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Biomedical subjects

E Kasper

Publications and source records attributed to E Kasper.

At least 19 recordsLinked to original sources

Cardiac troponin T and C-reactive protein as markers of acute cardiac allograft rejection.

Due to myocyte damage and an associated inflammatory response, it is possible that cardiac troponin T and C-reactive protein (CRP) concentrations may correlate with the histologic grade of rejection in endomyocardial biopsy samples obtained from patients who have received a heart transplant. In this study, 704 blood samples were obtained from 145 different heart transplant recipients just prior to endomyocardial biopsy. Plasma specimens were assayed for troponin T and CRP concentration and the results compared with the assigned International Society of Heart and Lung Transplantation (ISHLT) histologic grade. Rejection was defined as an ISHLT grade of 3A or higher. The negative predictive values were near 80% in all cases, and a statistically significant increase in median troponin T concentration was observed across ISHLT grades. After the first month posttransplantation, the specificity of the troponin T test (cutoff 0.1 ng/ml) was 95% and increased to 98% when false positives seen in renal disease patients were excluded. Both tests demonstrated poor sensitivity and positive predictive value for rejection. Neither CRP nor troponin T had sufficient sensitivity to serve as an alternative to endomyocardial biopsy in the diagnosis of acute cardiac allograft rejection. However, the troponin T test had a high specificity, especially when patients with renal insufficiency were excluded, and could serve as an adjunct test in this setting. When combined with a normal serum creatinine, a troponin T > or =0.1 ng/ml prior to endomyocardial biopsy correlated with graft rejection in almost all cases, making biopsy unnecessary.

Biomarkers↗

The relationship between cerebral blood flow velocities and the amount of blood clots in computed tomography after subarachnoid haemorrhage.

127 patients with aneurysmal subarachnoid haemorrhage (SAH) were analyzed for the relationship between the amount of blood clots as detected by initial computed tomography (CT) up to 48 hours after SAH and changes of blood flow velocities as measured using transcranial Doppler ultrasonography (TCD). All patients were operated on within 72 hours after SAH. Patients who presented with remarkable brain oedema or with pathological intracranial pressure (ICP) due to mass effects of a haematoma, and who were in a poor neurological condition classified according to Hunt-Hess as grade V were excluded from this study. Serial TCD examination of the middle cerebral arteries (MCA) and anterior cerebral arteries (ACA) started within 48 hours after SAH and were performed daily up to three weeks. A statistically significant correlation between blood load designated according to Fisher's grading as group CT I-CT IV and mean flow velocities (MFV) was found in groups CT I, II, and III. High values of MFV in MCA examinations were noted in patients with severe SAH (group CT III)--161 cm/s, and low values in patients without SAH (group CT I)--119 cm/s. Patients with haematocephalus and/or haematoma without a mass effect (group CT IV) had lower blood flow velocities than patients with severe SAH (group CT III) but values were higher than in patients without SAH (group CT I). The number of days for which MFV in the MCA was > 120 cm/s and was statistically (p < 0.05) correlated with the amount of blood clots as observed in the respective CT (in group CT I, II, and III). MFV values in the anterior cerebral artery (ACA) were lower than those obtained in the middle cerebral artery (MCA) in all groups. Statistically significant (p < 0.05) differences were noted between groups CT I and CT III (first and third week) and between groups CT I and CT IV (third week). If the SAH was extensive in the CT scan, pathological values of MFV > 90 cm/s were observed in ACA, and this was more pronounced in group CT III than in group CT IV. Blood flow velocities obtained via TCD were registered to compare side-to-side differences and particularly high differences were observed in patients with severe SAH. It is concluded that the amount of blood clots in the initial computed tomography after SAH is significantly correlated with cerebral blood flow velocity measurements by TCD.

Adolescent↗

Development of cholinergic and GABAergic neurons in the rat medial septum: effect of target removal in early postnatal development.

During normal development of the nervous system, the target fields influence the survival and differentiation of projection neurons, but the factors regulating this interaction remain obscure. In the present study, we have raised the question whether the target region is essential for the postnatal development and maintenance of two different types of central projection neurons, cholinergic and GABAergic septohippocampal cells. In early postnatal rats (P5, P10), the hippocampus was eliminated by unilateral intrahippocampal injections of the excitotoxin N-methyl-D-aspartate. After a long survival time (at P70), we have immunostained serial sections of the septal region with antibodies against choline acetyltransferase (ChAT), the acetylcholine-synthesizing enzyme, or the calcium-binding protein parvalbumin (PARV) which is known to be contained in GABAergic septohippocampal neurons. In the medial septum ipsilateral to the lesioned side, about 60% of ChAT-immunoreactive neurons and 62% of PARV-immunoreactive neurons were found in adulthood even after complete elimination of the hippocampus. Some immunoreactive cells appeared heavily shrunken, but electron microscopic analysis revealed ultrastructural characteristics typical for medial septal neurons obtained from controls. Our results indicate that target elimination during development affected both types of projection cells, although only the cholinergic cells are known to be responsive to target-derived factors.

