[Acute Chest Pain: A Stepwise Approach to Management]. / Der akute Thoraxschmerz ­ Schritt für Schritt.

Acute chest pain is one of the most important cardinal symptoms in medicine. There are several important differential diagnoses for chest pain. Therefore, a thorough history and physical examination, as well as the 12-lead ECG and laboratory tests are crucial. In clinical practice, it is useful to distinguish between cardiac chest pain and other forms of chest pain in order to treat patients appropriately and to exclude potentially life-threatening conditions.

[Taxus poisoning: an unusual cause of acute heart failure]. / Das Gift der Eibe: eine ungewöhnliche Ursache der akuten Herzinsuffizienz.

Taxines are the active, poisonous constituents in yew plants (Taxus spp.) and can result in life-threatening cardiac toxicity. Rapid elimination of yew plant material and administration of active charcoal can limit absorption of toxins. Treatment is confined to supportive care. Therapeutic interventions such as utilization of digoxin immune fab, hemodialysis and temporary cardiac pacing may be utilized. Extracorporeal life support should be considered for severe cases.

The renin-angiotensin aldosterone system and osteoporosis: findings from the Women's Health Initiative.

New users of RAAS inhibitors, including ACE inhibitors and ARBs, have a small increased risk for fracture in the first 3 years of use, with a reduced risk of fracture with longer duration of use. INTRODUCTION: Pharmacological inhibitors of the renin-angiotensin aldosterone system (RAAS) are used to treat hypertension. However, the relationship of these medications to osteoporosis is inconsistent, and no study has included simultaneous measurements of both incident fractures and bone mineral density (BMD). METHODS: The association of RAAS inhibitor use (n = 131,793) with incident fractures in new users of these medications in women in the Women's Health Initiative over a minimum median follow-up of 6.5 years was assessed by Cox proportional hazard models. The association of incident fractures by a cumulative duration of use of these medications (< 3 years.) and (> 3 years.) was also estimated. Subgroup analysis of fracture risk by RAAS inhibitor use confined to women with hypertension was also performed (n = 33,820). The association of RAAS inhibitor use with changes in BMD of the hip was estimated by linear regression in 8940 women with dual energy X-ray absorptiometry measurements. RESULTS: There was no significant association between RAAS inhibitor use and all fractures in the final adjusted multivariable models including hip BMD (HR 0.86 (0.59, 1.24)). However, among users of RAAS inhibitors, including ACE inhibitors and angiotensin receptor blockers (ARBs), hazard ratios for all incident fracture sites in final multivariable models including hip BMD showed dramatic differences by duration of use, with short duration of use (3 years or less) associated with a marked increased risk for fracture (HR 3.28 (1.66, 6.48)) to (HR 6.23 (3.11, 12.46)) and use for more than 3 years associated with a reduced fracture risk (HR 0.40 (0.24, 0.68) to (HR 0.44 (0.20, 0.97)) . Findings were similar in the subgroup of women with a history of hypertension. There was no significant change in BMD of the hip by RAAS inhibitor use. CONCLUSIONS: In postmenopausal women, use of RAAS inhibitors, including ACE inhibitors and ARBs, is associated with an increased risk for fracture among new users of these medications in the first 3 years of use. However, long-term use (> 3 years) is associated with a reduced risk. Consideration for fracture risk may be part of the decision-making process for initiation of these medications for other disease states.

[The new reimbursement for psychiatry and psychosomatics - challenges, opportunities and risks of the new financing system]. / Das neue Entgeltsystem für Psychiatrie und Psychosomatik - Herausforderungen, Chancen und Risiken einer neuen Leistungsvergütung.

With the implementation of §â€Š17 d KHG which provides for the introduction of a new, much more performance-based and transparent reimbursement system for psychiatric and psychosomatic hospitals, the Federal Ministry of Health sends the psychiatric and psychosomatic facilities in Germany into a previously unexplored area. Since 2013, there is the possibility of voluntary participation in the new system. Valid from 2015, every other institution will have to deal with the new challenges, opportunities and risks coming along with the structural changes, even though this fact will not have any impact on the individual hospital revenue budget until the end of 2016. There is still some time left to get used to the new system. This paper summarises the key data on the new reimbursement system and explains its content as well as how it works. In addition to that this paper goes into the classification system and clarifies what is essential for a solid preparation. Finally, it comments on the most common criticisms emerging since 2009. How the new system will develop remains to be seen. The fact that it will evolve seems to be certain in terms of a "learning system". It is up to all parties to promote the learning process so as to make effective use of existing potential and keep risks to a minimum.

