Determinant role of education in the ethical aspects of resuscitation: a German/Hungarian comparison

Introduction, objectives: Bioethical principles concerning Do Not Attempt Resuscitation (DNAR) orders are connected significantly with education according to our previous investigation. In order to confirm the hypothesis, Hungarian results were compared with the data gained from a highly qualified homogeneous group of German doctors, showing similar cultural traditions. Methods: The questionnaire investigated the factors influencing DNAR orders as functions of intensive medical experience, ideological view and professional education, using a 5-point visual analogue scale. Answers were assigned to categories of autonomy, futility, obtainable quality of life, resource utilization and a category of other factors detailed later. Results: The DNAR decision and termination of resuscitation are to almost the same extent determined by futility (3.29+-0.75; 3.49+-0.71) and obtainable quality of life (3.13+-1.31; 3.47+-1.34). The opinion of head of department was also important (3.24+-1.35; 3.23+-1.36). Patient's autonomy played an important role (3.15+-0.85; 2.36+-1.48) in decision making. In comparison with the Hungarian results, the only significant difference was found in the field of patient's autonomy in both not starting (p<0.0002) and terminating resuscitation (p<0.02) in favour of German doctors respecting it. Discussion: The results support the original hypothesis that consideration of modern bioethical principles, and especially the patient's autonomy are related to the level of the doctor's education. Comparing to Hungarian data there is only a minimal difference in other bioethical points, while the population of German doctors interviewed appreciated the patient's autonomy significantly higher. There should be greater discussion of ethical considerations in cardiopulmonary resuscitation education.     

Poly(adenosine diphosphate ribose) polymerase inhibition modulates spinal cord dysfunction after thoracoabdominal aortic ischemia-reperfusion

OBJECTIVE: Spinal cord injury (SCI) remains a source of morbidity after thoracoabdominal aortic reconstruction. These studies were designed to determine whether PJ34, a novel ultrapotent inhibitor of the nuclear enzyme poly(adenosine diphosphate ribose) polymerase (PARP) could modulate neurologic injury after thoracic aortic ischemia reperfusion (TAR) in a murine model of SCI. METHODS: Forty-one anesthetized male mice were subject to thoracic aortic occlusion (11 minutes) through a cervical mediastinotomy followed by 48 hours of reperfusion (TAR) under normothermic conditions. PJ34-treated mice (PJ, n = 12) were given 10 mg/kg PJ34 intraperitoneally 1 hour before ischemia and 1 hour after unclamping. The control group (UN, n = 21) received normal saline intraperitoneally 1 hour before ischemia and 1 hour after unclamping. Sham animals (n = 10) were subject to thoracic aortic exposure with no aortic clamping and similar intraperitoneal normal saline injections. PARP-1-/- (KO, n = 8) mice were subjected to the same conditions as the UN mice. Blinded observers rated murine neurologic status after TAR by using an established rodent paralysis scoring system. Murine spinal cords were subjected to cytokine (GRO-1) protein analysis as a marker of inflammation and immunohistochemical analysis (hematoxylin-eosin and PAR staining). Paralysis scores (PS) and GRO-1 levels were compared with analysis of variance, and survival data were compared with chi 2 . RESULTS: Immediately after TAR, UN and PJ mice had severe neurologic dysfunction (PS = 5.8 +/- 0.1 and 4.6 +/- 0.6, respectively; P > .05), which was significantly worse than the KO mice (PS = 1.0 +/- 0.7, P < .001). After 6, 24, and 48 hours KO mice had no discernable neurologic injury (PS = 0). Six hours after TAR, PJ mice significantly improved (PS = 1.1 +/- 0.73, P < .001) and remained improved at 24 (PS = 0.7 +/- 0.6) and 48 hours (PS = 0.6 +/- 0.6). UN mice did not improve their PS, and Sham mice showed no neurologic abnormality at any time during these experiments. The mortality at 48 hours was 0% for PJ and KO mice, 43% for UN (P = .012), and 0% for Sham. GRO-1 levels were significantly decreased in PJ and KO versus UN mice (UN, 583 +/- 119 vs PJ, 5.8 +/- 0 vs KO, 5.3 +/- 1.4 mg/pg; P < .0001). Immunohistochemistry showed evidence of decreased PAR staining and ventral motor neuron injury in PJ mice. CONCLUSIONS: Genetic deletion of PARP or inhibition of its activity (PJ34) rescued neurologic function in mice subjected to TAR. PARP inhibition might represent a novel therapeutic approach for prevention of SCI after TAR.     

