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Biomedical subjects

M Weis

Publications and source records attributed to M Weis.

At least 37 records · Page 2Linked to original sources
PubMed2000

An association between microvascular endothelial dysfunction, transcardiac nitric oxide production and pro-inflammatory cytokines after heart transplantation in humans.

Endothelial dysfunction anticipates the development of transplant coronary artery disease (TxCAD) observed more than 1 year after transplantation (HTx). We investigated whether in patients early after HTx myocardial inducible and constitutive nitric oxide synthases (iNOS; cNOS) are expressed and cardiac nitric oxide production occurs. Moreover, a possible relationship to alterations in endothelium dependent and independent vasomotor function was assessed. Forty-two transplant recipients were studied 37 +/- 5 days after HTx. Microvascular coronary flow velocity reserve (CFVR) was tested endothelium dependent (acetylcholine; 30 microg/min x 5 min/i.c.) and independent (adenosine; 160 microg/min x 5 min/i.c.) by Doppler flow wire. Flow velocity increase by a factor greater than 2 was considered normal. Quantitative coronary angiography was used to assess epicardial vasomotor function in response to the same stimuli. Myocardial iNOS and cNOS gene expression were detected by semiquantitative reversed transcriptase polymerase chain reaction. Plasma nitrite levels (microM) were measured by spectrophotometry. Cytokines (TNF-alpha, IL-6; pg/ml) were measured by enzyme linked immunosorbent assay. In 26.1% of patients (n = 11; group A) an impaired endothelium dependent CFVR (1.65 +/- 0.23 increase) was observed; in 73.9% (n = 31, group B) a normal endothelium dependent CFVR (3.0 +/- 0.7 increase; P = 0.003) was observed. Myocardial iNOS and cNOS gene expression did not differ between the two groups. Transcardiac cytokine production was noted in 58.8% of patients for IL-6 and in 53.3% for TNF-alpha. Coronary sinus (CS) levels of TNF-alpha, IL-6 and nitrite were higher in group A. A significant increase in nitrite production was found only in patients with impaired endothelium dependent CFVR (aorta: 43.9 +/- 3.7 vs CS: 52.8 +/- 5.6, P = 0.05), suggesting transcardiac nitric oxide production. In addition, CS nitrite levels correlated with CS TNF-alpha levels in patients with impaired CFVR (r = 0.44, P = 0.003). Microvascular endothelium dependent CFVR is impaired in 26% of patients early after HTx. Activation of cytokines and the NO pathway seem to be involved in this vasomotor dysfunction The association between cardiac nitric oxide production and TNF-alpha in this group indicates a chronic high immunologic process, which may represent an early and important target for therapy and prevention of TxCAD.

Adenosine↗
PubMed2000

Heart allograft endothelial cell dysfunction. Cause, course, and consequences.

Allograft coronary endothelial cells can serve as potent stimulators (antigen-presenting cells) as well as targets of allogeneic lymphocyte reactivity. Independent of the cause leading to endothelial cell injury after transplantation, endothelial cell activation and dysfunction occurs, associated with modification in endothelial cell-dependent molecule expression. The prevalence of coronary endothelial vasomotor dysfunction is approximately 20-30% during the first year, and 30-40% in the long-term follow-up. Importantly, no association is detectable between endothelial dysfunction and intimal thickness, suggesting two distinct entities of allograft vasculopathy. Early predictors of vasomotor dysfunction are proinflammatory cytokines and endothelin expression. Repetitive subendocardial ischemia during myocardial stress (due to microvascular dysfunction) may result in an impairment of left ventricular function. In non-transplant patients coronary endothelial dysfunction predicts cardiac events during long-term follow-up. It is reasonable that early administration of endothelial-protective compounds is necessary for protection of allograft endothelial dysfunction and vasculopathy during follow-up. The explanted donor heart may offer a potential for gene therapy techniques including modification of allograft phenotype and modulation of the host alloimmune response. Other protective strategies may include improvement of cardioplegic solutions and reperfusion strategies, recovery of the imbalance between vasoactive mediators, and treatment with HMG-CoA-reductase inhibitors and/or ACE inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Beat-to-beat measurement of cardiac output by intravascular pulse contour analysis: a prospective criterion standard study in patients after cardiac surgery.

