Biomedical subjects

K Ulm

Publications and source records attributed to K Ulm.

At least 37 records · Page 2Linked to original sources

PubMed2000

Fecal bacterial activity in symptomatic carbohydrate malabsorption: effect on the fecal short-chain fatty acid ratio.

BACKGROUND: It is still not clear why only some patients with carbohydrate malabsorption experience symptoms. In a previous study on healthy fructose malabsorbers an increased degradation of fructose in anaerobic fecal cultures from symptomatic malabsorbers was found, indicating increased bacterial activity. In the present study, the same investigation was repeated in patients with nonspecific abdominal complaints and fructose malabsorption. Moreover fecal short-chain fatty acids (SCFA), products of colonic bacterial fermentation of carbohydrates were measured. PATIENTS AND METHODS: A standard quantity of fructose (500 mg) was added to anaerobic fecal cultures from 25 patients (nine men, 16 women; median of age 53 years, range 36-69 years). The fructose degradation rate was assessed using photometry, and interpreted as representing bacterial activity in the colon. In 14 of the patients, SCFA levels were also measured using chromatography on a capillary column. RESULTS: 10 of the 25 patients had a history of symptoms after ingesting fructose-containing foods, and also showed symptoms during the test; 6 patients had symptoms either in their history or during the test; and the remaining 9 were free of symptoms. There were no differences in the H2 increase. The fructose degradation rate was higher in symptomatic malabsorbers (255 mg vs. 217 mg), but the difference was not significant. However, there was a strong inverse correlation between this bacterial activity and the acetate level, with r = -0.822 (P = 0.000) and r = -0.868 (P = 0.000) in the rank correlation. The correlation for propionate was r = 0.479 (P = 0.083), and that for butyrate was r = 0.599 (P = 0.024). CONCLUSIONS: This study failed to confirm a significant correlation between fecal bacterial activity and the occurrence of symptoms in patients with fructose malabsorption. However, the interesting correlation with the SCFA raises questions regarding possible connections between colonic bacteria, carbohydrate malabsorption, and the beneficial effect of this pattern of SCFA in several colonic diseases.

Adult↗

PubMed2000

Modern imaging methods versus clinical assessment in the evaluation of hospital in-patients with suspected pancreatic disease.

OBJECTIVE: Various modern imaging procedures such as endoscopic retrograde cholangiopancreatography (ERCP), computed tomography (CT), and endoscopic ultrasonography (EUS) have been shown to be highly accurate in the diagnosis of specific disorders of the pancreas. However, prior information often causes bias in the interpretation of these results. Little information is available concerning the value of these examinations in the primary and differential diagnosis of suspected pancreatic disease-particularly in comparison with clinical evaluation, including laboratory tests and transabdominal ultrasound (TUS). METHODS: Clinical and imaging information (EUS, ERCP, and CT) was collected for 184 inpatients who were referred over a 5-yr period for evaluation of suspected pancreatic disease. On the basis of patient history, laboratory tests, and the results of routine TUS, one gastroenterologist, who was unaware of any of the other procedures or the final diagnosis, made a presumptive clinical diagnosis. CT and ERCP images and EUS videotapes were then analyzed by three different and independent examiners, who had the same clinical information except for the TUS results, but were completely blinded to the results of the other examinations and the patients' diagnoses. The final diagnoses were obtained by surgery, histology, and cytology, plus a follow-up of at least 1 yr (mean 35 months) in all noncancer cases. RESULTS: The final diagnoses were: normal pancreas (n = 36), chronic pancreatitis without a focal inflammatory mass (n = 53) or with a focal inflammatory mass (n = 18), and pancreatic malignancy (n = 77). Clinical evaluation, including ultrasonography, achieved a sensitivity for pancreatic disease of 94% but a specificity of only 35%. The figures for the sensitivity and specificity of the three imaging procedures were 93% and 94%, respectively, for EUS; 89% and 92% for ERCP; and 91% and 78% for CT (p < 0.05 for the specificity of clinical assessment vs all three imaging tests, p > 0.05 for comparison of the three imaging procedures). In the differential diagnosis between cancer and chronic pancreatitis as well as between malignant and inflammatory tumors, there was no difference among clinical assessment and the three imaging tests. CONCLUSIONS: In a group of patients with a high suspicion of pancreatic disease, little additional sensitivity in the diagnosis of pancreatic disease is provided by sophisticated imaging procedures such as EUS, ERCP, and CT, in comparison with clinical assessment including laboratory values and TUS. However, the specificity can be substantially improved. To confirm the diagnosis, one of the three examinations is needed, depending on the suspected disease and local expertise. The imaging procedures should be performed in a stepwise fashion for specific purposes, such as exclusion of pancreatic disease and the planning of treatment in chronic pancreatitis and pancreatic cancer.

