Suizide in der stationären Psychiatrie unter Beihilfe einer SterbehilfevereinigungFälle aktiver Sterbehilfe?

The debate on passive and active euthanasia has met a controversial echo both in the German-speaking media and in professional publications within recent years. This discussion, however, largely excluded mentally ill patients. Also, euthanasia advocacy groups have usually distanced themselves from euthanasia in psychiatric patients. We report here two cases from our hospital in which inpatients with affective disorders committed assisted suicide during a hospital pass. We discuss these events under the assumption that these are cases of questionable active euthanasia in mentally ill patients whose judgement was considerably compromised by their disorder.     

Evaluation of clinical relevance of examining K-ras, p16 and p53 mutations along with allelic losses at 9p and 18q in EUS-guided fine needle aspiration samples of patients with chronic pancreatitis and pancreatic cancer

AIM： To establish an optimum combination of molecular markers resulting in best overall diagnostic sensitivity and specificity for evaluation of suspicious pancreatic mass.
METHODS： Endoscopic ultrasound （EUS）-guided fine needle aspiration cytology （FNA） was performed on 101 consecutive patients （63 males, 38 females, 60 ± 12 years; 81 with subsequently diagnosed pancreatic cancer, 20 with chronic pancreatitis） with focal pancreatic mass. Samples were evaluated on-site by an experienced cytopathologist. DNA was extracted from Giemsa stained cells selected by laser microdissection and the presence of K-ras, p53 and p16 somatic mutations was tested by cycling-gradient capillary electrophoresis （CGCE） and single-strand conformation polymorphism （SSCP） techniques. In addition, allelic losses of tumor suppressor genes p16 （INK4, CDKN2A） and DPC4 （MADH4, SMAD4） were detected by monitoring the loss of heterozygosity （LOH） at 9p and 18q, respectively.
RESULTS： Sensitivity and specificity of EUS-guided FNA were 75% and 85%, positive and negative predictive value reached 100%. The remaining 26% samples were assigned as inconclusive. Testing of molecular markers revealed sensitivity and specificity of 70% and 100% for K-ras mutations （P 〈 0.001）, 24% and 90% for p53 mutations （NS）, 13% and 100% for p16 mutations （NS）, 85% and 64% for aUelic losses at 9p （P 〈 0.001） and 78% and 57% for allelic losses at 18q （P 〈 0.05）. When tests for different molecular markers were combined, the best results were obtained with K-ras ＋ LOH at 9p （92% and 64%, P 〈 0.001）, K-ras ＋ LOH at 18q （92% and 57%, P 〈 0.001）, and K-ras ＋ LOH 9q ＋ LOH 18q （96% and 43%, P 〈 0.001）. When the molecular markers were used as complements to FNA cytology to evaluate inconclusive samples only, the overall sensitivity of cancer detection was 100% in all patients enrolled in the study.
CONCLUSION： EUS-guided FNA cytology combined with screening of K-ras mutations an     

Erythropoietin facilitates the return of spontaneous circulation and survival in victims of out-of-hospital cardiac arrest

Background

Erythropoietin activates potent protective mechanisms in non-hematopoietic tissues including the myocardium. In a rat model of ventricular fibrillation, erythropoietin preserved myocardial compliance enabling hemodynamically more effective CPR.

Objective

To investigate whether intravenous erythropoietin given within 2 min of physician-led CPR improves outcome from out-of-hospital cardiac arrest.

Methods

Erythropoietin (90,000 IU of beta-epoetin, n = 24) was compared prospectively with 0.9% NaCl (concurrent controls = 30) and retrospectively with a preceding group treated with similar protocol (matched controls = 48).

Results

Compared with concurrent controls, the erythropoietin group had higher rates of ICU admission (92% vs 50%, p = 0.004), return of spontaneous circulation (ROSC) (92% vs 53%, p = 0.006), 24-h survival (83% vs 47%, p = 0.008), and hospital survival (54% vs 20%, p = 0.011). However, after adjusting for pretreatment covariates only ICU admission and ROSC remained statistically significant. Compared with matched controls, the erythropoietin group had higher rates of ICU admission (92% vs 65%, p = 0.024) and 24-h survival (83% vs 52%, p = 0.014) with statistically insignificant higher ROSC (92% vs 71%, p = 0.060) and hospital survival (54% vs 31%, p = 0.063). However, after adjusting for pretreatment covariates all four outcomes were statistically significant. End-tidal PCO₂ (an estimate of blood flow during chest compression) was higher in the erythropoietin group.

