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Biomedical subjects

K Ulm

Publications and source records attributed to K Ulm.

At least 19 recordsLinked to original sources
PubMed1991

A statistical method for assessing a threshold in epidemiological studies.

I describe a method for estimating and testing a threshold value in epidemiological studies. A threshold effect indicates an association between a risk factor and a defined outcome above the threshold value but none below it. An important field of application is occupational medicine where, for a lot of chemical compounds and other agents which are non-carcinogenic health hazards, so-called threshold limit values or TLVs are specified. The method is presented within the framework of the logistic regression model, which is widely used in the analysis of the relationship between some explanatory variables and a dependent dichotomous outcome. In most available programs for this and also for other models the concept of a threshold is disregarded. The method for assessing a threshold consists of an estimation procedure using the maximum-likelihood technique and a test procedure based on the likelihood-ratio statistic R, following under the null hypothesis (no threshold) a quasi one-sided chi 2 distribution with one degree of freedom. This use of this distribution is supported by a simulation study. The method is applied to data from an epidemiological study of the relationship between occupational dust exposure and chronic bronchitic reactions. The results are confirmed by bootstrap resampling.

Bronchitis↗
PubMed1991

Evaluation of antiarrhythmic drug effects with simultaneous analysis of single ventricular premature contractions, couplets and salvos.

To improve the clinical value of ambulatory Holter electrocardiographic (ECG) monitoring as a tool of antiarrhythmic therapy control, a new statistical model was developed. In a patient group at increased risk of sudden cardiac death, the spontaneous variability of ventricular arrhythmias was assessed, with simultaneous consideration of single ventricular premature complexes, couplets and salvos. The study included 100 patients who suffered from coronary heart disease or idiopathic dilated cardiomyopathy and for whom greater than 30 ventricular premature complexes/h and couplets had been demonstrated on the last Holter ECG before the study. Between 3 and 12 Holter recordings were made for each patient in a drug-free state; the mean follow-up period was 260 days (maximum 1,403). The mean hourly values of the ectopic events (EE) were assessed separately for ventricular premature complexes, couplets and salvos. The spontaneous variability (SV) was calculated for single ventricular premature complexes, couplets and salvos as SV = log (EEday 2 + 0.01/EEday 1 + 0.01) and linked in one, two and three dimensions. Compared with the consideration of only one type of arrhythmia (one-dimensional model), the simultaneous use of two or three types of arrhythmia (two- or three-dimensional model) resulted in considerably lower reduction and aggravation rates as sufficient proof of drug effects. With control intervals up to 1 week, the one-dimensional model yielded reduction rates for ventricular premature complexes, couplets and salvos of -63%, -90% and -95%, respectively. In contrast, with the three-dimensional model, the rates were -28%, -72% and -88%. The corresponding aggravation values were +370, +1,114% and +2,189% versus +38%, +256% and +747%.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗
PubMed1991

[Possibilities and limits of epidemiology in the evaluation of carcinogenic effect].

The epidemiological studies dealing with the effect of man-made mineral fibres are evaluated. They serve as an example for the possibilities and also the limitations of epidemiology. The factors are discussed, which complicate this evaluation. Criteria are mentioned which can be used the demonstrate no effect of the exposure. Finally some methods are proposed which can improve the use of epidemiology especially in occupational medicine.

Carcinogens↗
PubMed1991

[Manifestations of Alzheimer's disease in daily living].

From the perspective offered by diagnostic criteria, cognitive rating scales and psychometric tests, Alzheimer's disease appears to be primarily a continuous decline of memory and intelligence. Changes in other areas of behaviour often go unrecognized at examination or are considered insignificant. A completely different view is offered by the reports of care-givers. Here, impairment of everyday activities, abnormal emotional and social behaviours are the most important features. To examine the everyday manifestation of Alzheimer's disease at greater detail, a questionnaire for care-givers was developed. Observations of patients' behaviours as recorded on this instrument demonstrate the presence of significant changes of affect and drive even in mild stages of the disorder. They show only weak associations with cognitive symptoms and cannot be explained as psychological reactions. The non-cognitive aspects of Alzheimer's disease deserve particular diagnostic and therapeutic interest.

