETTING: Observational study in a university hospital. PATIENTS: 15 patients with acute myocardial infarction, 25 patients with unstable angina, 15 patients with stable angina, and 12 controls. MAIN OUTCOME MEASURES: CD40L/CD154 on platelets, P-selectin/CD62P on platelets, soluble CD40L/CD154 serum concentrations. RESULTS: Mean (SD) CD40L/CD154 expression on platelets was 6.2 (2.8) MFI (mean fluorescence intensity) in the infarct group, 11 (3.3) MFI in the unstable angina group (p < 0.001 v infarction), 3.6 (0.9) MFI in the stable angina group (p < 0.01 v infarction; p < 0.001 v unstable angina), and 3.2 (1.0) MFI in the controls (p < 0.01 v infarction; p < 0.001 v unstable angina; NS v stable angina). Soluble CD40L/CD154 concentration was 5.2 (1.1) ng/ml in the infarct group, 4.2 (0.7) ng/ml in the unstable angina group (p < 0.001 v infarction), 2.9 (1.0) ng/ml in stable angina group (p < 0.001 v infarction and unstable angina), and 3.0 (0.5) ng/ml in the controls (p < 0.001 v infarction and unstable angina; NS v stable angina). At a six months follow up, there was lower expression of CD40L/CD154 on platelets in patients with unstable angina (12.3 (3.6) v 3.8 (1.2) MFI, p < 0.0001) and acute myocardial infarction (6.2 (2.8) v 3.5 (0.8) MFI, p < 0.01) compared with their admission values six months earlier. Patients with unstable angina who needed redo coronary angioplasty (PTCA) or who had recurrence of angina were characterised by increased CD40L/CD154 expression on platelets compared with the remainder of the study group (recurrence of angina: 12.7 (3.2) v 9.7 (1.6) MFI, p < 0.05; re-do PTCA: 14.3 (4.2) v 10.3 (2.1) MFI, p < 0.05). CONCLUSIONS: Both CD40L/CD154 on platelets and soluble CD40L/CD154 are raised in patients with unstable angina and myocardial infarction. These findings suggest that CD40-CD40L/CD154 interactions may play a pathogenic role in triggering and propagation of acute coronary syndromes.

Aged↗

Phagocytic function in cyclists: correlation with catecholamines and cortisol.

Flow cytometer measurements were made of the basal variations in peripheral blood functional monocytes and granulocytes over the course of a training season (January to November) of a cycling team. Parallel determinations were made of plasma concentration of catecholamines (chromatography) and cortisol (RIA) in a search for neuroendocrine markers. The results showed the greatest phagocytic capacity to occur in the central months (March, May, and July), coinciding with the greatest number and highest level of competitive events with good correlation with a peak in epinephrine during these months (r(2) = 0.998 for monocytes and r(2) = 0.674 for granulocytes). No good correlations were found between phagocytosis and norepinephrine or cortisol. The highest values for phagocytosis and epinephrine concentration were found in May. These results suggest that blood epinephrine concentration could be a good neuroendocrine marker of sportspeople's phagocytic response.

Adult↗

Treating hypertrophic scars for 12 or 24 hours with a self-adhesive hydroactive polyurethane dressing.

Treatment with a self-adhesive hydroactive polyurethane dressing (Cutinova thin, Beiersdorf AG, Hamburg, Germany) applied over a period of eight weeks has been shown to have a beneficial effect on hypertrophic scars. However, the use of such dressings during the daytime on visible parts of the body is often problematic and might lead to reduced compliance. In the present study the effect of 12-hour (overnight) treatment was compared with the results of a 24-hour treatment regimen with the same dressing. The dressings were applied over an eight-week period. Evaluation of the hypertrophic scars was by clinical assessment and measurement of colour difference to normal skin, elevation and elasticity. In addition, the patients assessed the treatment effects (questionnaire) and photographs were taken. Under both regimens an improvement in the scar colour (redness) and visual assessment scores took place. The patients also gave a positive assessment of the effects of the treatment. After eight weeks there were no relevant differences between the scars treated with the self-adhesive dressings for 12 hours (overnight) and those treated for 24 hours per day.

Adhesives↗

Fathers of children with diabetes mellitus and their role in coping strategies in the family.

