Enhancement of the antiproliferative activity of cis-diamminedichloroplatinum(II) by quercetin

We have shown previously that the flavonoid quercetin (3,3',4',5,7-pentahydroxyflavone) enhances the antiproliferative activity of cis-diamminedichloroplatinum(II) (cis-DDP) in vitro. In order to investigate whether this observation could be exploited in cancer treatment, we tested this drug combination in human tumor xenografts. The established human large-cell cancer of the lung (LXFL 529) was implanted s.c. into nude mice. Tumors were allowed to grow to a mean diameter of approximately 5 mm and the animals were subsequently treated intraperitoneally with quercetin, cis-DDP or a combination of both. Treatment was given 3 times at 3-day intervals. Twenty milligrams quercetin per kg body weight caused no inhibition in tumor growth compared to untreated controls; 3 mg cis-DDP per kg body weight with the same time schedule reduced tumor growth, compared to quercetin-treated and control animals. Concomitant treatment with 20 mg quercetin and 3 mg cis-DDP per kg body weight reduced tumor growth to a significantly greater degree than cis-DDP alone. Toxicity of this treatment was relatively low as determined by measurements of the body weight of the mice. A combination of 4 mg or 5 mg cis-DDP with 20 mg quercetin per kg body weight also reduced tumor growth compared to single cis-DDP treatment. The toxicity of treatment with these increased doses was high, as shown by the high lethality and the loss of body weight of surviving animals.     

Pullout strength of anterior spinal instrumentation: a product comparison of seven screws in calf vertebral bodies

A lot of new implant devices for spine surgery are coming onto the market, in which vertebral screws play a fundamental role. The new screws developed for surgery of spine deformities have to be compared to established systems. A biomechanical in vitro study was designed to assess the bone–screw interface fixation strength of seven different screws used for correction of scoliosis in spine surgery. The objectives of the current study were twofold: (1) to evaluate the initial strength at the bone–screw interface of newly developed vertebral screws (Universal Spine System II) compared to established systems (product comparison) and (2) to evaluate the influence of screw design, screw diameter, screw length and bone mineral density on pullout strength. Fifty-six calf vertebral bodies were instrumented with seven different screws (USS II anterior 8.0 mm, USS II posterior 6.2 mm, KASS 6.25 mm, USS II anterior 6.2 mm, USS II posterior 5.2 mm, USS 6.0 mm, USS 5.0 mm). Bone mineral density (BMD) was determined by quantitative computed tomography (QCT). Failure in axial pullout was tested using a displacement-controlled universal test machine. USS II anterior 8.0 mm showed higher pullout strength than all other screws. The difference constituted a tendency (P = 0.108) when compared to USS II posterior 6.2 mm (+19%) and was significant in comparison to the other screws (+30 to +55%, P < 0.002). USS II posterior 6.2 mm showed significantly higher pullout strength than USS 5.0 mm (+30%, P = 0.014). The other screws did not differ significantly in pullout strength. Pullout strength correlated significantly with BMD (P = 0.0015) and vertebral body width/screw length (P < 0.001). The newly developed screws for spine surgery (USS II) show higher pullout strength when compared to established systems. Screw design had no significant influence on pullout force in vertebral body screws, but outer diameter of the screw, screw length and BMD are good predictors of pullout resistance.     

Osteoporosis Before Lung Transplantation: Association with Low Body Mass Index, but Not with Underlying Disease

Due to progress in lung transplantation, post-transplantation osteoporosis becomes an important problem. We determined bone mineral density (BMD) in 74 lung transplantation candidates, among them 24 patients with cysticfibrosis, 16 with chronic obstructive pulmonary disease, 14 with pulmonary fibrosis, and 11 with pulmonary hypertension. The mean T score (+/- SD) was -2.6 +/- 1.3 at femoral neck (FN), -2.2 +/- 1.6 at Ward's triangle (WT) and -2.3 +/- 1.5 at lumbar spine (LS). Osteoporosis was found in 61% of the patients at FN, 45% at WT and 50% at LS. Patients with different underlying lung diseases were similarly affected, not only those with cystic fibrosis but also others, including patients with pulmonary hypertension. No association was found between BMD and age, gender, menstrual condition in women and testosterone level in men. A negative correlation was found between chronic glucocorticoid use and T scores. Body mass index correlated positively (p < 0.01) with T scores at any site and the correlation was also significant for the 2 largest subgroups. Loss of lung function (FEV1) also was associated with lower T scores. No correlation was found between BMD and biochemical indices of bone turnover. Multivariate analysis revealed BMI and glucocorticoid use as independent risk factors. We conclude that osteoporosis is a very common condition in patients with end-stage pulmonary disease, independent of the underlying diagnosis. In view of additional bone loss under immunosuppressive treatment after lung transplantation, early diagnosis and prevention of osteoporosis in the pretransplant period should receive high priority.     

