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Biomedical subjects

T Kruse

Publications and source records attributed to T Kruse.

At least 19 recordsLinked to original sources

The influences on human longevity by HUMTHO1.STR polymorphism (Tyrosine Hydroxylase gene). A relative risk approach.

A new method based on the recently developed relative risk approach is introduced, and applied to data from Italian centenarian study (965 subjects aged from 13 to 109 years old) for investigating influences on longevity by Tyrosine Hydroxylase (TH) gene variability. The strategic parameterization enables the model to disentangle the various ways by which HUMTHO1.STR alleles (alleles 6, 7, 8, 9, 10*, 10, as defined according to the number of repeats) may contribute in reducing or increasing the hazard of death with different patterns of influences. Among all the alleles, we have found that allele 10* (10 imperfect repeats) shows a remarkable dominant and beneficial effect that reduces the log hazard of death in an additive manner. The results confirm that HUMTHO1.STR polymorphism is involved in the modulation of human longevity.

Adolescent↗

Mutations in the ALK-1 gene and the phenotype of hereditary hemorrhagic telangiectasia in two large Danish families.

Mutations in the ENG gene on chromosome 9 (HHT 1) and in the ALK-1 gene on chromosome 12 (HHT 2) have been reported as causes of hereditary hemorrhagic telangiectasia (HHT). HHT 1 has been correlated with a higher prevalence of pulmonary arteriovenous malformations than HHT 2. Other distinct phenotype-genotype correlations have not been described. The prevalence of HHT in the county of Fyn, Denmark, was 15.6 per 100,000 on January 1, 1995. All living patients and their first-degree relatives were invited to attend a detailed clinical examination and blood was drawn for mutation analysis. In two families mutations were identified in exon 8 of the ALK-1 gene. In family 6 we found a T1193A mutation. In this family a high prevalence of PAVM and severe GI bleeding was documented, while in family 8 with a C1120T mutation no individuals with PAVM were identified and only one patient had a history of severe GI bleeding. No mutations in the endoglin locus were found in either family.

Activin Receptors↗

Investigation on molar mass, solubility and enzymatic fragmentation of xylans by multi-detected SEC chromatography.

Four xylan samples from different origin were investigated, using a multi-detector, size exclusion, chromatographic system with two chromatographic column sets and mobile phases differing in the DMSO:water ratio. Molar mass distribution could be analysed best using a mobile phase of DMSO:water (90:10) with addition of 0.05 M LiBr, a system offering good solubilisation of the polymers and a proper chromatographic separation. SEC analysis in aqueous systems provided information on solubility and aggregation of xylans. A comparison of UV- and RI-signals in different systems gave further information on lignin impurities, which in some cases were involved in aggregation phenomena. Both analytical systems were applied to study the enzymatic fragmentation of xylans. Combining the information derived from the two systems can differentiate between the enzymatic degradation of the well-dissolved and the associated polymer fractions.

Bromides↗

C-signal: a cell surface-associated morphogen that induces and co-ordinates multicellular fruiting body morphogenesis and sporulation in Myxococcus xanthus.

In Myxococcus xanthus, morphogenesis of multicellular fruiting bodies and sporulation are co-ordinated temporally and spatially. csgA mutants fail to synthesize the cell surface-associated C-signal and are unable to aggregate and sporulate. We report that csgA encodes two proteins, a 25 kDa species corresponding to full-length CsgA protein and a 17 kDa species similar in size to C-factor protein, which has been shown previously to have C-signal activity. By systematically varying the accumulation of the csgA proteins, we show that overproduction of the csgA proteins results in premature aggregation and sporulation, uncoupling of the two events and the formation of small fruiting bodies, whereas reduced synthesis of the csgA proteins causes delayed aggregation, reduced sporulation and the formation of large fruiting bodies. These results show that C-signal induces aggregation as well as sporulation, and that an ordered increase in the level of C-signalling during development is essential for the spatial co-ordination of these events. The results support a quantitative model, in which aggregation and sporulation are induced at distinct threshold levels of C-signalling. In this model, the two events are temporally co-ordinated by the regulated increase in C-signalling levels during development. The contact-dependent C-signal transmission mechanism allows the spatial co-ordination of aggregation and sporulation by coupling cell position and signalling levels.

