Value of alignment osteotomy of the proximal tibia in the endoprosthesis period]

AIM OF THE STUDY: To evaluate the value of high tibial osteotomy in times of growing numbers of endoprostheses we compared our personal with other results of this method as well as of the unilateral sledge prosthesis. MATERIAL AND METHODS: Between 1972 and 1993 the high tibial osteotomy as described by Coventry was performed in 105 patients. 98 patients could be examined clinically-radiologically and evaluated with a questionnaire. The indication for surgery was given in patients with unilateral arthrosis without affection of the retropatellar joint and without significant ligamentous instability. The varus deviation was in no case more than 10 degrees. The average follow-up for the clinical-radiologic examination was 9.4 years. RESULTS: 77 patients (78.6%) were satisfied with the outcome of the surgery. Here it was seen that neither age nor pain or instability had an influence on this judgement. The walking distance on the other hand had a significant influence. Stair climbing and range of motion were significantly important as well. 23 patients gave the judgement "excellent", 31 "good", 36 "satisfactory" and 8 patients were "not satisfied". A significant influence of patient age on the judgement could not be proven. The division in the Japanese Score showed "good" results in 14%, "moderate" in 81% and "poor" in 5%. 13 knee joints (13.3%) were absolutely pain-free and in 67 cases (68.4%) there were a definite pain reduction. A significant correlation between the preoperative axis deviation and pain could not be found. An average flexion of 97.5 degree and an extension deficit of 3.3 degree on average was seen. A significant difference of range of motion dependent on age groups could not be found. In 42 knees (42.9%) the lateral ligaments were clinically stable, in 35 cases (35.7%) there was a first degree lateral stress gap and in 21 cases (21.4%) there was a second degree lateral instability. A significant correlation between the instability and age or pain could not be proven. 13 revision surgeries including 9 endoprosthesis implantations were performed. CLINICAL RELEVANCE: The study showed a high level of satisfaction with an exact surgical indication. When seeing the growing number of implanted uni- or tricompartmental endoprostheses the procedure of tibial osteotomy can be suggested for patients with unilateral arthrosis without retropatellar arthrosis, with an axis deviation less than 15 degrees, with unaffected cartilage of the contralateral compartment and without ligamentous insufficiency independent of patient age.     

Effect of patient age on use of the knee joint score

AIM OF THE STUDY: Clinical studies are done with the help of scores though different factors of influence lower comparability. The underlying study examines the influence of patient age as this always presents a certain span. METHOD: 96 degree I damaged knee joints were examined by 3 examiners using the Larson-, Lysholm-, Marshall-, HSS- and OAK-score. Furthermore ratings by a VAS and the Tegner activity score were done. With the Friedman test, the rank correlation coefficient by Spearman and the contingency chart by Bowker it was tested if the examiners and the scores rate equally. To find out the influence of the age three age groups were made up. RESULTS: The examiners judged significantly different excluding the Marshall and the OAK scores. In between two examiners no significant difference could be found between the young and the middle-aged patient group. Between two other examiners no significant difference was found only for the Lysholm and the HSS score in the young group and only for the Lysholm score in the middle-aged group. In the group of the senior patients no significant difference for the scores by Lysholm, Marshall and OAK were found. In the comparison of the second examiner pair no significant differences could be proven by the scores by Larson, the OAK and the HSS. All other comparisons were significantly different. In the comparison of all five scores significant differences were seen between the Larson score and the HSS and the Lysholm and the HSS. The Lysholm score proved to be the strictest, the HSS to be the leanest. CONCLUSION: Especially for the senior patients in dependency of the examiner and the chosen score significant differences were found concluding that the relevance of results lessens for future times as the score results drop with patient age anyway. The age span in one study should have a maximum of 10-20 years to reduce the influence of age on the final result.     