Adolescent↗

PubMed1999

Heart-rate turbulence after ventricular premature beats as a predictor of mortality after acute myocardial infarction.

BACKGROUND: Identification of high-risk patients after acute myocardial infarction is essential for successful prophylactic therapy. The predictive accuracy of currently used risk predictors is modest even when several factors are combined. Thus, establishment of a new powerful method for risk prediction independent of the available stratifiers is of considerable practical value. METHODS: The study investigated fluctuations of sinus-rhythm cycle length after a single ventricular premature beat recorded in Holter electrocardiograms, and characterised the fluctuations (termed heart-rate turbulence) by two numerical parameters, termed turbulence onset and slope. The method was developed on a population of 100 patients with coronary heart disease and blindly applied to the population of the Multicentre Post-Infarction Program (MPIP; 577 survivors of acute infarction, 75 deaths during a median follow-up of 22 months) and to the placebo population of the European Myocardial Amiodarone Trial (EMIAT; 614 survivors of acute myocardial infarction, 87 deaths during median follow-up of 21 months). Multivariate risk stratification was done with the new parameters and conventional risk factors. FINDINGS: One of the new parameters (turbulence slope) was the most powerful stratifier of follow-up mortality in EMIAT and the second most powerful stratifier in MPIP: MPIP risk ratio 3.5 (95% CI 2.2-5.5, p<0.0001), EMIAT risk ratio 2.7 (1.8-4.2, p<0.0001). In the multivariate analysis, low left-ventricular ejection fraction and turbulence slope were the only independent variables for mortality prediction in MPIP (p<0.001), whereas in EMIAT, five variables were independent mortality predictors: abnormal turbulence onset, abnormal turbulence slope, history of previous infarction, low left-ventricular ejection fraction, and high mean heart rate (p<0.001). In both MPIP and EMIAT, the combination of abnormal onset and slope was the most powerful multivariate risk stratifier: MPIP risk ratio 3.2 (1.7-6.0, p<0.0001), EMIAT risk ratio 3.2 (1.8-5.6, p<0.0001). INTERPRETATION: The absence of the heart rate turbulence after ventricular premature beats is a very potent postinfarction risk stratifier that is independent of other known risk factors and which is stronger than other presently available risk predictors.

Aged↗

PubMed1999

Invasion marker PAI-1 remains a strong prognostic factor after long-term follow-up both for primary breast cancer and following first relapse.

