Search PubMed⌕ Search

Biomedical subjects

W Lehmacher

Publications and source records attributed to W Lehmacher.

At least 37 records · Page 2Linked to original sources
PubMed1999

Considerations on the statistical design of the ATMI study.

The ATMI study of prevention of mediastinitis after cardiac surgery uses the total amount of therapeutic interventions measured by the TISS-28 score as the primary endpoint. The study is designed as an adaptive group-sequential plan with three sequences, as experiences with the TISS-28 in cardiac intensive care units are scarce. According to the Bauer-Köhne method the sample sizes of the second and third sequences can be calculated in a data-driven manner after the results of the previous interim analyses are available. Thus the first trial phase can be considered as an internal pilot study.

APACHE↗
PubMed1999

Adaptive sample size calculations in group sequential trials.

A method for group sequential trials that is based on the inverse normal method for combining the results of the separate stages is proposed. Without exaggerating the Type I error rate, this method enables data-driven sample size reassessments during the course of the study. It uses the stopping boundaries of the classical group sequential tests. Furthermore, exact test procedures may be derived for a wide range of applications. The procedure is compared with the classical designs in terms of power and expected sample size.

Acne Vulgaris↗
PubMed1999

Requirements for demonstrating clinical efficacy: statistical aspects.

Usual statistical practice in inference on the comparison of two treatment effects is based on significance tests. In the positive case, it is unlikely that the observed difference is based only on random variation, and a decision is made that there is a real superiority. In the negative case, no conclusion on a missing difference is possible. In both cases, statistical tests fail to describe the magnitude of the underlying effect. Confidence intervals are more suitable for demonstrating clinical efficacy. Their advantages and applications are discussed.

Clinical Trials as Topic↗
PubMed1998

Antibacterial and sebosuppressive efficacy of a combination of chloramphenicol and pale sulfonated shale oil. Multicentre, randomized, vehicle-controlled, double-blind study on 91 acne patients with acne papulopustulosa (Plewig and Kligman's grade II-III).

In a 3-armed, multicentre, randomized, double-blind, vehicle-controlled study involving 91 patients with acne papulopustulosa, Plewig's grade II-III, evidence could be provided of a significant reduction of the propionibacteria as well as a subosuppressive effect (squalene reduction) under a combination of 1% chloramphenicol (CAS 56-75-7) and 0.5% pale sulfonated shale oil versus the alcoholic vehicle (1-2 ml twice daily). Likewise, monotherapy with chloramphenicol resulted in a significant reduction in bacteria compared to the vehicle. The combination therapy was superior to the monotherapy with regard to the sebosuppressive effects. Based on a kinetics test carried out for a total of 2 h, a clinically relevant percutaneous absorption of chloramphenicol was ruled out. The chloramphenicol serum level was between < 5.0 microgram/l to 180 microgram/l (average 25 micogram/l). This is important because with systemic application (peroral, i.v.), the therapeutic chloramphenicol level is > 25 mg/l (25,000 microgram 1). None of the blood count and serum parameters were pathologically changed in a clinically relevant way before and after the therapy. An induction of resistance against chloramphenicol in the propionibacteria could be excluded. No adverse events and side effects occurred. The topical therapy of acne papulopustulosa with chloramphenicol as a monosubstance or in combination with pale sulfonated shale oil represents an effective and safe local antibiotic treatment possibility.

Acne Vulgaris↗
PubMed1997

National rates and regional differences in sensitization to allergens of the standard series. Population-adjusted frequencies of sensitization (PAFS) in 40,000 patients from a multicenter study (IVDK).

Sensitization rates to contact allergens vary between centers and are influenced by sex and age. Eliminating the latter 2 factors by standardization of data by age and sex, the present analysis addresses possible differences between centers remaining after elimination of these confounders, and analyzes other factors which might influence rates, e.g., the MOAHL index. Overall standardized rates were well within the range reported in previous studies and may be regarded as representing the rates of the "patch test population" in Central Europe (e.g., nickel sulfate 12.9%, fragrance mix 10.5%, balsam of Peru 7.3%, thimerosal 5.6%). For this analysis, data of those departments which contributed more than 2000 patients, or of those with extreme proportions concerning sex, age and occupational cases were selected. Patients from these 10 departments differed considerably with regard to the items of the MOAHL index and with regard to standardized rates. The items of the MOAHL index proved to be suitable for describing different patch test populations and for explaining some differences between centers. Only 'atopic dermatitis' seems to have little influence on (standardized) rates. Face dermatitis is not yet represented in the MOAHL index, but should be included, together with age > 40 years, in an extended index (acronym: MOAHLFA). Regional allergen exposure (with striking differences between East Germany, West Germany and, to a lesser extent, Austria) seems to have a great influence on the sensitization pattern observed in a department. In addition, sociological factors may influence sensitization rates, which is exemplified by high rates of nickel allergy in a socially defined subgroup. Future studies should focus on these factors, as well as on factors concerning patch test practices and quality control.