OBJECTIVE: To evaluate the accuracy of a new pulse contour method of measuring cardiac output in critically ill patients. DESIGN: A prospective criterion standard study. SETTING: Cardiac surgery intensive care unit in a university hospital. PARTICIPANTS: Nineteen cardiac surgery patients requiring intensive care treatment with pulmonary artery catheters after surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The pulse contour cardiac output monitor uses transpulmonary bolus thermodilution measurements to calibrate the system. In each patient, the pulse contour cardiac output values were compared with conventional thermodilution. The method described by Bland and Altman and linear regression analysis were used for comparison. The mean difference (bias) +/- standard deviation of differences (precision) was 0.31 +/- 1.25 L/min for pulmonary bolus thermodilution cardiac output versus pulse contour cardiac output and 0.21 +/- 0.73 L/min for pulmonary bolus thermodilution cardiac output versus transpulmonary bolus thermodilution cardiac output. Linear regression (correlation) analyses were pulse contour cardiac output = 0.97 thermodilution + 0.53 (r = 0.88), and transpulmonary cardiac output = 0.87 thermodilution + 1.09 (r = 0.96). There was a small increase 60 minutes after recalibration but not a statistically significant difference between pulse contour cardiac output and pulmonary bolus thermodilution cardiac output (p = 0.52). CONCLUSIONS: Bias and precision are acceptable, and the system provides results that agree with conventional thermodilution. This study demonstrates the clinical applicability of the pulse contour cardiac output monitoring system.

Adult↗
PubMed2000

In vivo depletion of B cells using a combination of high-dose cytosine arabinoside/mitoxantrone and rituximab for autografting in patients with non-Hodgkin's lymphoma.

We performed a pilot study including rituximab (Mabthera; IDEC-C2B8, Hoffmann-La Roche) with a sequential high-dose therapy protocol in 15 patients with follicular and three patients with mantle cell lymphoma and studied the potential of the chemoimmunotherapy to induce depletion of malignant B cells in vivo. Our treatment protocol included induction with three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy, followed by peripheral blood stem cell (PBSC) mobilization using high-dose cytosine arabinoside (2 g/m2 every 12 h, days 1 and 2) and mitoxantrone (10 mg/m2, days 2 and 3) (HAM), preceeded by rituximab (375 mg/m2). The proportion of CD19+ B cells in blood and bone marrow decreased from 1.2 +/- 0.4% to 0.13 +/- 0. 1% (P = 0.01) and from 2.7 +/- 0.8% to 0.8 +/- 0.5% (P = 0.03) respectively. The number of t(14;18)-positive cells in blood and bone marrow progressively decreased with treatment, as assessed by the quantitative real-time PCR assay in four patients. Conversion to PCR-negativity was achieved in the peripheral blood (PB) of seven informative patients. Leucaphereses were performed during the granulocyte colony-stimulating factor (G-CSF)-supported leucocyte recovery phase. In 17 of 18 patients, a median of 15.1 x 106 CD34+ cells/kg body weight (BW) could be harvested by a single procedure for enrichment by an immunomagnetic method. Leucapheresis products contained 51.3 +/- 28.8 x 104 CD19+ B cells/kg BW (mean) and were t(14;18) PCR negative in all seven informative patients. These data compare favourably with results obtained in patients treated with the same regimen without rituximab. The high-dose therapy (n = 12 patients), including total body irradiation (14.4 Gy) and cyclophosphamide (200 mg/kg BW), was also preceeded by rituximab. Recovery of neutrophils to > 0.5 x 109/l and of platelets to > 20 x 109/l required a median of 13.5 and 11.5 d (range 11-24 and 9-24 d) respectively. In conclusion, the addition of the CD20 antibody to chemotherapy ensured tumour depletion in vivo and allowed the collection of PBSCs devoid of tumour cells and with conserved engraftment capability.