Activities of Daily Living↗
PubMed1991

[Value of synthetic (Kennedy-LAD) augmentation in replacement of the anterior cruciate ligament].

In chronically ACL-deficient knees, ACL replacement was performed in 31 cases with an one-third patellar tendon (Brückner-Jones) and in 50 cases with a quadriceps-patellarperiosteum-patellar tendon autograft (Marshall-MacIntosh) augmented with the Kennedy LAD. Anterior laxity measured with the KT 1000 arthrometer revealed a side-to-side difference of less than or equal to 3 mm in 90% (77% without augmentation), a high rate of muscle strength quotient of uninjured to treated knee of about 1 (greater than 1 without augmentation) and early recovery of ability to participate in the same sports as before in 54% of patients (45% without augmentation) demonstrate statistically significant better results of ACL replacement when a synthetically augmented autograft was used.

Adolescent↗
PubMed1990

A simple method to calculate the confidence interval of a standardized mortality ratio (SMR)

In analyzing standardized mortality ratios (SMRs), it is of interest to calculate a confidence interval for the true SMR. The exact limits of a specific interval can be obtained by means of the Poisson distribution either within an iterative procedure or by one of the tables. The limits can be approximated in using one of various shortcut methods. In this paper, a method is described for calculating the exact limits in a simple and easy way. The method is based on the link between the chi 2 distribution and the Poisson distribution. Only a table of the chi 2 distribution is necessary.

Confidence Intervals↗
PubMed1990

A multicentre mortality study of workers exposed to ethylene oxide.

A multicentre cohort study was carried out to study the possible association between exposure to ethylene oxide and cancer mortality. The cohort consisted of 2658 men from eight chemical plants of six chemical companies in the Federal Republic of Germany who had been exposed to ethylene oxide for at least one year between 1928 and 1981. The number of subjects in the separate plants varied from 98 to 604. By the closing date of the study (31 December 1982) 268 had died, 68 from malignant neoplasms. For 63 employees who had left the plant (2.4%) the vital status remained unknown. The standardised mortality ratio for all causes of death was 0.87 and for all malignancies 0.97 compared with national rates. When local state rates were used the SMRs were slightly lower. Two deaths from leukaemia were observed compared with 2.35 expected (SMR = 0.85). SMRs for carcinoma of the oesophagus (2.0) and carcinoma of the stomach (1.38) were raised but not significantly. In one plant an internal "control group" was selected matched for age, sex, and date of entry into the factory and compared with the exposed group. In both groups a "healthy worker effect" was observed. The total mortality and mortality from malignant neoplasms was higher in the exposed than in the control group; the differences were not statistically significant. There were no deaths from leukaemia in the exposed group and one in the control group.

Cause of Death↗
PubMed1990

[Spontaneous variability of ventricular arrhythmias in follow-up of anti-arrhythmia therapy].

The question of the reliability of ambulatory Holter monitoring for assessment of antiarrhythmic treatment has not been adequately resolved. Even though treatment efficacy had been individually assessed with Holter monitoring in the CAST study, during long-term treatment with class IC antiarrhythmic drugs, there were more deaths among patients receiving active drug than in those in the placebo group. Basic biostatistical considerations: Due to the spontaneous variability of frequency and complexity of ventricular arrhythmias, parametric models were developed with the aid of which normal ranges for spontaneous variability of singular ventricular premature complexes (VPC), couplets and salvos can be calculated. We designed a model which enables rapid visual analysis of the results: spontaneous variability = log (EE Day 2 + 0.01/EE Day 1 + 0.01) where EE is the number of ectopic events. For both days, the mean values per hour are applied. The use of parametric models prerequisites normal distribution of the data which can be achieved with logarithmic transformation. A constant is added to all mean values to preclude the mathematically-inadmissible form of log 0. The magnitude of the constant results in some degree of underestimation of the spontaneous variability. We chose the smallest constant, c = 0.01, consistent with a normal distribution of data. Figure 1 shows the normal range of the variability quotients for VPC in patients with cardiac disease and complex ventricular arrhythmias. The contiguous regions above and below the normal range designate active areas indicative of reduction or aggravation. Determinants of spontaneous variability: Frequency of arrhythmias: The number of VPC per unit of time exerts considerable influence on the spontaneous variability. The more infrequent an arrhythmia, the greater is the fluctuation to be anticipated. The differences in the variability of VPC, couplets and salvos are almost exclusively due to their differing frequencies since, in the presence of comparable frequency, they cannot be distinguished statistically from each other (Figure 2). Type and extent of underlying cardiac disease: In our patient population, there were no differences in spontaneous variability of arrhythmias between patients with coronary artery disease and those with dilated cardiomyopathy (Figure 3). Although in patients with coronary artery disease, as compared to those with noncoronary disease, a higher degree of spontaneous variability has been reported for VPC but, due to the inhomogeneity of the latter group, valid comparison is encumbered. The ejection fraction, the left ventricular filling pressure and the end-diastolic volume do not exert meaningful influence on the spontaneous variability (Figures 4 to 6).(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Arrhythmia Agents↗
PubMed1989