Benign cystic mesothelioma, a rare tumor of the peritoneum

We report the case of a 28-year-old woman, who presented with acute abdominal and pelvic pain, the appearance of appendicitis. Because of her symptoms urgent operation was performed. Appendicetomy was performed, during the operation multiple cystic lesions were discovered on the right ovary and the peritoneal surface of the mesentery. Laparatomy was performed with removal of the visible cystic lesions, which contained mucous fluid. Final histology revealed benign cystic mesothelioma, which is a rare lesion of the peritoneum, occurring mainly in women in reproductive age. The etiology of cystic mesothelioma is still unclear. The short-term prognosis is favourable, but high recurrence rate. Some authors reported effective intraperitoneal chemotherapy, but no clinical study is available about long term outcome. We hope that surgical eradication was effective to prevent recurrence. One year after the operation the patient is complaint and symptom free.     

Aldose reductase inhibition counteracts oxidative-nitrosative stress and poly(ADP-ribose) polymerase activation in tissue sites for diabetes complications

This study evaluated the effects of aldose reductase inhibition on diabetes-induced oxidative-nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation. In animal experiments, control and streptozotocin-induced diabetic rats were treated with or without the aldose reductase inhibitor (ARI) fidarestat (16 mg . kg(-1) . day(-1)) for 6 weeks starting from induction of diabetes. Sorbitol pathway intermediate, but not glucose, accumulation in sciatic nerve and retina was completely prevented in diabetic rats treated with fidarestat. Sciatic motor nerve conduction velocity, hindlimb digital sensory nerve conduction velocity, and sciatic nerve concentrations of two major nonenzymatic antioxidants, glutathione and ascorbate, were reduced in diabetic versus control rats, and these changes were prevented in diabetic rats treated with fidarestat. Fidarestat prevented the diabetes-induced increase in nitrotyrosine (a marker of peroxynitrite-induced injury) and poly(ADP-ribose) immunoreactivities in sciatic nerve and retina. Fidarestat counteracted increased superoxide formation in aorta and epineurial vessels and in in vitro studies using hyperglycemia-exposed endothelial cells, and the DCF test/flow cytometry confirmed the endothelial origin of this phenomenon. Fidarestat did not cause direct inhibition of PARP activity in a cell-free system containing PARP and NAD(+) but did counteract high-glucose-induced PARP activation in Schwann cells. In conclusion, aldose reductase inhibition counteracts diabetes-induced nitrosative stress and PARP activation in sciatic nerve and retina. These findings reveal the new beneficial properties of fidarestat, thus further justifying the ongoing clinical trials of this specific, potent, and low-toxic ARI.     

Delineation of myotoxicity induced by 3-hydroxy-3-methylglutaryl CoA reductase inhibitors in human skeletal muscle cells