In 1991, our group was the first to report the prognostic strength of plasminogen activator inhibitor type 1 (PAI-1) in primary breast cancer. The prognostic impact of invasion markers PAI-1 and urokinase-type plasminogen activator (uPA) on disease-free survival (DFS) and overall survival (OS) in breast cancer has since been independently confirmed. We now report on the prognostic impact of PAI-1 and uPA after long-term median follow-up of 77 months for our cohort (n = 316). Levels of uPA, PAI-1, and cathepsin D were determined in tumor tissue extracts by immunoenzymatic methods. S-phase fraction (SPF) was measured flowcytometrically in paraffin sections. Using log-rank statistics, optimized cutoffs were found for PAI-1 (14 ng/mg), uPA (3 ng/mg), cathepsin D (41 pmol/mg), and SPF (6%). In all patients, various factors (PAI-1, uPA, nodal status, SPF, cathepsin D, grading, tumor size, hormone receptor status) showed significant univariate impact on DFS. In Cox analysis, only nodal status (p < 0.001, RR: 3.1) and PAI-1 (p < 0.001, RR: 2.7) remained significant. In node-negative patients (n = 147), PAI-1, uPA, and SPF had significant univariate impact on DFS, whereas in Cox analysis, only PAI-1 was significant. PAI-1 was also significant for DFS within subgroups defined by established factors. In CART analysis, uPA enhanced the prognostic value of PAT-1 and nodal status for determination of a very-low-risk subgroup. For OS, only lymph node status and PAI-1 were significant in multivariate analysis. PAI-1 levels in the primary tumor were also a significant prognostic marker for survival after first relapse in both univariate and multivariate analysis.

Adult↗

PubMed1999

Prognostic significance of urokinase (uPA) and its inhibitor PAI-1 for survival in advanced ovarian carcinoma stage FIGO IIIc.

Strong evidence has accumulated on the prognostic value of tumour-associated proteolytic factors in patients afflicted with solid malignant tumours, including advanced ovarian cancer. We evaluated the prognostic impact of the protease urokinase plasminogen activator (uPA) and its inhibitor PAI-1 on overall survival in patients with advanced ovarian cancer stage FIGO IIIc in order to select patients at risk. uPA and PAI-1 antigen were determined by ELISA in primary tumour tissue extracts of 86 ovarian cancer patients FIGO stage IIIc enrolled in a prospective study. Univariate and multivariate analyses were performed using the Cox proportional hazard model. The time-varying coefficient model of Gray was used to assess the time-dependent strength of prognostic factors tumour mass, uPA and PAI-1 on overall survival. In all patients, uPA and PAI-1 (optimized cut-offs of 2.0 and 27.5 ng mg(-1) protein respectively), in addition to the traditional prognostic parameters of residual tumour mass, nodal status, grading and ascites volume, were of prognostic significance in univariate analysis for overall survival. Even in patients with residual tumour mass (n = 43), the statistically independent prognostic impact of PAI-1 persisted, allowing further discrimination between low- and high-risk patients. In multivariate analysis, residual tumour mass (P < 0.001, relative risk (RR) 4.5), PAI-1 (P < 0.001; RR 3.1) and nodal status (P = 0.022, RR 2.6) turned out to be strong, statistically independent prognostic parameters. Evaluation of the time-dependent prognostic impact of residual tumour mass and PAI-1 on overall survival (n = 86, 50 months) revealed that the prognostic power of these factors increased with time. In patients with advanced ovarian cancer, both residual tumour mass and PAI-1 are statistically independent strong prognostic factors. Even within patient subgroups with or without residual tumour mass, PAI-1 allowed selection of patients at risk who might benefit from individualized therapy protocols.

Adult↗

PubMed1999

Risk-group discrimination in node-negative breast cancer using invasion and proliferation markers: 6-year median follow-up.

