Amount of systemic steroid medication is a strong predictor for the use of complementary and alternative medicine in patients with inflammatory bowel disease: results from a German national survey

OBJECTIVES: Previous studies have suggested that inflammatory bowel disease (IBD) patients rank high among users of complementary and alternative medicine (CAM). To further elucidate this phenomenon, we sent questionnaires to a large sample of IBD patients in Germany to determine the patterns and predictors of their CAM use. METHODS: Pretested 73-item questionnaires were mailed to a randomly selected representative sample of 1000 IBD patients from the approximately 16,000 members and associates of the German Crohn's and Colitis Association. Predictors of CAM use were evaluated by logistic regression models. RESULTS: Completed questionnaires were returned by 684 patients (female patients, 61.4%; Crohn's disease patients, 58.3%; ulcerative colitis patients, 38.2%). Of the 671 adult respondents, 344 (51.3%) had experience with CAM, and significantly more of the ulcerative colitis patients (59.8%) than the Crohn's disease patients (48.3%) had experience with CAM. There was no difference by gender. Homeopathy (52.9%) and herbal medicine (43.6%) were the most commonly used types of CAM. The most frequent personal reasons for CAM use were the search for an "optimum treatment" (78.9%) and the wish to stop taking steroids (63.8%). Using logistic regression, we found that total cortisone intake (P = 0.0077), but not duration of disease, was a strong predictor of CAM use. Other predictors were experience with psychosomatic and psychotherapeutic support (P = 0.0029), relaxation techniques (P = 0.0284), an academic education (P = 0.0173), a diet utilizing whole grains (P = 0.0123), and a normal body weight (P = 0.0215). Although 80% of patients indicated that they were interested in using CAM in the future, only 24.7% felt sufficiently informed about it. CONCLUSIONS: More than 50% of a large group of German IBD patients had used CAM. Prolonged or intensive steroid treatment, an academic education, active ways of coping, and a health-conscious life-style are associated with CAM use. Given the potential side effects and interactions, the treating physician should focus on thorough information about the benefits and limitations of conventional and complementary treatment options, especially for IBD patients who have received prolonged or intensive steroid treatment.     

Hepatic fatty acid synthesis is suppressed in mice with fatty livers due to targeted apolipoprotein B38.9 mutation

Humans and genetically engineered mice with hypobetalipoproteinemia due to truncation-producing mutations of the apolipoprotein B (apoB) gene frequently have fatty livers, because the apoB defect impairs the capacity of livers to export triglycerides (TGs). We assessed the adaptation of hepatic lipid metabolism in our apoB-38.9-bearing mice. Hepatic TG contents were 2- and 4-fold higher in heterozygous and homozygous mice, respectively, compared with wild-type mice. Respective in vivo hepatic fatty acid synthetic rates were reduced to 40% and 15% of the wild-type rate. Hepatic mRNAs for sterol regulatory element-binding protein (SREBP)-1c, fatty acid synthase (FAS), and stearoyl coenzyme A desaturase-1 were coordinately decreased. FAS and SREBP-1c mRNA levels were strongly and positively correlated with each other and inversely correlated with hepatic TGs, suggesting that impaired TG export is a potent inhibitor of fatty acid synthesis. In contrast, levels of plasma beta-hydroxybutyrate and of hepatic carnitine palmitoyl transferase and peroxisome proliferator-activated receptor-alpha mRNAs were not altered, implying that beta-oxidation was not affected. Fasting followed by refeeding increased hepatic fatty acid synthesis 56-fold over fasting in normal and heterozygous mice but only 24-fold in homozygous mice. Parallel changes occurred in FAS and SREBP-1c mRNAs. Thus, impairment of very low density lipoprotein export downregulates hepatic fatty acid synthesis, but the adaptation is incomplete, resulting in fatty livers. The signals mediating suppression of FAS and SREBP-1c levels remain to be identified.     

