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T Neumann

Publications and source records attributed to T Neumann.

At least 55 records · Page 3Linked to original sources

[Double ventricular excitation in dual atrioventricular node conduction physiology: catheter ablation of the slow conduction pathway of the dual atrioventricular node].

A variety of electrocardiographic manifestations of dual AV nodal physiology have been reported. The specific subtype dual ventricular response is considered as a very rare phenomenon. We present the case of a 53 year old lady who suffered from paroxysmal regular tachycardias for more than seven years. In the last 6 months the symptomatology of the cardiac arrhythmia changed to more persistent und irregular rhythm disturbances. Treatment with class Ia antiarrhythmic drugs and beta-blocking agents failed. The latter even seemed to worsen her very disturbing palpitations. After examination of the ECG recordings, the diagnosis of dual AV nodal physiology with double ventricular response was made--the lady was referred to our institution for electrophysiological testing and radiofrequency catheter ablation of the slow pathway. An invasive electrophysiological study reconfirmed the diagnosis of a dual AV nodal conduction pattern with irregular double ventricular response. The radiofrequency catheter ablation of the the slow pathway achieved a complete cessation of the double ventricular response. This satisfactory outcome was confirmed by analysis of a postinterventional 24 hour holter recording and an exercise stress test. During a follow-up period of three months, the patient remained free of symptoms and there was no recurrence of dual AV nodal conduction physiology in the surface ECG.

Atrioventricular Node↗

Characterization of a novel 21-kb deletion, CFTRdele2,3(21 kb), in the CFTR gene: a cystic fibrosis mutation of Slavic origin common in Central and East Europe.

We report a large genomic deletion of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, viz., a deletion that is frequently observed in Central and Eastern Europe. The mutation, termed CFTRdele2,3(21 kb), deletes 21,080 bp spanning introns 1-3 of the CFTR gene. Transcript analyses have revealed that this deletion results in the loss of exons 2 and 3 in epithelial CFTR mRNA, thereby producing a premature termination signal within exon 4. In order to develop a simple polymerase chain reaction assay for this allele, we defined the end-points of the deletion at the DNA sequence level. We next screened for this mutation in a representative set of European and European-derived populations. Some 197 CF patients, including seven homozygotes, bearing this mutation have been identified during the course of our study. Clinical evaluation of CFTRdele2,3(21 kb) homozygotes and a comparison of compound heterozygotes for deltaF508/CFTRdele2,3(21 kb) with pairwise-matched deltaF508 homozygotes indicate that this deletion represents a severe mutation associated with pancreatic insufficiency and early age at diagnosis. Current data show that the mutation is particularly common in Czech (6.4% of all CF chromosomes), Russian (5.2%), Belorussian (3.3%), Austrian (2.6%), German (1.5%), Polish (1.5%), Slovenian (1.5%), Ukrainian (1.2%), and Slovak patients (1.1%). It has also been found in Lithuania, Latvia, Macedonia and Greece and has sporadically been observed in Canada, USA, France, Spain, Turkey, and UK, but not in CF patients from Bulgaria, Croatia, Romania or Serbia. Haplotype analysis has identified the same extragenic CF-haplotype XV-2c/KM. 19 "A" and the same infrequent intragenic microsatellite haplotype 16-33-13 (IVS8CA-IVS 17bTA-IVS 17bCA) in all examined CFTRdele2,3(21 kb) chromosomes, suggesting a common origin for this deletion. We conclude that the 21-kb deletion is a frequent and severe CF mutation in populations of Eastern- and Western-Slavic descent.

Alleles↗

Perfusion-contraction mismatch with coronary microvascular obstruction: role of inflammation.