Immunotherapy of patients with hormone-refractory prostate carcinoma pre-treated with interferon-gamma and vaccinated with autologous PSA-peptide loaded dendritic cells--a pilot study.

PURPOSE: We conducted a pilot trial to assess the feasibility and tolerability of a prime/boost vaccine strategy using interferon-gamma (IFN-gamma) and autologous dendritic cells (DCs) pulsed with HLA-A2-specific prostate-specific antigen (PSA) peptides (PSA-1 [141-150]; PSA-2 [146-156]; PSA-3 [154-163]) for the treatment of 12 patients with hormone refractory prostate carcinoma. PATIENTS AND METHODS: All patients were vaccinated four times with intracutaneously injected PSA-peptide loaded DCs after subcutaneous administration of IFN-gamma 2 hr before DC administration (50 microg/m(2) body surface). Objectives were safety, clinical benefit, clinical and biochemical response, quality of life, and immunological parameters. RESULTS: The vaccination was well tolerated without any vaccination-associated adverse events. One partial and one mixed responder were identified, four patients showed stable diseases. Two patients had a decrease and four a slow-down velocity slope in the PSA serum level. All responders showed a positive DTH-response, but only two a slight increase in PSA-peptide specific T-lymphocytes. CONCLUSION: The immunotherapy with IFN-gamma and PSA-peptide loaded DCs was feasible and well tolerated. The observed responses imply a potential antitumor activity.

Comparison of 1-hour and 3-hours paclitaxel infusion pharmacokinetics: results from a randomized trial.

PURPOSE: Aim of this study was to characterize the difference in pharmacokinetics (PK) of paclitaxel (PAC) after 1-h and 3-h infusion in humans and to define a pharmacodynamic relationship between PAC PK and myelotoxicity. PATIENTS AND METHODS: PAC PK were studied during the first PAC application in the first treatment cycle (1 treatment cycle = 6 PAC applications) in 25 patients. This patient group represents a subgroup of a large clinical study with neurotoxicity as primary endpoint. These 25 patients were those patients who were willing to give additional blood samples. The group size was sufficient for a full description of the PK of PAC. PAC was administered at 100 mg/m(2) weekly by 1-h (n = 12) or 3-h (n = 13) infusion to patients with advanced cancer (lung, breast, ovarian, cervix, and head and neck). Total PAC was quantified by high-performance liquid chromatography (HPLC). Pharmacokinetic parameters were calculated by noncompartmental and model-dependent methods. The leukocyte and neutrophil decrease during a 6-week treatment period was calculated by the percentage in decrease of white blood cell count (WBC) and absolute neutrophil count (ANC) as well as the area over the curve (AOC) of WBC and ANC. RESULTS: The area under the curve (AUC), the plasma clearance (Clp), the volume of distribution at steady state (V(ss)), the mean residence time (MRT) and the distribution half-life (t(1/2)) of PAC(tot) were not different in the two application modes. The elimination half-life (t1/2) and maximum plasma concentration C(max) were significantly different. No significant differences in the percentage of reduction of WBC and ANC were seen. Calculation of AOC of WBC showed a borderline significant difference (p = 0.0547) in case of WBC and no significant difference in case of ANC between the two PAC schedules. A considerable variance of AOC was observed. CONCLUSION: The pharmacokinetic study of total PAC of the two schedules investigated showed significant differences in the elimination half-life, which is longer in case of the 1-h infusion of PAC and in the maximum plasma concentration, which is higher in case of the 1-h infusion. The two schedules showed a similar myelotoxicity with a trend of less toxicity in the 1-h procedure.

Double-blind randomised placebo-controlled phase III study of an E. coli extract plus 5-fluorouracil versus 5-fluorouracil in patients with advanced colorectal cancer.