p-Chloroamphetamine- and d-Fenfluramine-Induced Brain Serotonin Release in Experimental Portal-Systemic Encephalopathy

Portal-systemic encephalopathy (PSE) is associated with increased brain turnover of serotonin (5-HT)in vivo but the brain 5-HT output seems to be unaltered. Recent results suggest, however, that an augmented neocortical 5-HT release in experimental chronic PSE may prevail under certain conditions. In the present study, neocortical extracellular 5-HT and 5-hydroxyindoleacetic-3-acid (5-HIAA) levels were measured in portacaval shunted (PCS) rats and sham-operated controls following local administration of p-chloroamphetamine (pCA) and d-fenfluramine (dFEN), two specific 5-HT releasing agents. The basal neocortical extracellular 5-HT concentrations were unaltered and the 5-HIAA levels were elevated in experimental PSE, supporting an unchanged brain 5-HT output despite elevated brain 5-HT metabolism. Perfusion with pCA or dFEN (5 μM; one 20-min pulse) produced marked increases in brain 5-HT release both in PCS and sham-operated rats compared with corresponding basal values. While no difference in the 5-HT response to dFEN administration was seen between sham (5-HT levels increased by 330%) and PCS (500%) rats, a clear difference (P<0.05) in the brain 5-HT output was observed between the two experimental groups following pCA perfusion (sham, 1100% versus PCS, 1470%). These results support our previous contention of an enhanced neocortical 5-HT output in experimental chronic PSE under certain pharmacological conditions.     

DNA repair synthesis in fibroblast strains from patients with actinic keratosis,squamous cell carcinoma,basal cell carcinoma,or malignant melanoma after treatment with ultraviolet light,N-acetoxy-2-acetyl-aminofluorene,methyl methanesulfonate,and N-methyl-N-nitrosourea

Summary Fibroblast strains derived from skin biopsies of patients with actinic keratosis (6), malignant melanoma (18), squamous cell carcinoma (11), and basal cell carcinoma (12) were investigated for DNA repair synthesis, with 16 fibroblast strains for normal donors as controls. Cells were exposed to UV light, the UV-like carcinogen (Ac)₂ONFln, and the methylating carcinogenes MeSO₂OMe and MeNOUr. Dose-response experiments, which included 10 dose levels, were performed, the data analyzed by linear regression, and the slope of the regression line (term: G ₀) used as a measure of DNA repair synthesis. The mean experimental variability of G ₀ of individual fibroblast strains was 9.5%–15.4%, depending upon exposure. For comparison of all cell strains belonging to the same skin malignancy group with those of the control group, G ₀ values of the individual strains were combined to yield group-specific weighted mean G ₀ values.In addition, the capacity to incise UV-damaged DNA was measured in 24 cell strains from patients with skin tumors using the alkaline elution technique. For quantitating DNA-incising capacity, the initial velocities of the elution curves were plotted versus the UV dose, and the slope of the resulting regression line was used to obtain the characteristic value E ₀. The mean experimental variability of E ₀ of individual strains was ±22%. These E ₀ values were combined to yield weighted mean values of groups.The fibroblast strains in the groups of patients with actinic keratosis and malignant melanoma were found to have normal mean G ₀ values when DNA repair synthesis was challenged with UV light or one of the three carcinogens. However, the squamous cell carcinoma group exhibited significantly lower mean G ₀ values after treatment with UV light (82% that of normal donors), (Ac)₂ONFln (70%), MeSO₂OMe (70%), and MeNOUr (69%). The basal cell carcinoma group showed significantly diminished repair synthesis upon treatment with UV light (81% that of normal donors) and MeSO₂OMe (67%). In contrast to these findings, in no skin malignancy group was post UV DNA-incising capacity (E ₀) significantly diminished, although it should be noted that group sizes were only half as large as for G ₀ determinations.These data may be interpreted as indicating that DNA excision repair is impaired in fibroblast strains from patients with squamous cell carcinoma and — to a lesser extent — basal cell carcinoma. This deficiency seems to pertain to several DNA repair mechanisms, as excision of both alkylation and UV-induced damage is involved. Although the repair impairments are statistically significant, the relative risks at which the investigated patients are do not seem to be high enough as to be of immediate practical value. Our results indicate further studies would be useful.Abbreviations XP xeroderma pigmentosum - UV light ultraviolet light - UVB UV light with the wavelength from 290 nm to 320 nm - (Ac)₂ONFln N-acetoxy-2-acetylaminofluorene - MeSO₂OMe methyl methanesulfonate - MeNOUr N-methyl-N-nitrosourea - ara-C 1--d-arabinofuranosyl cytosine This work was supported by the Deutsche Forschungsgemeinschaft, SFB 136Dedicated to Professor E. Hecker on the occasion of his 60th birthday     