The 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins) are widely used and well tolerated cholesterol-lowering drugs. In rare cases, side effects occur in skeletal muscle, including myositis or even rhabdomyolysis. However, the molecular mechanisms are not well understood that lead to these muscle-specific side effects. Here, we show that statins cause apoptosis in differentiated human skeletal muscle cells. The prototypical representative of statins, simvastatin, triggered sustained intracellular Ca(2+) transients, leading to calpain activation. Intracellular chelation of Ca(2+) completely abrogated cell death. Moreover, ryanodine also completely prevented the simvastatin-induced calpain activation. Nevertheless, an activation of the ryanodine receptor by simvastatin could not be observed. Downstream of the calpain activation simvastatin led to a translocation of Bax to mitochondria in a caspase 8-independent manner. Consecutive activation of caspase 9 and 3 execute apoptotic cell death that was in part reversed by the coadministration of mevalonic acid. Conversely, the simvastatin-induced activation of calpain was not prevented by mevalonic acid. These data delineate the signaling cascade that leads to muscle injury caused by statins. Our observations also have implications for improving the safety of this important medication and explain to some extent why physical exercise aggravates skeletal muscle side effects.     

Thiocyanatochromium(III) complexes with pilocarpine and the analytical determination of this alkaloid (author's transl)]

Thiocyanatochromium(III) Complexes with Pilocarpine and the Analytical Determination of this Alkaloid A new reinecke salt-like compound NH₄[Cr(NCS)₄ (pilocarpine)₂] · H₂O was obtained from K₃[Cr(NCS)₆] and pilocarpine in the molten state. The constitution of the complex anion was proven by means of a series of double decomposition reactions with amines and cobalt(III)-amine bases. The structure and the thermal stability of the title compound were studied by means of UV and IR spectroscopy and derivatography. The slightly soluble compounds pilocarpine H[Cr(NCS)₄ (aniline)₂] and pilocarpine · H[Cr(NCS)₄ (morpholine)₂] were used for the oxidimetric and spectrophotometric determination of pilocarpine.     

Regulation of myocardial oxygen consumption by perfusion pressure in isolated fibrillating canine heart

In order to evaluate whether perfusion pressure or coronary flow affect myocardial oxygen metabolism, oxygen consumption of the isolated fibrillating blood-perfused canine heart was investigated at perfusion pressures of 100, 150, and 200 mm Hg. To obtain different coronary flow rates at a given coronary perfusion pressure, -adrenergic blockade by phenoxybenzamine (10 mg/kg b.w.) was applied, resulting in an increase in coronary flow and a decrease in myocardial oxygen extraction. Myocardial oxygen consumption was increased by elevation of perfusion pressure in both the control and phenoxybenzamine-pretreated group. At the same level of perfusion pressure there was no significant difference between the oxygen consumption of control and phenoxybenzaminepretreated preparations. It can be concluded that in the isolated fibrillating canine heart oxygen consumption is primarily regulated by perfusion pressure, and is independent from coronary blood flow.     

Prevalence of rheumatoid arthritis in the South-Transdanubian region of Hungary based on a representative survey of 10,000 inhabitants

OBJECTIVE: To assess the prevalence of rheumatoid arthritis (RA) in a representative study of the South Transdanubian region of Hungary. METHODS: Ten thousand individuals aged between 14-65 years were interviewed. The stratified sample was representative for age, sex and urban/rural residence structure of the regional population of the South-West Hungarian region. As a second step, all individuals with possible RA were asked to undergo a clinical investigation to confirm the diagnosis of RA according to the American Rheumatism Association (ARA) 1987 criteria. Of 10,000 interviewed individuals, 632 reported having RA or symptoms including digital pain, stiffness, and/or swelling. Two hundred and twenty-four individuals were investigated clinically. Individuals fulfilling the 1987 ARA criteria were considered as having definite RA, and their clinical data were evaluated. RESULTS: RA was confirmed in 13 cases. The male/female ratio was 3/10. The prevalence of RA among individuals aged 14-65 years was 0.37% (95% confidence interval, CI: 0.26-0.51), 0.23% (95% CI: 0.15-0.35) in men and 0.48% (95% CI: 0.35-0.64) in women. CONCLUSION: The prevalence of RA in the South Transdanubian region of Hungary is similar to those of other recent studies from other regions around the world.