Biomedical subjects
W Köpcke
Publications and source records attributed to W Köpcke.
Validation of methods for the assessment of cataract progression in the Roche European-American Anticataract Trial (REACT)
The Roche European-American Anticataract Trial (REACT) will assess the effect of antioxidants on progression of cataract in humans. This report evaluates the methods used in REACT. Seventy three subjects (139 eyes) with cortical (C), posterior subcapsular (P), nuclear (N) or mixed cataract were seen twice within two weeks for eye examinations, assessments of visual function, lens photographs and CCD images. The degree of cataract and nuclear color (NC) were assessed with subjective (LOCS III) and objective (computerized, CASE 2000 CCD) methods. Repeat visit values were used to calculate intraclass correlation coefficients (r1) and 95% tolerance limits (TL). A clinically significant change (CSC) was defined as one step in LOCS III. The relative power of each method to detect cataract change and sample sizes needed to achieve statistically significant results were calculated. The r1 values for visual function tests ranged from 0.76 to 0.88; if these tests of visual function were used to detect a clinically significant change in cataract severity, sample sizes of 840 to 2707 per group would be needed. The r1 values for LOCS III were 0.88 to 0.97, and sample sizes ranged from 50 to 135 per group. The r1 values for the CCD were 0.93 to 0.98, and sample sizes ranged from 1 to 42 with poorer values relating to measurement of P. We conclude that the methods used in REACT are reproducible. The analytical algorithms in the image analysis programs did not permit differentiation between C and P opacification; therefore, P cataract is best measured with LOCS III. REACT sample sizes are adequate to detect a difference of 0.2 LOCS III units/year between the mean rates of cataract progression in two groups.
Decreased high-density lipoprotein cholesterol and increased low-density cholesterol levels in patients with colorectal adenomas.
OBJECTIVE: To study the relation between serum lipoprotein levels and the frequency of colorectal adenomas, the benign precursors of colorectal cancer. DESIGN: Cross-sectional. SETTING: University hospital in Germany. PATIENTS: The study included 822 of 1124 consecutive patients who underwent colonoscopy at our institution (302 patients were excluded because of malignant disease, chronic inflammatory bowel disease, familial polyposis, partial colectomy, or other chronic diseases). Of the 822 study patients, 194 had colorectal adenoma. MEASUREMENTS: Serum cholesterol fractions (high-density lipoprotein [HDL], low-density lipoprotein [LDL], and very low-density lipoprotein [VLDL]) and presence or absence of adenomas; univariate and logistic regression analyses were carried out to evaluate the association between serum HDL, LDL, and VLDL cholesterol levels and the frequency of colorectal adenoma. RESULTS: Univariate analysis of the total patient group showed that the HDL cholesterol level was inversely related to the frequency of colorectal adenoma (odds ratio, 0.36; 95% Cl, 0.21 to 0.62) and that LDL and VLDL cholesterol levels were positively associated with adenoma frequency (odds ratio, 2.31 [Cl, 1.36 to 3.92] and 1.72 [Cl, 1.03 to 2.86], respectively). Univariate analysis of the subgroup of 89 patients with high-risk adenomas showed an inverse association between such adenomas and HDL cholesterol (odds ratio, 0.37; Cl, 0.18 to 0.76). A logistic regression analysis that included age and body mass index showed an association between lipoprotein levels and the presence of adenomas. The relative strength (in descending order) of these associations was as follows: HDL, LDL, VLDL, and total serum cholesterol. A logistic regression analysis of patients with high-risk adenoma showed a significant association between such adenomas and the HDL cholesterol level. CONCLUSIONS: Patients with colorectal adenomas have lower HDL cholesterol levels and higher LDL and VLDL cholesterol levels; these lipoproteins may have prognostic significance for the development of colorectal adenomas.
Increased risk of 'high-risk' colorectal adenomas in overweight men.