Persistent symptoms in patients with Crohn’s disease in remission: An exploratory study on the role of diet

Objectives: Patients with Crohn’s disease (CD) often report food hypersensitivities with gastrointestinal (GI) symptoms despite being in clinical remission. We aimed to identify the most frequent symptoms and dietary triggers in such patients, and also explored whether a strict elimination diet may reduce their GI symptoms.

Methods: We assessed GI symptoms and dietary triggers in 16 patients with CD in clinical remission. Of these, 12 patients subsequently participated in a dietary intervention trial: two weeks on a habitual diet including wheat and dairy products followed by two weeks of a strict elimination diet. The severity of seven symptoms (overall symptoms, abdominal pain, bloating, abnormal feces, wind, fatigue, and musculoskeletal pain) was measured by using visual analog scales throughout the four weeks intervention period.

Main results: The most common symptoms were abdominal pain, wind, bloating, odorous wind/feces, and diarrhea. Dairy and wheat products were reported as the most frequent dietary symptom triggers. All symptoms improved (p?Conclusion: Our exploratory study suggests that dietary interventions such as an elimination diet may reduce GI symptoms in patients with CD in remission.     

Von der Grundlagenforschung in die Klinik

The discovery of human embryonic stem cells at the end of 1998 had a strong influence on the development of stem cell research and led to controversial discussions. The first therapeutic application of adult blood stem cells began after their discovery in 1963 and was accepted as an authorized therapy in the early 1980s. The way from basic research to therapeutic use needed about 20 years and was also discussed in a controversial way similar to the discussions of today. The regulatory environment at that time, however, allowed a quick translation of the results from basic research to the clinic. Today many new stem cell therapies for a multitude of diseases are under development. Their clinical realization is regulated by the AMG (Arzneimittelgesetz). For nonclinical research as well as for clinical research, specific regulations are enacted to guarantee a structured and safe launch. Time, know how and money for planning, request for authorization and conduction of a clinical trial should not be underestimated. For clinical application of stem cell products authorization by the proper authorities is mandatory.     

Androgen substitution with testosterone undecanoate in survivors of bilateral testicular cancer requires individually‐adjusted injection intervals

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? There is insufficient documentation on androgen substitution with intramuscular testosterone undecanoate, a new injection depot formulation, in anorchid men. This prospective study explores the efficacy and safety and contributes to the treatment recommendations on substitution with intramuscular testosterone undecanoate in bilaterally orchiectomized survivors after germ cell cancer.

OBJECTIVES

? To explore the efficacy and safety of testosterone undecanoate (TU) (Nebido®; Bayer Schering Pharma AG, Berlin, Germany) in patients with bilateral germ cell testicular cancer (GCTC) who have switched androgen substitution from testosterone enanthate (Primoteston Depot®, Bayer Schering Pharma AG).

PATIENTS AND METHODS

? In total, 47 bilaterally orchidectomized GCTC patients were included in a prospective study to monitor serum gonadal hormones, biochemical safety and symptoms of hypogonadism based on the Aging Males’ Symptoms scale during TU treatment for a 28‐week period.

