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Biomedical subjects

F Krummenauer

Publications and source records attributed to F Krummenauer.

69 records · Page 4Linked to original sources

Randomised trial of mycophenolate mofetil versus azathioprine for treatment of chronic active Crohn's disease.

BACKGROUND: Crohn's disease is a chronic inflammatory disease of the alimentary tract. Azathioprine is an effective agent in the management of chronic active Crohn's disease leading to long term remission of disease activity. Such treatment leads to limited efficacy or side effects in a small subset of patients. AIMS: To compare efficacy and side effects of treatment with azathioprine plus corticosteroids versus mycophenolate mofetil (MMF) plus corticosteroids in patients with chronic active Crohn's disease. METHODS: Seventy patients with chronic active Crohn's disease (Crohn's disease activity index (CDAI) greater than 150) were randomised for treatment with azathioprine/cortisone or MMF/cortisone. Corticosteroid dosage was tapered according to a standard protocol. Disease activity was monitored by clinical scores after one, two, three, and six months. RESULTS: Treatment of patients with moderately active (CDAI 150-300) Crohn's disease with MMF/cortisone led to a significant reduction in clinical activity scores comparable to treatment with azathioprine/cortisone. Treatment of patients with highly active Crohn's disease (CDAI greater than 300) with MMF/cortisone caused significant suppression of clinical activity earlier than azathioprine/cortisone treatment. Treatment with MMF/cortisone was associated with few adverse effects. CONCLUSION: Treatment of chronic active Crohn's disease with MMF plus cortisone appears to be effective and well tolerated and should be considered in patients allergic to azathioprine or in whom azathioprine has failed.

Anti-Inflammatory Agents↗

Reference values for vertebral artery flow volume by duplex sonography in young and elderly adults.

BACKGROUND AND PURPOSE: Vertebrobasilar ischemia has been attributed to a reduction of net vertebral artery flow volume, the product of mean flow velocity and the cross-sectional area of the vessel. It can be determined by duplex sonography. There are no reference values for vertebral artery flow volume in an age group representative of patients with cerebrovascular disease. METHODS: We examined 50 nonvascular neurological patients (age 55.8+/-14.0 years). Flow velocities and vessel diameters were recorded in the intertransverse (V2) segments bilaterally, and the flow volume was calculated according to the following equations: (1) Q1=time-averaged mean velocity times area and (2) Q2=(time-averaged maximum velocity/2)times area. RESULTS: Flow velocities and vessel diameters tended to be lower on the right side, resulting in a lower flow volume. Flow volumes (according to Equation 1) were 77.2+/-29.8 mL/min on the right side, 105.3+/-46.4 mL/min on the left side, and 182.0+/-56.0 mL/min net. Side-to-side differences were not significant. Flow volumes calculated with the 2 equations did not differ significantly. An age dependence could not be shown, but vessel diameters and net vertebral artery flow volumes were significantly lower in women than in men. The normal range for net vertebral artery flow volume defined by the 5th to 95th percentiles is between 102.4 and 301.0 mL/min. This wide range is due to the high interindividual variability of the parameters. CONCLUSIONS: On the basis of the reference values presented here, the association of decreased vertebral artery flow volume and vertebrobasilar ischemia should be reevaluated. Additional areas for investigation include the quantification of collateral flow in the vertebral arteries in carotid artery occlusive disease and their contribution to overall cerebral blood flow volume.

Adult↗

Assessment of coronary artery bypass grafts: value of different breath-hold MR imaging techniques.

