[Hip arthroscopy after luxatio obturatoria. With contralateral unstable pelvic ring fracture]. / Hüftgelenkarthroskopie nach Luxatio obturatoria. Bei kontralateraler instabiler Beckenringfraktur.

Traumatic dislocation of the hip is a severe injury. Even in cases of an early uncomplicated repositioning there is a high risk of associated intra-articular injuries, such as lesions of the labrum, ruptures of the ligament of the head of the femur and loose bodies. The degree of damage caused by dislocation of the hip becomes apparent with a highly increased risk of developing postinjury osteoarthritis after dislocation of the hip. Some of the major intra-articular damage resulting from hip dislocation, e.g. loose bodies, can be detected by computed tomography and magnetic resonance imaging and can be effectively addressed by hip arthroscopy, thus aiming at reducing the acute symptoms and the risk of postinjury osteoarthritis. The force effect which causes dislocation of the hip can generate severe associated extra-articular injures as in the case described with an unstable fracture of the pelvis. This supplementary injury had to be considered while planning the operative therapy and rehabilitation. A patient presented after a traffic accident with a luxatio obturatoria on the right side and a complex fracture of the left pelvis including the posterior ring and the anterior wall of the acetabulum. After reposition of the right hip and operative therapy of the left side, a loose body was identified in the right hip joint during the computed tomography control of the osteosynthesis. Before patient mobilization extraction of the intra-articular loose body was performed arthroscopically. This was done in consideration of the reduced possibility of distraction due to the osteosynthesis on the contralateral side. Attention was particularly paid to the risk of intra-abdominal fluid extravasation (IAFE). This syndrome is described as a severe complication during hip arthoscopy especially in cases of defects of the hip capsule as assumed after hip dislocation and magnetic resonance imaging.

A prospective cohort study on the impact of darbepoetin alfa on quality of life in daily practice following anemia treatment guideline revisions.

OBJECTIVE: This study aimed to evaluate the impact of darbepoetin alfa (DA) on hemoglobin (Hb) levels and quality of life (QoL) in cancer patients with anemia in current daily practice following several revisions of anemia treatment guidelines. METHODS: This was a prospective, multi-center, observational study across Germany in non-myeloid cancer outpatients with chemotherapy-induced anemia treated with DA. Age, sex, cancer type, stage, and therapy, performance status, anemia status and treatment, and Hb concentrations were recorded for up to 18 weeks in a web-based registry. Optional QoL assessments were collected at baseline and at the end of DA treatment. MAIN RESULTS: Of 984 eligible patients, 978 had complete anemia data, 492 also had complete QoL data. In the 978 patients, mean age was 64 (standard deviation, SD 12) years, 62% of patients were women. Breast (26%) and gastrointestinal (22%) cancer were most prevalent. Therapy was palliative in 44% of patients and initiated with curative intent in 29%. Mean baseline Hb was 9.5 (SD 0.9) g/dL, which increased by an average of 1.2 g/dL. In 67% of patients Hb increased either to 10-12 g/dL or by ≥2 g/dL; no Hb response was seen in 219 patients (22%); increases of 0 to 1, >1 to 2, and >2 g/dl were seen in 216 (22%), 265 (27%), and 278 (28%) patients, respectively. Anemia treatment did not result in any significant differences of performance status. However, QoL improvements were significantly greater in Hb responders, although a linear relationship with Hb increments was lacking. None of 47 fatal cases was considered related to treatment with DA. CONCLUSION: Patients treated with DA in routine clinical practice had increases in Hb and reported improvement in QoL. Due to the uncontrolled design, no conclusions can be made regarding causality to treatment and the clinical relevance of the improvement.

[Chilaiditi's syndrome complicated by subdiaphragmatic perforated appendicitis: unusual manifestation of a rare condition]. / Chilaiditi-Syndrom mit subdiaphragmal perforierter Appendizitis : Ungewöhnliche Manifestation einer seltenen Erkrankung.

We report on a case of an 80-year-old female patient who presented to the emergency room of with right upper quadrant abdominal pain since the day before. During the initial diagnostic an abdominal x-ray study revealed an air-filled colonic section of the bowel under the right hemidiaphragm corresponding to Chilaiditi's sign. The clinical symptoms and laboratory results were mild at this time. After 12 h the patient developed right upper quadrant peritonitis due to a perforated, subdiaphragmatic appendicitis based on Chilaiditi's syndrome. During surgical treatment the cecum and parts of the ascending colon were found to be interposed between the liver and right hemidiaphragm. A right hemicolectomy was performed which led to complete recovery of the patient. In addition to presenting this interesting case this article highlights the regime of the diagnostics and therapy of a complication of the very rare condition of Chilaiditi's syndrome.

