Mindfulness and relaxation treatment reduce depressive symptoms in individuals with psychosis.

INTRODUCTION: Self-help is increasingly accepted for the treatment of mental disorders, including psychosis, as both a provisional first step and a way to bridge the large treatment gap. Though mindfulness-based interventions do not belong to first line treatment strategies in psychosis and randomized controlled trials are lacking, encouraging preliminary findings speak for the usefulness of this approach. For the present study, we examined whether patients with psychosis benefit from mindfulness bibliotherapy. METHODS: A sample of 90 patients with psychosis (including a subsample with a verified diagnosis of schizophrenia) took part in the study via the Internet. Following baseline assessment, participants were randomized to either a mindfulness group or a Progressive Muscle Relaxation (PMR) control group and received the respective self-help manual including accompanying audio files. Symptom change was measured six weeks after the baseline assessment with self-rating scales including the Paranoia Checklist. The retention rate was 71%. The quality of the online dataset was confirmed by various strategies (e.g., psychosis lie scale; examination of response biases). The trial was registered at the ISRCTN registry (ISRCTN86762253). RESULTS: No changes across time or between groups were noted for the Paranoia Checklist. Both conditions showed a decline in depressive and obsessive-compulsive symptoms at a medium effect size (per protocol and intention to treat analyses). DISCUSSION/CONCLUSION: The study provided partial support for the effectiveness of self-help mindfulness and PMR for depression in psychosis. Whether mindfulness delivered by a licensed therapist might lead to improved treatment adherence and a superior outcome relative to PMR remains to be established. The results underscore that bibliotherapy is a worthwhile approach to narrow the large treatment gap seen in psychosis.

Effect of a low-fat diet enriched either with rapeseed oil or sunflower oil on plasma lipoproteins in children and adolescents with familial hypercholesterolaemia. Results of a pilot study.

BACKGROUND/OBJECTIVES: There is convincing evidence that unsaturated fatty acids exert favourable effects on plasma cholesterol levels. However, it is not clear which type of oil has the most pronounced effect, especially not in paediatric patients. The aim was to compare two low-fat diet regimes enriched with either monounsaturated fatty acids by rapeseed oil (RO) or polyunsaturated fatty acids by sunflower oil (SO) in children affected with familial hypercholesterolaemia (FH). SUBJECTS/METHODS: Twenty-one children aged 6-18 years affected with FH were enrolled in this randomized and double-blind pilot trial. The subjects and their families were trained to adhere to a low-fat/low-cholesterol diet. All visible fats were to be replaced by either RO or SO (14-27 g/day) for 13 weeks. Dietary adherence was controlled by repeated 4-day dietary records; plasma lipids, lipoproteins and risk markers were assessed at baseline and post-intervention. Out of 21 subjects, 16 could be followed-up after 6 months. RESULTS: Both fat-modified diets resulted in significant reduction in total cholesterol concentrations of 9.4% (RO P<0.005 vs SO P<0.05) and low-density lipoprotein (LDL) cholesterol concentrations of 12.7% (P<0.005) for RO and 11.3% (P<0.05) for SO. The reduction of the LDL/high-density lipoprotein (HDL) cholesterol ratio (RO 9% vs SO 3.5%) and high-sensitivity C-reactive protein (RO 16.8% vs SO 1.7%) were not statistically significant, respectively. In most participating families, a change in eating habits could be observed. CONCLUSIONS: A fat-modified diet enriched with RO seems to have very similar effects on cholesterol levels as with SO. However, our study suggests that RO has possibly more favourable effects concerning cardiovascular risk profile. Both diets appear to be feasible and were well accepted among our subjects. Although these results are promising, larger trials will be required to validate our findings.

The role of stimulus complexity, spectral overlap, and pitch for gap-detection thresholds in young and old listeners.