OBJECTIVE: Our aim was to evaluate the patency of coronary artery bypass grafts and to detect graft stenosis using different breath-hold MR imaging techniques. SUBJECTS AND METHODS: Twenty-two patients with 59 grafts (14 internal mammary artery grafts and 45 saphenous vein grafts) and 76 distal anastomoses (singular and sequential grafts) were studied using a 1.5-T scanner. A two-dimensional T2-weighted breath-hold half-Fourier acquisition single-shot turbo spin echo (HASTE) sequence and a three-dimensional breath-hold contrast-enhanced MR angiography sequence (fast imaging with steady-state free precession) were performed. For MR angiography, a bolus of 20 ml of gadopentetate dimeglumine was used. Time delay for contrast injection was calculated by a test bolus. The gold standard was coronary angiography performed within 14 days of MR imaging. All images were evaluated independently by two radiologists. RESULTS: With the HASTE sequence, 95% of the patent grafts were recognized (42/44); specificity was 93% (14/15). MR angiography had both a sensitivity (41/44) and specificity (14/15) of 93%. Interobserver agreement for both sequences was good (Cohen's kappa = 87%; McNemar test, p = 56%). Forty-nine (83%) of 59 patent distal graft anastomoses were revealed with the HASTE sequence; 38 (64%) of 59 were seen on contrast-enhanced angiography. With HASTE imaging, only two of eight hemodynamically significant graft stenoses were detected. MR angiography revealed only four of eight significant graft stenoses. CONCLUSION: The HASTE sequence and three-dimensional MR angiography proved to be useful MR techniques when evaluating the patency of coronary artery bypass grafts. However, reliable detection of graft stenosis does not yet seem possible with these imaging techniques.

Aged↗

[Cohen's kappa or McNemar's test? A comparison of binary repeated measurements].

This article intends to illustrate the combination of McNemar's significance test and Cohen's kappa coefficient in the comparison of repeated binary measurements. Both methods are standard statistical tools of major relevance for the evaluation and comparison of clinical imaging methods and thus have an impact on the corresponding publications. The interpretation of results obtainable with these methods will be illustrated to facilitate their use based on recent statistical software. Examples will further outline limitations and possible pitfalls in their application to clinical data.

Data Interpretation, Statistical↗

[Individually dosed levothyroxine with 150 micrograms iodide versus 100 micrograms levothyroxine combined with 100 micrograms iodide. A randomized double-blind trial].

BASIC PROBLEM AND OBJECTIVE: Intrathyroid deficiency and the influence of thyroid stimulating hormone (TSH) are the main pathogenetic factors in the development of endemic euthyroid goitre. Goitre reduction is achieved with either administration of levothyroxine, which diminishes hypophyseal TSG production, or of iodide. Aim of this study was to compare the efficacy of treatment with a dose-fixed combination of levothyroxine plus iodide with that of an individualized dosage of levothyroxine plus iodide. PATIENTS AND METHODS: After randomization 49 patients with euthyroid goitre (24 women, 25 men, aged 20-43 years) were treated for 12 weeks in a double-blind trial. Patients in group A received levothyroxine in a weight-adapted dosage (75,100 or 150 micrograms) plus 150 micrograms iodide, while those in group B were given a fixed dosage of 100 micrograms levothyroxine plus 100 micrograms iodide. Basal TSH, thyroid hormones, iodide excretion, hyperthyroid score and sonographic volume of the thyroid were determined before treatment and after 12 weeks. RESULTS: Basal TSH levels were reduced in both groups (P < 0.0001), without significant difference between the two groups (median relative change: group A 78.1%, group B 52.8%). Thyroid volume was decreased independently of the form of treatment (P < 0.0001) (median relative reduction: group A 37.6%, group B 30.9%; difference not significant). Iodide excretion rose in both groups, without significant difference (group A 107%, group B 49%). There was hardly any change of the hyperthyroid score in both groups. There were no side effects. CONCLUSION: Both forms of medication were equally efficacious and well tolerated in the treatment of euthyroid goitre.

Adult↗

Viral and host factors in the prediction of response to interferon-alpha therapy in chronic hepatitis C after long-term follow-up.