Adult↗
PubMed1996

[Pharmacokinetics and effects of xylazine (Rompun) in dogs].

Six beagle dogs were treated with xylazine hydrochloride (1 mg/kg i.m.). The plasma xylazine concentration was measured by HPLC. Additionally, clinical effects were registered (cardiac rate, respiratory activity, electrocardiogram, body temperature, motoric activity, attention, analgesia). Maximum plasma concentrations were measured after 15 minutes (476 ng/ml). The plasma half-life was 24 minutes. Sedation was registered over one hour (xylazine concentration of more than 150 ng/ml). Within the first 30 minutes after treatment (xylazine concentration of more than 300 ng/ml), a low-grade analgesia was observed. In contrast, cardiac and respiratoric depression and also significantly diminished body temperature were registered over 2 to 3 hours.

Analgesia↗
PubMed1996

Investigation of the therapeutic equivalence of different galenical preparations of O-(beta-hydroxyethyl)-rutosides following multiple dose peroral administration.

Oxerutins (O-(beta-hydroxyethyl)-rutosides, HR, Venoruton) are available in different releasing galenical formulations for the treatment of chronic venous insufficiency (CVI). In order to investigate the biopharmaceutical relevance of the releasing properties of the galenical forms the therapeutic efficacy between the commercially available forms was investigated (500 mg sustained release film tablets, 300 mg sustained release film tablets, 300 mg normally releasing capsules) in comparison to an aqueous solution and placebo. In total 100 female patients with CVI grade II participated. The study was carried out following a randomized, placebo controlled design with parallel treatment groups. Following a two-week run-in phase patients were treated for 12 weeks with different posologies of HR (2 x 1/d 500 mg, 3 x 1/d 300 mg, 1 x 1000 mg/d as aqueous solution). Main criterion was the reduction of leg volume following 12 weeks treatment. Subjective criteria were descriptively evaluated. All four HR treatments were significantly superior to placebo (p < 0.0008). The different posologies had no influence on the efficacy. The therapeutic efficacy is independent of the in vitro rate of release. The available forms are regarded as bioequivalent.

Aged↗
PubMed1996

[Prevalence of motile salmonellae in egg-laying hens at the end of the laying period].

A total of 3504 hens of the layer-type from 122 flocks (belonging to 89 farms), each with more than 10,000 animals, were culturally examined at the time of slaughter. Of these hens, 2112 (60.3%) from 74 flocks (60.7%) were obtained from 21.3% of the laying-hen farms in a selected region of Lower Saxony in Germany. The other hens came from the remaining part of Lower Saxony and seven other German states (Brandenburg, Mecklenburg Vorpommern, North Rhine Westphalia, Schleswig Holstein, Saxony, Saxony Anhalt, and Thuringia). After arrival at the slaughter house, a random sample of 29 layers was collected from each of the flocks, and liver and spleen, as well as cecal samples, were separately cultured for each bird. Motile salmonellae could be proved in 365 (10.4%) layers from 67 flocks (54.9%). In the selected region, 48 out of 74 flocks (64.9%) and 289 out of 2112 layers (13.7%) were Salmonella-positive. However, the isolation frequency of salmonellae did not differ significantly between flocks of brown and white layers. These Salmonella (S.) isolates could be serologically assigned to 6 different serovars, namely S. enteritidis (SE), S. infantis (SI), S. livingstone (SL), S. typhimurium (ST), S. indiana (SID) and S. cerro; only one isolate of serogroup D1 was incompletely serotyped. SE was detected in 5.8% of the hens from 47.5% of the tested flocks, of which 4.6% of the animals and 32.8% of the flocks came from the selected region in Lower Saxony. The SE isolates were classified into 12 different lysotypes. In 41 out of 58 SE-positive flocks (70.7%), the isolates belonged to lysotype (lt) 4, in 12 flocks (20.7%) to lt 8, in 5 flocks (8.6%) to lt 7, and in 3 flocks (5.2%) to lt 11. A total of 190 (93.1%) out of 204 isolates of the serovar SE carried plasmids. All the plasmid-positive SE-strains harboured the serovar-specific 37 MD virulence-plasmid, nine of them (4.4%) in conjunction with a second and eight strains (3.9%) with a second and a third smaller plasmid.