Factors reflecting two major aspects of tumour biology, invasion (urokinase-type plasminogen activator (uPA), plasminogen activator inhibiter (PAI-1), cathepsin D) and proliferation (S-phase fraction (SPF), Ki-67, p53, HER-2/neu), were assessed in 125 node-negative breast cancer patients without adjuvant systemic therapy. Median follow-up time was 76 months. Antigen levels of uPA, PAI-1 and cathepsin D were immunoenzymatically determined in tumour tissue extracts. SPF and ploidy were determined flow-cytometrically, Ki"'-67, p53, and HER-2/neu immunohistochemically in adjacent paraffin sections. Their prognostic impact on disease-free (DFS) and overall survival (OS) was compared to that of traditional factors (tumour size, grading, hormone receptor status). Univariate analysis determined PAI-1 (P < 0.001), uPA (P = 0.008), cathepsin D (P = 0.004) and SPF (P = 0.023) as significant for DFS. All other factors failed to be of significant prognostic value. In a Cox model, only PAI-1 was significant for DFS (P < 0.001, relative risk (RR) 6.2). In CART analysis for DFS, the combination of PAI-1 and uPA gave the best risk group discrimination. For OS, PAI-1, cathepsin D, tumour size and ploidy were statistically significant in univariate, but PAI-1 was the only independently significant factor in Cox analysis (P < 0.001, RR 8.9). In particular, this analysis shows that PAI-1 is still a strong and independent prognostic factor in node-negative breast cancer after extended 6-year median follow-up.

Adult↗

PubMed1999

Nonparametric analysis of dose-response relationships.

A nonparametric method, isotonic regression, is proposed for analyzing a dose-response relationship and for assessing a threshold value. There are several advantages of this method compared to parametric models. No specific form of the relationship (type of model and use of the covariates) is required. The only assumption is monotonicity. Rejection of specific hypothesis can be based on the result of a permutation test. Several applications (para-aramid, crystalline silica, and PNOC) are presented. In these examples the dose-response relationships are analyzed. Where a relationship is present the existence of a threshold is investigated.

Dose-Response Relationship, Drug↗

PubMed1999

Silica dust and lung cancer in the German stone, quarrying, and ceramics industries: results of a case-control study.

BACKGROUND: A work force based case-control study of lung cancer was performed in non-silicotic subjects exposed to crystalline silica to investigate the association between silica dust and lung cancer excluding the influence of silicosis. METHODS: Two hundred and forty seven patients with lung cancer and 795 control subjects were enrolled, all of whom had been employed in the German stone, quarrying, or ceramics industries. Smoking was used as a matching criterion. Exposure to silica was quantified by measurements, if available, or otherwise by industrial hygienists. Several indices (peak, average and cumulative exposure) were used to analyse the relationship between the level of exposure and risk of lung cancer as odds ratios (OR). RESULTS: The risk of lung cancer is associated with the year of and age at first exposure to silica, duration of exposure, and latency. All odds ratios were adjusted for these factors. Considering the peak exposure, the OR for workers exposed to high levels (>/=0.15 mg/m3 respirable silica dust which is the current occupational threshold value for Germany) compared with those exposed to low levels (<0.15 mg/m3) was 0.85 (95% CI 0.58 to 1. 25). For the time weighted average exposure the OR was 0.91 (95% CI 0.57 to 1.46). The OR for the cumulative exposure was 1.02 (95% CI 0. 67 to 1.55). No increase in risk was evident with increasing exposure. CONCLUSIONS: This study shows no association between exposure to crystalline silica and lung cancer. The exclusion of subjects with silicosis may have led to dilution with respect to the level of exposure and therefore reduced the power to detect a small risk. Alternatively, the risk of getting lung cancer may be restricted to subjects with silicosis and is not directly linked to silica dust.

Adult↗

PubMed1999

HER-2/neu gene amplification by fluorescence in situ hybridization allows risk-group assessment in node-negative breast cancer.