Adult↗
PubMed2000

Coronary vasomotor dysfunction in the cardiac allograft: impact of different immunosuppressive regimens.

Immunosuppression may have an important impact on early graft coronary endothelial injury. We investigated functional and morphologic coronary alterations, myocardial expression, and cardiac release of possible mediators of allograft vasculopathy within 6 months after cardiac transplantation with respect to different immunosuppressive regimens. Epicardial and microvascular endothelium-dependent and endothelium-independent vasomotor function and epicardial intimal thickening were measured in 8 transplant recipients treated with cyclosporin A (CyA), azathioprine, and prednisone (group 1), 9 transplant recipients treated with tacrolimus (TKL), azathioprine, and prednisone (group 2), and 14 patients treated with TKL, mycophenolate mofetil (MMF), and prednisone (group 3). The gene expressions of inducible and endothelial nitric oxide synthase (iNOS and eNOS), endothelin-1, prostacyclinsynthase, and thromboxansynthase were analyzed in endomyocardial biopsy specimens using semiquantitative reverse transcription polymerase chain reaction. Transcardiac cytokine release, endothelin-1, and nitrate-release were determined from plasma samples. Epicardial endothelial dysfunction (vasoconstriction to acetylcholine > 10%) and microvascular smooth muscle cell dysfunction (flow velocity increase to adenosine and nifedipine < 2.0) were enhanced in heart transplant recipients immunosuppressed with TKL, azathioprine, and prednisone. The prevalence of epicardial dysfunction was 78% in group 2 versus 44% and 46% in group 1 and 3 (p < 0.05), respectively. The prevalence of microvascular dysfunction was 56% in group 2 versus 13% and 7% in group 1 and 3 (p < 0.02), respectively. Coronary vasomotor dysfunction was associated with increased myocardial iNOS expression (p < 0.05), decreased eNOS expression (p < 0.05), and enhanced cardiac immunoreactive interleukin-6 (p < 0.01). Coronary intimal thickening was not different between the groups. The combination of TKL and MMF appears to be superior to TKL and azathioprine (and comparable to CyA and azathioprine) concerning preservation of early coronary vasomotor function, eNOS expression, iNOS suppression as well as cardiac interleukin-6 release. This may have an important impact on subsequent development of transplant coronary atherosclerosis.

Adult↗
PubMed2000

Report of five novel and one recurrent COL2A1 mutations with analysis of genotype-phenotype correlation in patients with a lethal type II collagen disorder.

Achondrogenesis II-hypochondrogenesis and severe spondyloepiphyseal dysplasia congenita (SEDC) are lethal forms of dwarfism caused by dominant mutations in the type II collagen gene (COL2A1). To identify the underlying defect in seven cases with this group of conditions, we used the combined strategy of cartilage protein analysis and COL2A1 mutation analysis. Overmodified type II collagen and the presence of type I collagen was found in the cartilage matrix of all seven cases. Five patients were heterozygous for a nucleotide change that predicted a glycine substitution in the triple helical domain (G313S, G517V, G571A, G910C, G943S). In all five cases, analysis of cartilage type II collagen suggested incorporation of the abnormal alpha1(II) chain in the extracellular collagen trimers. The G943S mutation has been reported previously in another unrelated patient with a strikingly similar phenotype, illustrating the possible specific effect of the mutation. The radiographically less severely affected patient was heterozygous for a 4 bp deletion in the splice donor site of intron 35, likely to result in aberrant splicing. One case was shown to be heterozygous for a single nucleotide change predicted to result in a T1191N substitution in the carboxy-propeptide of the proalpha1(II) collagen chain. Study of the clinical, radiographic, and morphological features of the seven cases supports evidence for a phenotypic continuum between achondrogenesis II-hypochondrogenesis and lethal SEDC and suggests a relationship between the amount of type I collagen in the cartilage and the severity of the phenotype.

Achondroplasia↗
PubMed2000

Coronary artery disease in the transplanted heart.