A cross-sectional study of workers in the chemical industry with occupational exposure to hexamethylenetetramine

Objectives: To assess the health effects of hexamethylenetetramine (HMT) on the airways and the skin of workers in the chemical industry. Methods: A cross-sectional study was performed with 17 employees of a HMT-producing chemical plant and 16 control subjects from the plant. In addition, we examined 4 out of 5 subjects who had left the production for medical reasons during the last 10 years. Anamnestic data, total and specific IgE to four environmental allergens, lung function and bronchial responsiveness to methacholine were assessed by standard procedures. Skin prick tests (SPT) and patch tests were performed with known sensitizing substances and HMT 100 mg/ml and 2% pet and aq. Results: A high number of exposed subjects and controls reported symptoms during the previous year (64.7% vs 68.8%), most of them were not related to work. Work-related symptoms and objective parameters did not show differences between groups. No sensitizations to HMT as assessed by SPT or patch tests were found. Among those who had left the HMT production for medical reasons, 2 former baggers showed sensitizations to HMT by patch tests. These reported eczema during exposure but lost symptoms after removal from exposure. Geometric mean HMT concentrations as assessed by personal sampling were 0.3 [95% confidence intervals (CI) 0.1; 0.9] mg/m³ in shiftleaders and 0.6 (95% CI 0.3; 1.1) mg/m³ in baggers. Conclusion: High exposures to HMT may cause allergic contact dermatitis. There was no evidence of an increased risk for occupational asthma at mean airborne HMT concentrations below 1 mg/m³. Received: 4 February 1999 / Accepted: 10 July 1999     

Methods of measuring susceptibility of anaerobic bacteria to trovafloxacin,including quality control parameters

Three methods approved by the National Committee for Clinical Laboratory Standards for testing the susceptibility of anaerobic bacteria were used to evaluate the fluoroquinolone, trovafloxacin. The methods gave essentially comparable results with 126 anaerobes and with three quality control strains. A collaborative study defined the quality control range for trovafloxacin MICs. Trovafloxacin had good in vitro activity against the more common anaerobes (MIC 90 <- 2.0 (g/ml).Trovafloxacin (CP-99,219) is a fluoroquinolone with a broad spectrum of antibacterial activity (1–3). Its in vitro spectrum includes many anaerobic bacteria (4).The National Committee for Clinical Laboratory Standards (NCCLS) currently recommends three different methods for testing the susceptibility of anaerobic bacteria (5). The standard reference method is an agar dilution procedure using Wilkins-Chalgren agar. Two alternative methods are an agar dilution technique using Brucella blood agar and a microdilution procedure using a broth version of Wilkins-Chalgren medium. It is important to determine whether these three procedures actually produce identical test results with each antimicrobial agent likely to be tested against anaerobes.     

Efficacy and tolerance of vinpocetine in ambulant patients suffering from mild to moderate organic psychosyndromes

The efficacy and tolerance of orally administered vinpocetine was investigated in patients suffering from mild to moderate organic psychosyndromes including primary dementia. Two hundred and three patients were included in a placebo-controlled, randomized double-blind, multicentre trial and received every day for 16 weeks either: 3 x 10 mg doses of vinpocetine, 3 x 20 mg doses of vinpocetine, or 3 x placebo. Patients were assessed on ratings of clinical global impression, cognitive performance and on measures of the quality of life including depressive illness. There were no clinically relevant side-effects reported and the frequencies of adverse events between patients treated with vinpocetine (30 mg or 60 mg) and placebo were comparable. Statistically significant improvements were found in favour of both active treatment groups compared to placebo in both confirmatory evaluations of efficacy of treatment: the "Global Improvement" (on the CGI scale) and cognitive performance (SKT). Vinpocetine was also superior to placebo in ratings of the "severity of illness". This study demonstrates the usefulness and efficacy of vinpocetine in the management of patients with moderate organic psychosyndromes. An apparently greater therapeutic efficacy of 3 x 10 mg vinpocetine compared with the higher vinpocetine dosage is statistically not significant.     

