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Biomedical subjects

A Hartmann

Publications and source records attributed to A Hartmann.

At least 199 records · Page 11Linked to original sources
PubMed1998

Evaluation of the genotoxic properties of paraquat in V79 Chinese hamster cells.

The genotoxic potential of the herbicide paraquat (PQ), an intracellular generator of superoxide, was comparatively tested in various genotoxicity tests with V79 Chinese hamster cells. PQ clearly induced cytotoxicity and chromosome aberrations but did not induce gene mutations at the HPRT locus or increased DNA migration in the comet assay under the same treatment conditions. Using a modified comet assay protocol with formamidopyrimidine-DNA glycosylase (FPG) protein, a DNA repair enzyme which specifically nicks DNA at sites of 8-oxo-guanines and formamidopyrimidines, we could not detect oxidative DNA base damage after PQ treatment. When cells were treated directly on the slides after lysis (i.e, after the cell membrane barrier was eliminated), increased DNA migration was observed after treatment with high PQ-concentrations. Our results suggest that PQ does not significantly induce DNA lesions relevant for HPRT gene mutations in cultivated V79 cells. Since PQ-induced chromosome aberrations only occur after treatment with high concentrations which totally prevent cell survival and are not preceded by an induction of DNA strand breakage in intact cells, their biological significance has to be questioned.

Animals↗
PubMed1998

Exercise-induced DNA effects in human leukocytes are not accompanied by increased formation of 8-hydroxy-2'-deoxyguanosine or induction of micronuclei.

The present study examined the effects of a short-distance triathlon on the induction of DNA effects in peripheral leukocytes, urinary excretion of oxidized DNA bases, and frequency of micronuclei in lymphocytes of human volunteers. Induction of DNA effects was measured as increased DNA migration using the alkaline comet assay. Increased DNA migration was found in leukocytes of all individuals at different time points after exercise and revealed a biphasic pattern. Twenty-four hours postexercise, elevated DNA migration was found, whereas lower values were detected 48 h after exercise. Seventy-two hours postexercise, the maximum increase in DNA migration was found and baseline values were still elevated after 120 h. A modified protocol of the comet assay for the detection of oxidized DNA bases revealed no differences in leukocytes before and directly after the triathlon. Urinary excretion of 8-hydroxy-2'-deoxyguanosine remained unaltered during the 5 consecutive days sampled. No differences were found in the micronucleus-frequency in lymphocytes before or 48 and 96 h after exercise. Our data suggest that DNA effects detected with the comet assay in leukocytes of humans after exercise are secondary effects that do not originate from oxidized DNA bases and do not result in chromosome damage.

8-Hydroxy-2'-Deoxyguanosine↗
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

Comparative biomonitoring study of workers at a waste disposal site using cytogenetic tests and the comet (single-cell gel) assay.

Workers exposed to environmental pollutants at a waste disposal site were studied for genotoxic effects with cytogenetic tests and the comet (alkaline single-cell gel) assay. Analyses were performed on peripheral blood samples of 44 workers at a waste disposal site (DM) and 47 subjects of a control group (VE) matched for gender, age, and smoking habits. Chromosomal aberrations were evaluated in 1,000 lymphocytes per individual, sister chromatid exchanges in 50 cells, and DNA migration (tail moment) was determined in 100 leukocytes. Structural chromosome aberrations were more frequent in DM than in VE, but only the frequency of acentric fragments and the percentage of aberrant cells (excluding gaps) was significantly increased. No significant difference was found for the mean frequency of SCE. A statistically significant difference was also seen with the comet assay. The mean tail moment was higher in DM than in VE. However, no correlation was found between cytogenetic data and the effects in the comet assay. The results of our study indicate that DNA effects in the comet assay represent an independent endpoint which might be useful for the biomonitoring of genotoxic effects in addition to established tests.

Adult↗
PubMed1998

[Effect of cardiac embolism sources on origin of territorial cerebral infarcts].