Animals↗
PubMed1995

Pattern analysis of human Salmonella enteritidis infection.

Information on salmonella serovar, community, and date of isolation concerning 10,368 cases of S. enteritidis (SE) infection and 1163 cases of S. typhimurium (ST) infection reported in 1992 to the Salmonella Data Bank of the Land of Brandenburg have been analyzed for clusters and trends on case/time diagrams. A breakdown by district provided a suitable degree of "resolution" for discrimination of "Episodes of Increased Case Frequency" (EICF) and 7 days moving averages. Thus 39 of the 44 districts of the Land were included in the evaluation of SE cases. The population size of the remaining 5 districts was too high for clear episode discrimination. EICFs were subdivided into (a) 16 outbreaks (another 10 outbreaks occurred outside EICFs), which had also been identified and officially reported by local health services as a result of compulsory investigation of cases and their social environment, and (b) 44 "case accumulations" (ACCs), which were only identified by retrospective analysis of the case/time diagrams. By this procedure, three case categories of distinct properties have been found for SE transmission from the animal reservoir to the human population: outbreaks, ACCs, and "truly sporadic cases" scattered over the district outside outbreaks and ACCs (Table 3). Truly sporadic cases (Table 6) represented the largest proportion of SE cases. ACCs accounted for 37% and outbreaks, for 12%. The most striking result concerns the ACCs, which cover slightly larger geographical areas (mean: 3.5 communities) and last longer (mean: 3 weeks, but up to 7 weeks) than officially recorded outbreaks (means: 2 communities and 2 weeks). SE-ACCs differed from SE outbreaks also in the seasonal pattern. Otherwise, ACCs met outbreak characteristics including the average number of persons involved (mean: 64, for outbreaks: 42; Table 4). The results suggest that SE-ACCs represent an important and distinct element in the SE epidemic. This conclusion is supported by a comparison of the findings with results obtained by the same procedure for ST cases. ST outbreaks do not differ from ST-ACCs in any respect, and both types of ST-episodes are of significantly shorter duration and comprise less people than episodes due to SE. The public health significance of the SE-ACCs as a newly detected and particular element of the current SE epidemic is discussed. In view of the epidemiological significance, i.e. the high proportion of all SE cases involved, it appears justified to develop methods for the early detection of ACCs and the search for the "missing link" between the cases and their source at the community level.

Humans↗
PubMed1994

ELISAs based on recombinant antigens for seroepidemiological studies on Toxoplasma gondii infections in cats.

Two recombinant Toxoplasma gondii polypeptides, H4 and H11, were tested as diagnostic antigens in enzyme-linked immunosorbent assays (ELISAs). The results obtained by ELISAs based on single H4 (H4-ELISA), on single H11 (H11-ELISA) and on a mixture of H4 and H11 (H4/H11-ELISA) were compared with results obtained by an ELISA based on traditional ELISA antigen (TEA-ELISA), an indirect fluorescent antibody test (IFAT), the Sabin-Feldman dye test (SFDT) and a direct agglutination test (DAT). A total of 306 cats from a suburban cat population were tested of which about 45% showed serological evidence of T. gondii infection. Infection rates varied from about 32% for cats kept indoors to about 55% for stray cats. Specificities > 99% were observed for all ELISAs based on the recombinant antigens (H4-ELISA, H11-ELISA and H4/H11-ELISA). The H4/H11-ELISA also reached a sensitivity of 95% which compared very favourably with those observed for the TEA-ELISA (98%) and for the IFAT (94%). Negative and positive predictive values for the H4/H11-ELISA were 96 and > 99%, respectively. Antibody titres measured by the H4/H11-ELISA also correlated well with those measured by the SFDT and the DAT. Hence, the H4/H11-ELISA appears to be a very suitable test for sero-epidemiological studies on T. gondii infections in cats.