Bacterial Proteins↗

[Epidermolysis bullosa simplex: genotype-phenotype correlation in Danish patients].

Epidermolysis bullosa simplex (EBS) is a group of autosomal dominant inherited skin disorders caused by mutations in the keratin genes K5 or K14. We examined five Danish families with EBS-Weber-Cockayne (WC) or EBS-Koebner (K) and two sporadic cases of EBS-Dowling-Meara (DM) in order to investigate the mutational spectrum and evaluate the genotype-phenotype correlation in Danish patients. Three new K14 mutations, one new and one previously described K5 mutation were identified by DNA sequence analysis. The positions of the EBS-DM mutations were consistent with previous studies, whereas the EBS-WC and EBS-K mutations were found in regions of the keratin genes not typically associated with this type of EBS mutations. In conclusion, we found a strict genotype-phenotype correlation. Furthermore, we found that the position of the mutation in the keratin gene is not the only determinant for severity of the disease; the nature of the amino acid substitution should also be considered when predicting the severity of the EBS disorder.

DNA Mutational Analysis↗

[Cell death in inflammatory heart muscle diseases--apoptosis or necrosis?].

Cell death can be induced by 2 different mechanisms: necrosis and apoptosis. Necrosis, on the one hand, is usually caused by unphysiological stress factors such as hyperthermia or hypoxia, apoptosis, on the other hand, is part of the normal organ development and controls for example immune responses. Morphologically, necrosis is characterized by swelling of cells and their organelles leading to the disruption of the cell membrane, which in turn causes an inflammatory reaction in the surrounding tissue. Morphological and biochemical criteria (Figure 1, Table 1) of apoptosis are the condensation of chromatin leading to the development of apoptotic bodies or membrane-enclosed vesicles containing oligonucleosomal DNA fragments. Important diagnostic tools of cell death (Table 2), such as the TUNEL test (Figure 2) or gel electrophoresis of extracted DNA (Figure 3) are based on the above mentioned biochemical characteristics, but a reliable differentiation of apoptotic versus necrotic processes is not always possible. Experimental studies in animals and studies in various diseases of the cardiovascular system were able to show that apoptosis in myocytes can be induced, an issue that has long been discussed controversially. Ischemia, reperfusion, and myocardial infarction were also shown to lead to apoptosis in cardiomyocytes, whereas cell destruction was caused mainly by necrosis. Several authors (Table 3) demonstrated apoptotic indices in cardiomyocytes of patients with dilatated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and patients with acute infarction from 0.25 to 35% by the use of the TUNEL test. Others were able to demonstrate an elevated expression of Fas-receptor in cells of atheroslerotic plaques in patients with atherosclerosis and high indices of apoptotic cardiomyocytes in patients with chronic heart failure. We investigated endomyocardial biopsies of patients with inflammatory cardiomyopathy, DCM without inflammatory reaction but the presence of adenoviral or cytomegaloviral genome and idiopathic DCM using the TUNEL test. The percentage of apoptotic cardiomyocytes in biopsies of patients with DCMi was 1.03 and in biopsies of patients with adenoviral genome 0.25, whereas in all other groups no apoptosis was found. If apoptosis plays a major role in myocardial diseases such as heart failure, arrhythmia and others, blocking this mechanism will have to be considered as a therapeutical strategy. Therefore, studies on the extent of apoptotic processes in diseased versus healthy cardiac tissue are of great importance.

Animals↗

[Angina pectoris in leiomyoma].