BACKGROUND AND PURPOSE: To test the association of cardiac sources of embolism with territorial type brain infarcts. METHODS: From a prospective cerebral ischemia data base the 106 consecutive patients with territorial type cerebral infarcts on computerized tomography were analyzed. The 85 consecutive patients with lacunar lesions served as a comparison group. The association of cardiac sources of embolism with territorial types infarcts was assessed using univariate Chi Square tests and logistic regression models. Cardiac sources of embolism were defined as:atrial fibrillation, left cardiac thrombi, valvular vegetations, wall motion and valvular abnormalities, left atrial enlargement, open foramen ovale, septal aneurysm, mitral valve prolaps, and aortic arch atherothrombosis (all findings--except for atrial fibrillation--assessed by echocardiography). RESULTS: Atrial fibrillation was significantly associated with territorial type infarcts (odds ratio 2.2, 95% confidence interval 1.01-4.8). This effect was independent of additional cardiac diseases, other cardiac abnormalities, carotid artery stenosis, and patient age. Most likely due to the small sample size, left cardiac thrombi only showed a non-significant trend towards an association with territorial infarcts (odds ratio 3.0, 95% confidence interval 0.7-12.3). The rate of all other cardiac findings did not differ significantly between the comparison groups. CONCLUSION: Atrial fibrillation and cardiac thrombi showed an association with territorial type infarcts. Other so-called cardiac sources of embolism--except for mechanical valves and bacterial endocarditis which were not represented in our sample--revealed no clinically relevant association with embolic brain infarct pattern.

Adult↗
PubMed1998

[Therapy of cerebral arteriovenous malformations].

The rapid development of modern endovascular, microsurgical, and radiation therapies has considerably expanded the treatment options for encephalic arteriovenous malformations (AVMs). Surgery has the longest history. Single or staged intravascular procedures (embolizations) using fast-acting glues, sclerotic agents, and thrombogenic coils serve to reduce the size of AVM to that suitable for extirpation and may reduce the risk of surgery. Radiation ("gamma-knife") therapy, most frequently used in small, non-operable AVMs, is also viewed by some authors as an alternative or even superior tool in small, operable malformations. Partial embolization to reduce the mass-effect of space-occupying AVMs, to reverse diaschisis, and to treat AVM-related seizure disorders is being discussed and practiced. Given the in part competing or even controversial options, the selection of optimal treatment for AVM patients is becoming increasingly difficult. Current management is impeded by the paucity of information on the exact risks of invasive therapies and by insufficient criteria for identifying patients at risk of spontaneous bleeding during the natural course, including the seriousness of such hemorrhage.

Cerebral Angiography↗
PubMed1998

[Model for cost-benefit relations of amblyopia screening].

BACKGROUND AND PURPOSE: In Germany, 750,000 children are born per year who should be screened for developmental visual defects in the age range 24-48 months. However, the established pediatric screening program is not sufficient to prevent amblyopia. The purpose of this study was to examine the cost-effectiveness of alternatives for amblyopia and microtropia screening. METHODS: Three options were compared: (1) an orthoptic screening carried out in the field, for instance in kindergartens, (2) an examiner-independent objective apparatus-based screening, and (3) a complete ophthalmological and strabismological examination carried out in a practice. The costs of screening, follow-up examinations and of the treatment were modelled for prevalences of 1% (microtropia) and 5% (amblyopia). The benefit due to treatment was calculated as the result of an avoided whole-person impairment of 3% and 1%. The income related, increased tax and health care payments were used to cover the costs. RESULTS AND CONCLUSIONS: In options (1) and (2) there were favorable cost-effective ratios. The practice-based option 3 was economically less promising. The higher the prevalence was, the higher the resulting cost-effectiveness.

Amblyopia↗
PubMed1998

Secondary dystonias.

Secondary or symptomatic dystonias are (1) often accompanied by other neurological deficits. (2) begin suddenly at rest and occur at rest from the onset, (3) are associated with different hereditary and environmental causes. From an aetiological point of view, secondary dystonias can be caused by focal brain lesions of various origin, neurodegenerative disorders, metabolic disorders of the central nervous system (CNS), and several drugs and chemicals that affect the basal ganglia, thalamus and brain stem. Furthermore, secondary (focal) dystonias can be caused by peripheral injury. In the following review, we will discuss epidemiology, genetics, pathogenesis, neuroimaging, neuropathology, clinical manifestation, clinical course and differential diagnosis of secondary dystonias. Therapeutic options are given depending on the aetiology and the topological type of dystonia.

Brain Diseases↗
PubMed1998

Crosstalk between cAMP and pheromone signalling pathways in Ustilago maydis.

In the phytopathogenic basidiomycete Ustilago maydis mating and dikaryon formation are controlled by a pheromone/receptor system and the multiallelic b locus. Recently, a gene encoding a G protein alpha subunit, gpa3, was isolated and has subsequently been implicated in pheromone signal transduction. Mutants deleted for gpa3 are sterile and nonpathogenic, and exhibit a morphology that is similar to that of mutants with defects in the adenylate cyclase gene uac1. We have found that the sterility and mutant morphology of gpa3 deletion strains can be rescued by exogenous cAMP. In these mutants and in the corresponding wild-type strains, exogenous cAMP stimulates pheromone gene expression to a level comparable to that seen in the pheromone-stimulated state. In addition, we demonstrate that uac1 is epistatic to gpa3. We conclude that Gpa3 controls the cAMP signalling pathway in U. maydis and discuss how this pathway feeds into the pheromone response.

