Biomedical subjects
W Klein
Publications and source records attributed to W Klein.
Fixation monitoring during radiation therapy for subfoveal neovascularization.
PURPOSE: The aim of the study was to determine movement of the fovea during each irradiation session by monitoring movement of the cornea. Knowing the extent of foveal deviation permits minimization of the field size. METHODS: (1) Eye movement was monitored in 10 patients during irradiation. A TV camera with an attached fixation light was installed 3 cm away from the cornea of the treated eye. The fixation light was positioned at a 10 degrees angle to the TV camera on the opposite side of the gantry, resulting in a 90 degrees angle between the optical axis of the eye and the irradiation beam. (2) The relationship between movement of the anterior and posterior eye segments of 10 volunteers was examined using a scanning laser ophthalmoscope (SLO). Volunteers were asked to fix their gaze on positioning lights installed in the SLO. Gaze movements of the anterior and posterior eye segments were recorded simultaneously. RESULTS: (1) The patients' ability to retain fixation differed interindividually. The median corneal deviation during 10 irradiation sessions was 1 mm mediolaterally and 0.7 mm craniocaudally. (2) Deviation of the fovea could be determined by monitoring deviation of the cornea. Measured by SLO, the correlation between movements of the anterior and posterior eye segments was 1:0.9 horizontally and 1:1.5 vertically. CONCLUSION: (1) Irradiation field size can be reduced, depending on the patient's fixation stability. (2) If monitoring reveals a foveal deviation beyond the 95% isodose, irradiation can be interrupted.
Etiology and response to drug treatment in heart failure.
Clinical trials in heart failure (HF) tend to randomize patients according to demographic characteristics and severity of left ventricular dysfunction, without taking account of the precise diagnosis. This article reviews results from recent trials suggesting that the etiology of HF, and particularly whether it is ischemic or nonischemic, may influence the long-term prognosis and the response to treatment. Some studies, but not all, suggest that nonischemic HF has a better prognosis than ischemic HF. The data on the benefits of angiotensin-converting enzyme inhibitors in ischemic versus nonischemic HF are conflicting. Carvedilol, and recently, bisoprolol have been shown to reduce mortality in ischemic and nonischemic HF, whereas metoprolol has, to date, improved prognosis only in dilated cardiomyopathy. Better responses to digoxin, amlodipine and amiodarone have been reported in non-ischemic HF. There is at present no clear explanation for the apparent therapeutic differences between ischemic and nonischemic HF. Absence of a rigorous definition of "nonischemic HF" in many studies makes interpretation of the results difficult. Further studies to clarify the effects of etiology of HF on the response to treatment could be particularly important for preventing progression to more advanced stages, in which any type of drug therapy may have limited value in prolonging survival. An individualized therapeutic approach, based on etiology of HF and possibly other factors such as plasma drug levels or the levels of neurohormones, could result in major progress in treating HF patients.
EDRF does not mediate coronary vasodilation secondary to simulated ischemia: a study on KATP channels and N omega-nitro-L-arginine on coronary perfusion pressure in isolated Langendorff-perfused guinea-pig hearts.