A clinical phase I/II trial with the monoclonal antibody cG250 (RENCAREX®) and interferon-alpha-2a in metastatic renal cell carcinoma patients.

PURPOSE: To evaluate the efficacy and safety of WX-G250, a chimeric monoclonal antibody that binds to carboxy anhydrase IX, combined with low-dose interferon-alpha (LD-IFNα) in patients with progressive metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Thirty-one patients, nephrectomized for the primary tumor, clear cell progressive mRCC, were enrolled to receive weekly infusions of WX-G250 (20 mg i.v.; week 2-12) combined with LD-IFNα (3 MIU s.c. 3 times/week; week 1-12). At week 16, patients were evaluated for response and stratified into two groups: (a) responders into the extended treatment group for an additional 6 weeks of treatment or (b) the progressive group with no further study treatment. RESULTS: Of the 31 treated patients, 26 were evaluable for response to treatment. Two patients showed partial remission and 14 patients had stable disease as assessed in week 16. One patient experienced partial remission resulting in a complete remission lasting at least 17 months. Nine patients had durable stable disease of 24 weeks or longer. Clinical benefit was obtained in 42% (11/26) patients. The median overall survival achieved was 30 months and the 2-year survival was 57%. Patients receiving extended treatment showed a significantly longer 2-year survival rate than discontinued patients (79 vs. 30%; P=0.0083). In general, treatment was well tolerated with little toxicity. CONCLUSION: Treatment with the antibody WX-G250 in combination with LD-IFNα is safe, well tolerated, led to clinically meaningful disease stabilization and demonstrated clinical benefit in this progressive mRCC patient population.

Cytoarchitectonic mapping of the human amygdala, hippocampal region and entorhinal cortex: intersubject variability and probability maps.

Probabilistic maps of neocortical areas and subcortical fiber tracts, warped to a common reference brain, have been published using microscopic architectonic parcellations in ten human postmortem brains. The maps have been successfully applied as topographical references for the anatomical localization of activations observed in functional imaging studies. Here, for the first time, we present stereotaxic, probabilistic maps of the hippocampus, the amygdala and the entorhinal cortex and some of their subdivisions. Cytoarchitectonic mapping was performed in serial, cell-body stained histological sections. The positions and the extent of cytoarchitectonically defined structures were traced in digitized histological sections, 3-D reconstructed and warped to the reference space of the MNI single subject brain using both linear and non-linear elastic tools of alignment. The probability maps and volumes of all structures were calculated. The precise localization of the borders of the mapped regions cannot be predicted consistently by macroanatomical landmarks. Many borders, e.g. between the subiculum and entorhinal cortex, subiculum and Cornu ammonis, and amygdala and hippocampus, do not match sulcal landmarks such as the bottom of a sulcus. Only microscopic observation enables the precise localization of the borders of these brain regions. The superposition of the cytoarchitectonic maps in the common spatial reference system shows a considerably lower degree of intersubject variability in size and position of the allocortical structures and nuclei than the previously delineated neocortical areas. For the first time, the present observations provide cytoarchitectonically verified maps of the human amygdala, hippocampus and entorhinal cortex, which take into account the stereotaxic position of the brain structures as well as intersubject variability. We believe that these maps are efficient tools for the precise microstructural localization of fMRI, PET and anatomical MR data, both in healthy and pathologically altered brains.

Efficacy and safety of inhaled recombinant interleukin-2 in high-risk renal cell cancer patients compared with systemic interleukin-2: an outcome study.