Thresholds for detecting a gap between two complex tones were determined for young listeners with normal hearing and old listeners with mild age-related hearing loss. The leading tonal marker was always a 20-ms, 250-Hz complex tone with energy at 250, 500, 750, and 1000 Hz. The lagging marker, also tonal, could differ from the leading marker with respect to fundamental frequency (f0), the presence versus absence of energy at f0, and the degree to which it overlapped spectrally with the leading marker. All stimuli were presented with steeper (1 ms) and less steep (4 ms) envelope rise and fall times. F0 differences, decreases in the degree of spectral overlap between the markers, and shallower envelope shape all contributed to increases in gap-detection thresholds. Age differences for gap detection of complex sounds were generally small and constant when gap-detection thresholds were measured on a log scale. When comparing the results for complex sounds to thresholds obtained for pure-tones in a previous study by Heinrich and Schneider [(2006). J. Acoust. Soc. Am. 119, 2316-2326], thresholds increased in an orderly fashion from markers with identical (within-channel) pure tones to different (between-channel) pure tones to complex sounds. This pattern of results was true for listeners of both ages although younger listeners had smaller thresholds overall.

Reduced side-effects of adjuvant hormone therapy in breast cancer patients by complementary medicine.

UNLABELLED: A clinical investigation (representing evidence-based medicine level III) was performed to evaluate the benefit of complementary medicine in breast cancer patients undergoing adjuvant hormone therapy (HT). PATIENTS AND METHODS: The patients (n=129) were treated according to international guidelines. All patients suffered from arthralgia and mucosal dryness induced by the adjuvant HT. To reduce these side-effects, the patients were complementarily treated with a combination of sodium selenite, proteolytic plant enzymes (bromelaine and papain) and Lens culinaris lectin. On the basis of case report formulas (CRFs), self assessment of defined side-effects of HT (arthralgia and mucosal dryness) were documented before as well as 4 and 8 weeks after complementary treatment. Validation was carried out by scoring from 1 (no side-effects/optimal tolerability) to 6 (extreme side-effects/extremely bad tolerability). RESULTS: The severity of side-effects of HT was reduced by complementary treatment with sodium selenite, plant enzymes (bromelaine and papain) and Lens culinaris lectin. The mean score of symptoms declined from 4.2 (before treatment) to 3.2 (after 4 weeks of treatment) to 2.7 (after 8 weeks of treatment) for arthralgia and from 3.2 (before treatment) to 2.9 (after 4 weeks of treatment) to 2.6 (after 8 weeks of treatment) for mucosal dryness, the primary aims of this investigation. The reduction of side-effects of HT was statistically significant (p<0.001 after 4 weeks and p<0.0001 after 8 weeks). CONCLUSION: This investigation demonstrates benefits of indication-based complementary treatment in breast cancer patients, e.g. reduction of side-effects of adjuvant HT. A randomized controlled trial is planned to integrate the complementary treatment with the combination of sodium selenite, proteolytic enzymes and Lens culinaris lectin into evidence-based medicine.

Omega-3-enriched broiler meat: 1. Optimization of a production system.

Consumer awareness of the health benefits of n-3 fatty acids is growing and is driving consumer demand for enriched food products. Enrichment of meat with n-3 fatty acids is an opportunity for the broiler production sector to add value to their product, but enrichment can increase the cost of production. A study was conducted to determine an optimal production strategy for n-3 enrichment of broiler meat using ground full-fat flaxseed. Low and high levels of dietary flaxseed (10 and 17%, respectively) were fed to broilers for 8 lengths of time (0, 4, 8, 12, 16, 20, 24, or 35 d) before processing at 35 d. Increasing the level or duration decreased feed intake, BW, and the percentage yield of carcass and breast. Flaxseed level and duration of feeding increased feed conversion ratios and the cost of production. Feeding flaxseed at 10 and 17% increased breast n-3 fatty acid levels by 7.65 and 13.70 mg/100 g of meat per day, respectively. In breast meat, the threshold level of 300 mg/g, required in Canada for labeling foods as a source of n-3 fatty acids, was reached at 12.1 and 24.1 d in the high and low flaxseed treatments, respectively. This was due primarily to a tripling of alpha-linolenic acid (18:3n-3) levels in the breast meat. Levels of the long-chain n-3 fatty acid eicosapentaenoic acid increased significantly in the breast meat with increased level and duration of flax feeding, indicating that birds were able to desaturate and elongate alpha-linolenic acid to eicosapentaenoic acid. To minimize cost, while achieving adequate breast meat n-3 enrichment, carcass weight, and meat yield, feeding 10% flaxseed for 24.1 d before processing is recommended as an optimal breast meat n-3 enrichment strategy. The optimal thigh meat n-3 enrichment strategy was to feed 10% flaxseed for 4.54 d before processing.