Conclusions

Erythropoietin given during CPR facilitates ROSC, ICU admission, 24-h survival, and hospital survival. This effect was consistent with myocardial protection leading to hemodynamically more effective CPR (Trial registration: http://isrctn.org. Identifier: ISRCTN67856342).     

A seed coat bedding assay shows that RGL2-dependent release of abscisic acid by the endosperm controls embryo growth in Arabidopsis dormant seeds

Seed dormancy is an ecologically important adaptive trait in plants whereby germination is repressed even under favorable germination conditions such as imbibition with water. In Arabidopsis and most plant species, dormancy absolutely requires an unidentified seed coat germination-repressive activity and constitutively higher abscisic acid (ABA) levels upon seed imbibition. The mechanisms underlying these processes and their possible relationship are incompletely understood. We developed a "seed coat bedding" assay monitoring the growth of dissected embryos cultured on a layer of seed coats, allowing combinatorial experiments using dormant, nondormant, and various genetically modified seed coat and embryonic materials. This assay, combined with direct ABA measurements, revealed that, upon imbibition, dormant coats, unlike nondormant coats, actively produce and release ABA to repress embryo germination, whatever the embryo origin, i.e., from dormant, nondormant, or never dormant aba seeds, unable to synthesize ABA. The persistent high ABA levels in imbibed dormant seeds requires the permanent expression of the DELLA gene RGL2, where it remains insensitive to gibberellins (GA) unlike in nondormant seeds. These findings present the seed coat as an organ actively controlling germination upon seed imbibition and provide a framework to investigate how environmental factors break seed dormancy.     

Keratin variants associate with progression of fibrosis during chronic hepatitis C infection

Keratins 8 and 18 (K8/K18) protect the liver from various forms of injury. Studies of liver explants from a large cohort of U.S. patients showed that K8/K18 mutations confer a risk to developing end-stage liver diseases, though which diseases are preferentially involved is unknown. We tested the hypothesis that K8/K18 variants are associated with chronic hepatitis C (CHC) and that their presence correlates with progression of fibrosis. Genomic DNA was isolated from peripheral blood of a well-characterized German cohort of 329 patients with CHC infection. Exonic regions were PCR-amplified and analyzed using denaturing high-performance liquid chromatography and DNA sequencing. Our findings showed: (1) amino acid altering keratin heterozygous variants in 24 of 329 CHC patients (7.3%) and non-coding heterozygous variants in 26 patients (7.8%), and (2) 3 new exonic K8 variants (T26R/G55A/A359T); 6 novel non-coding variants and one K18 coding variant (K18 S230T; 2 patients). The most common variants were K8 R341H (10 patients), K8 G62C (6 patients) and K8 I63V (4 patients). A novel and exclusive association of an intronic KRT8 IVS7+10delC deletion in all 10 patients with K8 R341H was observed. Notably, there was a significant association of exonic, but not of intronic K8 variants with increased fibrosis. In conclusion, previously described and novel K8 variants are present in a German population and collectively associate with progression of fibrosis in CHC infection. The unique 100% segregation of the most common K8 variant, R341H, with an intronic deletion suggests that one of these two genetic changes might lead to the other.     

Complications of radiotherapy of uterine cervix carcinoma

The retrospective analysis of 242 patients treated for uterine cervix cancer at VUKEO Brno within 1977-1982 has been realized. The patients being only treated with radiotherapy alone using the external 42 MeV X-ray betatron beam irradiation of the pelvis, and the vaginal and intrauterine application of 226Ra, were included in this study. The complications of therapy were evaluated in accordance with the grade of severity, location and time of their source. The radiotherapeutical complications of the 2nd stage appeared for 27 patients (11.2%), and the complications of the 3rd stage appeared for 8 patients (3.3%). The total five-years' survival rate is 71%, 92% for 37 patients in the Ib stage, 78% for 105 patients in the IIa, b stages, and 54% for 100 patients in the IIIa, b stages.     