The primary aim of this study was to evaluate the toxicity (mucositis, diarrhea and leucopenia) of a therapy with 5-fluorouracil (CAS 51-21-8; 5-FU) plus an E. coli extract (LC-Extract, Laves coli extract, Colibiogen inject, cell-free soluble fraction from lysed E. coli, Laves strain) in comparison with 5-FU plus placebo. Secondary endpoints included general toxicity, response rate according to WHO, survival time and quality of life. 164 patients with advanced colorectal cancer were enrolled in this randomised, placebo-controlled, double-blind, multicenter phase III study. The treatment consisted of 0.167 ml/kg/d LC-Extract or placebo followed by 500-750 mg/m2/d 5-FU on five consecutive days, repeated every three weeks for up to six treatment cycles. 158 (77 verum, 81 placebo) patients were evaluable for toxicity, 144 (72 verum, 72 placebo) evaluable for response. The therapy with LC-Extract was well tolerated. Adverse events that occurred during the study were mainly judged as 5-FU- or tumor-related. Toxicity from treatment with 600 mg/m2/d 5-FU in both treatment groups was very low. After treatment with 750 mg/m2/d 5-FU patients in the placebo-group experienced a higher CTC toxicity than in the LC-Extract groups. Remission rate and survival time showed a slight trend in favour of LC-Extract. These results suggest a positive benefit-risk ratio of the additional application of LC-Extract to 5-FU in the treatment of advanced colorectal cancer especially for administration of high doses of 5-FU.

Phase II study of combined 5-fluorouracil/ Ginkgo biloba extract (GBE 761 ONC) therapy in 5-fluorouracil pretreated patients with advanced colorectal cancer.

The aim of the study was to evaluate the efficacy, tolerability and quality of life in 5-fluorouracil (5-FU) pretreated colorectal cancer patients after combined 5-FU and Ginkgo biloba extract GBE 761 ONC (i.e. the Ginkgo biloba special extract EGb 761(R)) therapy. Following conventional 5-FU therapy, 44 patients (32 evaluable for response) with advanced progressive colorectal cancer were treated every 3 weeks with courses of 350 mg GBE 761 ONC as a 30 min i.v. infusion on days 1-6 followed by 500 mg/m(2)/d 5-FU as a 30 min i.v. infusion on days 2-6. The response to therapy was evaluated after the second and fourth course of treatment. The data of 32 patients could be evaluated for efficacy. We observed a progression of disease in 22 patients, no change in 8 patients and a partial response in 2 patients (overall response = 6.3%). Seventeen of 22 patients with observed progressive disease showed further progression after two cycles, two after three cycles and three after four cycles. The median survival time was 9.5 months (7.7-11.5 months). GBE 761 ONC was well tolerated. Adverse events that occurred during the study were mainly myelosuppression and gastrointestinal symptoms and were judged to be 5-FU related or consistent with liver toxicity and thus tumour related. Our results suggest a good benefit-risk ratio of the combined 5-FU and GBE 761 ONC therapy as second line treatment in metastatic colorectal cancer. The survival time was similar to that known from second line treatment according to the Ardalan scheme. Since an improvement was observed in some patients despite the failure of the conventional 5-FU pretreatment, it would be interesting to evaluate whether the application of 5-FU plus GBE 761 ONC as a first line treatment is of benefit.

Phase II study with 5-fluorouracil and ginkgo biloba extract (GBE 761 ONC) in patients with pancreatic cancer.

The aim of the study was to evaluate the efficacy and tolerability of as well as the quality of life under treatment with 5-fluorouracil (CAS 51-21-8, 5-FU) combined with parenteral GBE 761 ONC (i.e. the ginkgo biloba special extract EGb 761) in patients with pancreatic cancer. Forty-eight patients with locally or metastatic advanced pancreatic cancer were treated within a phase II study. The treatment was repeated every three weeks until progression. Response to therapy was evaluated after 2 and 4 treatment courses. Thirty-two patients were evaluable for response. Progressive disease was observed in 22 (68.8%) patients, no change in 7 (21.9%) patients and partial response in 3 (9.4%) patients (overall response = 9.4%). GBE 761 ONC was well tolerated. Adverse events which occurred during the study consisted mainly of myelosuppression and gastrointestinal symptoms and were judged as 5-FU-related or consisted of liver toxicity, respectively, and were judged as tumour-related. These results suggest a good benefit-risk ratio of the combination of 5-FU and GBE 761 ONC in the treatment of pancreatic cancer. In comparison with the results of studies with either 5-FU or gemcitabine as single agents the combination of 5-FU/GBE 761 ONC shows comparable response rates. The toxicity of the 5-FU/GBE 761 ONC combination was low. This combination therapy therefore warrants further clinical investigation, such as a controlled clinical trial against 5-FU or gemcitabine monotherapy.