Impact of complementary treatment of breast cancer patients with standardized mistletoe extract during aftercare: a controlled multicenter comparative epidemiological cohort study.

OBJECTIVES: To investigate the safety and efficacy of complementary treatment of breast cancer patients with the standardized mistletoe extract (sME) HELIXOR in routine practice during aftercare through a multicenter comparative epidemiological cohort study with 53 randomly selected hospitals/practices representatively distributed in Germany, including oncologists, gynaecologists and general practitioners. PATIENTS AND METHODS: Data from 741 screened patients fulfilling the inclusion/exclusion criteria were checked. Of these, 681 patients were eligible for the final analysis of the study group (with sME n = 167) and the control group (n = 514). Efficacy (development of disease/therapy-induced signs and symptoms; quality of life) and safety (number and severity of adverse events) of complementary treatment in breast cancer patients treated with sME in the aftercare period were determined. RESULTS: Complementary treatment of breast cancer patients with sME during the aftercare period of approximately 5 years after terminating recommended standard therapies resulted in significantly fewer (p < 0.001) complaints of patients (56.3% study group versus 70.0% control group). The reduced number of disease/therapy-related sign/symptoms (e.g. mucositis, fatigue, pain, headache) correlated to a significantly improved quality of life. Adverse drug reactions to the sME treatment were mostly mild and self limiting. CONCLUSION: Complementary treatment with the sME HELIXOR proved to be beneficial for breast cancer patients since it significantly improved quality of life and significantly reduced persistant signs/symptoms of the disease/treatment during the validated aftercare period of approximately five years.

Reparación de polapso vaginal anterior con malla de prolene / Anterior vaginal prolapse repair with prolene mesh

ANTECEDENTES: La reparación del prolapso vaginal anterior presenta una alta tasa de recurrencia. La colporrafia anterior con malla de prolene es una buena alternativa quirúrgica que ha obtenido buenos resultados a largo plazo. OBJETIVO: Evaluar el resultado anatómico y la evolución de la colporrafia anterior con malla de prolene. MÉTODO: Estudio de cohorte prospectivo para evaluar el resultado quirúrgico. RESULTADOS: Ingresaron 35 pacientes con una edad promedio de 61,4 años; 85,7% de ellas estaba en postmenopausia y 3% utilizaba terapia hormonal de reemplazo. La principal patología asociada fue la incontinencia de orina de esfuerzo (54,3%). El estado del piso pelviano preoperatorio correspondió a 31,4% cistocele grado II, 48,6% cistocele grado III y 20% cistocele grado IV. Se asoció prolapso uterino en 88,6% de los casos y 74,3% con prolapso de la pared posterior. No hubo complicaciones intraoperatorias. Hubo complicaciones postoperatorias en 4 pacientes (11,4%). Una paciente presentó erosión de la malla (2,9%). El seguimiento fue de 1 a 11 meses. En la evaluación postoperatoria de las pacientes con cistocele grado II 80% corrigió a grado 0; para cistocele grado III 72% corrigió a grado 0. Un 11% llegó a grado I y 17% grado II. Para el grupo con cistocele grado IV, 71% resultó en grado 0 y 29% grado II. CONCLUSIÓN: La técnica presentada solucionó un severo problema de calidad de vida de las pacientes afectadas. Se requiere un mayor número de casos y tiempo de seguimiento para su recomendación definitiva.