Animals↗

Factors affecting various biomarkers in untreated lung cancer patients and healthy donors.

The purpose of the present communication was to determine in lung cancer patients and healthy donors if there was a possible association between cancer and biomarkers of cytogenetic damage and ras p21 oncoprotein levels, and if various exogenous confounding factors (such as smoking habit) and endogenous ones (age, sex, etc.) could affect these biomarkers. Peripheral blood and plasma were collected from 31 lung cancer patients prior to treatment and 35 healthy donors of a similar socioeconomic status and from the same region in Poland. Chromosomal aberrations (CA), sister chromatid exchanges (SCE), high frequency cells (HFC), and proliferative rate index (PRI) were examined from the blood and ras p21 oncoproteins from the plasma. These parameters were used as biomarkers of genotoxic anomalies. All the biomarkers were examined for their relationship to confounding factors of age, sex, smoking habit, and immediate family cancer history. Results were analyzed by a t-test, analysis of variance (ANOVA), and stepwise multivariate regression analysis. All types of CA (including and excluding gaps), percent aberrant cells, SCE, and ras p21 oncoproteins were statistically significantly higher in cancer patients than in the healthy donors. Although there were smaller numbers of females in the cancer patients group who were older than the males, there was a difference due to sex (gender) with statistically significant increases in females for CA, SCE, and HFC, but there was no increase for ras p21 oncoproteins. Cytogenetic damage was not related to other cancers in the immediate families of the groups. All major CA parameters differed significantly between smokers and non-smokers in the cancer patients group, and SCE and HFC differed in the healthy donors group. Such parameters also showed a significant variability with the number of cigarettes smoked and the years of smoking habit. Multivariate regression analyses showed a significant association between cytogenetic damage, ras p21 oncoproteins, and cancer. In conclusion, cytogenetic damage and ras p21 oncoproteins in this study appear to be biomarkers associated with cancer, but have not been proved causally, and confounding factors such as age, sex (gender), and smoking can have an impact on them.

Adult↗

Biological monitoring of workers exposed to emissions from petroleum plants.

This paper presents some of the results from the Commission of the European Communities collaborative research program (contract number EV5V-CT92-0221), whose aim is to investigate the relationship between exposure to petroleum emissions, benzene, and induction of genetic damage in human cells. Twenty-four workers from petroleum plants in Poland and 35 unexposed controls were examined for cytogenetic effects and ras oncoprotein levels and their relationship to confounding factors (e.g., smoking habit, sex family cancer history, and seasonal influence). Preliminary data of chromosome aberrations (CA) and sister chromatid exchanges (SCE) showed differences among sampling subgroups. In this present study, the levels of ras p21 proteins were determined and further analyses of CA, SCE, high frequency cells (HFC), and proliferative rate index (PRI) have been undertaken. Results show that the exposed group has statistically significant increases in CA, and percent of aberrant cells. There were no differences between exposed and unexposed groups in SCE, HFC, PRI, or the levels of ras p21 proteins. Smoking was found to statistically significantly affect levels of CA, percent of aberrant cells, SCE, HFC, and ras proteins. Sister chromatid exchanges were also statistically significantly sex dependent (7.5 breaks/cells for females and 6.8 breaks/cell for males). There were no statistically significant differences for CA, percent aberrant cells, SCE, HFC, or ras p21 protein levels in subgroups characterized according to cancer cases reported in the immediate family. A seasonal variability was shown with statistically significant increases in various biomarkers in the winter. Unexposed groups also showed increases due to smoking and season. The nonsmoking group individuals also showed statistically significant increases in cytogenetic damage with exposure.

Adult↗

Effect of U-50,488H on the contractile response of cardiomyopathic hamster ventricular myocytes.

We examined the effects of a selective kappa opioid receptor agonist (U-50,488H) on the contractile properties of single ventricular myocytes from 127 day old control (F1B) and cardiomyopathic (BIO 14.6) hamsters. Myocytes in bicarbonate buffered solution with 1.5 mM [Ca2+] were electrically stimulated with field electrodes in the bath. Length changes were monitored via myocyte edge tracking. Twitch amplitude and the velocity of cell shortening were less in the cardiomyopathic hamster myocytes than in age-matched hamsters (P less than or equal to 0.05). There was a concentration-dependent effect of U-50,488H (0.1-20 microM) to decrease twitch amplitude and shortening velocity in both control and cardiomyopathic myocytes (P less than or equal to 0.001). In cells loaded with the Ca2+ indicator indo-1 the negative inotropic action of U-50,488H was associated with a decreased indo-1 fluorescence transient amplitude. There was no difference in the negative inotropic effect of U-50,488H on control and cardiomyopathic cells. Thus, the CM hamster does not demonstrate a different contractile response to U-50,488H.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