A close relationship exists between regional myocardial blood flow (RMBF) and function during acute coronary inflow restriction (perfusion-contraction matching). However, the relationship of flow and function during coronary microvascular obstruction is unknown. In 12 anesthetized dogs, the left circumflex coronary artery was perfused from an extracorporeal circuit. After control measurements, 3,000 microspheres (42 micrometer diameter) per milliliter per minute inflow were injected to cause a microembolism (ME, n = 6). With unchanged systemic hemodynamics and RMBF, posterior systolic wall thickening (PWT) decreased from 19.8 +/- 1.9% SD at control to 13.3 +/- 4.0, 10.3 +/- 3.8, and 6.9 +/- 4.7% (P < 0.05 vs. control) at 1, 4, and 8 h, respectively. For comparison, inflow was progressively reduced to match PWT to that of the ME group at 1, 4, and 8 h (stenosis, STE, n = 6). RMBF in the STE group was reduced in proportion to PWT. Infarct size was not different among groups (6.5 +/- 4.5 vs. 3.4 +/- 3.2%). However, the number of leukocytes infiltrating the area at risk was significantly greater in the ME group than in the STE group. Coronary microembolization results in perfusion-contraction mismatch and is associated with an inflammatory response.

Anesthesia↗

Centrosome amplification and instability occurs exclusively in aneuploid, but not in diploid colorectal cancer cell lines, and correlates with numerical chromosomal aberrations.

Measurement of the nuclear DNA content allows classification of human cancers as either diploid or aneuploid. To gain further insight into mechanisms of aneuploidy, we compared the cytogenetic profile of mismatch-repair-deficient diploid versus mismatch-repair-proficient aneuploid colorectal carcinoma cell lines using comparative genomic hybridization and spectral karyotyping. Aneuploid carcinomas revealed an average of 19 chromosomal imbalances per cell line. Such numerical aberrations were exceedingly scarce in the diploid tumors. This pattern of chromosomal aberrations is consistent with a mechanism involving the impairment of chromosome segregation fidelity during mitotic cell division. In support of this idea, we demonstrate the exclusive occurrence of centrosome amplification and instability in all of the aneuploid tumor cell lines analyzed. All diploid tumors contained centrosomes that were functionally and structurally indistinguishable from those in normal human fibroblasts. Due to the observed differences in centrosomes between these two classes of tumors, we incubated the cells with the microtubule depolymerizing drugs nocodazole and griseofulvin. Our results indicate that the aneuploid tumor cell lines have an increased sensitivity to these reagents and a delay in aster formation and microtubule regrowth. However, microtubule nucleation was initiated from one or two centers in both the diploid and aneuploid cells. These observations support the notion that the integrity of the centrosome plays a central role in the development of aneuploidy. Genes Chromosomes Cancer 27:183-190, 2000. Published 2000 Wiley-Liss, Inc.

Aneuploidy↗

No protection of the porcine kidney by ischaemic preconditioning.

One or more episodes of sublethal ischaemia and reperfusion delay infarct development during subsequent, sustained ischaemia in the heart and skeletal muscle. The present study tested whether or not such ischaemic preconditioning (IP) also protects the kidney. Enflurane-anaesthetized pigs underwent 60 min of right renal vessel occlusion (RVO), followed by 8 h of reperfusion without (placebo group, n = 8) or with three preceding cycles of 10 min RVO and 10 min reperfusion (IP group, n = 8). After 8 h of reperfusion, kidneys were oliguric in both groups (placebo group: 23 +/- 21 ml x h(-1), IP group: 24 +/- 27 ml x h(-1)). A transient polyuric phase occurred in the IP group at 2 h reperfusion. The reperfused kidneys did not excrete inulin, creatinine or urea in both groups, although renal blood flow during reperfusion was similar to baseline. Morphological damage ranged in both groups from single cell necrosis to disseminated patchy necrosis; the number of pyknotic cells tended to be higher in the IP group than in the placebo group (27.0 +/- 7.1 vs. 15.6 +/- 5.6%, n.s.). In anaesthetized pigs, IP did not therefore attenuate renal dysfunction and morphological damage resulting from 60 min of renal normothermic ischaemia followed by 8 h of reperfusion.

Animals↗

Diastolic dysfunction and collagen structure in canine pacing-induced heart failure.