BACKGROUND: Repair of anterior vaginal prolapse present a high rate of recurrence. Anterior colporrhaphy plus prolene mesh is a surgical option with optimal long term results. OBJECTIVE: To evaluate anatomical results and evolution of anterior colporrhaphy with prolene mesh. METHOD: A prospective cohort study was made to evaluate the surgical outcomes. RESULTS: 35 patients were recruited with a median age of 61.4 years. 85.7% of them were in postmenopausal status and 3% were using hormone replacement therapy. Stress urinary incontinence was associated in 54.3% of the cases. The pelvic floor stage at entry was 31.4% cysthocele stage II, 48.6% stage III and 20% cysthocele stage IV. Uterine prolapse was present in 88.6% of cases and the posterior wall was compromised in 74.3%. There were no intraoperatory complications. Postoperatory complications occurred in 4 patients (11.4%). Only in one case the mesh eroded (2.9%). The follow up was from 1 to 11 months. Of the patients with cysthocele stage II at the moment of evaluation, 80% were at stage 0. For cysthocele stage III 72% turned to stage 0. 11% turned to stage I and 17% to stage II. The cases that presented cysthocele stage IV 71% were at stage 0 and 29% at stage II. CONCLUSION: This technique solved an important quality of life problem of the affected patients. A higher number of cases and time of follow up is needed to recommend this technique definitely.

Safety and efficacy of local administration of contractubex to hypertrophic scars in comparison to corticosteroid treatment. Results of a multicenter, comparative epidemiological cohort study in Germany.

OBJECTIVES: To investigate the safety and efficacy of Contractubex administration to hypertrophic scars in routine out-patient practice and to compare it to corticosteroid treatment. PATIENTS AND METHODS: This was a multicenter, retrospective cohort study, based on 38 randomly selected practices representatively distributed in Germany, including dermatologists and general practitioners. Data from 859 patients fulfilling the inclusion criteria were assessed and analyzed. Of these, 771 patients were eligible for the per protocol treatment with Contractubex (n=555) and corticosteroid (n=216). The safety and efficacy of local administration of Contractubex to hypertrophic scars was compared to corticosteroid treatment. RESULTS: At the end of defined treatment periods (minimum 28 days for local therapy with 1 intralesional corticosteroid application), normalization of the pre-treatment pathological parameters (erythema, pruritus, consistency) of hypertrophic scars was more frequent (42.5%) after Contractubex per protocol treatment as compared to corticosteroid per protocol treatment (22.2%). After adjusting imbalances of baseline characterisics between the treatment groups by the propensity score, the odds ratio was 2.274, demonstrating a significant superiority (p<0.001) of Contractubex treatment as compared to corticosteroid treatment. The time to normalization of erythema, pruritus and consistency was significantly (p=0.034) shorter with Contractubex treatment (median 344 days) than with corticosteroids (median 507 days). No unexpected or severe adverse events occurred in the Contractubex-treated patients. Apart from moderate pruritus (10% Contractubex vs. 1% corticosteroids), adverse events were significantly (p<0.001) more frequent in corticosteroid-treated patients (teleangiectasias 15% vs. 7% Contractubex; cutaneous atrophy of scars 10% vs. 2% Contractubex; cutaneous atrophy of scar surrounding skin tissue 11% vs. 1% Contractubex). CONCLUSION: For the primary aim of this study (assessment of normalization of erythema, pruritus, and consistency of hypertrophic scars) and for time to normalization, local administration of Contractubex was significantly more effective than corticosteroid treatment. Concerning safety, Contractubex treatment was associated with significantly less adverse events (e.g. teleangiectasias, cutaneous atrophy of scars and surrounding skin tissue) than topical corticosteroid application.

Antifilarial activity in vitro of polycarpol and 3-O-acetyl aleuritolic acid from cameroonian medicinal plants against Onchocerca gutturosa.

Previous results have revealed the antifilarial activities of crude extracts and pure compounds from some Cameroonian medicinal plants against Onchocerca volvulus and Onchocerca gutturosa. In our efforts to find new filaricidal agents against adult male O. gutturosa worms, we have isolated and screened three compounds: polycarpol and polyveoline from Polyalthia suaveolens (Annonaceae) and 3-O-acetyl aleuritolic acid from Discoglypremna caloneura (Euphorbiaceae). Only polycarpol and 3-O-acetyl aleuritolic acid exhibited significant inhibitory activities on the vitality of adult male worms of O. gutturosa using Amocarzine as positive control compound. The motility reduction values were 28.6 and 57.1%, and the inhibition of MTT reduction values 80.0 and 64.8% respectively.