Several authors have alluded to the possible involvement of EDRF (NO) in ischemia-induced coronary artery dilation. Alternatively, it has been suggested that opening of ATP-dependent K channels could play a key role in this context. We studied the effects of sulfonylureas and NG-nitro-L-arginine (LNNA), a specific inhibitor of endothelial NO (EDRF) synthesis, on ischemia-induced coronary vasodilation in isolated Langendorff-perfused guinea pig hearts arrested with 15 mM KCl in normal Tyrode, and isolated pig coronary arteries precontracted with 43 mM KCl. In Isolated Langerdorff-perfused guinea pig heart, when hypoxia was simulated by switching 100% O2 in the perfusate to 100% N2, coronary perfusion pressure (CPP) fell from 90 cm H2O by 45 +/- 5 cm H2O. In the presence of LNNA, a specific inhibitor of NO synthetase in endothelial cells, CPP dropped by 44 +/- 6 cm H2O (n = 6; +/- SEM, no statistically significant). On biochemical simulation of ischemia (addition of iodoacetate [IAA]), CPP dropped 40 +/- 6 cm H2O, and in experiments performed under the same conditions but in the presence of LNNA, CPP dropped by 38 +/- 5 cm H2O (n = 6; +/- SEM; not statistically significant). When ischemia was simulated metabolically by equimolar replacement of 10 mM glucose with 2-deoxyglucose (DOG), an inhibitor of glycolysis CPP decreased by 24 +/- 1 cm H2O (n = 6; +/- SEM) after 15 minutes. This fall in CPP was almost prevented by 20 microM glibenclamide, whereas in the presence of 20 microM LNNA the DOG-induced decrease in CPP was not significantly inhibited, and CPP decreased by 22 +/- 2.6 cm H2O (n = 6; +/- SEM). In isolated pig coronary artery rings, maximal tension, achieved by depolarizing the smooth muscle cells by 43 mM KCl, decreased by 37 +/- 7% upon simulated hypoxia by replacing 100% O2 with 100% N2 in the perfusate (n = 6; +/- SEM) in arteries with intact endothelium. In arteries without endothelium, maximal tension also dropped by 35 +/- 6% (not statistically significant). In the same experiments the decrease in tension could be largely inhibited in the presence of 50 microM glibenclamide. Our results clearly show that in isolated perfused guinea pig hearts, as well as in isolated pig coronary arteries, EDRF does not play a decisive role in the coronary dilatory response to hypoxia and ischemia.
Observations on the effect of glibenclamide on noninvasive clinical parameters of myocardial ischemia.
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Evaluation of ROM1 as a candidate gene in generalised progressive retinal atrophy in dogs.
Generalised progressive retinal atrophy (gPRA) is a heterogeneous group of hereditary diseases causing degeneration of the retina in dogs and other animals. The genetic origin is unknown in most cases. We have screened the coding sequence of the ROM1 gene for disease causing mutations in Tibetan Terriers, Miniature Poodles, Dachshunds and Chesapeake Bay Retrievers by single strand conformation polymorphism analysis (SSCP). Two polymorphisms have been identified by sequencing, one in exon 1 in all examined breeds (position 210: G-->A; Gly40Arg and position 252: G-->T; Ala53-Ser). Another polymorphism was present in exon 2 (position 1150: C-->T and position 1195: C-->T) segregating in Miniature Poodles. None of these polymorphisms were cosegregating with gPRA rendering a disease causing mutation in the ROM1 gene unlikely.
Perioperative ventricular dysrhythmias in patients with structural heart disease undergoing noncardiac surgery.
UNLABELLED: Noncardiac surgical patients with preoperative ventricular dysrhythmias and structural heart disease may be at increased risk of adverse cardiac outcome. We evaluated how anesthesia and surgery affect the course of ventricular dysrhythmias (premature ventricular beats [PVB] and repetitive forms of ventricular beats [RFVB]: couplets and nonsustained ventricular tachycardia) noted preoperatively in patients with structural heart disease and whether the frequency of ventricular dysrhythmias affects cardiac outcome. In a prospective study, 70 patients scheduled for noncardiac surgery with structural heart disease and RFVB on preoperative Holter electrocardiogram were continuously monitored intraoperatively and for 3 days postoperatively. Holter tracings were analyzed for rhythm, medians of total PVB and RFVB per hour. Preoperative RFVB recurred intraoperatively in 35% and postoperatively in 87% of patients. There was a significant intra- and postoperative decrease of total PVB per hour (P < 0.05) and RFVB per hour (P < 0.01). Frequency of ventricular dysrhythmias in the five patients suffering adverse outcome (unstable angina, n = 1; congestive heart failure, n = 4) did not significantly differ from those with good outcome. We conclude that in noncardiac surgical patients with structural heart disease and RFVB, the frequency of ventricular dysrhythmias is not associated with adverse cardiac outcome. IMPLICATIONS: Using continuous electrocardiogram monitoring, we investigated whether the frequency of perioperative ventricular dysrhythmias independently affects outcome in patients with structural heart disease undergoing noncardiac surgery. The incidence of perioperative dysrhythmia in patients with an adverse outcome (8%) did not differ from those with a good outcome.
