Über die Entstehung von „Bolzengeschossen“ bei Verwendung präparierter Viehbetäubungsapparate

Zusammenfassung Einige gebräuchliche Modelle unter den Viehbetäubungsapparaten verfügen über Gummipuffer und Rückholfedern. Durch diese Bestandteile wird der vorschnellende Bolzen gebremst und in seine Ausgangsposition zurückgebracht. Wenn man den Gummipuffer und die Rückholfeder vor der Schußabgabe entfernt, kann der Bolzen abreißen und zu einem frei fliegenden Geschoß werden. In einem Suizidfall ist unter solchen Umständen ein 17 cm langes Bolzenstück durch die Stirn in die Schädelkapsel eingedrungen.     

Behandlung einer akuten monoblastären Leukämie bei einem Säugling mit einer Glutarazidurie Typ I

Glutaric aciduria type 1 (GA1) is caused by an inherited deficiency of the enzyme glutaryl coenzyme A dehydrogenase (GDH) involved in the degradation of lysine, hydroxylysine, and tryptophan. Affected infants develop unspecific neurological symptoms and macrocephaly. Deterioration of the neurological status, so-called encephalopathic crisis can be triggered by catabolism and is usually incompletely reversible. We report on a 4-year-old girl with GA1 who presented with acute monoblastic leukemia at the age of 8 months. She was treated with combination chemotherapy according to current standards. Despite the elevated risk of metabolic imbalance during infections in neutropenia, encephalopathy crises could be avoided by reduced intake of lysine and tryptophan, a high-energy diet, and supplementation with carnitine.     

Axillary-coronary artery bypass reconstruction as an alternative in coronary artery reoperations

BACKGROUND AND AIMS: The increasing incidence of reoperations in coronary surgery associated with higher perioperative risks is a challenge for refinement of the surgical methods. The aim of the work is to prove the feasibility and satisfactory intermediate results of minimally invasive axillary-coronary artery bypass reconstruction in redo coronary surgery in case the left internal mammary artery had already been harvested. MATERIAL AND METHODS: Three patients (six months, two and six years after primary coronary artery bypass grafting) admitted for redo coronary surgery because of a recurrence of angina and proven malfunction of the left internal mammary artery-left anterior descending coronary artery anastomosis. An axillary-coronary venous graft was performed via left anterior small thoracotomy (LAST) on a beating heart in all three cases. RESULTS: Excellent patency of the graft was noted on control angiography within 9 days after the procedure together with good clinical improvement in midterm follow-up. CONCLUSION: Minimally invasive axillary-coronary artery bypass via LAST access in redo coronary surgery is a good alternative in cases where the left internal mammary artery cannot be used.     

Endocrine patterns in patients with benign and malignant prostatic diseases

BACKGROUND: The known importance of the endocrine system, particularly of steroid hormones, for development of the prostate gland and the fact that steroid hormones act as immunmodulators prompted us to compare hypophyseal, adrenal, and gonadal hormones, including cortisol, in patients with benign and malignant prostatic diseases. METHODS: Patients with newly diagnosed, untreated prostate cancer (PC) (n = 75) and, as a control population, those with untreated lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) (n = 159) entered this prospective study. In all patients, the following parameters were obtained by serum analysis: prostate-specific antigen (PSA), human luteinizing hormone (hLH), human follicle-stimulating hormone (hFSH), testosterone, estradiol (E2), cortisol, and dehydroepiandrosterone-sulphate (DHEA-S). Serum samples were collected of fasting patients between 7. 30-10.00 AM. RESULTS: Age was comparable in both groups (PC: 65.6 +/- 7.6 years (mean +/- standard deviation) vs. controls: 64.9 +/- 8. 1 years; P = 0.56). HFSH (PC: 6.6 +/- 3.9 mIU/ml; controls: 8.4 +/- 6.4 mIU/ml; P = 0.04), hLH (PC: 5.3 +/- 4.8mIU/ml; controls: 7.6 +/- 6.2 mIU/ml; P = 0.009), and estradiol (PC: 25.8 +/- 12.7 pg/ml; controls: 32.6 +/- 12.6 pg/ml; P = 0.0003) were significantly lower in PC patients than controls. Cortisol (PC: 16.7 +/- 4.2 microg/dl; controls: 13.5 +/- 4.3 microg/dl; P < 0.0001) was significantly higher in cases. The difference for cortisol and estradiol concentrations between PC patients and controls held true in all life-decades. Serum concentrations for DHEA-S and testosterone were comparable between PC and control patients. In PC patients, none of the endocrine parameters correlated to serum PSA or clinical/pathological stage. CONCLUSIONS: Patients with newly diagnosed, untreated PC yielded significantly higher cortisol and lower estradiol serum concentrations than controls. The known effect of cortisol on the immune status warrants further studies.     