Systemic IL-2 is an effective treatment for low to intermediate risk mRCC patients, its efficacy is marginal in high-risk cases. Therefore, other treatment approaches are required for this population. Ninety-four high-risk patients with RCC and pulmonary metastases were treated with inhaled plus concomitant low-dose subcutaneous rhIL-2. Clinical response, survival and safety were compared with those from IL-2 given systemically at the registered dose and schedule in 103 comparable historical controls. In the rhIL-2 INH group, treatment consisted of 6.5 MIU rhIL-2 nebulized 5x/day and 3.3 MIU rhIL-2 SC once daily. The rhIL-2 SYS group received treatment which consisted of intravenous infusion of 18.0 MIU/m2/day rhIL-2 or SC injection of 3.6-18.0 MIU rhIL-2. Some patients in both groups also received IFNalpha. Mean treatment durations were 43 weeks rhIL-2 INH and 15 weeks rhIL-2 SYS. Significantly longer overall survival and progression-free survival durations were observed in the rhIL-2 INH group. The probability of survival at 5 years was 21% for the rhIL-2 INH group. No patients survived 5 years in the rhIL-2 SYS group. A multivariate analysis of overall survival adjusting for differences in baseline characteristics between the two treatment groups resulted in a risk ratio of 0.43 (95% CI 0.30-0.63; P < 0.0001). The data suggested an association between the response (SD or better) and survival, especially in the rhIL-2 INH group. The inhalation regimen was well tolerated. This outcome study suggests that administration of rhIL-2 by inhalation is efficacious and safe in high-risk mRCC patients with pulmonary metastases, who have no other treatment option available.

A phase II trial of gemcitabine in combination with 5-fluorouracil (24-hour) and folinic acid in patients with chemonaive advanced pancreatic cancer.

BACKGROUND: Gemcitabine (Gemzar) and 5-fluorouracil (5-FU) plus folinic acid (FA) both have proven activity in the treatment of patients with advanced pancreatic cancer. The present study was initiated to investigate the efficacy of gemcitabine in combination with 5-FU-FA. PATIENTS AND METHODS: Thirty-eight patients, median age 60 years (range 34-70) with inoperable, stage IV, pancreatic cancer were enrolled into the study and treated on an outpatient basis. All except one patient received at least one cycle of treatment with gemcitabine (1000 mg/m2), followed by FA (200 mg/m2) and 5-FU (750 mg/m2) administered as a 24-hour continuous infusion on days 1, 8, 15 and 22 of a 42-day schedule. No patient had received prior chemotherapy or radiotherapy. All 38 patients were assessed for efficacy, toxicity and time to progressive disease. RESULTS: Two patients (5%), achieved a partial response and thirty-four patients (89%) achieved stable disease. There were two early deaths (< or = 4 weeks). The median time to progression was 7.1 months (range 0.4-18.1+; 95% confidence interval (95% CI): 5.3-7.9 months). Three patients had a progression-free interval of greater than 12 months and 12 of 38 patients (32%) survived longer than 12 months. The median overall survival was 9.3 months (range 0.5-26.5; 95% CI: 7.3-13.0 months). The incidence of grade 3 and 4 toxicities was low. CONCLUSIONS: The combination of gemcitabine and 5-FU-FA is active and well tolerated and seems to offer an improvement in progression-free interval over both gemcitabine monotherapy and 5-FU-FA therapy.

Effect of current and forthcoming European legislation and standardization on the setting of quality specifications by laboratories.

A network of national and international guidelines and directives developed in the last few decades by various bodies will lead to a new concept of total quality for medical laboratory services comprising legislative regulations on national and international levels, standardizations backed up by legislation and recommendations of professional societies. One example is the IVD Directive of the European Community. It will not only stimulate accreditation in the field of laboratory medicine, but also necessitate numerous standardization activities which are presently co-ordinated by the European Committee for Standardization (CEN). Another standardization example is the development of quality management systems, mainly by ISO. The ISO 9000 series has become the most successful family of standards world-wide. Meanwhile, specific standards for the needs of laboratories (ISO 17025), and in particular of medical laboratories (ISO 15189), are being worked out. A new trend to develop quality management systems towards total quality management systems can be observed including additional aspects such as economic and quality interests of society, customers and owners of laboratories. The goal of all activities is to create a network of confidence which provides some guarantee to the clients, i.e. the physicians and their patients, that they will receive a high-quality medical laboratory service.

Follow-up of breast cancer patients.

The existing follow-up standard for breast cancer patients has been reviewed by a representative trial involving 1,004 curatively treated patients, who underwent surgery between 1977 and 1987. The objective of the study has been to establish whether intensive diagnostics of recurrences and metastases will lead, as a result of the follow-up, to life prolongation or improvement of life quality, and which methods will be adequate to achieve this goal. The analysis has shown that metastases are recognized only insignificantly earlier, and that improvement of survival is not achieved. The results of the trial have led to a recommendation for an effective follow-up programme for breast cancer patients, with emphasis on subtle case history data and exact clinical investigations.

