The dangers of overdocumentation.
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Biomedical subjects
Publications and source records attributed to G Rudolph.
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22 psychotherapy outcome studies used in the Bernese meta-analysis by Grawe, Donati and Bernauer (1994) for a treatment comparison between behavioural and psychoanalytic-psychodynamic treatment concepts were reanalysed by 12 expert psychotherapy researchers independent of each other. Three clinical criteria served as basic criteria for the assessment of the methodological quality of the 22 comparative studies: treatment dosage, therapists' competence or expertise, and an adequate realisation of the intended treatment concept. The expert ratings were then compared with an evaluation of an assessment of a research team from the University of Ulm and with the one from the Bernese research team. Contrary to the Bernese meta-analysis, both the experts and the Ulm research group conclude that only 5 or 8 of the 22 studies, respectively, could be accepted for a relatively fair comparison between the treatments under study. Out of the 5/8 studies, none could be considered fully suitable for a treatment comparison, at the most only moderately suitable. These remaining 5 or 8 studies, respectively, do not prove superiority of one treatment over the other. Hence, the "Dodo Bird Verdict" stands up under scrutiny.
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BACKGROUND/AIMS: Primary sclerosing cholangitis is characterized by progressive fibrotic inflammation and obliteration of intra- and extrahepatic bile ducts. Ursodeoxycholic acid treatment leads to improvement of biochemical parameters of cholestasis and in part also of liver histology. During treatment, obstruction of major ducts may lead to deterioration of liver function, which may be prevented by endoscopic dilation of the stenoses. Controlled trials for evaluation of the beneficial effects of ursodeoxycholic acid treatment and of endoscopic measures in patients with major duct stenoses have become clinically difficult. Estimation of survival probabilities without treatment allows comparison of actuarial survival with the estimated survival probabilities. METHODS/RESULTS: We studied survival in 65 patients with PSC treated with ursodeoxycholic acid (750 mg/day) and by endoscopic measures whenever necessary. Patients with decompensated cirrhosis in whom transplantation was foreseen were excluded. The study was started in May 1987 and the mean follow-up period was 45.0+/-3.5 (mean+/-SEM) months. Liver histology was performed in each of the patients before entry into the study and revealed that 21% were in stage 1, 37% in stage 2, 21% in stage 3 and 20% in stage 4. Of 65 patients, 12 had major duct stenosis at entry and another 11 developed major duct stenosis during ursodeoxycholic acid treatment, which was successfully treated by repeated endoscopic balloon dilations. The actuarial Kaplan-Meier survival probabilities without liver transplantation after treatment with ursodeoxycholic acid and dilation of major duct stenoses were significantly improved compared to the predicted survival rates with p=0.001. CONCLUSIONS: Ursodeoxycholic acid does not prevent major bile duct occlusion. When ursodeoxycholic acid treatment and endoscopic opening of duct stenoses are combined, survival may be significantly improved.
BACKGROUND: Carotid cavernous fistulas are cerebral artenovenous shunts which may present with ocular or orbital signs. Direct fistulas are distinguished from dural shunts with respect to the anatomical situation. PATIENTS: We report on two patients with spontaneous dural carotid cavernous fistulas with multiple feeding vessels. Both patients required endovascular embolization. RESULTS: Therapy was successful in both patients. We present an overview of the clinical picture, the diagnostic procedure, the differential diagnosis and the therapeutic possibilities in this clinical entity. CONCLUSION: Both patients prove the importance of an immediate differential diagnostical classification so that a specific neuroradiological diagnostic can be ensured. Today's advanced endovascular technology offers therapeutic options with less risk for the patient than in recent years.