In a collective of 112 node-negative breast cancer patients, we compared the prognostic impact of HER-2/neu gene amplification (AMP) determined by fluorescence in situ hybridization (FISH) and HER-2/neu protein overexpression (EXP) measured by immunohistochemistry (IHC) with traditional prognostic factors (tumor size, grade, steroid hormone receptor status, menopausal status) and tumor invasion markers uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 determined by enzyme immunoassay (ELISA). Median follow-up in patients still alive at time of analysis was 7 years. Automated FISH and IHC were performed on parallel-cut formalin-fixed paraffin-embedded tissue sections. HER-2/neu AMP was detected by FISH in 31% and HER-2/neu EXP was measured by IHC in 41% of the cases. In 13% of the tumors, both AMP and EXP were found. FISH and IHC results were concordant in 56% of all analyzed cases. In univariate analysis, HER-2/neu AMP significantly predicted both disease-free (DFS) and overall survival (OS). HER-2/neu EXP was significant for OS, only. In multivariate analysis of all analyzed prognostic factors, HER-2/neu AMP was the only independent predictive factor for both DFS and OS. CART analysis revealed that HER-2/neu AMP together with the combination uPA/PAI-1 allowed optimal risk-group assessment after a 7-year median follow-up: patients with low levels of both uPA and PAI-1 and no HER-2/neu AMP had a significantly lower relapse rate (4.6%) than the remaining patients (32%). In conclusion, HER-2/neu gene AMP determined by FISH allowed a more accurate risk-group assessment than HER-2/neu protein EXP measured by IHC. Combining the HER-2/neu gene status measured by FISH with levels of tumor invasion markers uPA and PAI-1 improves clinically relevant risk-group assessment. In addition to its prognostic strength, the significant impact of HER-2/neu AMP on OS may reflect its ability to predict resistance to systemic therapy.

Adult↗

PubMed1998

Renal cell cancer correlated with occupational exposure to trichloroethene.

A previous cohort-study in a cardboard factory demonstrated that high and prolonged occupational exposure to trichloroethene (C2HCl3) is associated with an increased incidence of renal cell cancer. The present hospital-based case/control study investigates occupational exposure in 58 patients with renal cell cancer with special emphasis on C2HCl3 and the structurally and toxicologically closely related compound tetrachloroethene (C2Cl4). A group of 84 patients from the accident wards of three general hospitals in the same area served as controls. Of the 58 cases, 19 had histories of occupational C2HCl3 exposure for at least 2 years and none had been exposed to C2Cl4; of the 84 controls, 5 had been occupationally exposed to C2HCl3 and 2 to C2Cl4. After adjustment for other risk factors, such as age, obesity, high blood pressure, smoking and chronic intake of diuretics, the study demonstrates an association of renal cell cancer with long-term exposure to C2HCl3 (odds ratio 10.80; 95% CI: 3.36-34.75).

Aged↗

PubMed1998

Disease-adapted relapse therapy for ovarian cancer: results of a prospective study.

Primary therapy of advanced ovarian cancer is standardized, the therapy in relapsed ovarian cancer however is still controversial. In a prospective study the benefit of secondary surgery and/or second-line chemotherapy were evaluated. 139 patients with relapsed ovarian cancer were stratified according to a treatment plan: patients with early relapse (recurrence-free interval 12 months) or primary progression during chemotherapy (n=43) were treated chemotherapeutically with etoposide (p.o. vs. i.v.). Patients with late relapse (recurrence-free interval >12 months, n=96) were referred, if possible, to a secondary debulking operation, followed by a platinum-based chemotherapy. Remission-rate, toxicity and survival time were analyzed. Median survival time in the group was 15 months compared to 30 months in patients with late relapse (p=0.0004). Within the group patients with secondary debulking and chemotherapy (n=59) had a statistically significant survival advantage compared to patients who had only chemotherapy (n=37) (38 vs. 12 months, p<0.0001). The unfavorable group of patients with early relapse should be treated chemotherapeutically, whereas in patients with late relapse a secondary debulking seems to improve prognosis.

Adult↗

PubMed1997

Bimodal distribution of angiographic measures of restenosis six months after coronary stent placement.