Acute infection with hepatitis C virus (HCV) develops into a chronic hepatitis in about 50-70% of patients. Treatment of these patients with interferon-alpha (IFN-alpha) results in a sustained long-term response in only 15-20% but causes numerous unwanted side-effects in a higher percentage of patients. The aim of our study was to define host or viral parameters that would allow identification of responders and non-responders to IFN-alpha prior to the onset of treatment. We studied a group of 87 patients suffering from chronic hepatitis C who were treated with IFN-alpha. After long-term follow-up, 18 patients (21%) showed a sustained response to IFN-alpha therapy (normalization of serum transaminases and loss of viral RNA from serum) for up to 7 years after therapy had ceased. By univariate and multivariate analyses, no host factors were found to be predictive of response to therapy. Neither the degree of inflammation or fibrosis in liver biopsy samples obtained before treatment nor immunogenetic factors (major histocompatibility complex II haplotype and tumour necrosis factor-alpha promoter polymorphism) were associated with response to therapy. In contrast, viral parameters showed a strong association with response to therapy. HCV genotype 3 was found significantly more frequently in responders (P = 0.034), and mean HCV RNA concentration was lower in responders (3.1 x 10(4)) than in non-responders (2.5 x 10(5)) (P = 0.01). By multivariate analysis, both HCV genotype and HCV RNA concentration were independent predictors of response to therapy. However, exact prediction of response to treatment for an individual patient was not possible on the basis of pretreatment viral RNA concentration or viral genotype. The best association with response to therapy was found to be clearance of HCV RNA from serum 3 months after the start of treatment (32 of 34 partial and sustained responders vs 0 of 53 non-responders; P = 0.001). In conclusion, determination of pretreatment viral factors, but not host factors, was significantly correlated with treatment response but did not give an accurate prediction for patients, whereas clearance of HCV RNA from serum after 3 months of therapy was predictive of response to therapy.

Adult↗

[Flow quantification of intracardiac shunt volumes using MR phase contrast technique in the breath holding phase].

PURPOSE: Comparison of a breath-hold, velocity-encoded, phase-difference magnetic resonance (MR) sequence for intracardiac shunt flow measurement with the invasive shunt size determination by oximetry. PATIENTS AND METHODS: 10 patients with different cardiac shunts (6 ASD/3 VSD/1 PDA) and four healthy individuals were investigated using a 1.5 Tesla Siemens Vision system. For flow measurements a breath-hold, velocity-encoded, phase-difference magnetic resonance (MR) sequence was used ('through plane', FLASH 2D-sequence, TR/TE 110/5 ms, 'velocity encoding' 250 cm/s). Mean flow (ml/R-R interval) in the ascending aorta, the pulmonary trunk, and the right and left pulmonary arteries was determined. The ratio of the mean flow in the pulmonary circulation (Qp: sum of the mean flows in the right and left pulmonary arteries) and the systemic circulation (Qs: mean flow in the proximal aorta) was compared with the Qp/Qs ratios determined by the invasive oxymetric technique. Oximetry was performed within 24 hours after MR imaging. RESULTS: In the 4 healthy individuals MR flow measurement yielded a Qp/Qs ratio of 0.96 +/- 0.15. In the 10 patients with the various shunt defects, the non-invasive shunt determination by MR gave a Qp/Qs ratio of 2.09 +/- 0.67. The percentage of the calculated shunt sizes was 47.05 +/- 17.45%. In the comparison with the results determined by the invasive oxymetric technique, the MR data showed a strong correlation of r = 0.87. CONCLUSIONS: Breath-hold, velocity-encoded, phase-difference MR-technique enables a reliable quantification of cardiac shunts within a short acquisition time.

Adult↗

Superior labrum and labral-bicipital complex: MR imaging with pathologic-anatomic and histologic correlation.

OBJECTIVE: The purpose of this study was to analyze the anatomic relationship between the superior labrum, the superior glenoid rim, the superior glenohumeral ligament, and the long head of the biceps tendon. MATERIALS AND METHODS: Seventeen cadaveric shoulder specimens underwent axial, oblique coronal, and oblique sagittal MR imaging on a 1.5-T imager. Unenhanced proton density- and T2-weighted spin-echo images with and without fat suppression, and T1-weighted fat-suppressed spin-echo images after intraarticular injection of gadolinium, were obtained of each specimen. The shoulders were then frozen and sectioned into 4-mm-thick slices, either transversely or oblique coronally. After gross anatomic correlation, histologic analysis was performed on 32 sections. RESULTS: A sublabral recess was present in 12 (71%) of 17 shoulders. MR arthrography was significantly better at showing the sublabral recess than was unenhanced MR imaging. Histologically, the synovial recess in all cases was covered by synovial lining cells. Intralabral altered histologic patterns were found in 20 (63%) of 32 labral sections. In addition to signs of degeneration, five sections of two specimens showed proliferating fibroblasts and vessels, as well as fibrosis, suggesting trauma. The presence or absence of altered intralabral histologic patterns was better assessed with T1-weighted fat-suppressed arthrograms than with unenhanced MR images. We found a close association grossly and histologically between the superior labrum and the biceps tendon. CONCLUSION: The attachment of the superior glenoid labrum to the glenoid rim shows great variability. In MR imaging, an overlap appears to exist between physiologic recesses of the superior labrum and a type 2 superior labrum anterior-posterior lesion. T1-weighted fat-suppressed MR arthrograms provided the best view of the superior labrum and the labral-bicipital complex.