BACKGROUND: In assessing the safety of medication use in breastfeeding, it is important to know whether the drug used by the mother will be present in the breastfed infant. Compared with data for tricyclic antidepressants (TCAs), which have generally not been found in the plasma of breastfed infants, there are few data on the use of serotonin selective reuptake inhibitors (SSRIs) in breastfeeding. This poses a dilemma for breastfeeding women and their treating clinicians, because of the enhanced tolerability of SSRIs compared with TCAs, and because some patients do not respond well to TCAs. METHOD: Sertraline and norsertraline plasma concentrations were measured in three breastfeeding mother-infant pairs. Maternal and infant plasma samples were drawn a few minutes apart. Two of the infants had an additional sample assayed without contemporaneous maternal samples examined. Drug assay was by high-performance liquid chromatography. Limit of reproducible quantifiability was 2 ng/mL, and limit of detectability was 1 ng/mL. RESULTS: Maternal sertraline dose ranged from 50 to 100 mg/day. All infant plasma samples showed low levels (< 2 ng/mL) of either sertraline and norsertraline or norsertraline alone. Breastfeeding was continued, and the infants have shown no adverse effects on short-term follow-up. CONCLUSION: These data suggest that sertraline and/or its almost inactive metabolite may be present at very low concentrations in the plasma of breastfed infants. No adverse effects were noted in the infants. Limitations of the findings and possible implications for the use of sertraline during breastfeeding are discussed.
Administration of cyclosporin A (CsA) may induce cholestasis, and this effect has been attributed to impaired hepatocellular uptake, transport, secretion and intestinal absorption of bile acids. Disturbances of the enterohepatic circulation may affect metabolism of bile acids. To test whether liver transplantation and treatment with CsA alters pool sizes or synthesis and turnover rates, we determined kinetics of primary bile acids in patients after orthotopic liver transplantation on CsA. Two male and four female patients were studied 6-20 months after transplantation. They had no overt signs of cholestasis, graft dysfunction or rejection. Kinetics of cholic acid (CA) and chenodeoxycholic acid (CDCA) were simultaneously determined after oral administration of [24-13C]-CA and [24-13C]-CDCA on the basis of isotope dilution in a single pool of bile acids. Ten healthy volunteers served as controls. After orthotopic liver transplantation, pool sizes, fractional turnover rates and synthesis rates of both primary bile acids, CA and CDCA were not significantly different from control subjects. In spite of the known interference of CsA with the enterohepatic circulation of bile acids, in the majority of patients after orthotopic liver transplantation without cholestasis, graft dysfunction of rejection, treatment with CsA does not disturb kinetics of primary bile acids.
The Schimmelpenning-Feuerstein-Mims syndrome (SFM), characterized by linear nevus sebaceous and ocular and neurologic abnormalities, is a sporadic condition without known familial cases or etiology. We report the occurrence of SFM in only one of two monozygotic (MZ) twins. After considering a variety of possible causative mechanisms, we suggest that a postzygotic dominant lethal mutation in mosaic form may best explain SFM and the discordancy for SFM in these MZ twins.
Alosetron is under clinical development for the treatment of schizophrenia. This study evaluated the effect of oral alosetron dosing on the pharmacokinetics of haloperidol, the latter being administered daily to 13 schizophrenic patients for 56 days. Alosetron 1 mg daily or placebo was given by random assignment for 2 weeks. After a two-week alosetron washout period (during which patients received placebo), patients received the alternate treatment for another two weeks. Serial blood samples were collected for high-performance liquid chromatography determination of plasma haloperidol, reduced haloperidol, and alosetron at selected times for 24 hours after administration of haloperidol and alosetron on study days 21 and 49. Mean pharmacokinetic parameters of haloperidol in the presence of alosetron and placebo treatments were not significantly (P > .05) different: dose-normalized Cmax (6.40 versus 5.75 ng/mL), dose-normalized Cmin (2.00 versus 1.90 ng/mL), dose-normalized AUC (85.97 versus 68.48 ng.hr/mL), and CL/f (78.23 versus 104.7 L/hr). A two-compartment model was used to assess the concentration- and time-independent pharmacokinetics of haloperidol after multiple dosing. The model confirmed that there was no change in the pharmacokinetics of haloperidol when alosetron was administered concomitantly. Mean AUC ratios of reduced haloperidol to haloperidol (0.18) in the presence of alosetron were similar to values obtained in the absence of alosetron, indicating that alosetron had no influence on the metabolism of haloperidol. Mean pharmacokinetic parameters of alosetron were similar to those in previous studies in healthy subjects.
