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W Lehmacher

Publications and source records attributed to W Lehmacher.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1990

[Risk profile and macroangiopathy in type II diabetics in medical practice].

The risk profile and the macro-vascular complications of patients with type II diabetes mellitus (NIDDM) was investigated in general practice patients for the first time in the FRG. It was the aim of the study to evaluate the efficacy of the therapy and possible improvements after detailed instructions in a random sample of well defined NIDDM in the greater Munich area. 290 NIDDM (187 female, 103 male) out of a total of 1500 patients treated by 22 general practitioners were randomly recruited for the study. First results indicated an excess morbidity of the NIDDM, e.g. 43.5% with HbA1c greater than 8%, hypertension in 73.8%, hypertriglyceridemia in 75%, hypercholesterolemia in 36.3% adipositas in 78%, and a micro/macro-albuminuria in 44.5%. A similar risk profile could be determined in cases with recently diagnosed NIDDM. The remarkable risk profile documents itself in the incidence of macro-vascular complications: 40.8% of the male and 43.2% of the female showed a peripheral arterial disease (pAVD), in 8% of all patients a carotid artery stenoses could be detected by means of doppler ultrasound technique; 46.6% of the male and 59.3% of the female patients showed symptoms of CHD. With the exception of the incidence of CHD in patients less than 64 years the duration of NIDDM had no influence on the macro-vascular complications as demonstrated in previous studies. The age however always had a significant influence on all three vascular regions examined. Albuminuria correlated as such with a number of risk factors showed a significant correlation with the incidence of pAVD and occurred more often in males with carotid artery stenoses. Other correlations established were: Hypercholesterolemia and FVIII ass. Ag respectively, and the incidence of carotid artery stenoses; blood pressure, F VIII ass. Ag and pAVD. In the female a negative correlation could be seen between the pAVD and the HDL-level. In patients with CHD sex specific correlations could be determined to blood pressure, HbA1c, c-peptide and triglyceride levels.

Adult↗
PubMed1989

Microangiopathy in patients on cyclosporine prophylaxis who developed acute graft-versus-host disease after HLA-identical bone marrow transplantation.

Severe microangiopathy has been reported as a rare complication of cyclosporine A (CsA) prophylaxis in allogeneic bone marrow transplantation (BMT). We found morphological and biochemical changes indicative of generalized endothelial damage in 49 of 66 allogeneic marrow graft recipients receiving cyclosporine, but none in 11 patients treated with methotrexate for prophylaxis of graft-v-host disease (GVHD). Changes occurred after engraftment of bone marrow and consisted of intravascular hemolysis with red cell fragmentation and de novo thrombocytopenia. They were preceded by a decrease in activated partial thromboplastin time and fibrinogen indicating activation of coagulation. Endothelial damage as the central lesion of microangiopathy was confirmed by a simultaneous increase of factor VIII related antigen. Severe microangiopathy was observed in ten patients and was fatal in seven. Risk factor analysis revealed a highly significant association of microangiopathy with severity of acute GVHD (aGVHD) (P less than .001) and use of CsA prophylaxis (P less than .001). Our data suggest endothelial damage as a result of cellular activation and subsequent release of cytokines in the course of a aGVHD, which is not inhibited by CsA prophylaxis.

Adult↗
PubMed1989

[To what extent have early cancer detection and preventive examination for cancer of the uterine cervix fulfilled established expectations?].

The results of cytological screening examinations of women are reported. The study was performed over a ten-year period and comprised 748,871 examinations of 281,705 women. Many long-term observations are among them. 28,171 women (10%) had more than five cytological repeat findings in this period. Basing on the presented dates the following aspects speak in favour of the effectivity of the screening examinations: 1. The decrease of cytological rates of discovery between first examination and repeated examination, 2. the new increase of rates of discovery in case of longer intervals between the examinations, 3. the shifting of the relation between dysplasias, carcinomata in situ and invasive carcinomas in favour of the less severe pathological changes. The rate of newly discovered cervical carcinomas decreased between 1971 and 1980 from 0.9% to 0.2%, the rate of newly discovered carcinomata in situ and severe dysplasias decreased from 3.5% to 1.2%. For future planning of screening programmes several problems have to be taken into consideration--for example, the low attendance rate of women at regular screening examinations, the high rate of false-negative cytological findings and questions of efficiency of programmes in repeatedly examined groups of population.