Aged↗

Determinants of calcium uptake of bovine pericardium for heart valve replacement: results of in vitro studies.

BACKGROUND AND AIMS OF THE STUDY: Reduction of biomaterial calcification is an important aim in the basic research of biological heart valves. An in vitro model was used to investigate the influence of serum calcium concentration and surface coverage with cells or basal proteins on calcium uptake of bovine pericardium. METHODS: Samples of glutaraldehyde-tanned bovine pericardium, stored in formaldehyde and detoxified with borohydride were incubated for two weeks with cell culture medium containing low (1.0 mmol/l) or physiologic (2.3 mmol Ca/l) calcium concentration. Specimens were either unseeded, completely surface-covered with rat fibrocytes (rf) or fibrin (fi), or incompletely seeded with rabbit cells (re). Quality of surface coverage was assessed by surface scanning electron microscopy and calcium content by atomic absorption spectroscopy. RESULTS: Serum calcium had a significant influence on calcium uptake (low versus physiological (1.58 +/- 2.45 mg/g versus 8.10 +/- 1.73 mg/g wet wt, p < 0.001). This may explain early calcification of bioimplants in children and patients on dialysis. Surface coverage significantly reduces calcium uptake (fi, 1.20 +/- 0.41 mg/g, rf, 4.20 +/- 1.70 mg/g, p < 0.001) but complete coverage is necessary (re, 6.98 +/- 1.64 mg/g, NS). CONCLUSIONS: In vitro testing of calcium uptake has proven to be a valuable tool for evaluation of biomaterial calcification.

Animals↗

In vitro effects of anticalcification treatment on the calcium uptake of bioprosthetic materials.

BACKGROUND AND AIM OF THE STUDY: The frequent need for re-replacement of tissue valves due to calcification remains their major disadvantage compared with mechanical implants. A variety of anticalcification treatments has been proposed but none has proved to prevent calcific degeneration. The study aim was to evaluate, in vitro, the time course of calcium uptake of procine and bovine biomaterials and the efficacy of anticalcification treatments. METHODS: Samples of glutaraldehyde-tanned biomaterials with (Carpentier-Edwards, Medtronic Intact, Hancock II, MZGTB) or without anticalcification treatment (Mitroflow) were incubated with culture medium containing physiological calcium levels. Specimens were then analyzed at two, four or eight weeks for their calcium content (mg/g wet weight). RESULTS: All specimens calcified over time, though the time courses for each were significantly different. Mitroflow and Intact valves accumulated high calcium levels rapidly during the first two weeks, with small further increases thereafter. Anticalcification treatment reduced calcium uptake of Carpentier-Edwards material during the first two weeks of incubation, but the material gradually attained comparable calcium levels at eight weeks. Hancock valves and the self-customized MZGTB valve showed the lowest calcium levels over the test period. CONCLUSIONS: This in vitro study documented major differences in calcium uptake of different biomaterials. Some anticalcification treatments render the material temporarily less susceptible to calcium binding but none can prevent calcification. In vitro testing has proved to be a valuable instrument for evaluating anticalcification treatments, but should be combined with evaluation of bioprosthesis surface interaction with circulating blood.

Animals↗

No primary association between LMP2 polymorphisms and extraspinal manifestations in spondyloarthropathies.