Best's vitelliform macular dystrophy is an early onset, autosomal dominant macular degeneration. Linkage analysis has previously mapped a disease locus in this disorder to the pericentromeric region of chromosome 11. We examined two families, one of German and one of Irish origin, both affected with this disorder. The Irish family (BTMD1) showed strong evidence for linkage to the previously reported locus on chromosome 11. Linkage of the disease locus to the same region of chromosome 11 has been significantly excluded in the German family (Fam E), thereby providing evidence of locus heterogeneity in this clinically unique condition.
Recently discovered personal notes of the German physician Wilhelm Behn, anatomist and physiologist give impressions of his stay in Paris (1834) as a medical student. At that time this town was the "Mecca of world medicine" where the predominance of physical and natural sciences and the persistence of the spirit of Enlightenment stopped that of "Naturalphilosophie". Among Behn's many acquaintances we can note those of Dupuytren, Flourens, Poiseuille, the professors of the Museum, the lecturers at the Académie des Sciences, etc. Some of his remarks give a correction to a too stiff image of his masters. Nodier and Chevreul inspired him for his zoophysiological researches. A pleasant note is given by the evocation of contemporary Parisian life with its distractions such as theaters, horse-races and restaurants.
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In patients with primary sclerosing cholangitis cholestasis is a prominent feature of the disease. We studied the effect of cholestasis and of ursodeoxycholic acid treatment on the biliary secretion of bile acids and lipids in ten patients with primary sclerosing cholangitis. Ursodeoxycholic acid treatment for 3 months led to an increase in the biliary secretion rates of total bile acids from 0.91 mmol/h to 1.47 mmol/h, mainly due to an increase in urosodeoxycholic acid, which represented 31% of biliary bile acids. With increasing cholestasis, the biliary enrichment of the bile acid pool with urosodeoxycholic acid decreased. Biliary output of endogenous bile acids on average was unchanged, but in patients with cholestasis and diminished output before treatment, it increased after ursodeoxycholic acid. Phospholipid secretion increased from 0.26 mmol/h to 0.43 mmol/h without correlation to the degree of cholestasis. Biliary cholesterol secretion on average was unchanged after ursodeoxycholic acid (0.1 versus 0.09 mmol/h) but, in patients with cholestasis and diminished output before treatment, it increased after ursodeoxycholic acid. The decreasing enrichment of the bile acid pool with ursodeoxycholic acid with increasing cholestasis may be related to its slight effect in advanced disease. The increase in biliary phospholipid secretion may represent another mechanism of action of urosodeoxycholic acid responsible for its beneficial effect in cholestatic liver disease.
Proteus syndrome is a congenital hamartomatous disorder characterized by partial overgrowth involving all germ layers. A somatic mutation model has been proposed since familial cases are extremely rare. We report on a 3-year-old girl with typical manifestations of Proteus syndrome, including local, asymmetric hypertrophy of various parts of the body. Total body length was reduced. Serum levels of IGF-I and especially IGF-II and their major growth hormone dependent binding protein (IGFBP-3) were significantly reduced, although growth hormone secretion after a pharmacological stimulus was normal. In vitro studies of fibroblasts derived from hypertrophied tissue showed normal IGF-I production and somewhat reduced IGF-II and IGFBP-3 production as compared to normal human skin fibroblasts. Affinity cross-linking experiments showed that fibroblasts of the affect tissue in Proteus syndrome produced an unusual pattern of IGF bindings proteins containing large amounts of an IGFBP with high affinity to IGF-II. The data suggest that IGF production is generally disturbed in Proteus syndrome with imbalanced levels of specific IGFBP in affected tissue.