Therapeutic use, efficiency and safety of the proteolytic pineapple enzyme Bromelain-POS in children with acute sinusitis in Germany.

The therapeutic efficiency and safety of the proteolytic enzyme bromelaine obtained from pineapple (Bromelain-POS, Ursapharm GmbH, Saarbrücken, Germany) was evaluated in children under the age of 11 years diagnosed with acute sinusitis. Data from 116 patients from 19 centres located across Germany were analysed in a pharmacoepidemiological cohort study. Patient cohorts were either treated with Bromelain-POS (N = 62), in combination with Bromelain-POS and standard therapies (N = 34), or with standard therapies (N = 20). The primary parameter measuring effectiveness of the different treatment groups was the duration of symptoms. The shortest mean period of symptoms was observed in patients treated with Bromelain-POS alone (6.66 days), followed by the standard therapy (7.95 days) and those treated with a combination of Bromelain-POS and the standard therapy (9.06 days). Patients of the Bromelain-POS monotherapy group showed a statistically significant faster recovery from symptoms (p = 0.005) compared to the other treatment groups. One 10-year-old male patient, with a known pineapple allergy, showed a self-limiting mild allergic reaction. No other unwanted side-effects were reported. This trial documents that the proteolytic pineapple enzyme Bromelain-POS is widely used in the treatment of young children diagnosed with acute sinusitis in Germany and that the use of proteolytic enzymes can benefit such patients.

Coenzyme Q10 serum levels in Huntington's disease.

Mitochondrial dysfunction contributes to the neurodegenerative process in Huntington's disease (HD). Coenzyme Q10 (CoQ10) enhances mitochondrial complex I activity and may therefore provide a therapeutic benefit in HD. We compared serum CoQ10 levels of previously untreated-and treated HD patients with those of healthy controls. CoQ10 did not significantly (ANCOVA F(dF 2, dF 55) = 2.57; p=0.086) differ between all three groups. However, the post hoc analysis showed no significant (p = 0.4) difference between treated HD patients ([CoQ10]: 88.12 [mean]+/-24.44 [SD], [range] 48.75-146.32 [pg/million platelets]) and controls (93.71+/-20.72, 65.31-157.94), however previously untreated HD patients (70.10+/-21.12, 38.67-106.14) had marked (p = 0.051) lower CoQ10 results than treated HD patients and controls (p = 0.017). Our results support that CoQ10 supplementation in HD patients may reduce impaired mitochondrial function in HD.

Retrolective, comparative, epidemiological cohort study with parallel groups design for evaluation of efficacy and safety of drugs with "well-established use".