Coronary artery disease in the transplanted heart limits the long-term success of cardiac transplantation. Intravascular ultrasound studies reveal a dual morphology with donor-transmitted and de novo plaques. Coronary vasomotor dysfunction may occur independently of morphological alterations. The disease is characterized by the interaction of activated T lymphocytes with cytokines and donor epicardial and microvascular endothelium. Various noxious stimuli contribute to the continuing inflammatory response. Consequently, adhesion molecule expression is upregulated, leukocytes migrate into the allograft, thrombocytes accumulate, and growth factors are expressed, finally resulting in functional and morphological chronic allograft lesions. Blocking the activation of T cells, CD4+ cytokines, and adhesion molecules may prevent endothelial injury and subsequent intimal thickening. Strategies to decrease the formation of anti-endothelial and anti-HLA-DR antibodies may also be protective, as may antiproliferative drugs, augmentation of endogenous nitric oxide bioactivity, and new immunosuppressive regimens. Revascularization procedures have a limited role in treating significant focal lesions. Retransplantation, the only definitive treatment, remains ethically controversial.

Animals↗
PubMed2000

Treatment of depression with methylphenidate in patients difficult to wean from mechanical ventilation in the intensive care unit.

BACKGROUND: Mechanical ventilation is often required to support patients in the intensive care unit (ICU) with life-threatening cardiovascular, respiratory, or neuromuscular disorders. Occasionally, difficulties related to weaning patients from this support occur owing to depression. The traditional and newer-generation antidepressant drugs have a relatively long latency of response that interferes with rehabilitation attempts in the ICU. Psychostimulants such as methylphenidate show a rapid onset of antidepressant activity and a benign side effect profile. METHOD: As consulting psychiatrists in the consultation-liaison service of a university hospital, we treated 7 patients with complex ICU courses presenting prolonged mechanical ventilation and psychomotor retardation associated with markedly depressed mood (DSM-IV criteria) by giving them methylphenidate. Methylphenidate was started on the first day at a dose of 2.5 mg p.o. in the morning and was increased by 2.5 mg each day with twice-a-day dosing in the morning and at noon until the patient responded or showed side effects. A maximum dose of 15 mg/day was not exceeded. Outcome evaluation was performed using the Clinical Global Impressions scale. RESULTS: Five (71 %) of 7 patients showed marked or moderate improvement in mood and activity within 3 to 4 days, and discontinuation of ventilator support was achieved within 8 to 14 days. Side effects with these 5 patients were not encountered. Of the remaining 2 patients (29%), 1 developed psychomotor agitation and anxiety within 4 days. Another patient showed only minimal improvement with regard to activity. CONCLUSION: Methylphenidate might be a rapidly effective and safe treatment for depression in difficult-to-wean patients hospitalized for life-threatening medical illness in the ICU. Implications for future research for this population of patients warrant formal randomized, prospective, clinical case-control evaluation.

Adult↗
PubMed1999

Modulation of coronary vasomotor tone by cytokines in cardiac transplant recipients.

BACKGROUND: Upon exposure to cytokines, endothelial cells may undergo profound alterations of vasomotor function. In this study, we characterized the relationship between coronary epicardial and microvascular vasomotor function and expression of specific cytokine patterns in human heart transplant recipients. METHODS: We studied 49 cardiac transplant recipients, without acute rejection or infection at an average of 6+/-3 months after transplantation. Coronary resistance vessel function was measured in an endothelium-dependent manner with acetylcholine (5 and 150 microg/5 min; intracoronary injection) and in an endothelium-independent manner with adenosine (400 and 800 microg/5 min; intracoronary injection) using an intracoronary Doppler flow wire. Simultaneous epicardial diameter changes were measured using quantitative coronary angiography. Coronary sinus and aortic serum levels of soluble interleukin (IL)-2 receptor and soluble tumor necrosis factor-a receptors (sTNF-R1 and sTNF-R2), TNF-alpha, and IL-6 were determined. Transcardiac cytokine release (coronary sinus minus aortic levels) was correlated with coronary vasomotor function. RESULTS: The highest amounts of cardiac cytokine release were observed for IL-6 (32+/-14% increase) and sTNF-R1 (26+/-13% increase). A significant inverse correlation between microvascular endothelial function and cardiac release of soluble IL-2 receptor (P=0.04) and IL-6 (P=0.03) was detected, whereas a positive correlation was observed to sTNF-R1 (P=0.004). Distal epicardial endothelial vasomotion was inversely correlated to transcardiac sTNF-R2 release (P=0.03). CONCLUSIONS: Cytokine production and activation, a common phenomenon early after heart transplantation, is related at least in part to endothelial vasomotor dysfunction of the epicardial and microvascular compartment. These results support the hypothesis that coronary endothelial dysfunction after cardiac transplantation is an immunologic phenomenon. Since endothelial dysfunction seems to be a crucial step in the pathogenesis of cardiac allograft vasculopathy, coronary cytokine suppression should be a therapeutic target of improved future immunosuppressive regimens.