Heart failure is characterized not only by systolic, but also by diastolic dysfunction. The present study tested whether or not diastolic dysfunction is associated with changes in tissue properties and collagen network structure. Heart failure was induced in seven chronically instrumented, conscious dogs by rapid left ventricular pacing (2 50 min(-1)). After 2-5 [mean: 4+/-1 (S.D.)] weeks pacing, heart failure was apparent from clinical symptoms (ascites, cachexia, edema, exercise intolerance) and hemodynamic parameters (significant increases of heart rate and left ventricular end-diastolic pressure and decreases of left ventricular maximal pressure, dP/dtmax and systolic wall thickening). The left ventricle was dilated, as indicated by a decrease of end-diastolic wall thickness (6.3+/-2.0 v 7.2+/-2.1 mm; P<0.05; sonomicrometry). The left ventricular end-diastolic pressure-strain relation (strain: relative change of end-diastolic wall thickness) was obtained during alterations of loading conditions by inferior caval vein and descending thoracic aortic occlusion. The slope of this relation increased from 85+/-20 to 428+/-188 in heart failure, indicating an increase of left ventricular stiffness. Collagen was stained with picrosirius red and analyzed using polarized light microscopy. In heart failure, the collagen volume fraction remained unchanged (1.9+/-1.2 v 2.3+/-1.3%; N.S.), while the nonuniformity of collagen orientation, as reflected by its standard deviation, was increased (11.1+/-1.8 v 6.1+/-0.4 o; P<0.05). The nonuniformity of collagen fiber orientation correlated with left ventricular stiffness [r=0.75].

Animals↗

Calcium responsiveness in canine pacing-induced heart failure.

The specific lesion(s) and potential compensatory alterations of excitation-contraction coupling in heart failure are not clear in detail. We therefore subjected five dogs to 2-5 weeks of rapid ventricular pacing until heart failure developed. Data obtained from these five dogs with pacing-induced heart failure were compared to data from six healthy controls. Under anesthesia, in situ steady state responses of regional contractile function to intracoronary calcium infusion were established. Maximal calcium-activated regional contractile function in dogs with heart failure was 46% less than in controls; calcium sensitivity was unchanged [pCa50 2.55+/-0.31 v 2.82+/-0.17 (+/-s.d.)]. Our data point to a decrease in maximal calcium-activated force and an unchanged calcium sensitivity if an unchanged calcium transient is assumed, or a compensatory increase in calcium sensitivity of failing myocardium if a decreased calcium transient is assumed.

Animals↗

Elastic properties of isolated thick filaments measured by nanofabricated cantilevers.

Using newly developed nanofabricated cantilever force transducers, we have measured the mechanical properties of isolated thick filaments from the anterior byssus retractor muscle of the blue mussel Mytilus edulis and the telson levator muscle of the horseshoe crab Limulus polyphemus. The single thick filament specimen was suspended between the tip of a flexible cantilever and the tip of a stiff reference beam. Axial stress was placed on the filament, which bent the flexible cantilever. Cantilever tips were microscopically imaged onto a photodiode array to extract tip positions, which could be converted into force by using the cantilever stiffness value. Length changes up to 23% initial length (Mytilus) and 66% initial length (Limulus) were fully reversible and took place within the physiological force range. When stretch exceeded two to three times initial length (Mytilus) or five to six times initial length (Limulus), at forces approximately 18 nN and approximately 7 nN, respectively, the filaments broke. Appreciable and reversible strain within the physiological force range implies that thick-filament length changes could play a significant physiological role, at least in invertebrate muscles.

Actin Cytoskeleton↗

Characterization of excitation-contraction coupling in conscious dogs with pacing-induced heart failure.