RESULTS

? During treatment, serum levels of total (TT) and calculated free testosterone (CFT) increased with simultaneously decreasing levels of FSH and LH. However, considerable variations in median levels of TT and CFT were observed during the study. The highest levels of TT and CFT were observed 1–2 weeks after each injection and the lowest immediately before the second injection. ? Insufficient levels of TT (<8 nmol/L) were observed in 10 patients, with nine of these during the second half of the first treatment cycle. Supernormal levels of TT (>35 nmol/L) were measured in 28 patients of which 26 occurred at least once during the first 3 weeks of each treatment cycle. ? A follow‐up review at median 39 months after study start showed a median steady‐state injection interval of 10 weeks, with an individual variability of 6–14 weeks. Symptoms according to the Aging Males’ Symptoms scale remained unchanged. No severe toxicity was encountered. Only one patient experienced transient elevation of serum alanine transaminase and aspartate transaminase with maximal Common Toxicity Criteria, grade 2.

CONCLUSIONS

? TU is safe and highly efficient for the treatment of anorchid GCTC survivors. ? Androgen substitution with TU in bilateral GCTC survivors requires individually‐adjusted injection intervals. In most cases, 10‐week intervals appear to be sufficient.     

Pericardial suction blood separation attenuates inflammatory response and hemolysis after cardiopulmonary bypass

OBJECTIVES: Retransfusion of pericardial suction blood (PSB) is critically considered under the aspect of the biocompatibility of the cardiopulmonary bypass (CPB). We investigated various indicators of inflammation and blood cell activation associated with CPB and re-transfusion of PSB during cardiac surgery. DESIGN: Thirty-five patients undergoing elective coronary artery bypass grafting were prospectively randomized into two groups. In group A (n = 15, retransfusion group) the pericardial suction blood was continuously retransfused during CPB, in group B (n = 20, no-retransfusion group) the suction blood was separated. Parameters indicating the status of the inflammation and blood cell activation were analyzed before and at the end of CPB, latest after 90 minutes on CPB. RESULTS: Patients' perioperative data did not differ between groups. The inflammatory markers C-reactive protein, PMN-Elastase and Interleukin-6 increased in both groups after CPB (p < 0.04) with significantly lower values in the no-retransfusion group (p < 0.02). Leukocytes and platelet activation markers beta-Thromboglobulin and soluble P-Selectin also experienced a significant elevation during observation time (p < 0.02) without any difference between the groups. Free hemoglobin and LDH tremendously increased during CPB with lower values in the no-retransfusion group. CONCLUSIONS: Cardiotomy suction is a major cause of hemolysis and contributes significantly to the systemic inflammatory response.     

Effects of poly-2-methoxyethylacrylate (PMEA)-coating on CPB circuits

Objectives. In this study, the immuno- and neuroprotective effect of a novel cardiopulmonary bypass coating was investigated. Design. Thirty nine patients scheduled for elective coronary artery bypass grafting were randomly assigned to either PMEA-coated (n?=?19) or non-coated CPB circuits (n?=?20). Pericardial suction blood was separated and retransfused only if needed at the end of operation. Neurocognitive functions were examined preoperatively and 7–10 days postoperatively using a standard neuropsychological test battery. Assuming an inflammatory etiology, the most cogent inflammatory markers were perioperatively analyzed. Results. Postoperatively, patients of the PMEA-coated group performed better in Go/NoGo and Mini-Mental-test than patients of the non-coated group (p?<?0.04). Other neurocognitive testing did not reveal significant differences between the groups. Although most inflammatory parameters showed a significant intraindividual increase during or shortly after CPB, there was no difference in inflammatory alteration between the groups. Conclusions. PMEA-coating of cardiopulmonary bypass surfaces revealed some minor benefits in preservation of neurocognitive functions after surgery. The immediate inflammatory response remained mostly unaffected. Suction blood separation may additionally contribute to proper postoperative outcome.