Tumor stage and early mortality for surgical resections in lung cancer

BACKGROUND: Postoperative mortality rates have been published in relation to operative procedure or preexisting pulmonary and extrapulmonary diseases. We analyzed our patients for the effect of the postoperative tumor stage on perioperative mortality. PATIENTS AND METHODS: Retrospective study of all thoracotomies for resections ( n=1281) in primary lung cancer from January 1987 to December 1997. Uni- and multivariate analysis was performed for operative procedure, mortality (30 and 90 days), tumor stage, sex, age, tumor localization, and completeness of resection. Radical resection was achieved in 91.9% of the patients. RESULTS: Overall postoperative deaths occurred in 4% and 7.3% of patients after 30 and 90 days respectively. Depending on the operative procedure the mortality after segmental resection ( n=116) was 0.9% and 1.7%, lobectomy ( n=621) 3.0% and 5.7%, sleeve lobectomy ( n=152) 5.3% and 7.9%, and pneumonectomy ( n=314) 6.7% and 12.5%, respectively. Within 30 and 90 days postoperatively deaths occurred, respectively, in 0.8% and 1.0% of stage I patients ( n=493), 5.4% and 5.4% of stage II ( n=147), 4.9% and 8.8% of stage IIIa ( n=388), 7.2% and 16.6% of stage IIIb ( n=148), 8.9% and 20.5% and of stage IV ( n=114). Multivariate analysis showed postoperative tumor stage to be the factor most closely related to within the first 90 days. CONCLUSIONS: Tumor stage but not type of resection is the strongest predictor of postoperative mortality in these subpopulations.     

Long-term treatment with amiodarone]

The aim of this study was to investigate the efficacy and the side effects of a long-term treatment with amiodarone. We analyzed the data of 41 patients in whom amiodarone therapy had been initiated between 1974 and 1984. Twenty-one patients had dilative cardiomyopathy, 14 patients had chronic myocardial infarction, four patients suffered from WPW syndrome with intermittent atrial fibrillation, one patient had aortic valve surgery, whereas in one patient there was no clinical evidence of a heart disease. All patients had salvos of ventricular extrasystoles, ventricular tachycardia or documented intermittent ventricular fibrillation. There have been seven drop-outs up to the present time. In each patient, the lowest antiarrhythmically effective dose was applied, which was generally higher in patients with low ejection fraction. Effective treatment of the ventricular tachycardia was achieved in 55-92% of patients and did not depend on the duration of treatment. In 10 patients in whom amiodarone therapy had to be stopped for various reasons. Sudden cardiac death was slightly more frequent than in the 24 patients treated with amiodarone, though the difference was not significant. In cases with a history of syncope the prognosis was poor, even with amiodarone therapy. Due to side effects, a dosage reduction or discontinuation of amiodarone treatment became necessary in 14 patients. Amiodarone proved to be an effective drug also for the long-term treatment of ventricular tachycardia, and possibly for the prevention of sudden cardiac death. With the exception of blue skin color, there was no accumulation of side effects, even during long-term treatment of several years.     

Weiterentwicklungen der Verriegelungsoptionen von intramedullären Implantaten

Modern, well-developed medullary nailing systems such as the T2 system can be used for a wide range of indications. In addition to fractures, malunions and osteotomies in the region of the shaft, locking systems are already configured for use in metaphyseal fractures and malunions. The material properties of the type II anodised titanium alloy are now optimized insofar as friction and wear rates are reduced and its mechanical properties are more physiological. The development of short compression screws that can be introduced axially into the nail makes it possible to block the locking screws in the region of the nail base and thus to achieve approximately fixed angles. This compression screw also allows finely tuned apposition of the main fragments and, if appropriate, to apply compression on the fracture or osteotomy.     

Additional costs for preventing the spread of methicillin-resistant Staphylococcus aureus and a strategy for reducing these costs on a surgical ward.

OBJECTIVE: To determine the added costs of hygienic measures (barrier precautions, isolation, and decontamination) required for MRSA carriers in German hospitals and possible strategies for cost reduction. DESIGN: On a septic surgical ward caring for 35% of all MRSA cases in a university hospital (1,182 beds), additional costs for personnel time and materials were calculated and medical charts of all MRSA cases admitted to the ward during 1 year were analyzed retrospectively. Twelve of the ward's 13 beds were located in rooms with at least 2 beds. PATIENTS: Four hundred ninety-eight MRSA carrier hospital-days (of 20 MRSA cases) could be assessed. All patients (80% men, 50% older than 74.5 years) had broken skin. RESULTS: In 95% of the cases, microbiological findings suggested transmission of MRSA during the current or a previous stay on this ward. The study found total avoidable costs of approximately 142,794.01 euros in 1 year, averaging 371.95 euros for one MRSA patient hospital-day and 9,261.56 euros per MRSA case. The most expensive single measure was blocked beds in multibed rooms (305.75 euros/day), which accounted for 82% of the extra costs. Costs most likely were underestimated. CONCLUSIONS: Daily additional case costs amounted to 96% of social security payments. Blocked beds in multibed rooms accounted for more than 80% of these excess costs. Isolation has been scientifically validated and is required by law in Germany. Building an adequate number of single-bed rooms should help prevent spread and would greatly lower the added costs of infection.     

Straf- und verfassungsrechtliche Gedanken zum Verbot des Klonens von Menschen

Ohne Zusammenfassung Lars Witteck und Christina Erich, Lehrstuhl für Deutsches und Ausl?ndisches Straf- und Strafprozessrecht, Universit?t Gie?en, Hein-Heckroth-Stra?e 3, D-35390 Gie?en