Age Factors↗
PubMed1994

Estimates of the radiation-induced mutation frequencies to recessive visible, dominant cataract and enzyme-activity alleles in germ cells of AKR, BALB/c, DBA/2 and (102xC3H)F1 mice.

Male mice of the genotypes AKR, BALB/c, (102/ElxC3H/El)F1 or DBA/2 were exposed to 3 + 3 Gy irradiation with a 24 h fractionation interval and mated to untreated Test-stock females. The offspring were screened for activity alterations of 10 erythrocyte enzymes as well as recessive specific-locus and dominant cataract mutations. The observed mutation rates per locus per gamete x 10(-5) for treated spermatogonia were 6.8, 4.9, 2.5 and 1.3 for enzyme-activity mutations, 8.6, 24.1, 22.8 and 31.4 for specific-locus mutations, and 0.7, 0.9, 0.6 and 2.5 for cataract mutations, respectively. Some variability from strain to strain in the frequency of radiation-induced mutations was observed. However, there was no consistent effect of genotype on the frequency of induced mutations and it is concluded that no effect of genetic background exists for the four genotypes tested. There is good agreement between the observed enzyme-activity mutation rate in children of survivors of the atomic bombings and the expected mutation rate based on results with mice. Results are therefore consistent with an estimation of human radiation-induced genetic risks based upon an extrapolation of experimental results in the mouse.

Alleles↗
PubMed1993

Tumor promotion in a breast cancer model by exposure to a weak alternating magnetic field.

In view of the methodological problems of epidemiological studies on associations between exposures to 50/60 Hz magnetic fields (MF) and increased incidence of cancers, laboratory studies are necessary to determine if 50/60 Hz MF are cancer promoters or can progress cancers. The objective of the present study was to determine if an alternating MF of low flux density exerts tumor-promoting or co-promoting effects in a model of breast cancer in female rats. Mammary tumors were induced by the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). A group of 99 rats was exposed to a homogeneous MF of 50 Hz, 100 microT (microtesla), for 24 h/day 7 day/week for a period of 91 days; another group of 99 rats was sham-exposed under the same environmental conditions as the MF-exposed rats. The exposure chambers were identical for MF-exposed and sham-exposed animals. DMBA was administered orally at a dose of 5 mg/kg at the first day of exposure and at weekly intervals thereafter up to a total dose of 20 mg per rat. The animals were palpated once weekly to assess the development of mammary tumors. In controls, DMBA induced tumors in about 40% of the animals within three months of first application. Eight weeks after DMBA application the MF-exposed rats exhibited significantly more tumors than sham-exposed animals. This difference in the rate of tumor development was observed throughout the period of exposure. At the end of the three-month period of MF exposure the tumor incidence in MF-exposed rats was 50% higher than in sham-exposed rats, the difference being statistically significant. Furthermore, the size of tumors as estimated by palpation was significantly larger in the MF-exposed compared to sham-exposed rats. The data demonstrates that long-term exposure of DMBA-treated female rats to an alternating MF of low flux density promotes the growth and increases the incidence of mammary tumors, thus strongly indicating that MF exposure exerts tumor-promoting and/or copromoting effects.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Comparison between the efficacy and tolerability of oxerutins and troxerutin in the treatment of patients with chronic venous insufficiency.

Oxerutins (Venoruton) and troxerutin (CAS 7085-55-4) are both mixtures of O-(beta-hydroxyethyl)-rutosides used for the treatment of chronic venous insufficiency. As di-O-(beta-hydroxyethyl)-rutosides and 7-mono-O-(beta-hydroxyethyl)-rutoside were found to be more active with regard to free radical scavenging compared to tri-O-(beta-hydroxyethyl)-rutoside the aim of this study was to compare oxerutins and troxerutin clinically. 12 female, post-menopausal patients with chronic venous insufficiency grade II participated in this double-blind study with random allocation to the treatment groups. They received 900 mg/day oxerutins or troxerutin for 12 weeks and were observed for 4 further weeks without treatment. Leg volumes (water displacement) and subjective symptoms (VAS, visual analogue scale) were evaluated before and following 2, 4, 8, 12 and 16 weeks. Both treatments were active in reducing leg volumes and in ameliorating subjective symptoms (mean volume reduction -167 +/- 157 ml x week). Volume reduction totalled to -261 +/- 154.2 ml x week for oxerutins and -73.2 +/- 97.1 ml x week for troxerutin. The difference is statistically significant (p = 0.04). The findings with subjective symptoms were in good accordance to the objective volume measurement. Oxerutins revealed a remarkable carry over effect.