Assessing antiarrhythmic drug efficacy: multivariate considerations.

The spontaneous variability of ventricular arrhythmias is the major problem in assessing antiarrhythmic drug efficacy. Efficacy is usually assessed on one form of ventricular premature beats, namely either single beats (VPC) or more complex forms like couplets or salvos. The reduction rates required to assume efficacy with a confidence of 95 per cent are 63 per cent for VPCs, 92 per cent for couples or 96 per cent for salvos. These rates are valid for two Holter electrocardiogram recordings within one week; otherwise the rates are higher and close to 100 per cent. In this paper we extend our ratio method for calculating these criteria to consider two or all three forms of ventricular premature beats simultaneously. The method is based on the first principal component. For use in practice we decided to calculate fixed criteria for each form of ventricular premature beats. For the combination of VPCs and couplets and a confidence level of 95 per cent, reduction rates of 42 per cent for VPC and 87 per cent for couplets are required. Both criteria must be fulfilled to assume the efficacy of a drug. These criteria are lower than those for each form alone. For all three forms together, reduction rates of 28, 72 and 88 per cent for VPC, couplets and salvos respectively are required.

Anti-Arrhythmia Agents↗
PubMed1988

Spontaneous variability of simple and complex ventricular premature contractions during long time intervals in patients with severe organic heart disease.

Calculations of the spontaneous variability of ventricular arrhythmias are usually based upon the results of Holter electrocardiograms recorded either successively or separated by a short time interval. Only recently was it shown that the variability of ventricular premature contractions increases with longer intervals. This study was undertaken to investigate the variability of simple and complex ventricular arrhythmias over long periods to derive efficacy criteria for long-term antiarrhythmic therapy. In a prospective study, the influence of the length of the time interval on spontaneous variability was investigated in 100 patients with coronary artery disease or idiopathic dilated cardiomyopathy and untreated ventricular arrhythmia Lown grade IV. Patient follow-up was carried out for 260 +/- 387 days. In each of the 498 ambulatory Holter tapes, the mean hourly arrhythmia count (AC) of ventricular premature contractions, couplets, and salvos was verified. The variability of arrhythmia counts between two Holter electrocardiograms was defined as the logarithm of the ratio of (ACday 2 + 0.01) to (ACday 1 + 0.01). The 95% intervals for these ratios were calculated as +/- 2 SD, considering the fact that all mean values did not differ significantly from zero. The lower limit of these intervals refers to the reduction that is required for assuming drug efficacy, whereas the upper limit refers to an aggravation. The 95% intervals were calculated for each of four ranges of control intervals (0-6, 7-89, 90-364, and greater than or equal to 365 days). They increased significantly with longer control intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

[Spontaneous variability of complex ventricular extrasystoles over a period of up to 4 years].