BACKGROUND: Restenosis has been perceived as the tail end of a normal distribution of the response of the vessel to the intervention. However, recent studies have described a bimodal distribution for de novo lesions after percutaneous transluminal coronary angioplasty. This finding suggests that some lesions may be more susceptible for restenosis. Whether this holds true for a wider spectrum of lesions undergoing stent placement is not yet known. The present study analyzes the frequency distribution of angiographic indexes of restenosis 6 months after coronary stent implantation. METHODS AND RESULTS: Quantitative angiographic evaluation was performed in 1084 lesions of 1084 patients before, immediately after, and 6 months after successful Palmaz-Schatz stent placement; this represented 80.4% of patients eligible for follow-up angiography. Principal end points of the analysis were angiographic indexes of restenosis at 6 months. Twenty-two lesions that became totally occluded at follow-up were excluded from most parts of the analysis. Diameter stenosis, minimal luminal diameter (MLD), and lumen loss at 6 months did not follow a normal pattern; the bimodal pattern was demonstrated through deconvolution that yielded two separate normal components delineating two lesion populations, which developed distinctively different degrees of lumen renarrowing. The first and larger subgroup of lesions, which was less prone to restenosis, was centered around a mean value of 27% for diameter stenosis and 2.19 mm for MLD, whereas the second subgroup, with a greater tendency for restenosis, was situated around a mean value of 68% for diameter stenosis and 0.76 mm for MLD. The intersection point between the two theoretical normal distribution components was 53.5% for diameter stenosis and 1.09 mm for MLD at follow-up. CONCLUSIONS: Frequency-distribution curves of angiographic indexes of restenosis after coronary stent placement have a bimodal pattern, suggesting the existence of two distinct populations with different propensity to restenosis. These findings may encourage future efforts for the timely identification of the subset with a higher risk as the target of specific antirestenotic strategies.

Aged↗

PubMed1997

Restenosis after coronary stent placement and randomization to a 4-week combined antiplatelet or anticoagulant therapy: six-month angiographic follow-up of the Intracoronary Stenting and Antithrombotic Regimen (ISAR) Trial.

BACKGROUND: Platelets and mural thrombus at the lesion site may play a key role in initiating the restenosis process after coronary interventions. The ISAR Trial provides a comparison of the outcomes of patients randomized to two different antithrombotic regimens administered for 4 weeks after successful coronary stent placement: combined antiplatelet therapy (aspirin plus ticlopidine) or a conventional anticoagulant regimen (phenprocoumon with initial overlapping heparin plus aspirin). Within the first 4 weeks after stent placement, combined antiplatelet therapy has been associated with a significant reduction of ischemic complications. In the present study, we examined whether combined antiplatelet therapy administered for 4 weeks after stent placement is able to reduce the process of restenosis at 6 months. METHODS AND RESULTS: Of 517 patients initially randomized, 496 were eligible for 6-month angiographic follow-up. Scheduled angiography was performed in 432 of the eligible patients (87.1%), 216 in each group. In a comparison of the two groups, there were no significant differences in clinical and procedural variables or in qualitative and quantitative lesion characteristics before and after stenting. At 6 months, minimal luminal diameter was 1.95+/-0.86 mm in the group with initial combined antiplatelet therapy and 1.90+/-0.87 mm in the group with initial anticoagulant therapy (P=.55). Late lumen loss was 1.10+/-0.81 and 1.15+/-0.75 mm (P=.54), and the restenosis rate was 26.8% and 28.9%, respectively (P=.70). Target lesion revascularization rate was 14.6% in the antiplatelet therapy group and 15.6% in the anticoagulant therapy group (P=.85). CONCLUSIONS: This study shows that combined antiplatelet therapy (aspirin plus ticlopidine) administered for 4 weeks after coronary Palmaz-Schatz stent placement does not result in a detectable benefit for the prevention of restenosis compared with conventional anticoagulant therapy (phenprocoumon with initial overlapping heparin plus aspirin).

Administration, Oral↗

PubMed1997

Major benefit from antiplatelet therapy for patients at high risk for adverse cardiac events after coronary Palmaz-Schatz stent placement: analysis of a prospective risk stratification protocol in the Intracoronary Stenting and Antithrombotic Regimen (ISAR) trial.