UNLABELLED: The randomized controlled clinical trial (RCT) is accepted as the "golden standard" for the evaluation of efficacy and safety of new drugs. In contrast, to demonstrate efficacy and safety of drugs with "well-established use" that have been on the European Community market for long time, observational comparative epidemiological studies can be used according to the European drug regulation directive. However, because comparative epidemiological cohort studies can share some risk of bias with other nonrandomized observational study designs, there is a need for an approach that could effectively reduce the bias risk in this type of studies. STUDY OBJECTIVES: The purpose of the study was to evaluate the therapeutic efficacy and safety of a long-term complementary therapy of primary, non-metastatic breast carcinoma patients treated with standardized European mistletoe extract Iscador("mistletoe") in addition to the conventional adjuvant oncologic therapy, and compared to the control group treated with the conventional therapy alone. METHODS: The multicenter, comparative, retrolective, pharmaco-epidemiological cohort study with parallel groups design and randomly selected centers that routinely used both treatments was carried out according to Good Epidemiological Practice rules under a standard operating procedure control. The test group patients received the mistletoe extract treatment subcutaneously for at least 3 months, while the control group patients of the same cohort was exclusively treated with the conventional therapy. The patients were followed up for at least 3 years or until death. The primary endpoint of efficacy was the incidence of adverse reactions to the conventional oncologic therapy. Secondary endpoints were change from baseline of the symptoms associated with the disease and treatment as well as overall survival. All endpoints were adjusted to baseline imbalance and confounders. Safety was assessed descriptively by the number of patients with adverse drug reactions (ADRs) attributed to the test treatment. RESULTS: 1442 patients (710 tests and 732 controls) were eligible for the "per protocol" analysis of efficacy and safety. At baseline, the test group had a more advanced disease and worse prognostic factors profile. After a median follow-up of 66 vs. 60 months, and a median mistletoe therapy duration of 52 months, significantly fewer test group patients (16.2%) than control patients (54.0%) developed ADRs attributed to the conventional therapy [adjusted odds ratio, OR (95% confidence interval, CI), OR = 0.47 (0.32-0.67), p < 0.001]. In the test group, the majority of the symptoms disappeared more frequently, and overall mortality hazard was significantly lower [adjusted hazard ratio, HR (95% CI), HR = 0.46 (0.22-0.96), p = 0.038] than in the control group. Systemic ADRs attributed to the test treatment developed in 0.8%, and local ADRs in 17.3% of the patients. ADR severity was mild to intermediate. Tumor enhancement was not observed. CONCLUSIONS: Complementary therapy of patients with primary, non-metastatic breast carcinoma with the mistletoe extract Iscador was safe and in comparison to the control group within the same study cohort showed considerably fewer ADRs attributed to concurrent conventional therapy, reduced disease symptoms, and suggested a significant improvement of survival. Despite some methodical limitations that require careful study planning and conduction as well as critical interpretation, the applied study design seems suitable to evaluate the efficacy and safety of drugs with "well-established use", particularly in oncology.

Proposals to enhance the quality of observational cohort studies.

For herbal medicinal products the methodology of observational cohort studies (observational studies, drug monitoring studies, Anwendungsbeobachtung) represents a useful addition to clinical trials. The key objectives are the documentation of efficacy in particular under conditions of everyday medical practice in authentic patients and the documentation of the safety profile. Supplementary to earlier activities, members of the "Clinical Trials of Herbal Medicinal Products" Working Party of the German Society for Phytotherapy have therefore again addressed the issue of observational cohort studies for to enhance the informative value and importance of this clinical research methodology. Recommendations were developed on quality aspects, methodological approaches of observation parameters, and for the reporting of the study's results. Properly planned and conducted observational cohort studies may contribute to the documentation and proof of well-established medicinal use according the EU Directive 2001/83/EC.

Implementation of the Vienna Hydrotherapy Group for Laryngectomees--a pilot study.

GOALS: Laryngectomy involves several problems for the individual, such as the need to cope with a stoma, adjustment to tracheostomal breathing, and the formation of a voice. Contact with water, resulting in aspiration, may prove fatal for laryngectomized patients in the absence of appropriate aids. The aim of this pilot study was to conduct a hydrotherapy group for laryngectomized patients and to evaluate its feasibility and outcome in relation to the goals of therapy. PATIENTS AND METHODS: Six male patients who had undergone laryngectomy were included in a pilot study. The patients underwent a structured hydrotherapy rehabilitation program (three times a week for 8 weeks), using a special underwater therapy device. The patients' posture was controlled by posturography and their endurance capacity by standard ergometry and the 6-min walk. The parameters of fatigue, expectoration, mobility, elasticity/flexibility, postural control/coordination, and general well being were registered on a visual analog scale (VAS). Quality of life was assessed by having the patients fill out the German version of the SF-36 Health Survey. MAIN RESULTS: Posturograpy findings showed an improvement of two subtests ( p<0.028). Exercise testing showed an improved endurance capacity ( p<0.028). The patients were able to walk a greater distance in the 6-min walking test ( p<0.028). The VAS also showed an improvement of endurance capacity ( p<0.028), fatigue ( p<0.028), expectoration ( p<0.043), mobility of the neck and shoulder ( p<0.027), flexibility ( p<0.027), postural control and coordination ( p<0.028), and general well being ( p<0.028). On the SF-36 Health Survey, the patients were improved in the items "Physical functioning" ( p<0.027), "Vitality" ( p<0.027) "Role-physical" ( p<0.026), and "Social functioning" ( p<0.043). CONCLUSIONS: A hydrotherapy group for laryngectomized patients proved to be safe, feasible, and effective in this pilot study.