Effect of Chronic Nicotine Treatment and its Withdrawal on the Vasopressinergic System in Rats

We have studied the effect of chronic nicotine treatment and its withdrawal on the hypothalamo-neurohypophyseal Vasopressinergic system in male Sprague-Dawley rats. They were subcutaneously infused with low and high doses of nicotine, free base (0.6 and 6.0 mg/kg/day, respectively) for 28 days, via Alzet osmotic pumps. The studies were carried out immediately after the period of infusion and 1, 7, 14 and 28 (the latter in high dose only) days later. Basal, high K⁺-stimulated and total vasopressin release from the superfused neural lobes, the residual vasopressin content in the neural lobes, and hypothalamus and plasma vasopressin concentration were measured by radioimmunoassay. Treatment with the high dose of chronic nicotine alone decreased vasopressin content in and release from the neural lobe and its plasma concentration, but it did not change significantly the vasopressin content in the hypothalamus. A similar pattern of changes in vasopressin release and plasma concentration, though less pronounced, was observed in the rats infused with the low dose of nicotine. The withdrawal of the high dose of chronic nicotine gradually returned the decreased plasma vasopressin concentration, and its content in and release from the neural lobe to control values within 2 weeks. However, vasopressin content in the hypothalamus started to decline 1 week after nicotine withdrawal and persisted to decline for at least 3 subsequent weeks. The withdrawal of the high dose was associated with a marked suppression of high K⁺-stimulated vasopressin release from the neural lobe for a period of 4 weeks. The withdrawal of the low dose of nicotine exhibited a significant decline in plasma vasopressin concentration for up to 2 weeks only following chronic nicotine withdrawal, tending to return subsequently to control levels.     

Role of insulin-like growth factor-1 in colon cancerogenesis: a case-control study

BACKGROUND: Our aim was to establish whether individuals who developed colon cancer have elevated blood levels of insulin-like growth factor-1 (IGF-1). METHODS: This was a case/control study in which 52 patients with colon cancer and a corresponding control group were investigated. Data on age, weight, height, and sex of subjects were recorded and levels of IGF-1 and growth hormone, as well as insulin and C-peptide levels, were measured in the morning before eating, 90 min after breakfast and again 90 min after lunch. RESULTS: We found significantly higher levels of IGF-1 in blood of colon cancer patients compared to the control group. No differences in the levels of growth hormone, insulin and C-peptide in blood were found between colon cancer patients and the control group. It was found that the increase of IGF-1 level was followed by a 3.15-fold increased risk for developing colon cancer. There were no differences in the levels of IGF-1 in blood in all three measurements in the group of colon cancer patients, whereas differences were found in the control group. We found differences in the levels of insulin and C-peptide in blood in all three measurements in both groups of patients. No differences were found in the levels of growth hormone in blood in all three measurements in both groups of patients. CONCLUSIONS: The results of this study suggest a positive correlation between the increased levels of IGF-1 and colon cancer and are thus consistent with the hypothesis that the level of IGF-1 plays an important role in the development of colon cancer.     

Liver transplantation in malignant disease

Liver transplantation for malignant disease has gained increasing attention as part of transplant oncology. Following the implementation of the Milan criteria, hepatocellular carcinoma (HCC) was the first generally accepted indication for transplantation in patients with cancer. Subsequently, more liberal criteria for HCC have been developed, and research on this topic is still ongoing. The evident success of liver transplantation for HCC has led to the attempt to extend its indication to other malignancies. Regarding perihilar cholangiocarcinoma, more and more evidence supports the use of liver transplantation, especially after neoadjuvant therapy. In addition, some data also show a benefit for selected patients with very early stage intrahepatic cholangiocarcinoma. Hepatic epithelioid hemangioendothelioma is a very rare but nonetheless established indication for liver transplantation in primary liver cancer. In contrast, patients with hepatic angiosarcoma are currently not considered to be optimal candidates. In secondary liver tumors, neuroendocrine cancer liver metastases are an accepted but comparability rare indication for liver transplantation. Recently, some evidence has been published supporting the use of liver transplantation even for colorectal liver metastases. This review summarizes the current evidence for liver transplantation for primary and secondary liver cancer.