OBJECTIVE: To investigate the potential role of the HLA-linked LMP2 (low molecular weight protein) gene polymorphisms in conjunction with DR4 and DR7 on extraspinal disease manifestations in HLA-B27 positive patients with spondyloarthropathy. METHODS: 172 patients with spondyloarthropathy, 46 healthy, HLA-B27 positive blood donors, and 99 unrelated controls were typed for HLA-class I and II antigens. LMP2 alleles were determined by polymerase chain reaction and subsequent restriction enzyme digestion. RESULTS: There were statistically non-significant increases of DR4 and DR7 in spondyloarthropathy subjects. However these differences did not relate to specific extraspinal manifestations. There were no significant differences in the LMP2 genotype distribution in the disease groups. All differences in LMP2 genotype frequencies disappeared when correcting for DR4, which was in linkage disequilibrium with the LMP2B allele. CONCLUSIONS: There is no independent association between LMP2 genotypes and the occurrence of uveitis or peripheral arthritis in HLA-B27 positive subjects with spondyloarthropathy. DR4 and DR7 do not contribute to these disease manifestations.

Adolescent↗

Childhood leukaemia and exposure to pesticides: results of a case-control study in northern Germany.

The association between childhood leukaemia and exposure to pesticides was examined in a population-based case-control study conducted in Lower Saxony, Northern Germany. Between July 1988 and June 1992, 219 newly diagnosed cases were identified, of whom 173 participated in the study. Two sex- and age-matched control groups were recruited: local controls from the same communities as the newly diagnosed cases of leukaemia and state controls from other randomly selected communities in Lower Saxony. An additional study group consisted of 175 cases of solid tumours. When the leukaemia cases were compared with the local controls, positive associations with parental occupational exposure, particularly agriculture-related exposure, were observed, which were statistically non-significant. A significant association was found for pesticide use in gardens (odds ratio = 2.52, 95% confidence interval: 1.0-6.1). No positive associations were seen when the leukaemia cases were compared to the state controls, but this finding could be explained by a higher proportion of state controls living in rural areas. In communities with a significantly elevated standardised incidence ratio of childhood leukaemia over the last decade (1984-1993), the prevalence of pesticide use in the garden was 21%, compared with the 10% in other communities. None of the examined risk factors were more common among cases of solid tumours. Our findings add some evidence to the hypothesis that pesticides are a risk factor for childhood leukaemia, and there are good reasons to consider abundant pesticide use in rural areas as a possible cause for clustering of childhood leukaemia.

Adolescent↗

[Clinical and economical outcome evaluation of dental care services received by German patients in countries outside the EU].

PURPOSE: During the past decade German patients developed an increasing tendency to dental health tourism in countries outside the European Union. The present investigation aimed at evaluating both clinical and economic outcome of dental care in these countries with regard to German directive standards. METHODS: Based on physical examinations performed by the Medizinische Dienst der Krankenversicherung Rheinland-Pfalz in the context of reimbursement or regress requests after dental care in countries outside the European Union, an individual treatment concept was designed and its direct costs from the patient's perspective were estimated according to German standards. Furthermore, the clinical outcome was evaluated and treatment concepts for the correction of clinically relevant findings were simulated; the corresponding costs were estimated. A descriptive cost-cost analysis has been performed from the patient's perspective and a secondary one from the health service's perspective. RESULTS: A total of 60 examinations (january 2001 to october 2002) were analysed. 29 of these 60 patients showed clinically relevant findings affording post treatment correction, among which 23 treatment concepts significantly disagreed with German directive standards. From the 60 patients' perspective median costs of 942 euro; for treatment outside the EU versus hypothetical costs of 750 euro; for treatment in Germany were observed. In addition, the 29 patients with clinically relevant findings affording corrective treatment implied median costs of 1,383 euro;. From the health service perspective, median costs of 761 euro; could be avoided due to treatments outside the EU, whereas median costs of 1,220 euro; were simulated due to necessary corrective treatments. CONCLUSION: From the patients' perspective dental care outside the EU has to be reconsidered both from a clinical and an economic point of view.

Costs and Cost Analysis↗

Case control study of neuroblastoma in west-Germany after the Chernobyl accident.