Adult↗
PubMed1999

Extracellular matrix structure after heart transplantation.

Following heart transplantation remodeling of the donor heart causes changes in the extracellular myocardial matrix. We investigated 20 right ventricular endomyocardial biopsies taken 17+/-4 days (group I, n=9) and 63+/-13 days (group II, n=11) after heart transplantation from 16 patients transplanted for end-stage cardiomyopathy (15 dilated/1 ischemic). Immunohistochemical staining for collagen I, collagen III, collagen IV, and fibronectin was used. Evaluation was performed at a magnification of 400x using a computer-assisted image analyzing system measuring the relative area stained by the immunoperoxidase method, the number of cells in the given area, and the total area. Collagen I per cell was 13.9+/-5.9 microm2 in group I and increased significantly 66+/-13 days after heart transplantation in the perimysium around the myocardial cells as well as in the endocardium to 49.9+/-15.1 microm2 (P<0.05). No quantitative change in collagen III was noted (75.7+/-12.4 versus 75.5+/-16.0 microm2 n.s.). Collagen IV was found in the perimysial, in the capillary bed and in the vascular network. Significant quantitative change in the amount of collagen IV was not found (64.1+/-12.6 versus 61.0+/-8.9 microm2). Fibronectin was found in the entire perimysial extracellular matrix and in the endocardium in relationship with collagen I and III. An increased amount of fibronectin from 87.09+/-9.9 microm2 (group I) to 140.8+/-17.9 microm2 (group II, P<0.05) was found. The cell area and cell diameters were not significantly different (group I; cell area 772+/-227 microm2, diameter 31.3 microm; group II; cell area 776+/-224 microm2, diameter 31.4 microm). It is concluded that remodeling of the donor heart after transplantation is characterized by a specific increase in collagen I and fibronectin, whereas a change in other collagen subtypes was not observed.

Analysis of Variance↗
PubMed1999

Endothelin in coronary endothelial dysfunction early after human heart transplantation.

BACKGROUND: Cytokines and growth factors released as part of the immune response to alloantigenic stimuli are capable of regulating endothelin-1 expression in the allograft. Endothelin plays a significant role as a modulator of coronary vascular reactivity in the early stages of atherosclerosis and may be important as a participant in and marker for cardiac allograft vasculopathy. METHODS: We characterized a possible relationship between morphological and functional coronary changes, transcardiac plasma endothelin level and myocardial endothelin-mRNA expression in 33 cardiac transplant recipients in the early, stable phase 5+/-3 months after orthotopic heart transplantation. Coronary microvascular function was determined as endothelium-dependent with acetylcholine and endothelium-independent with adenosine using intracoronary Doppler-FloWire. The percentage of the epicardial diameter changes was measured using quantitative coronary angiography. Intravascular ultrasound was performed to quantify intimal hyperplasia. Cardiac endothelin uptake or release was determined by measuring plasma endothelin levels in the coronary sinus and aorta. Myocardial endothelin-gene expression was determined using semiquantitative RT-PCR. RESULTS: The aortic endothelin levels were significantly increased in transplant recipients compared to nontransplanted patients (11.8+/-2.2 vs 7.2+/-0.9 fmol/mL; P < 0.001). Endothelin uptake was noticed in the majority of patients, and the amount of endothelin uptake was correlated to microvascular (r = 0.37; P < 0.05) and epicardial (r = 0.41; P < 0.03) endothelium-dependent vasodilatation. High mRNA signal intensity was associated with significantly reduced coronary flow response to acetylcholine compared to patients with low myocardial gene expression (coronary flow reserve 2.4+/-0.9 vs 3.4+/-0.8, respectively; P < 0.005). Morphological coronary changes early after transplantation were not correlated to endothelin plasma levels or myocardial gene expression. CONCLUSION: Coronary endothelial vasomotor dysfunction after cardiac transplantation is associated with an increased myocardial endothelin mRNA expression and decreased endothelin-uptake by the heart. We postulate that early activation in the endothelin system may have a pivotal role in the acceleration of the atherosclerotic process in transplant patients.