A 72-year-old patient presented himself with typical symptoms of coronary heart disease and was scheduled for invasive diagnostic procedures. Cardiac risk factors were smoking and arterial hypertension. The physical examination was inconspicious. In the laborchemistry a hemoglobin of 79 g/l with a mean corpuscular volume of 63 fl and a mean corpuscular hemoglobin of 20 pg was conspicuous. The serum iron was with 42 micrograms/dl in the lower norm. Transferrin, bili-rubin and lactate dehydrogenase were normal. Then in the gastrointestinal investigations he was diagnosed with a leiomyoma of the intestine that led to chronic anaemia and additionally to chest pain characteristic for angina pectoris. After the removal of the tumor and normalization of hemoglobin this patient was free from symptoms of the disease. The coronary angiography revealed a complex stenosis of the right coronary artery with collaterales and not significant stenosis both of the left coronary arteries. In patients with angina pectoris anaemia as the possible and only cause of angina ought to be verified. It is therefore necessary after normalization of hemoglobin and clarification of the cause for the anaemia to apply a test for coronary ischemia.

Aged↗

Interactions between pacemakers and security systems.

Electromagnetic fields arising from a variety of different sources have been shown to interfere with normal pacemaker function. This study evaluated the possible interactions between two modern security systems and different pacemaker types. Fifty-three patients (27 single chamber pacemakers, 25 dual chamber pacemakers) have been tested routinely for their pacemaker function. Thirty-eight patients presented with unipolar sensing and 15 with bipolar sensing. The patients were asked to walk through an installed security system, an antitheft device, and electromagnetic access device with different field strengths while a six-channel ECG monitored the patients. The pacemaker systems were first measured in their basic programmed modes, then the intervention frequency was changed to 100/min and, thereafter, the maximum sensitivity without T wave oversensing was added. In the security system with the highest field strength (2,700 mA/m), a pacemaker malfunction could be observed in 13% of the monitored patients. In one case, a pacemaker (VVIR) switched to ventricular safety pacing (VOO mode). In the security system with the lower field strength (1,600 mA/m) we found a pacemaker malfunction in 4% of the tested patients. In the antitheft device (50 mA/m), in the electromagnetic access device (300 mA/m), and in pacemaker systems with bipolar sensing, none of these dysfunctions were observed. Phantom programming as described previously did not occur in any of the systems. Persons who are often in the vicinity of security systems should be equipped with a bipolar pacemaker system. Our findings indicate that patients with pacemakers should avoid contact with security systems.

Adult↗

Lack of pharmacokinetic interaction between tiagabine and erythromycin.

This study was conducted to investigate the effects on the pharmacokinetics of tiagabine at steady state when coadministered with therapeutic doses of erythromycin. Tiagabine doses of 4 mg twice daily and erythromycin doses of 500 mg twice daily were administered for 4 days in an open-label, crossover, two-period interaction trial in 13 healthy volunteers. No statistically significant differences in maximum plasma concentration (Cmax), area under the concentration-time curve (AUC tau), or half-life (t1/2) of tiagabine were observed when tiagabine was administered alone or in combination with erythromycin. A statistically significant treatment effect was observed for time to maximum concentration (tmax; 0.72 after tiagabine alone versus 0.56 hours after administration with erythromycin). No statistically significant differences were seen between men and women except in tmax and t1/2; these differences were thought to be of no clinical significance. The decrease in tmax seen in women in this study is interpreted as a differential effect of erythromycin on gastric emptying of females and not as an interaction between tiagabine and erythromycin. No changes in laboratory parameters or vital signs were attributable to trial medication. The most common treatment-emergent adverse events that were possibly related to trial medication were central nervous system effects (e.g., headache, dizziness); all adverse events were transient, the majority were rated mild in severity, and did not require additional action. Coadministration of erythromycin in healthy subjects does not significantly affect the pharmacokinetics of tiagabine at the doses tested.

Adult↗

[Transmyocardial laser revascularization and rehabilitation].