Influence of postoperative complementary treatment with lectin-standardized mistletoe extract on breast cancer patients. A controlled epidemiological multicentric retrolective cohort study.

This epidemiological study was performed to evaluate the influence of postoperative complementary treatment with lectin-standardized mistletoe extract (sME) on breast cancer patients. The design (retrolective cohort analysis with parallel groups) and conduct of the study were in agreement with current standards for prospectively randomized clinical trials. A cohort of 1,248 breast cancer patients on postoperative chemo-, radio-, hormone-therapy were studied in 27 randomized centers. Patients with complementary medications other than sME were excluded from the evaluation and the final analysis was performed on data of 689 patients. From this cohort 219 patients received a complementary treatment exclusively with sME (therapy group), while 470 patients were without complementary treatment (control group). The median follow-up time was 284 days (therapy group) and 285 days (control group). The primary end-point of the study was to determine the impact of complementary sME treatment on disease- or therapy-induced adverse reactions in breast cancer patients. Imbalances for causal effects (covariates) were adjusted by propensity scores. Final evaluation was performed by estimating the linear regression between change in symptom score and propensity score with all data and using the regression line to calculate the change in symptom score expected for each patient. Tumor-associated events were evaluated by number and time until event. The safety of sME treatment was analysed in terms of number, severity, duration and outcome of adverse reactions. As compared to breast cancer patients without complementary treatment (control group), the administration of sME (therapy group) resulted in a significant reduction of adverse reactions induced by the tumor-destructive therapies (e.g. nausea, gastro-intestinal tract symptoms, depression, fatigue, mental symptoms) and prolonged relapse-free intervals, most pronounced for UICC stages IIa and IIb. The rate of sME-associated adverse reactions was 12.8%. All side-effects were mild to moderate, predominantly local skin reactions and self-limiting without therapeutic intervention. Complementary treatment of breast cancer patients with lectin-standardized mistletoe extract (sME) proved to be a well tolerated optimization of standard tumor-destructive therapies, mainly improving quality of life and relapse-free intervals in defined UICC stages.

[Cerebral hemodynamics in carbon dioxide applications]. / Zerebrale Hämodynamik bei Kohlendioxidapplikationen.

INTRODUCTION: We compare the effect of carbon dioxide (CO(2)) dry and wet applications on cerebral hemodynamics. METHODS: On 22 volunteers measurements were taken during CO(2) application. 10 probands were examined in CO(2) wet application (1,100-1,300 mg/l) and 12 probands in CO(2) dry application (500 g in a 800 l bathtub). The cerebral blood flow velocity (CBFV) in the middle cerebri artery (MCA) was measured as a parameter of cerebral hemodynamics by means of transcranial doppler sonography. Furthermore were recorded CO(2) expiratory concentration (CO(2)et), blood pressure, and sublingual temperature. RESULTS: At CO(2) wet application the CBFV increased during therapy phase by 15% (p = 0.001), parallel to the rise of the CO(2)et by 18% (p = 0.01). During CO(2) dry application CBFV decreased by 11% (p = 0.007), body temperature increased significantly by 0.2 degrees C. CONCLUSION: CO(2) applications have influence on cerebral hemodynamics. Assuming constant diameters of the great brain vessels, CO(2) wet application shows a raising and CO(2) dry application a reducing influence on cerebral blood flow. This influence will attain therapeutic relevance.

[Effects of active and passive movement stimuli on cerebral hemodynamics and the cerebral metabolism]. / Wirkungen kinetischer Stimuli auf die zerebrale Hämodynamik und den zerebralen Stoffwechsel am Beispiel von aktiven und passiv ausgeführten Bewegungen.