Anticoagulants↗
PubMed1992

[Treatment of acute ankle sprains. Comparison of the efficacy and tolerance of 2 indomethacin-gel preparations].

In a controlled randomized double-blind study, the effectiveness and tolerance of two gels containing the active substance indomethacin used in the treatment of acute sprains of the ankle were compared. Reduction in swelling and the evaluation of pain served as the criteria for the success of treatment. Over a treatment and observation period of two weeks, the parameters decreased rapidly and equally in both groups. At no time were statistically remarkable differences observed for any of the parameters. With respect to the main target parameter, the two preparations were seen to be of equal therapeutic effectiveness. Nor were there any differences in the tolerance of the two indomethacin gels.

Administration, Topical↗
PubMed1992

c-myc mRNA expression in non-Hodgkin's lymphomas.

Steady state c-myc mRNA levels determined by Northern blot analysis were examined in non-Hodgkin's lymphomas (NHL) of both high (n = 29) and low malignancy (n = 18), and in non-specific chronic lymphadenitis (n = 6). High grade NHL, classified according to the updated Kiel classification, revealed significantly larger amounts of c-myc mRNA compared with low grade NHL and lymphadenitis. mRNA levels in non-specific lymphadenitis were lower than in low grade NHL, but the differences were not statistically significant. No correlation between c-myc mRNA levels and the immunologic phenotype was discernible. Growth fractions of the NHL were determined by immunostaining with the monoclonal antibody Ki-67. Significant correlations between the percentages of Ki-67-positive cells, as well as the amounts of c-myc mRNA, and classification into high or low grade NHL were found. However, the percentage of Ki-67 positive cells and c-myc mRNA levels in individual cases and in the various histologic entities of NHL did not correlate. Our results indicate the overexpression of the c-myc gene in NHL, and a highly significant correlation of steady state c-myc mRNA levels with the prognosis-related histomorphologic Kiel classification of NHL into different subgroups of low and high grade malignancy.

Antigens, Neoplasm↗
PubMed1992

Factors which provoke post-infarction depression: results from the post-infarction late potential study (PILP).

Symptoms of depression in the majority of patients immediately following acute myocardial infarctions (AMI) resolve rapidly; they are an adjustment reaction. However, in a group of 552 male patients there were 80 (14.5%) patients with persistent major depressive symptoms during a finite period after AMI. Infarction size was assessed by maximum creatine kinase levels, the QRS-complex and the occurrence of late potentials. These measures did not correlate with the degree of depressed moods in these groups. An arrhythmic event in the early hospitalization phase, a recurrent infarction, dyspnoea, and persistent angina pectoris before the AMI were significantly related to more profound degrees of depression. Patients who reported serious life-events in the last 2 yr before AMI, or who suffered from exhaustion and fatigue in the prehospital phase were subject to significantly higher levels of depression. A prodromal phase prior to hospitalization free of bodily symptoms and the use of denial were related to low levels of depression. The logistic regression model incorporating all univariate significant variables revealed that symptoms of exhaustion and fatigue prior to AMI had the strongest independent correlation with post AMI depression.

Activities of Daily Living↗
PubMed1992

[The use of ELISA systems for control of epizootics: safety of test standards using batch assays].

One of the advantages of ELISA techniques is to achieve a higher degree of safety by standardization. Bases of these standardizations should be, if available, international or national standards in combination with cutoff definitions. The cutoff definitions should be expressed, separate for the main kinds of samples, defined as a dilution of the standard. Those definitions can replace the mostly awkward and involved test descriptions as usual in official regulations. To guarantee a high grade of reliability it is a matter of urgent necessary to test (if possible by the producer) each serial (lot) of ELISA and to describe their capacities with regard of sensitivity and specificity. Separate pretests may be done with the main kinds of samples with well known reactions (negative and weak positive). The results are to compare to those of the cutoff-related dilutions of the standard in the same matrix. These descriptions of the capacities of each serial (lot) are safe bases for use of the serial. Key concepts are the quotients of the minimum positive value divided by the maximum negative or alternatively the mean value of the positive minus the threefold standard deviation divided by the mean value of the negative plus the threefold standard deviation.

Animals↗