In a prospective study, the influence of the length of the time interval on spontaneous variability was investigated in 100 patients with CAD or IDC and untreated ventricular arrhythmia of Lown grade IV. Patient follow-up was carried out over 260 +/- 387 days. In each of the 498 ambulatory Holter tapes, the mean hourly arrhythmia count (AC) of couplets and salvos was verified. The variability of ACs between two Holter ECGs was defined as the logarithm of the quotient AC day 2(n + 0.01)/AC day 1(n + 0.01). The spontaneous distribution of variability quotients (means +/- 2 SD) was defined separately for couplets and salvos and for each of four ranges of control intervals (0-6 days, 7-89 days, 90-364 days, greater than or equal to 365 days). The percentage change in arrhythmia count necessary to establish drug efficacy (R), was calculated according to the formula R(%) = (10(0) - 10(-2SD].100, whereas the percentage change necessary to prove aggravation of arrhythmia (A) was assessed by the formula A(%) = (10(0) + 10(+2SD].100. For couplets, R extended from 90%, 94%, 98% to 99%; A increased from 1114%, 1895%, 6153% to 14032%, respectively. For salvos, R remained almost unchanged at a high level with 95%, 98%, 98%, 99%. The figures of A were 2189%, 4650%, 5698% and 9650%, respectively. It is concluded that the spontaneous variability of complex ventricular arrhythmias is remarkably high with short control intervals and increases further with longer ones.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗
PubMed1988

[Spontaneous variability of ventricular arrhythmias in relation to the kind and extent of underlying heart disease].

The influence of the underlying heart disease on the spontaneous variability of ventricular arrhythmias was investigated prospectively in 53 patients (25 CHD, 28 IDC) with frequent and complex ventricular arrhythmias. In each patient, two consecutive ambulatory 24-h Holter ECGs were prepared and in each tape the mean hourly arrhythmia count (AC) was determined separately for singular VPCs, couplets, and salvos. The spontaneous variability between the two long-term ECGs was defined as the logarithm of the ratio (ACday 2 + 0.01)/(ACday 1 + 0.01). The 95% confidence intervals of the stated types of arrhythmias were calculated as +/- 2 SD. The results were analyzed as a function of the underlying etiology, NYHA class, and left ventricular ejection fraction. There were no differences between patients with CHD and IDC. The extent of left ventricular dysfunction did not have any influence either. In patients of NYHA class 3 there was a higher spontaneous variability of VPCs, couplets and salvos than in patients of NYHA class 2, but the differences could not be ensured statistically. We conclude from the results that the validation of an antiarrhythmic treatment can be performed independently from the nature of the underlying heart disease and the left ventricular ejection fraction. However, it remains unclear whether a greater variability must be expected in patients of NYHA class 3 than in patients of NYHA class 2.

Adult↗
PubMed1987

Cytotoxic effects of ether lipids and derivatives in human nonneoplastic bone marrow cells and leukemic cells in vitro.

The effects of 2-lysophosphatidylcholine (2-LPC), the alkyl lysophospholipid derivatives (ALP) 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) and 1-O-hexadecyl-sn-glycero-3-phospho-trimethyl-ammonio-hexanol, the 2-acetamide analog of platelet-activating factor (PAF) 1-O-octadecyl-2-acetamide-sn-glycero-3-phosphocholine, the thioether lysophospholipid derivative (TLP) BM 41.440 and the ether-linked lipoidal amine CP-46,665 on tritiated thymidine uptake and trypan blue dye exclusion were tested in vitro in various freshly explanted cell samples from human nonneoplastic bone marrow and human leukemias. In both assay systems, a dose range of 1-20 micrograms/ml of the compounds was tested after 24, 48 and 72 hr of coincubation with the cells. The trypan blue dye exclusion revealed statistically significant preferential cytotoxicity in leukemic cells for three compounds with the order of quantitative selectiveness: ET-18-OCH3 greater than BM41.440 greater than 2-acetamide analog of PAF. CP-46,665 was the most toxic compound, but did not reveal significant differences between nonneoplastic bone marrow and leukemic cells when added in concentrations greater than 1 microgram/ml. The trimethyl-ammonio-hexanol compound showed only minor activity in the majority of tests, when added at concentrations less than 20 micrograms/ml. 2-LPC was rather ineffective. The tritiated thymidine uptake showed only preferential antiproliferative effects towards leukemic cells of ET-18-OCH3 and, sometimes, within the dose time frame tested of BM 41.440. All compounds tested except 2-LPC and the trimethyl-ammonio-hexanol compound were active also in this assay (inhibition of uptake greater than 50% of the controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1987

[Spontaneous variability of ventricular extrasystoles: criteria for validating anti-arrhythmia therapy in relation to the length of the control interval].