Adult↗
PubMed1998

Alterations of autonomic cardiac control in anorexia nervosa.

BACKGROUND: The authors investigated autonomic cardiac function in anorexia nervosa. METHODS: Forty-eight patients, who in the present or past met the DSM-III-R criteria for anorexia nervosa, and 16 normal control subjects participated in a standardized analysis of heart rate variability during supine and standing postures. RESULTS: Several heart rate variability parameters showed an inverse correlation to the present weight of the anorexic subjects. The values of the spectral power analyses were significantly (p < .01) lower in patients (n = 18) weighing less than 75% of ideal weight when compared to the results found in the control group; however, the heart rate variability parameters of anorexic subjects with restored weight (n = 12) did not differ from those of the control subjects. CONCLUSIONS: The obtained results provide evidence for autonomic cardiac dysfunction in acutely ill anorexic patients. Further research is required to elucidate possible clinical consequences of these findings.

Adolescent↗
PubMed1998

Prognostic significance of coronary flow reserve on left ventricular ejection fraction in cardiac transplant recipients.

BACKGROUND: Cardiac allograft vasculopathy is a common phenomenon in epicardial and microvascular vessels. Intramyocardial vessel disease may lead to small, stellate infarcts. The present study tested the impact of microvascular vasomotor function on changes in left ventricular systolic function in the long-term follow-up after cardiac transplantation. METHODS: Seventeen consecutive cardiac transplant patients, 40+/-21 months after cardiac transplantation, without angiographically visible cardiac allograft vasculopathy and without episodes of acute rejection were included in the study. Coronary microvascular reactivity was assessed by the endothelium-dependent stimulus acetylcholine (50 microg i.c.) and by the endothelium-independent stimulus dipyridamole (0.56 mg/kg i.v.) utilizing an Doppler catheter. Radionuclide ventriculography was performed at the time of coronary flow measurement and repeated 2 years later to correlate changes in left ventricular ejection fraction with the coronary flow reserve measurement 2 years previously. RESULTS: There was a statistically significant correlation between endothelium- independent coronary flow reserve to dipyridamole and changes in ejection fraction at rest (r=0.59; P < 0.01) and during exercise (r=0.48; P < 0.05). Twenty-four months later, patients with a coronary flow reserve to dipyridamole < 2.5 showed a significant decline in ejection fraction during exercise (-7 +/- 5%) compared to patients with a coronary flow reserve > 2.5 (1.1+/-5%; P=0.003). Coronary flow reserve to acetylcholine was not correlated with a reduced ejection fraction during exercise. CONCLUSIONS: Endothelium-independent microvascular dysfunction has prognostic importance for deterioration of left ventricular function in cardiac transplant recipients without angiographically visible coronary artery stenoses. These results reinforce the concept that microvascular and epicardial vessel disease after transplantation are two distinct entities with different functional consequences.

Adolescent↗
PubMed1998

Endothelium-dependent microvascular vasomotion and its correlation with vasoactive mediators early after cardiac transplantation in humans.