OBJECTIVE: In isolated cardiac preparations of non-failing hearts from different species, including man, there is a positive force-frequency relation which is reversed into a negative relation in preparation from failing hearts. Whether or not such relations between ventricular function and heart rate hold true in the in situ heart is not clear at present. Mechanical restitution and postextrasystolic potentiation might serve as alternative measures of excitation-contraction coupling. METHODS: Eleven dogs were instrumented with a left ventricular micromanometer, ultrasonic crystals for the measurement of regional wall thickness, two hydraulic occluders around the descending aorta and the inferior caval vein, and left atrial and ventricular pacing leads with a subcutaneous pacemaker. Left ventricular dP/dtmax, as an isovolumic phase index, and systolic wall thickening, as an ejection phase index, were plotted versus heart rate, and heart rate was increased by left atrial pacing from rest to 200 min-1 in increments of 25 min-1. In a subset of dogs, left ventricular filling was controlled and the frequency range expanded by the bradycardic agent UL-FS 49. Measurements were performed in the presence and absence of autonomic blockade (hexamethonium, atropine). Mechanical restitution and postextrasystolic potentiation were determined as normalized dP/dtmax and systolic wall thickening, respectively, of the extra- and postextrasystolic beat versus defined variations of the extrasystolic time interval (250-550 ms). Following control studies, heart failure was induced by rapid left ventricular pacing at 250 min-1 for 20 days +/- 6 (SD) and measurements repeated. Isolated left ventricular trabeculae from non-failing and failing hearts were studied during stimulation at 0.2-4 Hz. RESULTS: Only with filling control and in the absence of autonomic blockade, was there a slightly positive relation between dP/dtmax and heart rate in the control state. Otherwise, the relation of dP/dtmax to heart rate was flat both in the control state and in heart failure. The relation between systolic wall thickening and heart rate in the control state was negative, unless filling was controlled, and it was flat in heart failure. In contrast, the time constants of mechanical restitution and postextrasystolic potentiation were increased significantly with heart failure from 91 +/- 25 (SD) to 164 +/- 13 ms and from 107 +/- 18 to 156 +/- 4 ms, respectively, for dP/dtmax and from 76 +/- 22 to 162 +/- 10 ms and from 101 +/- 17 to 160 +/- 17 ms, respectively, for systolic wall thickening. These time constants were, however, insensitive to UL-FS 49 and autonomic blockade. There was a negative force-frequency relation in left ventricular trabeculae from non-failing hearts at higher calcium concentrations, where it was flat in trabeculae from failing hearts. CONCLUSION: Time constants of mechanical restitution and postextrasystolic potentiation are more sensitive than the steady state relation of ventricular function and heart rate to characterize the impairment of excitation-contraction coupling in heart failure.

Animals↗

Proteomics--a new way for drug target discovery.

The results of the genome projects and the obvious problems with handling, storing and interpretation of generated data pose a lot of pressure on existing strategies in drug target discovery and development of new therapeutic concepts. Genomic data, i.e. DNA/RNA sequences identified by subtractive expression pattern analysis, are not enough per se for a clear identification of a therapeutic target, mainly because proteins and not DNA/RNA are the loci for drug mode-of-action. The effects seen on the gene expression level are only a response to drug effects on the protein level. In addition, there is not always a direct correlation between gene expression and protein expression. Therefore, the major focus of current efforts in drug discovery is the linkage between the genes and the function. One of the most powerful technologies for this purpose is now evolving and has been designated as Proteomics.

Animals↗

Myocardial, skeletal muscle, and renal blood flow during exercise in conscious dogs with heart failure.