Cyclic AMP↗
PubMed1998

Mitogenic short-term effects on hepatocytes and adrenocortical cells: phenobarbital and reserpine compared to carcinogenic and non-carcinogenic fluorene derivatives.

The adrenal cortex has a low physiologic cell renewal and shows only a moderate cell replication even after contralateral adrenalectomy. Although rather unsusceptible to the malignancy-inducing action of carcinogens, a single oral dose of various tumorigenic xenobiotics induced an additive mitotic response of adrenocortical cells studied after 48 h. Presently we report on three different response patterns in rats. First, a selective mitostimulation of the zona glomerulosa occured after reserpine associated with a loss of body weight, thymus and liver weight. These are unspecific stress effects and occur also after exogenous ACTH. Second, hepatomitogenic and liver-enlarging congeners, e.g. fluorene (FEN), fluorenone (FON) and 4-benzoyl-FON, but also the genotoxic 2-acetylaminofluorene (2-AAF) and 2,4,7-trinitro-FON induced a selective mitotic response of the zona fasciculata (ZF). After the lowest effective dose of FEN or FON the afore-mentioned effects occured simultaneously, but were absent in the high dose group (only studied with fluorene). The 2-benzyl and 2-benzoyl-substituted derivatives were ineffective at all. Third, a bizonal response was found only after phenobarbital (PB) or the lowest effective FEN dose. The preventive action of a low PB dose on the 2-AAF-induced ZF response indicates a modified metabolism. We conclude that the rapid mitotic ZF response is an endogenously mediated net effect of interactions between metabolic and various adaptive mechanisms. The latter are reported to be activated in a stressor-dependent manner and converge in the adrenals. In this way the early mitotic ZF response could reflect indirectly 'specific' proliferation-prone properties of xenobiotics.

Adrenal Cortex↗
PubMed1998

Endothelium-dependent and endothelium-independent flow reserve in vascular regions supplied by the internal mammary artery before and after bypass grafting.

OBJECTIVE: It was the goal of this study to compare endothelium-dependent and endothelium-independent flow reserve in vascular regions supplied by the left internal mammary artery before and after bypass graft surgery. METHODS: The native internal mammary artery in situ was investigated in 13 patients (age 61.8 +/- 8.0 years) with angiographically proven coronary artery disease. The internal mammary artery after bypass grafting was investigated in ten patients (age 60.8 +/- 7.3 years) 3.5 +/- 2.8 years after the operation. Flow reserve was evaluated endothelium-dependent with acetylcholine (ACh 25 and 50 microg i.c.) and endothelium-independent with nitroglycerin (NTG 0.3 mg i.c.) followed by papaverin (10 mg i.c.). Flow indices were calculated from intraluminal Doppler blood flow velocity measurements and the vascular cross-sectional area as determined by quantitative angiography. An index for vascular resistance was defined as the ratio of pressure gradient and resting or peak flow. RESULTS: After endothelium-dependent stimulation with acetylcholine 25 microg (50 microg), flow in the internal mammary increased by 352.3 +/- 152% (412 +/- 145%) before surgery, whereas it increased only by 213 +/- 134% (193 +/- 120%) after surgery (P < 0.05). Endothelium independent stimulation with papaverin resulted in a flow increase of 391 +/- 234% before surgery vs. 315 +/- 135% after surgery (n.s.). The resistance index decreased after endothelium-dependent stimulation with acetylcholine 25 microg(50 microg) to 35 +/- 16.8% (28 +/- 8.9%) before surgery, whereas it decreased only to 59 +/- 26% (72 +/- 43%) after surgery (P < 0.05). Endothelium independent stimulation with papaverin resulted in a decrease of the vascular resistance index to 31 +/- 14% before surgery vs. 32 +/- 14% after surgery (n.s.). CONCLUSION: Vascular regions supplied by the internal mammary artery as a graft demonstrate a significantly reduced endothelium-dependent flow reserve but a preserved endothelium-independent flow reserve as compared to vascular regions supplied by the native internal mammary artery. The selective decrease in endothelium-dependent flow reserve may be due to microvascular changes in the myocardial region supplied by the internal mammary artery after bypass grafting.

Aged↗
PubMed1998

[Improved diagnosis of early cerebral infarct by the combined use of diffusion and perfusion].