BACKGROUND: The Intracoronary Stenting and Antithrombotic Regimen (ISAR) Trial is a randomized study in which antiplatelet therapy is compared with anticoagulant therapy after coronary stent placement, showing a significantly lower rate of noncardiac and cardiac events with antiplatelet therapy. The present study is a report of the analysis of a prospective risk stratification protocol in the ISAR Trial and the association with the incidence of adverse cardiac events and stent vessel occlusion. METHODS AND RESULTS: In all 517 patients randomized in the ISAR Trial, risk stratification was done with a list of 18 clinical, procedural, and angiographic variables: 165 patients with two or fewer criteria were classified as low risk, 148 patients with three criteria were classified as intermediate risk, and 204 patients with four or more criteria were classified as high risk. Within a 30-day follow-up, cardiac event rate (death, myocardial infarction, repeat intervention) was 6.4% for high-risk, 3.4% for intermediate-risk, and 0% for low-risk patients (P<.01). Stent vessel occlusion occurred in 5.9%, 2.7%, and 0%, respectively (P<.01). There was no significant difference between anticoagulant and antiplatelet therapy in the low- and intermediate-risk groups. In high-risk patients, however, the cardiac event rate was 12.6% with anticoagulant therapy and 2.0% with antiplatelet therapy (P=.007), and the rate of stent vessel occlusion was 11.5% and 0%, respectively (P<.001). CONCLUSIONS: This risk stratification protocol can help to identify patients at risk for adverse cardiac events and stent vessel occlusion. Patients in the high-risk group had the most benefit from antiplatelet therapy. These data suggest that antiplatelet therapy is the therapy of choice after coronary stenting specifically for patients with acute ischemic syndromes, difficult procedures, or suboptimal final results.

Angioplasty, Balloon, Coronary↗

PubMed1997

Neurotoxicity of long-term low-level exposure to carbon disulphide: results of questionnaire, clinical neurological examination and neuropsychological testing.

OBJECTIVE: Carbon disulphide (CS2) is highly neurotoxic. There is ample evidence of damage to the peripheral and central nervous system. The air concentration at which such adverse effects can first be observed is presently a subject of controversy. METHODS: In a cross-sectional study of CS2-exposed workers from the viscose industry and healthy controls, data on neurological complaints, basic laboratory diagnosis, clinical neurological examination and neuropsychological testing were evaluated. Data were from 222 workers in the viscose industry exposed to CS2 and 191 employees from the same factory with similar physical and psychological stress factors but without occupational contact with neurotoxic substances. Multiple linear or multiple logistic regression analysis was used to check for statistical differences. RESULTS: The median of the CS2-measurements using personal air sampling was below the current maximum concentration permissible (MAK value) in Germany (10 ppm) in all departments. The threshold limit value was, however, exceeded in almost 10% of the persons investigated. Exposure fluctuated between < 0.2 and 65.7 ppm (median of all departments was 4.02 ppm). As a parameter of internal exposure, CS2-metabolite 2-thio-1,3-thiazolidine-4-carboxylic acid (TTCA) concentrations in the urine of the exposed persons were between < 0.16 and 10.9 mg/g creatinine (median 1.43 mg/g). CONCLUSIONS: Neither an increase in subjective complaints nor an increase in pathological findings in clinical-neurological and neuropsychological examination could be found in persons exposed to CS2 at the exposure levels described.

Adult↗

PubMed1997

Electrophysiological investigation of central, peripheral and autonomic nerve function in workers with long-term low-level exposure to carbon disulphide in the viscose industry.