The present study characterizes the hemodynamic and neurohumoral responses to moderate treadmill exercise in conscious dogs with pacing-induced heart failure. Seven dogs were instrumented with a left ventricular micromanometer, ultrasonic crystals for the measurement of systolic wall thickening, left atrial and aortic catheters for the injection of colored microspheres and reference withdrawal, respectively, and ventricular pacing leads with a subcutaneous pacemaker. Dogs were run on a treadmill at a speed of 5 km/h. After control studies, heart failure was induced by rapid left ventricular pacing at 250 beats/min for (mean +/- SD) 23 +/- 6 days. In the control state, cardiac output was increased from 4.5 +/- 1.5 to 7.9 +/- 1.4 l/min (P < 0.05 vs. rest). With heart failure, cardiac output was decreased to 2.5 +/- 0.5 l/min at rest (P < 0.05 vs. control state) and was only 3.0 +/- 0.3 l/min during exercise (P < 0.05 vs. control state; not significant vs. rest). Myocardial and, more so, skeletal muscle blood flows at rest were reduced in heart failure; their increases with exercise were attenuated. An increase in renal blood flow during exercise in the control state was no longer seen in heart failure. Increases in plasma catecholamines and lactate during exercise were more pronounced in heart failure. In conclusion, in heart failure, the increase in cardiac output during exercise was largely attenuated. Increased catecholamine levels may have contributed to splanchnic vasoconstriction and preferential distribution of cardiac output into the working skeletal muscle.

Animals↗

Intercurrent complications in chronic alcoholic men admitted to the intensive care unit following trauma.

OBJECTIVE: A chronic alcoholic group following trauma was investigated to determine whether their ICU stay was longer than that of a non-alcoholic group and whether their intercurrent complication rate was increased. DESIGN: Prospective study. SETTING: An intensive care unit. PATIENTS: A total of 102 polytraumatized patients were transferred to the ICU after admission to the emergency room and after surgical treatment. Of these patients 69 were chronic alcoholics and 33 were allocated to the non-alcoholic group. The chronic-alcoholic group. met the DSM-III-R and ICD-10 criteria for alcohol dependence or chronic alcohol abuse/harmful use. The daily ethanol intake in these patients was > or = 60 g. Diagnostic indicators included an alcoholism-related questionnaire (CAGE), conventional laboratory markers and carbohydrate-deficient transferrin. MEASUREMENT AND RESULTS: Major intercurrent complications such as alcohol withdrawal syndrome (AWS), pneumonia, cardiac complications and bleeding disorders were documented and defined according to internationally accepted criteria. Patients did not differ significantly between groups regarding age, TRISS and APACHE score on admission. The rate of major intercurrent complications was 196% in the chronic alcoholic vs 70% in the non-alcoholic group (p = 0.0001). Because of the increased intercurrent complication rate, the ICU stay was significantly prolonged in the chronic-alcoholic group by a median period of 9 days. CONCLUSIONS: Chronic alcoholics are reported to have an increased risk of morbidity and mortality. However, to our knowledge, nothing is known about the morbidity and mortality of chronic alcoholics in intensive care units following trauma. Since chronic alcoholics in the ICU develop more major complications with a significantly prolonged ICU stay following trauma than non-alcoholics, it seems reasonable to intensify research to identify chronic alcoholics and to prevent alcohol-related complications.

Adolescent↗

Therapy of alcohol withdrawal syndrome in intensive care unit patients following trauma: results of a prospective, randomized trial.

OBJECTIVES: To assess the effect of three different alcohol withdrawal therapy regimens in traumatized chronic alcoholic patients with respect to the duration of mechanical ventilation and the frequency of pneumonia and cardiac disorders during their intensive care unit (ICU) stay. DESIGN: A prospective, randomized, blinded, controlled clinical trial. SETTING: A university hospital ICU. PATIENTS: Multiple-injured alcohol-dependent patients (n=180) transferred to the ICU after admission to the emergency room and operative management. A total of 180 patients were included in the study; however, 21 patients were excluded from the study after assignment. INTERVENTIONS: Patients who developed actual alcohol withdrawal syndrome were randomized to one of the following treatment regimens: flunitrazepam/clonidine (n=54); chlormethiazole/haloperidol (n=50); or flunitrazepam/haloperidol (n=55). The need for administration of medication was determined, using a validated measure of the severity of alcohol withdrawal (Revised Clinical Institute Withdrawal Assessment for Alcohol Scale). MEASUREMENTS AND MAIN RESULTS: The duration of mechanical ventilation and major intercurrent complications, such as pneumonia, sepsis, cardiac disorders, bleeding disorders, and death, were documented. Patients did not differ significantly between groups regarding age, Revised Trauma and Injury Severity Score and Acute Physiology and Chronic Health Evaluation II score on admission. In all except four patients in the flunitrazepam/clonidine group, who continued to hallucinate, the Revised Clinical Institute Withdrawal Assessment for Alcohol Scale decreased to <20 after initiation of therapy. ICU stay did not significantly differ between groups (p=.1669). However, mechanical ventilation was significantly prolonged in the chlormethiazole/haloperidol group (p=.0315) due to an increased frequency of pneumonia (p=.0414). Cardiac complications were significantly (p=.0047) increased in the flunitrazepam/clonidine group. CONCLUSIONS: There was some advantage in the flunitrazepam/clonidine regimen with respect to pneumonia and the necessity for mechanical ventilation. However, four (7%) patients had to be excluded from the study due to ongoing hallucinations during therapy. Also, cardiac complications were increased in this group. Thus, flunitrazepam/haloperidol should be preferred in patients with cardiac or pulmonary risk. Further studies are required to determine which therapy should be considered.