Family structure and social disadvantage are thought to have adverse effects on the outcome of diabetes mellitus (DM). While there are data on family functioning and maternal coping in relation to some measures of metabolic control, little is known about the role of fathers in respect to coping and outcome of DM. We are presently conducting prospective studies to assess the role of fathers in families with children with DM. In addition, family functioning and psychosocial factors are being investigated in relation to putative effects on metabolic control. Structured questionnaire studies are being performed in 182 children and adolescents with type 1 DM. Similar questions are also put to the families. Mean age of the patients is 12.9 years, range 1.8-18 years, with an equal distribution between the sexes. Metabolic control as assessed by the mean of the last four HbA1c values (HPLC method; intra-assay coefficient of variation [CV] 2.1-3.3%, interassay CV 2.6-4.3%) is 7.4%; range 5.0-14.8%. The patients attend outpatient clinics at an average interval of six weeks. Structured educational in-patient programs are attended by less than one-third of the patients. There is a large prevalence of unemployment in the families. In the majority of cases mothers accompany their children to the clinic while fathers are absent. It is the mothers who adjust daily insulin doses, take care of food preparation and ensure the children's self-assessment. In conclusion, our preliminary data suggest that the role of fathers in diabetes management is rather passive and emotionally labile. Special educational programs targeted towards the fathers of children with DM and towards improving parental interactive strategies are urgently needed to better use parental resources of coping and support.

Adaptation, Psychological↗

Head-to-head comparison of dipyridamole, dobutamine and pacing stress echocardiography for the detection of myocardial ischemia in an animal model of coronary artery stenosis.

To compare the sensitivity of dipyridamole, dobutamine and pacing stress echocardiography for the detection of myocardial ischemia we produced a physiologically significant stenosis in the left circumflex artery of 14 open-chest dogs (range: 50 to 89% reduction in luminal diameter). In each study, dobutamine (5 to 40 microg kg(-1) min(-1) in 3-min stages) and pacing (20 bpm increments, each 2 min, up to 260 bpm) were performed randomly, and then followed by dipyridamole (up to 0.84 mg/kg over 10 min). The positivity of stress echocardiography tests was quantitatively determined by a significant (P<0.05) reduction of or failure to increase absolute and percent systolic wall thickening in the stenotic artery supplied wall, as compared to the opposite wall (areas related to the left anterior descending artery). Systolic and diastolic frozen images were analyzed off-line by two blinded observers in the control and stress conditions. The results showed that 1) the sensitivity of dobutamine, dipyridamole and pacing stress tests was 57, 57 and 36%, respectively; 2) in animals with positive tests, the mean percent change of wall thickening in left ventricular ischemic segments was larger in the pacing (-19 +/- 11%) and dipyridamole (-18 +/- 16%) tests as compared to dobutamine (-9 +/- 6%) (P = 0.05), but a similar mean reduction of wall thickening was observed when this variable was normalized to a control left ventricular segment (area related to the left anterior descending artery) (pacing: -16 +/- 7%; dipyridamole: -25 +/- 16%; dobutamine: -26 +/- 10%; not significant), and 3) a significant correlation was observed between magnitude of coronary stenosis and left ventricular segmental dysfunction induced by ischemia in dogs submitted to positive stress tests. We conclude that the dobutamine and dipyridamole stress tests showed identical sensitivities for the detection of myocardial ischemia in this one-vessel disease animal model with a wide range of left circumflex artery stenosis. The pacing stress test was less sensitive, but the difference was not statistically significant. The magnitude of segmental left ventricular dysfunction induced by ischemia was similar in all stress tests evaluated.

Animals↗

Generation of human high-affinity antibodies specific for the fibroblast activation protein by guided selection.

Four completely human antibody derivatives [single-chain-antibody fragments (scFvs)] with specificity for the general tumor stroma marker fibroblast activation protein (FAP) were isolated by guided selection. Highly diverse IgG, IgM and IgD isotypes comprising heavy-chain variable domain libraries were generated using cDNAs derived from diverse lymphoid organs of a multitude of donors. Three of the human scFvs were converted into bivalent minibodies and expressed in eukaryotic cells for further functional characterization. Binding-competition studies and analysis by fluorescence-activated cell sorting showed high-affinity binding (10--20 nM) for two clones and recognition of the same epitope as the murine guiding antibody. The minibodies were successfully used for immunohistology of a variety of human carcinoma biopsies, revealing specific staining of stromal fibroblasts. Therefore, they should be suitable for in vivo diagnostic and tumor-targeting studies and, because of their completely human origin, be superior to murine or humanized antibody derivatives.

Amino Acid Sequence↗

Time-of-day variations in different measures of sleepiness (MSLT, pupillography, and SSS) and their interrelations.

The aim of the present study is to analyze how well physiological measures of sleepiness derived from pupillography and the Multiple Sleep Latency Test correlate with a subjective measure, the Stanford Sleepiness Scale (SSS) score. The results are based on data from 12 healthy participants, who underwent these tests every 2 hr from 7:00 a.m. until 11:00 p.m. Sleep latencies were correlated with four different variables derived from pupillography and the SSS score. The results indicate that the physiologically based variables correspond very well. This is reflected by similar patterns of time-of-day variations, a good agreement at the group level, and correlations at the individual level, whereas the SSS shows a quite different pattern of variation. The two physiological measures of sleepiness seem to reflect the same aspect of the level of tonic central nervous activation, which is not correlated with the subjective feeling of sleepiness.

Adult↗