BACKGROUND: Epidemiologic studies have suggested that the incidence of colorectal carcinoma may be related to overnutrition, but retrospective analysis of its relation to the body mass index (BMI: kg/m2) has produced conflicting data. METHODS: To avoid as many sources of statistical bias as possible, the relation between BMI and the presence of colorectal adenomas was investigated in a cross-sectional study. RESULTS: Two thousand twelve consecutive colonoscoped patients were investigated (532 patients with malignancies or other conditions associated with weight loss were excluded). The relation between BMI and observed colorectal adenomas was evaluated by a logistic model controlling for other prognostic factors such as age, sex, and serum cholesterol level. The subgroup of "high-risk" adenomas with an increased risk of malignant transformation was positively associated with the BMI in men of the age group 50.5-68.1 years (quintiles III and IV: odds ratio for the top quintile vs. the lowest quintile, 3.21; 95% confidence interval, 1.15-8.98). CONCLUSIONS: It was concluded that the risk of developing high-risk adenomas tends to be increased in men who are overweight and that this association is independent of the positive association with the serum cholesterol level recently described.
Increased serum deoxycholic acid levels in men with colorectal adenomas.
BACKGROUND: Epidemiological and animal studies have suggested that the secondary bile acid deoxycholic acid is cocarcinogenic in colorectal cancer, but this hypothesis was not confirmed by case-control studies investigating fecal bile acids. METHODS: Individual serum bile acid concentrations were investigated in 25 men and 25 women with colorectal adenomas and in an equal number of age- and sex-matched controls by gas-liquid chromatography. RESULTS: Deoxycholic acid levels were significantly higher in the sera of men with colorectal adenomas (1.70 +/- 0.59 vs. 1.16 +/- 0.39 mumol/L, P < 0.0005) and in a combined analysis of both sexes (1.47 +/- 0.78 vs. 1.08 +/- 0.39 mumol/L, P < 0.0025). Six- and 12-month follow-up measurements of deoxycholic acid concentrations in a subgroup of 22 men and 17 women showed higher serum levels in men with adenomas, indicating that measurement of deoxycholic acid concentration may be a reliable parameter to investigate its pathogenetic role in colonic neoplasia. CONCLUSIONS: The data of this study support the hypothesis that deoxycholic acid may play a role in the pathogenesis of colorectal cancer.
Early neuroleptic intervention in schizophrenia: are prodromal symptoms valid predictors of relapse?
All recently completed controlled two-year studies on intermittent, early neuroleptic intervention treatment have failed to compare favourably with studies on maintenance treatment concerning relapse prevention. The reason for this failure is still unclear. Therefore the implicit, but as yet unproven, hypothesis that a relapse can be predicted from prodromal symptoms was tested from the perspective of our German multicentre study. Results demonstrate that this is not the case. Possible reasons for and clinical implications of this negative finding are discussed.
Intermittent medication, coping and psychotherapy. Interactions in relapse prevention and course modification.
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Predictive value of serum procollagen-III-peptide for the survival of patients with cirrhosis.
The value of the aminoterminal procollagen-III-peptide (P-III-P) in predicting death or survival was evaluated in a group of 43 patients with proven postnecrotic or alcoholic cirrhosis. Patients were followed-up prospectively for 2 years. The prognostic value of P-III-P was compared with the Child classification, fasting and postprandial serum bile acids, and standard laboratory tests such as bilirubin, prothrombin index, pseudocholinesterase, albumin, GOT, GPT, gamma-GT, and clinical findings such as ascites, encephalopathy (assessed with the number connection test = NCT), and nutritional status. Between patients who died and those who survived the following 2 years, there were significant differences in the following parameters at the time of inclusion in the study: encephalopathy judged by NCT (p = 0.001), serum albumin (p = 0.0012), postprandial serum bile acids (p = 0.0024), fasting serum bile acids (p = 0.0025), pseudocholinesterase (p = 0.0044), GOT (p = 0.015), bilirubin (p = 0.016), and prothrombin index (p = 0.01). None of the other parameters investigated, including SP-III-P (p = 0.46), revealed any statistically significant differences between patients who died and survivors. The prognostic significance of laboratory tests and recorded clinical findings was evaluated, either alone or in combination with life-table analysis using the Cox model. SP-III-P, alone or in combination with other parameters, failed to improve prediction of mortality in patients with cirrhosis. In comparison to the Child classification (p = 0.0004) the combination of NCT and postprandial serum bile acids showed a similar ability (p = 0.0003) to predict patient survival.