BACKGROUND: To explore possible causes of a 1988 incidence peak of infant neuroblastoma in west German regions which were contaminated with more than 6000 Bq/m2 Cs137 from the Chernobyl accident. The primary working hypothesis was that parents of the diseased children had been contaminated by an excessive intake of locally produced food, especially mushrooms or deer. DESIGN: Case control study with 1:2 (cases:controls) matching. Data were collected from the children's parents by questionnaires and telephone interviews. SETTING: Nation-wide study (former FRG) based on the German Childhood Cancer Registry. SUBJECTS: Cases born in 1988 and reported with a neuroblastoma to the registry until March 1992. Population-based healthy controls, matched for age, sex and residence at time of diagnosis. RESULTS: The working hypothesis could not be confirmed by the study, because the parents of cases tended to eat less locally grown food than the parents of controls (RR = 0.63, 95% CI:0.20-1.97). Possible influence factors which previously have been described to be associated with neuroblastoma incidence could not be confirmed by the study. Parental exposure to herbicides and pesticides was associated with the occurrence of neuroblastoma (RR = 4.2, 95% CI:1.4-12.9). Neuroblastoma stage distribution in the contaminated regions was shifted towards lower stages as compared to the less contaminated regions and previous age cohorts. CONCLUSIONS: The study does not show additional evidence that the observed increase in neuroblastoma incidence might have been caused by exposure to fallout from the Chernobyl accident. The observed shift towards lower clinical stages may rather indicate increased diagnostic awareness. The association between neuroblastoma and parental exposure with herbicides and pesticides resulted from an extensive exploratory data analysis and needs to be confirmed in further studies.

Child, Preschool↗

Case control study on childhood leukemia in Lower Saxony, Germany. Basic considerations, methodology, and summary of results.

In two municipalities in Lower Saxony statistically valid clusters were observed, which attracted great public interest. Committees were set up to initiate a large variety of on-the-spot-investigations. Finally, it was decided to conduct a case control study throughout Lower Saxony to explore potential risk factors which might explain the observed clusters. A limited number of already established and currently discussed hypotheses was chosen for investigation. The study was based on patients registrated at the German Children's Cancer Registry (GCCR). For each child with leukemia diseased between 1988 and 1993 two population-based controls (local and state controls) and one tumour control were selected. Data were collected by means of a questionnaire self-administered by the parents and a telephone interview. In addition, measurements of electromagnetic fields and radon were performed and inspections of the child's birth record were made for the purpose of confirming a potential association between parenteral vitamin K prophylaxis and leukemia or tumours. This paper presents the concept and basic considerations of the study, its design and statistical evaluation. Response rates and a summary of results will be presented, too. The paper will serve as a reference for subsequent publications about more detailed analyses of specific potential risk factors. 425 parents of diseased children and 610 of non-diseased children were asked for participation. The rates of response were 82% for families with diseased and 71% for families with non-diseased children. In total, 781 parents participated in the study. The most important results are as follows: The Greaves' hypothesis (9, 10) was supported by the following results: In children diseased with leukemia, vaccinations were less frequent, virus-related infections occurred more rarely, these children were more frequently first-born children and more frequently breast-feed, and they possibly had fewer contacts with other children in infancy. Our data do not show a significant association between parenteral vitamin K prophylaxis and leukemia or tumours (17). Measurements of electromagnetic fields show a weak association between high-level exposure and an increased risk of developing leukemias. Children who were X-rayed more than four times or were born prematurely and had received intensive care treatment show a positive association with occurrence of leukemia, but the number of these patients was very small and these factors are not independent. The only potential job-related hazard was paternal exposure to plastic and resin fumes. The incidence of miscarriages and abortions was increased in mothers of children with leukemia. Our study did not confirm the hypotheses, that leukemia is associated with gestational age, with consumption of alcohol, nicotine, and medicaments during pregnancy. Nor was any association detected with exposure to wood preservatives and insecticides or with a high socio-economic status. The number of patients living in municipalities with increased incidence of leukemia was too small to show statistically valid results. However, it is noteworthy that some of the above-mentioned risk factors were observed also in these children. One of the purposes of a nation-wide case control study which is currently performed at the GCCR is to validate and complete these results.

Case-Control Studies↗