Primary sclerosing cholangitis is a cholestatic disease of the liver characterized by progressive fibrotic inflammation and obliteration of the extra- and/or intrahepatic bile ducts. There is no effective therapy. We, therefore, studied the safety and efficacy of ursodeoxycholic acid in patients with primary sclerosing cholangitis with or without additional ulcerative colitis. In a 1-year ursodeoxycholic acid treatment period, which preceded the controlled study period, ursodeoxycholic acid was well tolerated in 22 of 24 patients with ulcerative colitis and in all three patients without ulcerative colitis. In two patients with ulcerative colitis the dose of 750 mg ursodeoxycholic acid/day led to diarrhea, but following reduction of the dose to 500 and 250 mg/day ursodeoxycholic acid was well tolerated. After 1 year of ursodeoxycholic acid treatment, 20 patients were randomly assigned to receive either ursodeoxycholic acid 750 mg/day or placebo. All of them finished a double-blind, placebo-controlled study period. During ursodeoxycholic acid treatment, the liver enzymes improved markedly. The difference in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma-glutamyltransferase between the placebo and ursodeoxycholic acid group was significant (p < 0.05). Following ursodeoxycholic acid treatment, pruritus and fatigue improved in half of the patients but the difference between the placebo and ursodeoxycholic acid group was not significant. According to the ethical guidelines, after 3 months of placebo treatment, the controlled study had to be discontinued because of a more than twofold increase of serum transaminases in 8/10 patients on placebo. After the end of the controlled study, all patients were continuously treated with ursodeoxycholic acid for up to 4 years.(ABSTRACT TRUNCATED AT 250 WORDS)
A new cluster arousal analysis system was developed to quantify microdisturbances in the sleep architecture. The system was evaluated in 10 healthy volunteers and the sleep of 23 outpatients with chronic low back pain was investigated before and after a special rehabilitative training. The comparison of sleep parameters before and after the treatment showed a significant reduction of the cluster disturbed sleep (CDS), whereas sleep efficiency and the number of stage shifts remained unchanged. The reduction of the CDS correlated with a reduction of depression scale. This cluster arousal analysis appears to be a sensitive tool for evaluating alterations in the sleep microstructure.
It is the merit of Paul Bert to have assigned as an important task to experimental physiology the investigation of mountain sickness, of immediate accommodation of the organism to high altitude, and of its long-term acclimatation. In his "Pression Barométrique" of 1878, he established the foundations of high-altitude physiology. In particular, he formulated the "law of partial pressure", the partial pressure of the atmospheric gases alone being responsible for their action on the organism. Paul Bert's historic role, for a long time nearly forgotten, has been recalled to memory by the Swiss medical historians E.H. Ackerknecht and N. Mani. Bert's line of investigation has been followed especially by Angelo Mosso of Turin and, more recently, by F. Verzár, A. von Muralt, A. Fleisch and other Swiss physiologists.
Treatment of patients with cholestatic liver diseases with ursodeoxycholic acid has been shown to have beneficial effects that may be related to a shift in the balance between hydrophilic and hydrophobic bile acids in favor of hydrophilic bile acids. During treatment of patients with primary sclerosing cholangitis with ursodeoxycholic acid, plasma concentrations of some endogenous bile acids decrease. To test whether the changes in plasma bile acids are due to decreases of their pool sizes or synthesis rates, we determined bile acid kinetics of cholic and chenodeoxycholic acid in six patients with primary sclerosing cholangitis, of whom four also had ulcerative colitis. All patients were studied before and 3 mo after the start of ursodeoxycholic acid treatment. Six healthy subjects served as controls. In patients with primary sclerosing cholangitis, pool sizes of cholic and chenodeoxycholic acid were considerably smaller than those in healthy controls; after ursodeoxycholic acid treatment they were unchanged. Fractional turnover and synthesis of cholic acid increased significantly after ursodeoxycholic acid administration. Fractional turnover of chenodeoxycholic acid also increased significantly, whereas synthesis of this bile acid was unchanged. Our data indicate that in patients with primary sclerosing cholangitis, pool sizes of bile acids are reduced. The decrease of levels of endogenous bile acids in plasma under ursodeoxycholic acid treatment despite unchanged bile acid pool sizes indicates redistribution of the bile acids into the enterohepatic circulation, probably because of improved hepatic clearance after ursodeoxycholic acid treatment.