Design and analysis of the HYPREN-trial: safety of enalapril and prazosin in the initial treatment phase of patients with congestive heart failure.
Since the introduction of angiotensin converting enzyme (ACE) inhibitors into the adjunctive treatment of patients with congestive heart failure, cases of severe hypotension, especially on the first day of treatment, have occasionally been reported. To assess the safety of the ACE inhibitor enalapril a multicenter, randomized, prazosin-controlled trial was designed that compared the incidence and severity of symptomatic hypotension on the first day of treatment. Trial medication was 2.5 mg enalapril or 0.5 prazosin. Subjects were 1210 inpatients with New York Heart Association (NYHA) functional class II and III. Patients who received enalapril experienced clinically and statistically significantly less symptomatic hypotension (5.2%) than the patients who received prazosin (12.9%). All patients recovered. It was concluded that treatment with enalapril was well tolerated and it is, therefore, unreasonable to restrict the initiation of treatment with enalapril to inpatients.
Depressive syndromes in schizophrenic patients after discharge from hospital. ANI Study Group Berlin, Düsseldorf, Göttingen, Munich.
A total of 364 schizophrenic outpatients who were stabilized for 3 months on continuous neuroleptic therapy after discharge from the hospital were rated according to three different scales for depressive syndromes (Brief Psychiatric Rating Scale anxious depression factor, AMDP/depression, and the self-rating PD-S depression scale). Between 19.5% and 27.5% of the patients were rated as depressed, or 35.7%-42.8%, when mild depressive syndromes were included. There were low, but significant correlations between demographic or life-event data and depression scores on the self-rating scale, whereas fewer correlations were found on the observer ratings. No associations were found between social adjustment and depression. Moderate correlations were found between measures of the apathetic syndrome and depression ratings, while observer ratings showed higher correlations than the self-rating. High depression scores, especially in the observer ratings, correlated with scales for global psychopathological assessment (CGI, GAS). There were significant correlations between extrapyramidal rigidity and observer rating depression scores, whereas the total amount of neuroleptics given had no influence. These results are interpreted on the basis of hypotheses about depressive syndromes in schizophrenia.
[Biochemical aspects of the evaluation of fixed drug combinations].
Various disciplines have to contribute to the general problem of the evaluation of fixed dose combination drugs, as for instance (clinical) pharmacology, biometry, scientific drug regulations and public health officials. The EC guideline 75/318/EWG and its eludications as well as the German "Arzneimittelprüfrichtlinien" of Dec. 14, 1989 (as referred to in the "Arzneimittelgesetz" of 1986) required that such issues concerning fixed dosage combination drugs must be considered and taken into account. In this framework it is the responsibility of biometry to both to guarantee the use of a valid study design to assure interpretation of the results and to quantify the reliability of pharmacological and clinical considerations. The following paper is concerned with biometrical aspects of the combination drug problem. Basic considerations from a clinical or a pharmacological point of view with respect to the question of whether fixed combination drugs are reasonable or not are not discussed. To support the use of combinations of drugs, a central argument is the improvement of the benefit risk relation compared with that of an adequate monotherapy. Beyond this the fixed combination drugs require additional arguments regarding the enhencement of the safety or the simplicity of the therapy fixing the ratio. It follows that fixed combination drugs have to be supported twice, first with respect to the combination itself, and second with respect to the fixed mixing ratio of its components. The biometrical aspects of the assessment of the gains from (fixed) drug combinations are related to the kind of benefit/risk improvement that is expected. In the first section we discuss some possible types of benefit and risk.(ABSTRACT TRUNCATED AT 250 WORDS)
Prophylactic sclerotherapy before the first episode of variceal hemorrhage in patients with cirrhosis.