The heart rate performance curve and left ventricular function during exercise in patients after myocardial infarction.
PURPOSE: The aim of the study was to investigate the heart rate turn point (HRTP) in the time course of the heart rate performance curve (HRPC) in patients after myocardial infarction, and the relationship between the HRTP, the left ventricular function, and the second lactate turn point (LTP2). METHODS: We studied the degree and the direction of the HRPC and the left ventricular ejection fraction (LVEF) in 49 male patients 57 +/- 8 d after their first posterior wall infarction (MI). An incremental cycle ergometer test was performed and three phases of energy supply were defined (I: aerobic; II: aerobic-anaerobic transition; III: anaerobic) via blood lactate LA concentration. HRTP and LVEF-turn points (LVEFTP) were assessed by linear turn point analysis. The degree and direction of the deflection of HRPC were described as factor k (k > 0.1: downward deflection; -0.1 < k < 0.1: linear time curse; k < -0.1: upward deflection). The LVEF was determined by RNA. The difference between Pmax and LTP2 was calculated for LVEF (delta LVEF). RESULTS: An HRTP could be found in 44 and a LVEFTP in 47 cases. The HRTP occurred at 85 +/- 17 Watt (W), which correlated (r = 0.95; P < 0.001) with the LTP2 (84 +/- 17 W) and the LVEFTP (84 +/- 17 W, r = 0.93; P < 0.001). From LTP2 to Pmax a significant decrease in LVEF was found. There was a correlation between the percentage of HRmax at the HRTP and k (r = 0.70), as well as delta LVEF (r = 0.56). CONCLUSIONS: To prevent myocardial overloading, it seems to be useful to determine the HRTP, which indicate the workload where LVEF decreases.
Myocardial infarction caused by an aneurysm of the left main coronary artery without evidence of Kawasaki disease.
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13th Meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): alternative testing methodologies for ecotoxicity.
There is growing public pressure to minimize the use of vertebrates in ecotoxicity testing; therefore, effective alternatives to toxicity tests causing suffering are being sought. This report discusses alternatives and differs in some respects from the reports of the other three groups because the primary concern is with harmful effects of chemicals at the level of population and above rather than with harmful effects upon individuals. It is concluded that progress toward the objective of minimizing testing that causes suffering would be served by the following initiatives--a clearer definition of goals and strategies when undertaking testing procedures; development of alternative assays, including in vitro test systems, that are based on new technology; development of nondestructive assays for vertebrates (e.g., biomarkers) that do not cause suffering; selection of most appropriate species, strains, and developmental stages for testing procedures (but no additional species for basic testing); better integrated and more flexible testing procedures incorporating biomarker responses, ecophysiological concepts, and ecological end points (progress in this direction depends upon expert judgment). In general, testing procedures could be made more realistic, taking into account problems with mixtures, and with volatile or insoluble chemicals.
[Diagnosis of heart failure].
Heart failure is a clinical syndrome caused by various etiologic factors. The physician should undertake every effort to identify potentially reversible causes that lead to heart failure. Therefore one should go through various non-invasive as well as invasive diagnostic procedures. The diagnostic tests can be helpful in identifying patients with a poor prognosis.
[Drug therapy of chronic heart failure].
Prevention of disease leading to cardiac dysfunction, improvement of quality of life and reduction of mortality are the primary objectives in the treatment of chronic heart failure. The therapeutic possibilities are various, including general advices, pharmacological therapy and surgical interventions. Standard medical treatment of systolic cardiac dysfunction contains ACE inhibitors, diuretics and cardiac glycosides. Beta-blocking agents, oral anticoagulation and antiarhythmic drugs can be used in addition. A therapeutic management of chronic heart failure tailored to the individual patient has nowadays become available due to multiple treatment options.