Comparative carcinogeniocities and reactivities of N-myristoyloxy-N-acetyl-2-aminofluorene and its 7-iodo derivative

Earlier studies showed that N-acetyl-2-aminofluorene (AAF) ismuch more carcinogenic than N-acetyl-2-amino-7-iodofluorene(AAIF). Subsequently it was found that substitution of C-8 ofguanine bases in DNA with AAF residues resulted in displacementof the guanine bases outside the DNA helix. This did not occurafter similar substitution with AAIF residues. As one approachto assessing the possible importance of this gross conformationaldifference to the carcinogenicity of AAF, the carcinogenic activitiesof two electrophilic esters, N-myristoyloxy-AAF and its 7-iododerivative, were compared by s.c. injection into male Fischerrats. On injection of a total of 64 µmol, each ester induceda high incidence of sarcomas, and the latent periods were similar.N-Myristoyloxy-AAIF was solvolyzed in aqueous media at aboutone-half the rate of N-myristoyloxy-AAF, and it was less than10% as reactive with native DNA as N-myristoyloxy-AAF. N-Myristoyloxy-AAFand N-myristoyloxy-AAIF were each less reactive than the correspondingacetoxy derivatives. These data suggest that the low carcinogenicityof AAIF as compared to that of AAF may not be associated withthe conformations of their adducts in the DNA. This differencein carcinogenicity may be related to differences in the ratesof metabolic activation and inactivation of these two amides.     

The "rubtest" and RAST]

The "rubtest" to induce an immediate reaction with various inhalative and ingestive allergens has proved to be a very reliable, easily demonstrable and extremely simple method for detection of allergy-type I, especially of the "highest-sensitivity-type". Recent examinations confirmed the clinical importance and the high correlation between the "rub-test", the IgE-titre (RAST) and the endpoint-skin test-titration.     

Phase I clinical trial of the farnesyltransferase inhibitor BMS-214662 given as a 1-hour intravenous infusion in patients with advanced solid tumors.

PURPOSE: BMS-214662 is a nonsedating benzodiazepine derivative that exhibits broad spectrum cytotoxicity against human solid tumor cell lines and potently inhibits farnesylation of the H-ras and K-ras oncogenic proteins. This report describes the initial Phase I clinical trial of the compound. The main objective of the study was to determine the dose-limiting toxicities and the maximum tolerated dose of BMS-214662 when administered as a single dose i.v. over 1 h every 21 days to patients with advanced solid tumors. EXPERIMENTAL DESIGN: Patients with advanced solid tumors and adequate organ function were eligible for the study. The dose was escalated according to a modified Fibonacci schedule after evaluating groups of at least three patients for toxicity during the first cycle of therapy at each dose level. Pharmacokinetic and pharmacodynamic studies were performed after administration of the two initial doses. RESULTS: The dose of BMS-214662 was escalated from 36 to 225 mg/m(2) through 5 intermediate dose levels in a total of 44 patients. Dose-limiting toxicities occurred in 3 of the 13 (23%) patients during the first cycle of treatment with 225 mg/m(2), consisting of grade 3 nausea/vomiting in 2 patients and grade 3 diarrhea in another patient. In addition, four of these patients experienced reversible grade 3 transaminitis, which was not considered to be dose-limiting. At the recommended dose for Phase II studies, 200 mg/m(2), the most common side effects were reversible transaminitis, nausea, and vomiting. Although there were no objective responses, one patient with pancreatic cancer continues to receive treatment more than 3.5 years after entering the study. BMS-214662 exhibited linear pharmacokinetics and had a mean biological half-life of 1.55 +/- 0.27 h and a total body clearance of 21.8 +/- 10.8 liters/h/m(2), with a low apparent volume of distribution at steady state (31.5 +/- 12.9 liters/m(2)). In patients treated with the recommended Phase II dose, the mean maximum plasma concentration of the drug was 6.57 +/- 2.94 microg/ml, and farnesyltransferase activity in peripheral blood mononuclear cells decreased to a nadir of 10.5 +/- 6.4% of baseline at the end of the infusion but fully recovered within 24 h. CONCLUSIONS: BMS-214662 can be delivered safely as a single 1-h i.v. infusion at a dose that results in pronounced inhibition of farnesyltransferase activity in peripheral blood mononuclear cells. However, the duration of enzyme inhibition was transient, recovering in parallel with the decline in plasma concentrations of this rapidly eliminated drug. Because indications of anticancer activity were observed in several patients, further optimization of the administration schedule for this promising new compound is warranted.