INTRODUCTION: In contrast to the well-examined cardiovascular changes during movement stimuli, up to now changes of cerebral hemodynamics and cerebral metabolism have rarely been studied. We investigated the question if active and passive movement stimuli cause changes in the cerebral hemodynamics and the cerebral metabolism. METHOD: Active and passive repetitive movement stimuli on 14 volunteers (8 females, 6 males, age 35 +/- 8 years) were examined. As a parameter of cerebral hemodynamics the mean and the peak blood flow velocity (mCBFV(MCA), pCBFV(MCA)) in the middle cerebral artery (MCA) were recorded by transcranial Doppler sonography. At the same time the noninvasive blood pressure (Penaz method) and the CO(2) expiration concentration were investigated on 8 volunteers of the collective. As cerebral metabolic parameters we examined in 4 volunteers additionally the cerebral respiratory chain enzyme cytochrome aa3 (ccytaa3) and the cerebral oxygen saturation (cHbO(2)) by the transcranial near infrared spectroscopy. With each volunteer 4 measurement series were carried out with a special active and passive exercise program for the right upper as well as the right lower extremity. Each measurement series was formed according to the evoked flow test (R. Aaslid): Exercises were carried out for 20 s, followed by a break of 20 s; this was repeated 10 times for each series. RESULTS: During active exercises of the right lower extremity we found an increase of 13.6% (p < 0.001) of pCBFV(MCA) and an increase of 3.8% (p = 0.003) of mCBFV(MCA). During passive exercises of the lower extremity the increases ran up to 12.3% (p < 0.001) for pCBFV(MCA) and 3.4% (p = 0.004) for mCBFV(MCA). The increases of pCBFV(MCA) came up to 12.5% (p < 0.001) at active exercises of the right upper extremity, those of mCBFV(MCA) to 3.5% (p = 0.15). During passive exercises of the upper extremity the pCBFV(MCA) increased by 12.2% (p < 0.001) and the mCBFV(MCA) by 4.6% (p = 0.007). Significant increases of ccytaa3 were measured during active exercises of the upper extremity (1.6%; p = 0.04) and of the lower extremity (2.7%, p = 0.007). We also found an increase of ccytaa3 during passive exercises of the upper extremity (1.5%, p = 0.04). Significant changes of cHbO(2) were measured with 2.5% (p < 0.05) at active exercises of the lower extremity. CONCLUSION: These studies show that active as well as passive clinical exercises cause an increase of cerebral blood flow velocity. We attribute the increase of cerebral hemodynamics and cerebral metabolism to cerebral activation and autoregulative mechanisms.

Catalytic inhibition of human DNA topoisomerase IIalpha by hypericin, a naphthodianthrone from St. John's wort (Hypericum perforatum).

St. John's wort (Hypericum perforatum) is the most widely used herbal medicine for the treatment of depression. However, concerns have arisen about the potential of its interaction with other drugs due to the induction of cytochrome P450 isozymes 1A2 and 3A4 by the components hypericin and hyperforin, respectively. Structurally similar natural products are often employed as antitumor agents due to their action as inhibitors of DNA topoisomerases, nuclear enzymes that modify DNA during cellular proliferation. Preliminary findings that hypericin inhibited the DNA relaxation activity of topoisomerase IIalpha (topo II; EC 5.99.1.3) led us to investigate the mechanism of enzyme inhibition. Rather than stabilizing the enzyme in covalent complexes with DNA (cleavage complexes), hypericin inhibited the enzyme prior to DNA cleavage. In vitro assays indicate that hypericin is a potent antagonist of cleavage complex stabilization by the chemotherapeutics etoposide and amsacrine. This antagonism appears to be due to the ability of hypericin to intercalate or distort DNA structure, thereby precluding topo II binding and/or DNA cleavage. Supporting its non-DNA damaging, catalytic inhibition of topo II, hypericin was shown to be equitoxic to both wild-type and amsacrine-resistant HL-60 leukemia cell lines. Moreover, hypericin was incapable of stimulating DNA damage-responsive gene promoters that are activated by etoposide. As with the in vitro topo II assay, antagonism of DNA damage stimulated by 30 microM etoposide was evident in leukemia cells pretreated with 5 microM hypericin. Since many cancer patients experience clinical depression and concomitantly self-medicate with herbal remedies, extracts of St. John's wort should be investigated further for their potential to antagonize topo II-directed chemotherapy regimens.