Endothelial dysfunction precedes and predicts transplant vasculopathy. We investigated the relationship between endothelial dysfunction and the vasoactive mediators nitric oxide and endothelin, 33.7 +/- 2.0 days after heart transplantation. Coronary flow was measured in 18 patients to determine the endothelial microvascular vasomotor response to acetylcholine. Endomyocardial biopsies were taken to determine the levels of gene expression of isozymes of endothelin and nitric oxide synthases (NOS). Blood samples from the coronary sinus and aorta were withdrawn for measurement of endothelin, nitrite and cytokines. Five patients (30%) showed an impaired coronary flow reserve response to acetylcholine, significantly higher inducible NOS gene expression and significant transcardiac nitrite production. Plasma nitrite correlated with tumour necrosis factor-alpha levels in coronary sinus and a transcardiac net extraction of endothelin was noted in all patients. In conclusion, 30% of patients develop endothelial dysfunction early after heart transplantation; this correlates with the expression and activation of vasoactive and immunomodulatory mediators, which may predict the development of transplant vasculopathy.

Endothelin-1↗
PubMed1998

Correlation between plasma clozapine concentration and heart rate variability in schizophrenic patients.

Forty schizophrenic patients treated with 50-600 mg/day of clozapine as monotherapy and 40 normal control subjects were tested for heart rate variability (HRV) which is mediated by the vagus nerve using acetylcholine as neurotransmitter. As compared to the control subjects, the patients showed essentially reduced HRV parameters which were negatively correlated with the plasma clozapine levels. Therefore, clozapine's anticholinergic effect is correlated to the plasma clozapine level when measured by the decrease of HRV. We suggest that HRV data might be useful as a predictor for plasma clozapine levels.

Adult↗
PubMed1998

[Modern technical aids in the teaching of medical physics and biophysics].

The set of analogous electric and electronic models of physical and biological processes tested in the teaching process of Medical Physics and Biophysics is discussed. Measuring arrangement of model, digital storage oscilloscope and personal computer allows to display, record, save and process any electric signal. This proposed arrangement offers new possibilities for more detailed description of selected types of signals generally not only in the teaching process.

Biophysics↗
PubMed1998

Soluble interleukin-2-receptor levels as a marker of coronary microvascular dysfunction after heart transplantation.

BACKGROUND: Immunologic mechanisms operating in a milieu of nonimmunologic risk factors constitute the principal stimuli that result in progressive cardiac allograft vasculopathy. Interleukin-2 has a central role in the development of cell-mediated immunity and is a key factor in the induction of a complex network of cytokines. On exposure to cytokines, endothelial cells can undergo profound alterations of vasomotor function. In this study we characterized the relationship between coronary microvascular function and soluble interleukin-2 receptor (sIL-2R) levels after human heart transplantation. METHODS: We studied 15 heart transplant recipients after an average follow-up time of 39+/-22 months. We measured coronary artery blood flow in an endothelium-dependent manner with acetylcholine (50 microg) and in an endothelium-independent manner with dipyridamole (0.56 mg/kg) by intracoronary Doppler catheter. Blood samples from the superior vena cava were drawn 3 to 12 months after transplantation (early value) and at time of the coronary artery flow measurement (present value). Coronary artery flow reserve was correlated to sIL-2R levels, which were determined by use of an enzyme-linked immunoabsorbent assay. RESULTS: We found a significant inverse correlation between impaired endothelium-mediated (p = 0.03) but not endothelium-independent relaxation of the coronary microvasculature and elevated sIL-2R levels. In heart transplant recipients without acute rejection or an infection episode, an sIL-2R-level of more than 800 U/ml was defined as a cutpoint, indicating disturbed endothelium-dependent microvascular function. Additionally, there was a conspicuous trend toward an inverse correlation between early elevated sIL-2R-levels and endothelium-dependent microvascular dysfunction (p = 0.06). CONCLUSIONS: The results of this study demonstrate the utility of sIL-2R, an index of immunologic activity, to be used as a marker and predictor of impaired endothelial microvascular function in heart transplant recipients. These observations support the hypothesis that after heart transplantation endothelial dysfunction in the microcirculation is an immunologic phenomenon.

Adult↗