OBJECTIVE: Neurotoxicity of carbon disulphide (CS2) is well known. The air concentration at the workplace at which such adverse effects can first be observed is the subject of controversial discussion. METHODS: In a cross-sectional study on CS2-exposed workers peripheral motor and sensory nerve conduction studies, somatosensory evoked potentials, thermotesting and investigation of forced respiration sinus arrythmia have been carried out. The data from 222 workers exposed to CS2 in the viscose industry were evaluated and compared with data from 191 employees from the same factory with similar physical and psychological stress factors but without detectable occupational contact to neurotoxic substances. Median exposure to CS2 was below the currently valid occupational-medical threshold limit value (MAK-value) of 10 ppm. Multiple linear or multiple logistic regression analysis was used to check for statistical differences. RESULTS: Binary evaluation (comparison of exposed persons versus controls after multiple linear regression) revealed a slightly lower value in the exposed group for the motor nerve conduction velocity (MNCV, -0.76 m/s, median 48 m/s), but a long way from pathological thresholds. No dose-response relationship could be found within the exposed group for any evaluation criteria of CS2-exposure. Somatosensory evoked potentials, thermotesting and analysis of heart rate variability yielded no indication of a neurotoxic effect of CS2. CONCLUSION: Isolated decrease of MNCV in binary evaluation is, with regard to the known mechanism of CS2-neurotoxicity and the lack of a dose-response relationship, obviously not due to toxic effects. We interpret our results as showing that an adverse effect of carbon disulphide at the exposure ranges found was not detectable in the exposed group.

Adult↗

PubMed1997

Angiogenin plasma levels during pregnancy.

OBJECTIVE: Our purpose was to determine the levels in plasma of angiogenin in healthy pregnant women and to examine whether there are differences between uncomplicated pregnancies and patients with the syndrome of hemolysis, elevated liver enzymes, and low platelets, preeclampsia-eclampsia, and highly pathologic Doppler flow findings without additional complications. STUDY DESIGN: Angiogenin was measured with a novel enzyme-linked immunosorbent assay. A case control and observational study was conducted in 68 healthy women from the tenth to fortieth weeks of pregnancy and in 18 patients with the syndrome of hemolysis, elevated liver enzymes, and low platelets, 21 with preeclampsia/eclampsia and 13 with highly pathologic Doppler flow findings at admission for delivery. RESULTS: Between the tenth and fortieth weeks of uncomplicated pregnancy angiogenin plasma levels rose from 150 to 250 ng/ml (significant correlation). In patients with highly pathologic Doppler flow findings angiogenin is significantly reduced compared with healthy pregnant matched pairs (150 vs 219 ng/ml, p < 0.01). CONCLUSION: Rising plasma angiogenin levels in pregnancy may reflect persisting placental transformation and remodeling processes: in patients with highly pathologic Doppler flow findings these processes are disturbed and thus placental function is impaired.

Adult↗

PubMed1997

Time-varying prognostic impact of tumour biological factors urokinase (uPA), PAI-1 and steroid hormone receptor status in primary breast cancer.

In breast cancer, several investigations have demonstrated that the tumour biological factors uPA urokinase-type plasminogen activator) and its inhibitor PAI-1 are statistically independent, strong prognostic factors for disease-free (DFS) and overall survival (OS). However, statistical analyses performed for varying follow-up periods suggested a time variation of prognostic strength. We therefore investigated the time-dependent prognostic power of uPA, PAI-1 and steroid hormone receptor status applying the time-varying coefficient model of Gray. uPA and PAI-1 were analysed by enzyme-linked immunosorbent assay in tumour tissue extracts from 314 breast cancer patients. Hormone receptors (oestrogen and progesterone) were determined by radioligand binding or by immunohistochemistry. Univariate and multivariate analyses (Cox proportional hazards model) of DFS and OS were performed for all patients, including 147 node-negative patients. Median follow-up of patients still alive at time of analysis (n = 232) was 58 months. Although initially of high prognostic impact, a continuous decrease over time in the prognostic power of hormone receptor status and uPA was observed. In contrast, the prognostic impact of PAI-1 increased over time and reached similar strength as the lymph node status. The time-dependent risk profile of prognostic factors may have important clinical implications in regard to follow-up and patients' individual risk situation. Evaluation of time dependency of prognostic factors may also give a more profound insight into the dynamics of breast cancer metastasis.

Adult↗