Adolescent↗
PubMed1989

[Are there risk factors for stenosing laryngitis? Results of the Southern Bavaria pseudo-croup study].

We tried to find a correlation between elevated air pollution levels and incidences of laryngitis (pseudocroup). Clinical data-obtained by questionnaire-from 418 children with laryngitis, viral shedding in rhinal secretion and data on air pollution as SO2, NO2 and dust levels were compared via correlation analyses. Boys with allergic diathesis and with signs for bronchial hyperreactivity were identified as a high risk group. The high incidence of laryngitis especially seen in the month of October could be explained by the increased number of RSV positive patients. There was no significant correlation between laryngitis and the air pollution levels during the time of observation.

Air Pollution↗
PubMed1989

[A 3-month, randomized double-blind dose-response study with 0-(beta-hydroxyethyl)-rutoside oral solutions].

The antioedematous effect of 0-(beta-Hydroxylethyl)-rutoside (HR)-drinking solutions with 600, 900, 1200 and 1500 mg active substance was tested in a randomized double-blind study against placebo with 30 female patients in the change of life. The decrease of the oedemas was measured by recording the change in the leg volume. The patients valued the symptoms "tired and heavy legs", "tenseness" and "tingling sensation". After 3 months the daily taking of HR-drinking solutions showed a significant decrease of leg volume. At the end of the treatment there was no significant difference between the four verum groups.

Administration, Oral↗
PubMed1987

[Determinants of plasma digoxin and digitoxin concentrations in elderly patients. A multivariate analysis].

In 1063 patients (greater than or equal to 60 years, 531 men, 532 women) the plasma concentration during digitalis maintenance therapy (metildigoxin, n = 356, beta-acetyldigoxin, n = 359, and digitoxin, n = 348) was determined and related to sex, age, body weight, serum potassium, renal function and the prescribed daily maintenance dose. Classification of treatment groups according to renal function (Crea less than or equal to 1.3 mg/dl parallel greater than 1.3 mg/dl) did not show any difference of the mean maintenance doses. In multiple linear regression analyses only a weak relationship between plasma digitalis concentration and the studied variables was found, which could be equally attributed to dose, creatinine and serum potassium in the digoxin derivative groups, whereas for digitoxin only body weight had a significant effect on the plasma concentration. During a maintenance dose of 0.07 or 0.1 mg/die which was given to 87% of patients in the digitoxin group, 70% were found to have plasma levels within the therapeutic range.

Acetyldigoxins↗
PubMed1985

The erythrocyte aggregation value as a measure of the risk of myocardial infarction and arteriosclerosis of peripheral arteries.

The erythrocyte aggregation value (AW) has been determined in groups of patients with and without coronary heart disease (CHD) and in a group of apparently normal subjects, using the Metricell apparatus as described by Kachel et al. The following results were obtained: There was a close correlation between the AW and the existence of CHD or arteriosclerosis of peripheral arteries. The precision of the retrospective prediction of CHD by this noninvasive test in male subjects aged over 45 years (total CHD prevalence = 0.494) was: sensitivity = 0.571, specificity = 0.767. The predictive value of positive tests (PVpos) was 0.706, of negative test (PVneg) 0.647. The discriminatory ability of the AW test was superior to that of serum cholesterol determinations or measurement of other CHD risk factors made in the same population. The AW rises exponentially with the total score for risk factors for CHD hazard for the subject. It appears, however, from the insignificant correlations observed that there is no direct connection between the AW and any single risk factor.

Cholesterol↗
PubMed1985

Diaplacental carcinogenic effects of 5-azacytidine in NMRI-mice.

5-Azacytidine was applied to NMRI-mice (1-2 mg/kg) either on gestation day 12, 14, or 16. In the first case it mainly induced leukemias, while in the latter experiments leukemias, lung adenomas and soft tissue sarcomas represent the main effects. The experiments performed on gestation day 14 led to tumor rates below the spontaneously occurring tumor frequencies in NMRI-mice. There is a clear-cut inverse dose-response relationship in leukemia induction, as the higher dose principally shows a lower degree of effectiveness. This, as well as a reduction of tumor frequency below control levels after application of this drug on day 14, can be explained by an "overkill" effect. The cytotoxic and embryolethal efficacy of the agent thus surpasses the transformation effects at the cellular genome. While a negative correlation between the general embryotoxicity of azacytidine and the simultaneous tumor inducibility is to be observed, there is no correlation at the target organ level between the embryotoxic and the carcinogenic effects.

Animals↗