[A retrospective determination of the validity of various methods of early detection of recurrence and metastasis of breast cancer]. / Retrospektive Ermittlung der Validität unterschiedlicher Methoden zur frühzeitigen Erkennung von Rezidiv und Metastasen des Mammakarzinoms.

The valid follow-up standard for mammary carcinoma was checked by means of a retrospective study with 1,004 curatively treated patients operated between 1977 and 1987. The aim of this study was to find out whether intensive diagnostics of recurrences and metastases resulted in early detection and prolongation of life and/or improvement of life quality. Evaluation of two groups (early detection and treatment as compared to late detection and treatment) showed that diagnosis was only slightly earlier (1,2 months) which did not lead to longer life. These results gave rise to recommendations for an efficient follow-up regime for patients with mammary carcinoma. Exact case history and clinical examinations are more important for asymptomatic patients than intensive diagnostics:

[New aspects of adequate postoperative prosthetic management following mastectomy]. / Neue Aspekte einer adäquaten postoperativen prothetischen Versorgung nach Mastektomie.

The availability of one unitised organ replacement model is no longer sufficient for adequate prosthetic care at any time. The first phase of a complex system of prosthetic care was completed by the development of "femi-Form", an epithesis master model, in 1982. Two more variants were introduced in 1986, "femi-Form S" and an interim prosthesis. The complex system of prosthetic care in its totality is considered to be an important step in public health. Great attention is given to it in the GDR for follow-up treatment in the context of tumour diseases. Manufacturers are expected to go to great lengths in developing adequate prosthetic devices for postoperative care. However, it is a challenge to the medical profession to speed up and generally support the introduction of this complex post-mastectomy system.

[Determination of active components of amrinone by analysis of pressure-volume results; use of the conductance (volume) catheter technic and rapid load change by balloon occlusion of the inferior vena cava]. / Bestimmung der Wirkkomponenten von Amrinon durch kontinuierliche Analyse der Druck-Volumen-Beziehungen; Anwendung der Conductance-(Volumen-)Kathetertechnik und der schnellen Laständerung durch Ballonokklusion der Vena cava inferior.

Endsystolic pressure-volume relationships (ESPVR) were determined using the conductance (volume) catheter-technique and the required rapid load changes by applying vasoactive drugs (nitroprusside = NP; phenylephrine = PE) or brief preload reduction by balloon occlusion of the vena cava inferior (BOVCI). With this load-independent index of contractility, we analyzed the hemodynamically active components of amrinone (AM) over a range of different LV-loading conditions. In 19 patients (study I) with still normal LV-function (LVF) in group A (dP/dtmax 1585 +/- 386 mmHg/s; n = 10) and impaired LVF in group B (dP/dtmax 1044 +/- 164 mmHg/s; n = 9) an infusion of AM, 1.5 mg/kg over 2 min, failed to induce changes in ESPVR (p greater than 0.05), but rather caused load changes, resembling like those seen with NP. During continuously paced heart rates (90/min) brief infusion phases with NP and PE provided the necessary load changes. In 11 patients (study II) with impaired LVF (dP/dtmax = 1177 +/- 163 mmHg/s) 2.5 mg/kg AM i.v. induced an increase in contractility, which was more pronounced after the additional application of dobutamine (DOB) at 10 micrograms/kg/min.; (1) Slope k rose from 0.52 to 0.80 mmHg/ml; (2) dP/dtmax increased by an average of 39% and 57% (p less than 0.01), respectively. The BOVCI provided the necessary load changes. Thus AM demonstrates its contractility-increasing effects in a dose-related fashion, probably (at least in part) via an increase in heart rate; inotropic effects further increased with the combination of AM and DOB. The use of the conductance technique for the assessment of ESPVR during acute decrease of preload by temporary BOVCI is innocuous to the patient, reproducible and can be carried out under the conditions of a routine cardiac catheter procedure. This technique seems to be useful in the assessment of relative inotropic effects of the newer cardiotonic drugs.

Effects of forskolin on left ventricular function in dilated cardiomyopathy.