PURPOSE: To evaluate the feasibility and the diagnostic efficacy of multislice diffusion-weighted and perfusion imaging in addition to FLAIR-TSE, T2w-GraSE and MR-angiography in the diagnosis of acute stroke. METHODS: 18 patients with acute stroke were examined at 1.5 Tesla (Gyroscan ACS-NT, Philips Medical Systems) within 6 (n = 9) and 6-48 (n = 9) hours, respectively, and followed at regular intervals. For diffusion imaging we used a multislice multishot EPI-SE sequence with navigator echo correction and cardiac gating. Perfusion imaging was done by means of a FFE-EPI sequence after bolus injection of Gd-DTPA. RESULTS: The diagnostic value of diffusion-weighted and perfusion imaging was significantly higher compared with FLAIR-TSE (p = 0.0023) and GraSE (p = 0.0012) during the first 6 hours. With FLAIR-TSE and GraSE first pathologic changes were seen after 4 hours. We detected perfusion deficit (rCBV < 10%) and a corresponding drop of the ADC in all infarcts larger than 1 cm in diameter. Within the area of low rCBV the combined analysis of diffusion and perfusion imaging allows to identify an infarct region with characteristics of a penumbra and one with characteristics of the infarct core. TTP was increased in the surrounding tissue. However, parts of this area were rarely included in the infarct. The final extension of the untreated infarct, as revealed by computed tomography, corresponded well to the perfusion deficit. CONCLUSIONS: Early ischaemic cerebral infarcts can be diagnosed with diffusion and perfusion imaging before pathological changes are visualized with other imaging modalities. The combined use may allow to distinguish the infarct core from surrounding, potentially salvageable tissue.

Adult↗
PubMed1998

Quantification of mRNA levels of endothelin receptor subtypes and preproEndothelin-1 in renal needle biopsies by competitive reverse transcriptase polymerase chain reaction.

The vasoconstrictive peptide endothelin-1 (ET-1) is an autocrine/paracrine peptide of putative pathophysiological importance in renal transplant medicine. The aim of the present study was to develop a method for analysis of gene expression of the renal endothelin system in humans. Only small amounts of tissue are available from renal cortical needle biopsies. Thus, in the present study we developed a quantitative assay based on the competitive reverse transcriptase polymerase chain reaction (RT-PCR) technology. We quantified endothelin A (ET(A)) and B (ET(B)) receptor subtype mRNAs and preproET-1 mRNA levels in renal cortex biopsies obtained before nephrectomy of healthy kidney donors. Mean (+/- SEM) mRNA levels of the ET(A) and ET(B) receptor subtypes in 26 living donors were 212 +/- 23 and 368 +/- 56 amol/microg total RNA, respectively. The preproET-1 mRNA level in 19 living donors was 213 +/- 28 amol/microg total RNA. The inter-assay coefficient of variation (CV) for the assay was 10%; the intra-assay CV was 6-13%. The competitive RT-PCR assay described provides an accurate tool for gene expression investigation of the human endothelin system in renal cortical needle biopsies.

Adult↗
PubMed1998

Hemodynamic sequelae of ventricular tachyarrhythmias on cerebral blood flow.

The present experiments were designed to compare the behavior of cerebral blood flow (CBF) during acute moderate and severe hypotensive episodes induced by either ventricular tachycardias (VT) or by hemorrhage. Using the microsphere method CBF was determined in 20 Sprague-Dawley rats during sinus rhythm (Group A), in 28 animals during high-rate VT (Group B) and in 10 animals after hemorrhage (Group C). According to the decrease in blood pressure and with respect to the lower threshold of cerebral autoregulation Group B was divided into 2 subgroups (B1: 80-130 mmHg; B2: 50-80 mmHg) retrospectively. While CBF remained constant in Group B1 (0.98 +/- 0.3 ml g-1 min-1 vs. 1.01 +/- 0.32 in controls, NS), CBF decreased markedly during severely hypotensive VT in Group B2 (0.52 +/- 0.2 ml g-1 min-1, p < 0.001 vs. A; p < 0.05 vs. C) and during hypovolemic hypotension in Group C (0.77 +/- 0.22 ml g-1 min-1 vs. A; NS). Cerebrovascular resistance and autoregulation indices indicated a maintenance of CBF regulation during hypovolemic hypotension and a failure during normovolemic hypotension. These findings indicate that the autoregulatory ability of the brain is substantially more stable during hypovolemic hypotension than during normovolemic hypotension. Therefore, the hemodynamic sequelae of acute hypotensive episodes on CBF depend on the underlying cause of hypotension.

Animals↗