The value of sclerotherapy as prophylaxis against the first episode of variceal hemorrhage has not been established. Therefore, we randomly assigned 133 patients with cirrhosis of the liver (of alcoholic origin in 66 percent), esophageal varices, and no previous intestinal bleeding to either prophylactic sclerotherapy (n = 68) or no prophylaxis (n = 65). The groups were comparable in hepatic function, endoscopic findings, and the pathogenesis of cirrhosis. All patients who subsequently had a first episode of variceal hemorrhage received sclerotherapy whenever possible. During a median follow-up of 22 months, variceal hemorrhage occurred in 28 percent of the patients receiving sclerotherapy and 37 percent of the controls (P = 0.3). Thirty-five percent of the sclerotherapy group and 46 percent of the control group died. The survival curves (Kaplan-Meier) of both groups were similar (P = 0.2). However, among patients with alcoholic and moderately decompensated cirrhosis (Child-Pugh group B), survival was significantly higher in those receiving sclerotherapy, although the risk of bleeding was only marginally reduced by this procedure. We conclude that prophylactic sclerotherapy does not significantly reduce the risk of bleeding from esophageal varices, but that a subgroup of patients with esophageal varices and moderately decompensated alcoholic cirrhosis may benefit from prophylactic sclerotherapy because of factors not solely attributable to prevention of an initial episode of variceal bleeding.
Essential thrombocythemia. Clinical characteristics and course of 61 cases.
Sixty-one patients with essential thrombocythemia (ET) were followed from 1974 through 1987 at the Medizinische Poliklinik. Fifty-one patients (84%) presented with thromboembolic complications, and eight patients (13%) with hemorrhages. In seven patients (12%), a thrombocytosis was detected accidentally. Disturbances of the microcirculation (67%), mainly of the fingers and toes (53%), were the most frequent thromboembolic symptoms. The mean age of all patients was 58 years (male patients, 61 years; female patients, 56 years). The average platelet count at diagnosis was 897,000/microliter. The average maximal platelet count was 1.231 X 10(6)/microliter (range, 500,000/microliter to 4 X 10(6)/microliter). Seventy-two percent had a moderate leukocytosis (average, 12,400/microliter), 34% a splenomegaly, 29% a hepatomegaly. Signs of hypermetabolism were infrequent, lactate dehydrogenase (LDH) and uric acid elevations, if present, were moderate. Bleeding time and viscosity were normal in most patients. Spontaneous platelet aggregation was increased in 81% of patients (n = 40). Platelet aggregation studies with the aggregation inducing substances adenosine diphosphonate (ADP), platelet activating factor (PAF), thrombin, collagen, and adrenalin showed hypoaggregation in most patients. Adrenalin-induced aggregation distinguished best between ET-patients and reactive thrombocytosis showing hypoaggregation in all ET-patients tested (n = 16) and in none of 22 controls. Bone marrow studies were performed in 57 patients. The histologic studies (done in 49 patients) were consistent with a chronic myeloproliferative disorder in all cases. In 41 cases (84%) the picture of a megakaryocytic myelosis was found, in 12 of these a granulocyte-rich form of megakaryocytic myelosis. Cytologic studies only (eight patients) did not differentiate ET well from reactive thrombocytosis. Platelet aggregation studies and bone marrow histology may be of help in the diagnosis of difficult cases of thrombocytosis. The Philadelphia status was negative in all cases studied (14 patients). Fourteen patients died. The causes of death were thromboembolic complications in probably 11 and acute leukemia in two patients. The probability of 10-year survival is 64% after a mean follow-up time of approximately 5 years. It appears that considering the average age of ET patients at diagnosis, life expectancy is close to normal.