The adenylate cyclase activator 17 beta-acetoxy-8, 13-epoxy-1 alpha,6 beta,9 alpha-trihydroxylabd-14-en-11-one (forskolin) was studied for its beneficial effect as therapeutic agent for the treatment of dilated cardiomyopathy (DCM). In 7 DCM-patients with normal (group A) and 8 DCM-patients with pathological dP/dtmax-values (group B), we analyzed serially (computer-assisted) the pressure/volume (P/V) effects as P/V-loops (microtip catheter/Tc-99m scintigraphy) and on-line MV02 (indirectly: Bretschneider equation) under dobutamine, 10 micrograms/kg/min i.v., and forskolin, 3 micrograms/kg/min i.v. For the total group (A + B) there was no change of contractility during forskolin (p greater than 0.05); with dobutamine, however, it rose by an average of +25%. The preload decline was more pronounced with forskolin (LVEDP by -27%) as compared to dobutamine (by-19%); while left ventricular (LV-)function improved moderately only with forskolin (by +9%) and significantly (by +34%) with dobutamine. Thus, forskolin improved LV-function primarily via reduction of preload in DCM-hearts and without rising metabolic costs. Beneficial hemodynamic effects with forskolin are quantitatively less as compared to those with dobutamine (accompanied by higher MVO2-costs). It is concluded that residual myocardial reserves in DCM are mobilized by dobutamine rather than forskolin. Serial P/V-loop and on-line MVO2 registration aided in the demonstration of forskolin efficacy as compared to dobutamine.

Comparative efficacy of the new cardiotonic agent DPI 201-106 versus dobutamine in dilated cardiomyopathy: analysis by serial pressure/volume relations and "on-line" MVO2 assessment.

DPI 201-106 (DPI) as a positive inotropic drug might be useful in treating dilated cardiomyopathy (DCM). In seven DCM patients with normal (group A) and eight DCM patients with abnormal (group B) left ventricular (LV) function, we analyzed serially (computer-assisted) pressure/volume (P/V) effects as P/V loops (microtip catheter/99mTc scintigraphy) using DPI (30 micrograms/kg X min i.v.) and dobutamine (DOB) (10 micrograms/kg X min i.v.) for quantitative comparison of hemodynamic effects. Contractility (dP/dtmax) improvement was greater with DPI (group A, +23%; group B, +47%) than with DOB (group A, +21%; group B, +32%), as was the simultaneous LV end-diastolic pressure decrease--DPI (group A, -39%; group B, -42%) versus DOB (group A, -21%; group B, -18%). LV efficiency increased with DPI (group A, +22%; group B, +55%), but myocardial oxygen consumption (MVO2) did not change significantly. Five of 15 patients showed an increase in dP/dtmax with DPI only; with DPI there were fewer "nonresponders" than with DOB. Thus, DPI increases contractility in DCM hearts while reducing preload rather than causing higher metabolic costs. Such beneficial hemodynamic effects appear to be stronger in the more impaired myocardium (group B patients) and quantitatively superior to those induced by DOB. This might indicate that residual myocardial reserves are more readily accessible to the influences of DPI than to those of DOB. Serial P/V loops and MVO2 assessment aided the demonstration of DPI's efficacy in a more complex way.

Analysis of the efficacy of the new cardiotonic agent TA-064.

TA-064 is a new cardiotonic agent which is also effective orally, according to investigations conducted in Japan. We analyzed computer-assisted alterations of pressure-volume relationships serially and of indirect myocardial oxygen consumption (MVO2) estimations on line during TA-064 influence in 16 patients with congestive cardiomyopathy: left ventricular function was moderately decreased in seven patients (group A) and drastically decreased in nine (group B). Results showed that TA-064, 8 micrograms/kg/min intravenously, exerted positive inotropic effects in both groups and induced mean maximal delta percentage changes at about 5 minutes of infusion as follows: left ventricular stroke work index +65% and +47%; dP/dtmax +61% and 59%; left ventricular efficiency +62% and 53%; MVO2 +31% and +11% (p less than 0.05). TA-064, 20 mg by mouth induced serum levels (group A = 23.8 +/- 12ng/ml and group B = 26.4 +/- 20 ng/ml) corresponding to the effects with dosages of 1 to 2 ng/kg/min intravenously (p greater than 0.05), thus implying that significant changes in left ventricular function require higher oral dosages. We conclude that TA-064 improves left ventricular function, primarily via a contractility increase, also in group B patients without toxic side effects. On-line indirect MVO2 assessment and analysis of serial pressure-volume relationships helped to provide a more complex definition of the mechanism and efficiency of the cardiotonic agent under study.