Transmyocardial laser revascularization (TMLR) is a new technique for patients with CAD or heart attack to revascularize ischemic areas of the myocardium in which the localisation or the condition of the vessels does not allow bypass grafting. This study shows the results in observation of patients before and during the first 3 months after TMLR. Of 110 patients operated on from 1994 to 1996, 86 were evaluated for well being (quality of life), using NYHA- and CCS-classification, stress test and nitril-scintigraphy at rest and under stress conditions. 51 patients, of whom 11 were females, underwent TMLR combined with coronary artery bypass graft (CABG). 35 male patients were treated singularly with TMLR. The average age in both groups was 59 years (+/- 23). All patients were subject to phase I rehabilitation in specialised institutions after being mobilised in the operating hospital. The evaluations took place on the day of admission to the hospital prior to surgery, within 10 days after surgery and 3 months following. The average stay in the rehabilitation-institution was between 4 and 6 weeks. Our findings demonstrate that both groups profited from the procedures, while the TMLR/CABG group showed a faster recovery and a better outcome. In comparison to 57% of the TMLR group, 85% of the patients in the TMLR/CABG group reported an improvement ranging from good to significant in quality of life assessments. The TMLR/CABG rated from an average of initially 3.4 (+/- 0.6) to 2.1 (+/- 0.8) after 3 months at NYHA- and 3.3 (+/- 0.7) to 1.7 (+/- 0.8) at CCS-classification. The TMLR group rated from 3.6 (+/- 0.5) to 2.4 (+/- 0.8) in NHYA- and from 3.4 (+/- 0.5) to 1.9 (+/- 0.7) on the CSS-scales. A remarkable improvement was noted in the stress test with an increase in power and endurance from 21 to 89 watts for the combined group and 8 to 81 watts for the TMLR treated patients, who generally recovered more slowly. The perfusion scan showed the same tendencies as previously reported but in some cases the results were not congruent with other findings. Overall, our findings indicate that there is a benefit for terminally symptomatic CAD patients after TMLR, but an observation period of 3 months does not allow for final conclusions on this matter. Rehabilitation seems to be of value for TMLR-patients since they have shown a markedly better performance following 3-month treatment, but further data from clinical randomised trials are needed to determine the influence of TMLR with short- and long-term rehabilitation on the prognosis of the disease.

Adult↗

Papillary muscle injury after blunt chest trauma.

In many cases blunt chest trauma involves cardiac lesions, such as pericardial effusion, aneurysma dissecans, or valvular rupture. Early diagnosis with routine transthoracic and/or transesophageal echocardiography is essential to prevent a fatal outcome. In the case reported, a previously healthy 68-year-old woman fell 7 meters from the roof of a barn and sustained blunt injury to the chest as well as fractures of the face. Physical examination revealed a systolic murmur at the cardiac apex, and chest x-ray film showed a severe pulmonary edema. Transesophageal echocardiography demonstrated a ruptured anterolateral papillary muscle with fourth degree mitral insufficiency. An immediate mitral valve replacement was necessary.

Accidental Falls↗

[Image transmission between hospitals. Technical and clinical testing of the equipment for digital image transmission between hospitals via the ordinary telephone network].

A standard PC-based equipment--"Multiview Photophone"--for two-way image conference between hospitals by means of digital images transmitted through ordinary telephone lines was tested. The technical and visual quality of scanned and transmitted pictures proved to be satisfactory, and ease of handling the equipment and transmission times were acceptable. The clinical test was made by image conferences between a neurological department in a general hospital and a neurosurgical department in a university hospital. CT-scans concerning 39 patients in a prospective series, for whom specialist advice from the neurosurgical department was found necessary, were transmitted. Four of nine acute patients were saved an "unnecessary" transferral to the neurosurgical department. The 30 elective patients were all found to benefit from the two-way conferences, since the decision time was reduced and the quality of information given to the patients and their relatives was improved.

Computer Communication Networks↗

Directions in antihypertensive treatment--our future from the past.