Antibody-based profiling of the phosphoinositide 3-kinase pathway in clinical prostate cancer.

PURPOSE: As kinase inhibitors transition from the laboratory to patients, it is imperative to develop biomarkers that can be used in the clinic. The primary objectives are to identify patients most likely to benefit from molecularly targeted therapies and to document modulation of the drug target. Constitutive activation of the phosphoinositide 3-kinase (PI3K) pathway and its downstream effectors, as a result of PTEN loss or by other mechanisms, occurs in a high proportion of prostate cancers, making it an ideal template for the design of clinical trials involving PI3K pathway inhibitors. Prostate cancers also present unique organ-specific challenges, in that tumors are heterogeneous and diagnostic tissue is extremely limited. EXPERIMENTAL DESIGN: Working within these limitations, we have developed a set of immunohistochemical assays that define activation of the PI3K pathway in clinical samples. Results and CONCLUSIONS: Using both univariate and multivariate analyses, we show that loss of PTEN is highly correlated with the activation of AKT, and this, in turn, is associated with the phosphorylation of S6, one of its main effectors. These three antibodies are potentially able to define a molecular signature of PTEN loss and/or AKT pathway activation in prostate cancer.     

Increase of regulatory T cells in the peripheral blood of cancer patients.

PURPOSE: T cells constitutively expressing both CD4 and CD25are essential for maintenance of self-tolerance and therefore have been referred to as regulatory T cells (Treg). Experimental tumor models in mice revealed that Tregs are potent inhibitors of an antitumor immune response. The current study was designed to determine whether cancer patients exhibit an expanded Treg pool. EXPERIMENTAL DESIGN: The frequency of Tregs in the peripheral blood of 42 patients suffering from epithelial malignancies and from 34 healthy controls was determined by flow cytometry. The immunoregulatory properties of CD4(+)CD25(+) and CD4(+)CD25(-) T cells were characterized by proliferation and suppression assays. Cocultures with natural killer (NK) cells were performed to determine the impact of Tregs on NK-mediated cytotoxicity. RESULTS: Patients with epithelial malignancies show an increase of CD4(+)CD25(+) T cells in the peripheral blood with characteristics of Tregs, i.e., they are CD45RA(-), CTLA-4(+), and transforming growth factor beta(+). Notably, CD4(+) T cells from cancer patients are characterized by an impaired proliferative capacity, which is restored to the extend of CD25-depleted CD4(+) T cells from control persons by prior removal of CD25(+) T cells. In contrast to CD4(+)CD25(-) T cells, isolated CD4(+)CD25(+) T cells from cancer patients were anergic towards T cell receptor stimulation. In addition, CD4(+)CD25(+) T cells suppressed the proliferation of CD4(+)CD25(-) T cells. When cultured together with CD56(+) NK-cells, CD4(+)CD25(+) T cells from cancer patients effectively inhibited NK-cell-mediated cytotoxicity. CONCLUSIONS: Thus, we provide evidence of an increased pool of CD4(+)CD25(+) regulatory T cells in the peripheral blood of cancer patients with potent immunosuppressive features. These findings should be considered for the design of immunomodulatory therapies such as dendritic cell vaccination.     

Quality of life outcomes after brachytherapy for early stage prostate cancer

PURPOSE: We compare general and disease specific health related quality of life in men undergoing brachytherapy for early stage prostate cancer to those undergoing radical prostatectomy and age matched healthy controls. MATERIALS AND METHODS: Cohorts consisted of 48 men treated with brachytherapy with and without pretreatment external beam radiation therapy (brachytherapy group), 74 who underwent radical prostatectomy (prostatectomy group) and age matched healthy controls from the literature. The RAND 36-item general health survey, University of California Los Angeles Prostate Cancer Index, American Urological Association symptom index, validated Cancer Interference with Life and Family Scales, and sociodemographic and co-morbidity questionnaires were completed 3 to 17 months after treatment. RESULTS: General health related quality of life did not differ greatly among the 3 groups. Urinary function (leakage) was worse in the brachytherapy group than in controls but better than in the prostatectomy group. Brachytherapy group patients had more irritative urinary symptoms and worse bowel function than controls. Sexual function and bother were worse in prostatectomy and brachytherapy groups than in healthy controls. Physical function, bodily pain, urinary function, and bother and American Urological Association symptom index scores improved with time after brachytherapy. Patients who underwent brachytherapy after external beam radiation performed worse in all general and disease specific health related quality of life domains compared to those who did not undergo pretreatment radiation therapy. CONCLUSIONS: At an average of 7.5 months after treatment the general health related quality of life of patients undergoing brachytherapy with and without pretreatment external beam radiation was similar to age matched controls, although urinary, bowel and sexual problems were reported. These problems appeared to improve during the first year after treatment. Much of the impairment in disease specific health related quality of life among patients undergoing brachytherapy may be attributed to pretreatment radiation.     