Calculations about the variability of PVCs are usually based upon the results of two Holter ECGs, either successive ones or separated by a short interval. No studies are available indicating whether the criteria calculated for short control intervals also holds true when evaluating chronic antiarrhythmic treatment over longer control periods. This study was performed to investigate the influence of the length of the control interval on the spontaneous variability and thus on the reduction of PVCs required to secure an antiarrhythmic effect. In a prospective study, 444 ambulatory ECGs were obtained in 90 patients with CAD or IDC and untreated ventricular arrhythmia of Lown grade IV. Patient follow-up was carried out over an average of 181 +/- 297 days. The degree of arrhythmia was expressed as the mean hourly PVC rate. The variability of PVC counts between two Holter ECGs was defined as the logarithm of the quotient PVCday 2(n + 1)/PVCday 1(n + 1). The spontaneous distribution of variability quotients was defined separately (mean +/- 2 SD) for each of four ranges of control intervals (0-6 days, 7-89 days, 90-364 days, greater than or equal to 365 days). The per cent reduction (R) in PVC frequency necessary to establish drug efficacy, was calculated according to the formula R (%) = 10(0)-10(-2SD) X 100, whereas the percentage change necessary to prove aggravation of arrhythmia (A) was assessed by the formula A (%) = 10(0)+10(+2SD X 100. R increased from 63% (0-6 days), 81% (7-89 days), 93% (90-364 days) to 98% (greater than or equal to 365 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗
PubMed1987

[Diagnosis of pulmonary hypertension using pulsed Doppler cardiography].

The accuracy of pulsed Doppler cardiography in predicting pulmonary hypertension was assessed in 70 patients (aged 16-72 years) with varying cardiac disease, who had undergone catheterization. Doppler velocity traces were recorded from four sampling sites in the pulmonary outflow tract and from the tricuspid valve. These results were compared to the invasive data. An inverse correlation (r = -0.77) was found between acceleration time (onset of RV ejection to peak pulmonary velocity) and mean pulmonary arterial pressure, with the sampling site in the centre of the pulmonary valves or of the RV outflow tract (r = -0.71). Acceleration time was inversely related to patient age but was not dependent on heart rate or on cardiac output. The sensitivity of the acceleration time was 85-91% for the diagnosis of moderate or severe pulmonary hypertension, and the predictive value was greater than 90%. The following measurements were less helpful in diagnosing pulmonary hypertension: peak velocity of pulmonary arterial blood flow, its mean acceleration, RV isovolumic relaxation time and the qualitative sign of a presystolic pulmonary flow wave induced by atrial contraction. A reversal of systolic flow at the level of the pulmonic valves, measured as time of forward flow in percent of RV ejection time, was found only in patients with moderate or severe pulmonary hypertension. This was a sensitive marker of an elevated pulmonary arterial resistance (greater than or equal to 95%), the mechanism of which is not yet fully understood.

Adolescent↗
PubMed1987

[Heart valve replacement in patients over age 60: analysis of the peri- and postoperative course compared to patients under age 60].

During recent years, advances in cardiology and cardiac surgery have led to an increased number of older patients submitted for heart valve replacement. The following retrospective study analyses perioperative risk and long-term prognosis of 168 patients older than 60 years of age, compared with 942 patients younger than 60 years of age with heart valve replacement. There was no significant difference in 7-year actuarial survival, late mortality, late complications and postoperative functional improvement for both groups. However, early mortality was higher in patients over 60 years of age than in the group of patients under 60 years (7.9% vs. 4.5% from 1980-85, p less than 0.05), especially when multivalvular replacement was performed or the patients were in preoperative functional class NYHA IV. The results indicate that in patients over 60 years of age, heart valve replacement can be performed with a good long-term prognosis and a marked improvement in the quality of life. Early mortality can be reduced to an acceptable rate if the patient is operated in time.

Adolescent↗