Clinical phase I study with one-hour paclitaxel infusion.

BACKGROUND: Paclitaxel (PAC) is one of the major anti-cancer drugs, effective in different tumors. Studies with 24-hour infusion with 135 mg/m2 and a three-hour infusion with 175 mg/m2 showed a significant schedule-dependent toxicity. We evaluated a one-hour infusion schedule within a phase I study to determine the dose limiting toxicity (DLT), the maximum tolerated dose (MTD), and the anti-cancer efficacy. PATIENTS AND METHODS: Patients with advanced malignant tumors were treated within cohorts by one-hour infusional paclitaxel starting with 150 mg/m2 and stepwise escalation with 25 mg/m2 increments. Therapy was repeated in three-week intervals. Cycles were repeated until progression. Toxicity was closely monitored, anti-cancer efficacy was only evaluated in those patients who received at minimum two treatment cycles. RESULTS: Thirty-four patients entered the study (11 NSCLC, five SCLC, seven ovarian cancer, one cervix cancer, nine MBC, one HN cancer). The MTD was PAC 250 mg/m2. The DLT was central and peripheral neuropathy (WHO grade 3). Other significant toxicities were fatigue, myalgia/arthralgia and paraesthesia. No significant myelotoxicity was observed. Totally twentyone patients were evaluable for response. A partial response was observed in five (24%) patients (two NSCLC, two ovarian cancer, one head and neck cancer). Three (14%) patients had stable disease and in 13 (62%) patients progressive disease was observed. CONCLUSIONS: Paclitaxel 225 mg/m2 on day 1 administered as one-hour infusion and repeated every three weeks can be given safely, featured no relevant myelotoxicity, and is the recommended dose for phase II studies.

Coding strategy of the S and M genomic segments of a hantavirus representing a new subtype of the Puumala serotype.

The hantavirus strain Vranica was previously reported to have been isolated from a bank vole in Bosnia-Hercegovina and associated with the occurrence of hemorrhagic fever with renal syndrome (HRFS) in humans. The complete cDNA nucleotide sequences of the small (S) and medium (M) genomic RNA segments of this virus were determined. Major open reading frames were found in the S and M segment between nucleotide positions 43 and 1341 coding for a polypeptide of 433 amino acid residues and between nucleotide positions 41 and 3,484 coding for 1,148 amino acid residues, respectively. The analysis and the alignment of the nucleotide and the derived amino acid sequences with known sequences of other hantavirus strains demonstrate that Vranica resembles Swedish strains and represents a new virus subtype of the Puumala serotype distinct from the subtypes represented by virus strains CG18-20 and Sotkamo.

[The diagnostic role of contrast medium-enhanced MR tomography in the diagnosis of the post-diskectomy syndrome. A prospective study of 109 patients]. / Diagnostischer Stellenwert der kontrastmittel-unterstützten MR-Tomographie in der Diagnostik des Postdiskektomie-Syndroms. Eine prospektive Untersuchung von 109 Patienten.

In a prospective study, 132 previously operated disc levels in 109 patients with failed back surgery syndrome (FBSS) were examined by MR imaging before and after intravenous application of a contrast agent (0.1 mmol Gd-DTPA/kg). The results were compared with current CT findings in 47 cases. The images were randomized and independently assessed by two experienced radiologists. A second intervention of a total of 30 disc levels was performed in 28 patients. Contrast-enhanced-MR imaging (CE-MRI) improved the differentiation of scar from recurrent disc herniation (RDH) compared to plain MRI and CT. Agreement between the two readers was significantly higher for CE-MRI than for the other two procedures (p < or = 0.001). CE-MRI additionally had the highest diagnostic accuracy (p < or = 0.001). The preoperative diagnosis made by CE-MRI was confirmed in 27 (90%) of the reoperated disc levels. Quantitative evaluation showed that there was no contrast enhancement in RDH as opposed to pronounced enhancement of 122% in scars (p < or = 0.001). Evaluation with respect to scar age revealed a significant difference (p < or = 0.01) in contrast enhancement between scars less and more than 2.5 years old.

Long-term mental sequelae of political imprisonment in East Germany.

