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Biomedical subjects

W Lehmacher

Publications and source records attributed to W Lehmacher.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1991

Analysis of the crossover design in the presence of residual effects.

When a residual effect is suspected in a two-period crossover trial, an analysis of the first-period data is often chosen instead of the potentially biased crossover analysis. This paper indicates how the usual crossover test has to be interpreted correctly and that its bias has two different consequences, namely a conservative or a liberal test decision if a positive (carryover) or a negative (withdrawal) residual effect exists. A multiple testing procedure is presented allowing for simultaneous crossover and first-period analysis controlling the experimental error rate. This procedure together with the correct interpretation of the crossover test enables many useful applications of crossover designs.

Bias↗
PubMed1991

[Patient-specific determinants of delay in goal-oriented patient behavior in acute myocardial infarct. Results of the post-infarct late potential study].

369 (63%) of 586 consecutive patients with confirmed myocardial infarction were admitted to hospital within 6 h of symptom onset. Patients' arrival to hospital followed a characteristic circadian distribution with a marked morning increase between 0600 and 1200 hours, and a corresponding decrease in the late night hours. There were no differences in the occurrence of late potentials and in ECG data between early and late arrival group. The early group (less than 5.9 h) was, however, characterized by significantly higher cardiac enzyme levels than the late group (greater than 6.0 h); they also experienced more arrhythmic events in the acute phase (16.0% vs. 9.7%; p less than 0.032). Catecholamines were significantly more often necessary (26.4% vs. 10.3%; p less than 0.0001). Six-month prognosis after AMI was markedly worse. The time between symptom onset and hospital arrival was not affected by age and risk factors. In univariate analysis, pain history and recurrent infarction also had no influence on delay of admission to hospital. The time interval was, however, significantly shorter when the acute event occurred during the night (18.4% vs. 8.3%; p less than 0.0001). Absence of prodromi in the prehospital phase (18.5% vs. 12.0%; p less than 0.04) and a higher socio-economic level (68.3% vs. 61.0%; p less than 0.077) also shortened the admission time, whereas a hyperactive behavioral pattern prolonged the delay time (21.1% vs. 28.9%; p less than 0.05).

Adult↗
PubMed1991

Procedures for two-sample comparisons with multiple endpoints controlling the experimentwise error rate.

Clinical trials are often concerned with the comparison of two treatment groups with multiple endpoints. As alternatives to the commonly used methods, the T2 test and the Bonferroni method, O'Brien (1984, Biometrics 40, 1079-1087) proposes tests based on statistics that are simple or weighted sums of the single endpoints. This approach turns out to be powerful if all treatment differences are in the same direction [compare Pocock, Geller, and Tsiatis (1987, Biometrics 43, 487-498)]. The disadvantage of these multivariate methods is that they are suitable only for demonstrating a global difference, whereas the clinician is further interested in which specific endpoints or sets of endpoints actually caused this difference. It is shown here that all tests are suitable for the construction of a closed multiple test procedure where, after the rejection of the global hypothesis, all lower-dimensional marginal hypotheses and finally the single hypotheses are tested step by step. This procedure controls the experimentwise error rate. It is just as powerful as the multivariate test and, in addition, it is possible to detect significant differences between the endpoints or sets of endpoints.

Biometry↗
PubMed1990

Increased serum levels of tumor necrosis factor alpha precede major complications of bone marrow transplantation.

Acute graft-versus-host disease, interstitial pneumonitis, endothelial leakage syndrome, and veno-occlusive disease are major complications of bone marrow transplantation. Though several new regimens for prophylaxis and treatment of these syndromes have been introduced, the overall incidence has been only slightly reduced over the last few years. We retrospectively analyzed tumor necrosis factor alpha (TNF alpha) serum levels between day -8 and day 100 after bone marrow transplantation in 56 patients transplanted in our unit for a variety of hematological diseases. In 34 patients with uneventful courses, mean TNF alpha levels rose to a maximum of 76 +/- 29 pg/mL. In contrast, 22 patients with major transplant related complications showed mean increases of TNF alpha of 492 +/- 235 pg/mL (P less than .0001). Increases of TNF alpha occurred before interstitial pneumonitis and severe acute graft-versus-host disease with a latency of 25 to 54 days. Early complications such as endothelial leakage syndrome and veno-occlusive disease were closely associated with increases of TNF alpha serum levels. Our study suggests two pathways of TNF alpha release: activation of host macrophages and stimulation of donor cells in the course of acute graft-versus-host disease. Cytokine monitoring should be helpful for prediction and earlier treatment of major transplant related complications.

Adolescent↗
PubMed1990

Dose rate and fractionation of total body irradiation in dogs: short and long term effects.

Variations of regimens of total body irradiation (TBI) were investigated in the dog as a preclinical model for bone marrow transplantation. Inactivation of hemopoietic precursor cells (CFU-GM) was studied following irradiation of marrow in vitro, following TBI at sublethal doses in vivo and following autologous transplantation of marrow obtained after sublethal TBI. Inactivation and recovery of CFU-GM as well as restoration of hemopoiesis following autologous transplantation was independent of the dose rate, but nadirs of blood counts were lower following sublethal TBI with the higher dose rate. Acute non-hemopoietic toxicity of TBI depended on the dose, the dose rate and the total treatment time and not on the fractionation regimen. At a total dose of 25 Gy acute mortality was prevented by prophylactic administration of oral, non-absorbable antibiotics. Late mortality was due to degenerative and autoimmune-like disorders with or without infections and to malignant tumors. Evaluation of long-term survival is still preliminary, since surviving dogs of two groups (10 Gy as single dose, 25 Gy as hyperfractionated TBI) have not yet reached the median survival time of their group. So far, long-term survival depended on the total dose (p = 0.05) and, possibly, the fractionation regimen (p = 0.12). The latency period until development of malignant tumors was influenced by the total doses given in the same treatment time (p = 0.05) and by the total treatment time for equal doses (p = 0.04). It was concluded that TBI at a low dose rate may give the best therapeutic ratio of inactivation of hemopoietic precursor cells to acute toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