[Clinical characterization of essential thrombocythemia in comparison with other myeloproliferative diseases and reactive thrombocytoses].
60 patients with essential thrombocythemia (ET) have been retrospectively and prospectively followed from 1974 through 1987. The presenting signs and symptoms and the course of the disease were analyzed and compared to 10 patients with persisting reactive thrombocytosis selected from 6,000 patients with reactive thrombocytosis and to 50 patients with other myeloproliferative diseases. 54 ET-patients presented with complications, 46 with thrombembolic, 3 with hemorrhagic problems and 5 with thrombembolic and hemorrhagic problems. In 6 patients ET was detected accidentally. Disturbances of the microcirculation, mainly of the fingers and the toes, were the most frequent symptom. The average maximal platelet count was 1,207,000/microliter. The average platelet count at diagnosis was 880,000/microliter. 16 patients had an elevation of the serum creatinine at diagnosis, which deteriorated during the course of the disease. Bone marrow examinations were performed in 56 patients, histology in 48 patients, cytology in 29 patients. In contrast to the clinical diagnosis the histological diagnosis was in 4 cases each polycythemia vera and myeloproliferative syndrome without further specification. 12 patients died thus far. The causes of death were thrombembolic complications in 9, acute leukemia in 2 patients, in 1 patient the cause of death is not known. 10 years after diagnosis 61% of the patients are still alive. It appears that ET is a more important risk factor for the disturbances of the micro- and macrocirculation than has been recognized until now. ET is, if thrombembolic complications are avoided, a disease with a relatively benign course.
[Prognostic parameters in liver cirrhosis, varicose bleeding and sclerosing therapy. Prospective comparison of a prognostic system with the Child classification obtained by discriminant analysis].
Prospective prognosis systems for predicting half-year death-rate after bleeding from oesophageal varices and sclerotherapy were tested on 129 patients. The receiver-operating-characteristic curves of three discriminant scores were compared with the Child-Pugh classification. It was found that the latter is still the best for prognosticating the course of the disease. A simplified discriminant score which contains as its only factors bilirubin and the Quick value does, however, give nearly as good information.
[Prospective controlled study of therapy of chronic myeloid leukemia (CML)].
The current status of the prospective German multicenter study on the therapy of chronic myelogenous leukemia (CML) is reported. After three years 188 of the projected 300 patients have been randomized. The duration of the study will be 8 years. The clinical characteristics of the randomized patients correspond well to those reported in the literature. Risk factors are distributed equally in both arms. One problem is the relatively high drop-out rate of about 12% thus far. Survival curves for the two treatment arms will be presented, although at present the number of patients having reached the end of the chronic phase is too small to allow definitive evaluation.
[Treatment of essential hypertension with a potassium-sparing diuretic combination. Results of a German multicenter study with Moduretic].
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Long-term sclerotherapy of bleeding esophageal varices in patients with liver cirrhosis. An evaluation of mortality and rebleeding risk factors.
Ninety-six liver cirrhosis patients with bleeding esophageal varices receiving long-term sclerotherapy with the flexible endoscope were studied prospectively to analyze mortality and rebleeding risk factors. The difference in the 1-year survival rates of Child's groups A (100%) and B (82%) versus Child's C patients (38%) was highly significant (p less than 0.001). Multivariate analysis revealed that, as single factors, serum bilirubin, grade of ascites, and prothrombin time and, as a combination, the four variables bilirubin, ascites, aspartate aminotransferase, and age distinguished best between survivors and non-survivors during the first 6 months after inclusion in the study. For the separation of rebleeders and non-rebleeders during the first 2 months, prothrombin time and grade of ascites gave the best distinction. Thus, cirrhotics with variceal hemorrhage, ascites, jaundice, and a prolonged prothrombin time remain a high-risk group also with long-term sclerotherapy.