This paper presents an assessment of the long-term mental sequelae of prolonged stress due to political persecution and imprisonment in the German Democratic Republic. Fifty-five former political prisoners with enduring psychiatric disorders were examined retrospectively in an exploratory study. The patients' experiences before, during, and after imprisonment were investigated using a semistructured interview. Psychopathological symptoms were assessed on clinical and self-rating scales; diagnostic classification was conducted according to DSM-III-R. The patients had experienced serious trauma, including psychological torture, long-term imprisonment, and solitary confinement. We diagnosed a characteristic syndrome involving symptoms of depression and anxiety with vegetative complaints and increased arousal. In 35 (64%) patients, the symptoms persisted over an extended period without improvement. This syndrome resembles psychiatric disorders found after other forms of political persecution. It may be concluded that prolonged individually experienced political stress situations, even if they are not life-threatening, may have long-term mental sequelae.

[Psychological disorders after political imprisonment in East Germany--attitude of victims]. / Psychische Störungen nach politischer Inhaftierung in der DDR--Sichtweisen der Betroffenen.

In an exploratory study we examined 55 patients who had been politically imprisoned in the GDR for at least six weeks and suffered from enduring mental sequelae of that imprisonment. Views of the patients were assessed by means of standardized open questions and rating scales. Patients reported on stressful conditions in prison, fears concerning the uncertain end of imprisonment, as well as on helpful aspects during and after imprisonment. In a cluster analysis two groups were separated: one group that found social relationships helpful for coping with their experiences and another one that did not feel helped by anybody in coping, 28% of the patients stated that the symptoms were not mainly due to experiences during imprisonment; 20% saw general positive effects of imprisonment on their life. Views of the patients were correlated with other variables such as psychopathological symptoms. The relevance of the findings is discussed briefly.

[Counting and differentiation of blood corpuscles with a simple flow cytometer]. / Zählen und Differenzieren von Blutkörperchen mit einem einfachen Durchflusszytometer.

The performance of a simple flow cytometer for counting of blood cells was checked. The counting of erythrocytes, platelets as well as the differential counting of lymphocytes, monocytes and granulocytes was obtained by means of simple sample preparation.

Water hardness and mortality in the Netherlands.

In 1975 central water softening was discouraged by the Public Health Council because of the statistical negative association found in 23 communities between the hardness of drinking water and death rate from Ischemic Heart Disease (I.H.D.) over the period 1958-1970. Further studies were carried out during the last decade by a specially assigned interdisciplinary Working Group of the Health Aspects of Central Water Softening. Recent studies showed that the release of metals (Pb and Cu) from household water distribution pipes was positively correlated with water calcium. Furthermore a significant negative correlation was found between hardness and pH for these types of water. The hypothesis that the Ca and Mg deficiency in areas with soft drinking water increases the risk of I.H.D. death rate was supported by the finding that food looses more Ca and Mg when it is cooked in soft water as compared to cooking in hard water. In contrast with earlier statistical investigations no significant relations were found over the period 1970-1977 between I.H.D. mortality and hardness of drinking water in 30 municipalities. The disappearance of the statistical relation could not be attributed to changes in water hardness. However, investigation of a group of 17 municipalities of which mortality and water quality data are known for three periods, 1958-1962, 1965-1970 and 1971-1977, showed that the inverse statistical relation between I.H.D. mortality and water hardness still existed but with decreasing significance of correlation coefficients. The provisional conclusion of the Working Group is that other factors than water hardness overrule to a large extent the potential effect on I.H.D. mortality. Central water softening down to 2-3 meq/l Ca probably will have no observable effect on mortality. Other studies are still continuing. In 1981 a final report will be presented to the Minister of Health and Environmental Protection.

Changes in the mineral composition of food as a result of cooking in "hard" and "soft" waters.

During the last decade many epidemiologists have found an inverse relationship between water hardness and cardiovascular mortality. It seems unlikely that this relationship can only be attributed to a deficiency of calcium and mangnesium in drinking water, because only 10-20% of the total daily intake of calcium and magnesium is derived from drinking water. The purpose of this study was to investigate changes in the mineral composition of food to investigate changes in the mineral composition of food when cooking with waters of different hardness. The most significant differences were found for calcium; the concentration of this element in potatoes and vegetables usually increased when cooking with hard-water types, while a decrease was noted when soft water was used for cooking.