[Cardiac manifestations of Lyme borreliosis with special reference to contractile dysfunction].
Borrelia burgdorferi infection (BBI) is suggested to be associated with dilated cardiomyopathy (IDC). Stanek et al. were able to cultivate Borrelia burgdorferi (BB) from myocardial biopsy tissue of a patient with longstanding dilated cardiomyopathy. Here we present a study in which we examined the effect of standard antibiotic treatment on the left ventricular ejection fraction (LV-EF) in patients with dilated cardiomyopathy associated with BBI. In this study we assessed the serum (IgG, IgM ELISA; Western Blot) and the history of 46 IDC-patients with specific respect spect to BBI (mean LV-EF: 30.4 +/- 1.3%; measured by cardiac catheterisation and echocardiography--length-area-volume method). All 46 patients received standard treatment for dilated cardiomyopathy: ACE-inhibitors, digitalis and diuretics. 11 (24%) patients showed positive serology and a history of BBI; 9 of these also had a typical history of tick bite and erythema chronicum migrans (ECM) and/or other organ involvement, 2 had no recollection of tick bite or EMC, but showed other BB-associated disorders (neuropathy, oligoarthritis). These 11 patients with BBI received standard antibiotic treatment with intravenous ceftriaxone 2 g bid for 14 days. 6 (55%) recovered completely and showed a normal LV-EF after 6 months, 3 (27%) improved their LV-EF and 2 (18%) did not improve at all. This amounts to 9 (82%) recovery/improvement in the BB-group. The 35 patients who did not show positive serology or a history of BBI did not receive antibiotic treatment. In this group without BBI 12 (26%) showed recovery/improvement following the standard treatment of dilated cardiomyopathy (see above). Our results indicate that BBI could play a decisive role in the development of dilated cardiomyopathy, especially in a geographical region as Graz, where BB is endemic. While aware of the small number of BB-patients in this study, we nevertheless conclude that, in a remarkable number of patients with signs of BBI, dilated cardiomyopathy could be reversed and LV-EF improved upon standard antibiotic treatment.
[Protection against myocardial ischemia by nisoldipine--an experimental study with valinomycin K-sensitive microelectrodes].
It has been shown that dihydropyridines exert a cardioprotective effect during experimental ischemia. This effect is reflected in a reduced K-efflux from the ischemic tissue. Recently we have shown that ischemic K-efflux is largely mediated by ATP-dependent K-channels. Using K-selective microelectrodes we studied the effect of nisoldipine on K-efflux during simulated ischemia (guinea pig papillary muscle immersed in paraffin oil; normal Tyrode solution, HEPES buffered, 100% O2-equilibrated, 37 degrees C). While ischemic K-efflux was Ca-dependent in stimulated preparations, it was independent of extracellular Ca in resting preparations. Our results show that nisoldipine leads to an inhibition of ischemic K-efflux during simulated ischemia. In resting preparations this inhibition is not a direct Ca-antagonistic effect, since withdrawal of extracellular Ca does not inhibit ischemic K-efflux but nisoldipine does. We suggest a direct effect of nisoldipine on the KATP channel which is mainly responsible for ischemic K-loss.
[Survival after poisoning due to intake of ten-times lethal dose of acetone].
HISTORY AND ADMISSION FINDINGS: A 42-year-old man was found unconscious, having swallowed 800 ml of an unknown liquid with suicidal intent. On admission, when his breath smelled strongly of acetone, he was intubated and ventilated, and several gastric lavages were performed. INVESTIGATION: The serum acetone concentration was 2000 mg/l, that in urine 2300 mg/l. The residue of the liquid in the bottle from which he had drunk was pure acetone. DIAGNOSIS, TREATMENT AND COURSE: Acetone poisoning having been established he was carefully hyperventilated, haemofiltration was performed over 16 hours and forced diuresis with high fluid intake was undertaken. His condition quickly improved and he was extubated after 14 hours. There was no subsequent evidence of organ damage. Repeated measurements of acetone in blood and urine indicated its elimination with a half-life of 11 hours. Literature search revealed that this was the second highest concentration of acetone in blood and urine followed by survival. CONCLUSION: This case demonstrates that, after acute acetone poisoning with an amount ten times the lethal dose, intensive care and rapid elimination of acetone can achieve sequelae-free survival.
