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     

Xanthine oxidase inhibition by allopurinol affects the reliability of urinary caffeine metabolic ratios as markers for N-acetyltransferase 2 and CYP1A2 activities

Objectives: To evaluate the in vivo effect of xanthine oxidase (XO) inhibition by allopurinol on the determination of polymorphic N-acetyltransferase 2 (NAT2) and cytochrome P450 1A2 (CYP1A2) with urinary caffeine metabolic ratios. Methods: In an open, prospective study involving 21 healthy subjects (eight fast, 13 slow NAT2 acetylators) allopurinol (300 mg perday) was administered orally on trial days 1–8, followed by a wash-out period of 8 days. Urinary caffeine tests (200 mg caffeine p.o.) were performed repetitively. Urine was collected for 8 h and venous blood samples for the determination of allopurinol, oxypurinol and uric acid were drawn. The urinary caffeine metabolites 1-methyluric acid (1MU), 1-methylxanthine (1MX), 1,7-dimethyluric acid (17MU), 1,7-dimethylxanthine (17MX), 5-acetylamino-6-formylamino-3-methyluracil (AFMU), plasma allopurinol and oxypurinol were analysed using high-performance liquid chromatography (HPLC). Results: During XO inhibition by allopurinol, the formation of 1MU from 1MX and therefore the XO ratio 1MU/1MX decreased to 15.9 (1.2)% [mean with (SEM)] of baseline values (P < 0.005). The NAT2 ratio AFMU/1MX decreased likewise to 56.7 (6.3)% (P < 0.005). AFMU/(AFMU + 1MX + 1MU), an alternative NAT2 ratio, remained constant, but the CYP1A2 ratio (AFMU + 1MX + 1MU)/17MU, used to express CYP1A2 activity, transiently increased to 167 (13)% (P < 0.005). The NAT2 phenotype did not influence CYP1A2 and XO ratios or plasma oxypurinol pharmacokinetics. Conclusions: Several caffeine metabolic ratios are commonly used to express the activities of NAT2, CYP1A2 and XO both in healthy volunteers and in polymedicated patients, although their reliability has not been evaluated thoroughly during concurrent drug administration. The findings of this study suggest that NAT2 phenotyping should be performed using the ratio AFMU/(AFMU + 1MX + 1MU) if an XO inhibitor may be present. It also shows that the determination of CYP1A2 activity with caffeine as a metabolic probe is considerably altered under these conditions. Thus, concomitant drug administration may impair the robustness of multiple pathways of the complex caffeine test. This points to the need for alternative probes, designed to assess only the activity of a single enzyme because, in contrast to healthy volunteers, in patients known or unknown drug interactions may often be present. Received: 10 August 1998 / Accepted in revised form: 5 October 1998     

Cardiac effects of beta-adrenoceptor antagonists with intrinsic sympathomimetic activity in humans: beta1- and/or beta2-adrenoceptor mediated?

The aim of this study was to find out whether cardiac responses to the beta-adrenoceptor antagonists with intrinsic sympathomimetic activity (ISA) xamoterol and celiprolol are mediated by cardiac beta1- or beta2-adrenoceptors or both. For this purpose we assessed, in six healthy male volunteers, the effects of xamoterol (100 and 200 mg, p.o.) and celiprolol (200, 600, and 1,200 mg, p.o.) on blood pressure, heart rate, and heart rate-corrected duration of the electromechanical systole (QS2c, as a measure of inotropism). Xamoterol, in both doses, increased systolic blood pressure and heart rate, transiently decreased diastolic blood pressure, and shortened QS2c; all these effects were attenuated after pretreatment of the volunteers with the beta1-adrenoceptor antagonist bisoprolol. Celiprolol, in all three doses, increased heart rate, decreased diastolic blood pressure, and shortened QS2c but only marginally increased systolic blood pressure. Bisoprolol did not attenuate these celiprolol effects but rather enhanced celiprolol effects on systolic blood pressure and heart rate. In a further set of experiments, we studied cardiovascular effects of celiprolol in six healthy volunteers whose beta2-adrenoceptors had been desensitized by a 2-week treatment with 3x5 mg/day terbutaline. Under these conditions, celiprolol failed to increase heart rate or to shorten QS2c. We conclude that, under resting conditions, in healthy volunteers, beta-adrenoceptor antagonists with ISA can exert increases in heart rate and contractility that are mediated by either cardiac beta1-adrenoceptor (xamoterol) or cardiac beta2-adrenoceptor (celiprolol) stimulation. Thus in the human heart, the ISA of beta-adrenoceptor antagonists can be a beta1- or beta2-adrenoceptor agonistic component.     

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.     

Ampicillin-sulbactam susceptibility testing criteria

In vitro studies in five different medical centers documented the susceptibility of 2,440 consecutive isolates of theEnterobacteriaceae against ampicillin-sulbactam disks of different potencies. For determination of MICs, both 2:1 or 1:1 ratios were used as long as the concentrations of sulbactam at the breakpoints remained the same, i.e. MIC 16/8.0 µg/ml or 8.0/8.0 µg/ml for the susceptible category. Disks containing 10 µg of ampicillin and 10 µg of sulbactam are still to be preferred with interpretive criteria of 15 mm for susceptible and 11 mm for resistant (MIC 64/32 µg/ml or 32/32 µg/ml). The reliability of the disk test actually diminished when the amount of sulbactam in the disk was increased.     

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.     

Repair and mutagenesis of plasmid DNA modified by ultraviolet irradiation or N-acetoxy-N-2-acetylaminofluorene.

Plasmid DNA was modified in vitro to various extents with N-acetoxy-N-2-acetylaminofluorene or UV irradiation. The modified plasmid DNAs were then used to transform Escherichia coli strains having different repair capabilities. Both survival and mutagenesis frequencies of the plasmid were measured as a function of the number of lesions per plasmid molecule. The majority of N-2-acetylaminofluorene (AAF) adducts, like thymine dimers, were repaired by the excision (uvrA+-dependent) pathway. In rec+ strains, dose-dependent mutagenesis occurred in either AAF- or UV-modified plasmid DNA. This is in contrast with results obtained in recA- strains, in which only AAF adducts gave rise to a lower, but dose-dependent, mutagenesis frequency. In these recA- strains there was no UV mutagenesis. Unlike what is observed with phages, induction of the "SOS" functions by UV irradiation of the bacteria prior to transformation did not increase the survival or the mutagenesis of the plasmid.