Future directions in antihypertensive treatment will rely on our present experience with antihypertensive drugs, on new concepts of cardiovascular regulation and on novel antihypertensive agents. At present, we seek early detection of hypertension; treatment should focus on normalization of blood pressure, the reversal or prevention of left ventricular hypertrophy, associated coronary artery disease and on the prevention of, or reparation of, myocardial fibrosis and microangiopathy. Therefore, combination therapy is advisable in severe cases, and any monotherapy should focus on the pharmacological principles compatible with these goals. ACE inhibitors and calcium antagonists appear to meet these requirements. There are, in addition, novel drugs i.e. angiotensin II receptor antagonists and renin inhibitors, as well as therapeutic stimulation of endothelial nitric oxide by L-arginine, the inhibition of endothelin-1 mediated vasoconstriction, and potassium-channel openers. All are examined in this contribution to delineate the perspectives in antihypertensive therapy.

Antihypertensive Agents↗

[Retrospective studies and prospects of therapy for hypertension].

Future trends in hypertensive treatment have to rely on our past and present experience with antihypertensive drugs as well as on emerging concepts of blood pressure regulation, on which some new drugs in the "pipeline" are based. Early detection of hypertension, before organ manifestations particularly in the heart, the kidney and the vessels occur, remain mandatory since in most of the patients with mild and moderate hypertension the high blood pressure is not diagnosed at all or treated inadequately. Prevention of cardiac, vascular, renal or metabolic complications has always been better for the patient and less costly than their repair or reparation. Our present treatment goals have often not reached far enough. Normalisation of blood pressure demonstrates only surrogate efficacy of our treatment. Our ultimate goal has to be improvement of total or cerebrovascular or cardiovascular and cardiac mortality. Important steps on that road are the prevention or reparation of cardiac hypertrophy, of the increased extracellular matrix and collagen deposition, the conservation of vascular integrity including both coronary and systemic microangiopathy and macroangiopathy. For the patient this means integrated care of his associated disorders that is of coronary artery disease, diabetes mellitus, lipid disorders, overweight and the metabolic syndrome. True health efficacy (= reduction of total or cerebro- and cardiovascular mortality) has been demonstrated so far only by blood pressure reduction with diuretics (thiazides) and beta-blockers in long term studies, whereas sufficient surrogate efficacy, the lowering of blood pressure, has been demonstrated with almost all the others drugs either in mono- or in combinationtherapy. Together with ACE-inhibitors, which have demonstrated their prognostic value in patients with heart failure of different causes, thiazides (as the most representative diuretic) and betablockade can be considered first line drugs in the treatment of hypertension. Long-term mortality trials for ACE-inhibitors in hypertension are needed, however, to prove that the anticipated benefit from the heart failure megatrials can also be taken for granted for hypertensive patients without coronary artery disease as well. All other drugs should not or not yet be considered first line medication, although treatment behavior in the US and in Europe shows wide-spread use of calcium antagonists in short- and long-acting dihydropyridine type hypertensive patients. No peer reviewed journal has so far published a randomized double-blind trial with the endpoint of total or cardiovascular mortality in hypertension using calcium antagonists. A recent case control study, as well as the preliminary data from MIDAS and GLANT, for which event rates are available in abstract form, suggest that short acting calcium-antagonists of the dihydropyridine type, though controlling blood pressure well, are not reducing mortality but show a trend to increase cardiovascular events particularly when given in higher doses. In contrast the unpublished data from a Chinese megatrial with dihydropyridines (STONE) demonstrate effective blood pressure reduction and benefit in mortality in a population that differs from patients in Europe and in the USA because of the low prevalence of coronary artery disease. No randomized, double blindly acquired data on mortality as the primary end of antihypertensive treatment are yet available for verapamil, diltiazem and the new class of longer acting calciumantagonists. Only when speculating from trials with calcium antagonists in coronary artery disease e.g. the DAVIT II study, one could imagine so far that prognostic benefit may be expected from drugs that do not or very little activate the adrenergic and the renin-angiotensin-aldosterone system and the baroreceptors and reduce or at least maintain heart rate. The need for double blind, randomized trials with the different Ca-antagonists is obvious, before a further w

Antihypertensive Agents↗