Fragmin in unstable angina pectoris or in non-Q-wave acute myocardial infarction (the FRIC study). Fragmin in Unstable Coronary Artery Disease.
The safety and efficacy of weight-adjusted, low-molecular-weight heparin (dalteparin) was compared with that of unfractionated heparin during 6 days of treatment in 1,482 patients with unstable angina or non-Q-wave myocardial infarction. Dalteparin, at a lower dose, was compared with placebo during the following 39 days. No significant outcome difference was found between the 2 treatment regimens in the unblinded phase (days 1-6). Between days 6-45 the rates of death, myocardial infarction, and recurrence of angina were comparable between the active treatment and placebo groups. The results suggest that twice-daily administration of subcutaneous dalteparin may be an effective and safe alternative to unfractionated heparin during the acute phase of unstable coronary artery disease. Prolonged treatment with dalteparin at a lower once-daily dose did not confer any additional benefit over aspirin (75-165 mg) alone.
Aberrant p21(CIP1/WAF1) protein accumulation in head-and-neck cancer.
p21(CIP1/WAF1) is an inhibitor of cyclin-dependent kinases and, in normal tissues including squamous epithelia, has been associated with cell-cycle exit and differentiation. As shown in this pilot study, however, the majority of head-and-neck squamous-cell carcinomas (HNSCC) display aberrant p21(CIP1/WAF1) expression: of 42 tumors analyzed by immunohistochemical staining, 28 (67%) over-expressed the p21(CIP1/WAF1) protein. Accumulation of p21(CIP1/WAF1) was independent of the histological grade of the tumors as well as the genetic status of the p53 gene. In many cases, most notably in poorly differentiated or undifferentiated HNSCC, p21(CIP1/WAF1)-positive cells were actively proliferating tumor cells, since they also expressed proliferating-cell nuclear antigen (PCNA) and Ki-67. Accumulation of p21(CIP1/WAF1) occurred through a post-transcriptional mechanism since, in contrast to immunohistochemical analysis of the p21(CIP1/WAF1) protein, in situ hybridization showed no increase of mRNA levels as compared with cells in normal mucosa (n = 25). Clinically, among the patients with p21(CIP1/WAF1)-over-expressing tumors, there was increased recurring disease (p = 0.03; chi2-test), shortened disease-free survival (p = 0.0019; log-rank test) and shortened overall survival (p = 0.0071; log-rank test). These in vivo data indicate that in many HNSCC, accumulated p21(CIP1/WAF1) is compatible with increased tumor-cell proliferation, and they provide preliminary evidence that p21(CIP1/WAF1) may be of prognostic and predictive significance.
Essential role of POU-domain factor Brn-3c in auditory and vestibular hair cell development.
The Brn-3 subfamily of POU-domain transcription factor genes consists of three highly homologous members-Brn-3a, Brn-3b, and Brn-3c-that are expressed in sensory neurons and in a small number of brainstem nuclei. This paper describes the role of Brn-3c in auditory and vestibular system development. In the inner ear, the Brn-3c protein is found only in auditory and vestibular hair cells, and the Brn-3a and Brn-3b proteins are found only in subsets of spiral and vestibular ganglion neurons. Mice carrying a targeted deletion of the Brn-3c gene are deaf and have impaired balance. These defects reflect a complete loss of auditory and vestibular hair cells during the late embryonic and early postnatal period and a secondary loss of spiral and vestibular ganglion neurons. Together with earlier work demonstrating a loss of trigeminal ganglion neurons and retinal ganglion cells in mice carrying targeted disruptions in the Brn-3a and Brn-3b genes, respectively, the Brn-3c phenotype reported here demonstrates that each of the Brn-3 genes plays distinctive roles in the somatosensory, visual, and auditory/vestibular systems.