Adult↗

Intensive care unit stay is prolonged in chronic alcoholic men following tumor resection of the upper digestive tract.

BACKGROUND: The prevalence of chronic alcohol misuse in patients with oral, pharyngeal, laryngeal or esophageal carcinomas exceeds 60%. No data is available, to our knowledge, on the morbidity and mortality of chronic alcoholics in surgical intensive care units (ICU) following tumor resection. We investigated whether the subsequent ICU stay in chronic alcoholics following tumor resection was prolonged and whether the incidence of pneumonia and sepsis was increased. METHODS: 213 patients with carcinomas of the upper digestive tract were evaluated regarding their drinking habits. Chronic alcoholics met either the DSM-III-R criteria for alcohol abuse or dependence. Conventional laboratory markers and serum carbohydrate-deficient transferrin were determined preoperatively. Major intercurrent complications during ICU stay such as an alcohol withdrawal syndrome, pneumonia and sepsis as well as the frequency of death were documented. RESULTS: Patients did not differ significantly between groups regarding age or APACHE score on admission to the ICU.121 patients were diagnosed as being chronic alcoholics, 39 as being social drinkers and 61 as being non-alcoholics. In chronic alcoholics the frequency of death was significantly increased. Due to the increased incidence of pneumonia and sepsis the ICU stay was significantly prolonged in chronic alcoholics by approximately 8 days. CONCLUSIONS: The increased mortality and morbidity rate demonstrates that chronic alcoholics undergoing major tumor surgery have to be considered as high-risk patients during their postoperative ICU stay. Further studies are required with respect to the immuno-competence of chronic alcoholics and the prevention of alcohol withdrawal syndrome, pneumonia and sepsis in these patients.

APACHE↗

Transfected parvalbumin alters calcium homeostasis in teratocarcinoma PCC7 cells.

Indirect evidence supports a protective role of some EF-hand calcium-binding proteins against calcium-induced neurotoxicity. Little is known about how these proteins influence cytosolic calcium levels. After cloning the parvalbumin cDNA into an expression vector, teratocarcinoma cells (PCC7) were transfected. Parvalbumin-transfected and mock-transfected cells were loaded with the calcium indicator fura-2 and were exposed, in the same dish, to different concentrations of the calcium ionophore A23187 or to KCI. The results show that parvalbumin-transfected PCC7 cells had much better calcium buffering capacity than control cells.

Calcimycin↗

Sternomastoid rhabdomyoma mimicking a thyroid nodule.

A case is presented of a euthyroid male in whom a right thyroid mass was discovered. Physical displacement of the right thyroid lobe by a mass determined on CT scan. Scintigraphy and ultrasound showed the mass to be separate from the thyroid. Fine needle aspirations did not predict the tumor. Surgical removal of an adult rhabdomyoma was uneventful. This case and review of the literature demonstrate the rare presentation of a rhabdomyoma as a suspected thyroid nodule.

Diagnostic Errors↗