A continuous‐flow,high‐throughput,high‐pressure parahydrogen converter for hyperpolarization in a clinical setting

Pure parahydrogen (pH₂) is the prerequisite for optimal pH₂‐based hyperpolarization experiments, promising approaches to access the hidden orders of magnitude of MR signals. pH₂ production on‐site in medical research centers is vital for the proliferation of these technologies in the life sciences. However, previously suggested designs do not meet our requirements for safety or production performance (flow rate, pressure or enrichment). In this article, we present the safety concept, design and installation of a pH₂ converter, operated in a clinical setting. The apparatus produces a continuous flow of four standard liters per minute of ≈98% enriched pH₂ at a pressure maximum of 50 bar. The entire production cycle, including cleaning and cooling to 25 K, takes less than 5 h, only ≈45 min of which are required for actual pH₂ conversion. A fast and simple quantification procedure is described. The lifetimes of pH₂ in a glass vial and aluminum storage cylinder are measured to be T_1C(glass vial) = 822 ± 29 min and T_1C(Al cylinder) = 129 ± 36 days, thus providing sufficiently long storage intervals and allowing the application of pH₂ on demand. A dependence of line width on pH₂ enrichment is observed. As examples, ¹H hyperpolarization of pyridine and ¹³C hyperpolarization of hydroxyethylpropionate are presented. Copyright © 2012 John Wiley & Sons, Ltd.     

Melatonin ameliorates low‐grade inflammation and oxidative stress in young Zucker diabetic fatty rats

The aim of this study was to investigate the effects of melatonin on low‐grade inflammation and oxidative stress in young male Zucker diabetic fatty (ZDF) rats, an experimental model of metabolic syndrome and type 2 diabetes mellitus (T2DM). ZDF rats (n = 30) and lean littermates (ZL) (n = 30) were used. At 6 wk of age, both lean and fatty animals were subdivided into three groups, each composed of 10 rats: naive (N), vehicle treated (V), and melatonin treated (M) (10 mg/kg/day) for 6 wk. Vehicle and melatonin were added to the drinking water. Pro‐inflammatory state was evaluated by plasma levels of interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), and C‐reactive protein (CRP). Also, oxidative stress was assessed by plasma lipid peroxidation (LPO), both basal and after Fe²⁺/H₂O₂ inducement. ZDF rats exhibited higher levels of IL‐6 (112.4 ± 1.5 pg/mL), TNF‐α (11.0 ± 0.1 pg/mL) and CRP (828 ± 16.0 µg/mL) compared with lean rats (IL‐6, 89.9 ± 1.0, P < 0.01; TNF‐α, 9.7 ± 0.4, P < 0.01; CRP, 508 ± 21.5, P < 0.001). Melatonin lowered IL‐6 (10%, P < 0.05), TNF‐α (10%, P < 0.05), and CRP (21%, P < 0.01). Basal and Fe²⁺/H₂O₂‐induced LPO, expressed as malondialdehyde equivalents (µmol/L), were higher in ZDF rats (basal, 3.2 ± 0.1 versus 2.5 ± 0.1 in ZL, P < 0.01; Fe²⁺/H₂O₂‐induced, 8.7 ± 0.2 versus 5.5 ± 0.3 in ZL; P < 0.001). Melatonin improved basal LPO (15%, P < 0.05) in ZDF rats, and Fe²⁺/H₂O₂‐ induced LPO in both ZL (15.2%, P < 0.01) and ZDF rats (39%, P < 0.001). These results demonstrated that oral melatonin administration ameliorates the pro‐inflammatory state and oxidative stress, which underlie the development of insulin resistance and their consequences, metabolic syndrome, diabetes, and cardiovascular disease.