Profiling of drugs and environmental chemicals for functional impairment of neural crest migration in a novel stem cell-based test battery.

Developmental toxicity in vitro assays have hitherto been established as stand-alone systems, based on a limited number of toxicants. Within the embryonic stem cell-based novel alternative tests project, we developed a test battery framework that allows inclusion of any developmental toxicity assay and that explores the responses of such test systems to a wide range of drug-like compounds. We selected 28 compounds, including several biologics (e.g., erythropoietin), classical pharmaceuticals (e.g., roflumilast) and also six environmental toxicants. The chemical, toxicological and clinical data of this screen library were compiled. In order to determine a non-cytotoxic concentration range, cytotoxicity data were obtained for all compounds from HEK293 cells and from murine embryonic stem cells. Moreover, an estimate of relevant exposures was provided by literature data mining. To evaluate feasibility of the suggested test framework, we selected a well-characterized assay that evaluates 'migration inhibition of neural crest cells.' Screening at the highest non-cytotoxic concentration resulted in 11 hits (e.g., geldanamycin, abiraterone, gefitinib, chlorpromazine, cyproconazole, arsenite). These were confirmed in concentration-response studies. Subsequent pharmacokinetic modeling indicated that triadimefon exerted its effects at concentrations relevant to the in vivo situation, and also interferon-ß and polybrominated diphenyl ether showed effects within the same order of magnitude of concentrations that may be reached in humans. In conclusion, the test battery framework can identify compounds that disturb processes relevant for human development and therefore may represent developmental toxicants. The open structure of the strategy allows rich information to be generated on both the underlying library, and on any contributing assay.

[Impact of implementation strategies on adherence rates to colorectal cancer (CRC) guidelines after polypectomy in a university hospital]. / Einfluss von Weiterbildungsmaßnahmen auf die leitliniengerechten Nachsorgeempfehlungen nach Polypektomie aus dem Dickdarm in einem Universitätsklinikum.

BACKGROUND: Colorectal cancer (CRC) is the second most common malignancy in Germany. Screening colonoscopies with polypectomy have been demonstrated to reduce the incidence of CRC. Detailed recommendations on scheduling screening and follow-up colonoscopies have therefore been included into national guidelines. Knowledge about CRC guidelines and adherence to guideline recommendations varies greatly among physicians. METHODS: We combined different implementation strategies (training courses, case discussion, handouts, wall charts) to improve adherence of recommendations for scheduling follow-up colonoscopy. To assess adherence, written recommendations given at discharge after inpatient treatment for polypectomy were analysed before (n = 111) and after (n = 83) the implementation of the above-mentioned implementation measures. Additional factors possibly influencing the recommendations of physicians were collected (histology, polyp size). RESULTS: The adherence to the CRC guideline before implementation of the above-mentioned measures was moderate. After intervention, there was a non-significant increase from 47 % to 53 %. Senior physician review and editing of the discharge summaries improved guideline adherence of recommendations to 69 %. Neither the education level of residents nor their affiliation to a certain department had an impact on the quality of the recommendations. Histology and in particular information on the resection status of the polyps in the pathology report (complete versus incomplete resection) had an influence of the recommended schedule. Furthermore, size of the polyps, but not the number, had a statistically significant influence on the quality of the recommendations. CONCLUSIONS: The inadequate improvement of guideline adherence can possibly be explained by the insufficient interactive and repetitive character of interventions. As the histology reports seem to have an influence on the recommendations in regards to the interval to the next colonoscopy, interdisciplinary teaching is necessary to improve guideline concurrent care.

Implications of pretreatment incisor inclinations for the achievement of cephalometric normal values-a study on two patient collectives.

PURPOSE: The objective was to clarify whether standardized multibracket therapies-differing only in finishing-wire dimensions (0.016â€¯× 0.022 inch vs. 0.017â€¯× 0.025 inch CNA [Connecticut New Archwire]) and excluding any extraction treatment or additional appliances other than intermaxillary elastics-can produce normal incisor inclinations starting from different baseline inclinations. METHODS: We analyzed pre- and posttreatment cephalograms of 156 patients (age: 15.6 ± 1.3 years) treated with Roth system (0.018 inch slot). Each archwire group (n = 89 or 67) was divided into subjects with initially retroclined, orthograde, or proclined upper and/or lower incisors (U1, L1). For the resultant 12 subgroups, descriptive statistics were compiled relative to five reference planes (NL, ML, NA, NB, BOP), followed by multiple intragroup (Kolmogoroff-Smirnoff and Wilcoxon signed-rank test) and intergroup (Kruskal-Wallis and Mann-Whitney U test) comparisons relative to NL or ML. RESULTS: The following intra- (1, 2) and intergroup (3, 4) differences were statistically significant (p ≤ 0.05) in both archwire groups: (1) post- vs. pretreatment inclinations in the subgroups initially retroclined U1, retroclined L1 and orthograde U1, but without normal values being achieved (subgroups retroclined U1, L1) or preserved (subgroup orthograde U1); (2) observed vs. expected alterations for the subgroups initially orthograde and proclined U1 and L1; (3) posttreatment inclinations for the subgroups initially retroclined vs. orthograde L1 and proclined L1; (4) observed alterations for the subgroups initially retroclined vs. proclined U1 and L1, but neither retroclined nor proclined vs. orthograde. Archwire thickness influenced the outcome to only a limited extent under the special circumstances of this study. CONCLUSION: The bracket/archwire combinations evaluated did not lead to normal incisor inclinations in most cases. Posttreatment values did significantly depend on the pretreatment situation. Most frequently, alterations were protrusive in direction, which notably even included incisors that showed norm values at the outset of treatment. It can be concluded that bracket torque will influence but not dominate incisor inclinations.

Detection of CTX-M-type extended-spectrum beta-lactamase (ESBLs) by testing with MicroScan overnight and ESBL confirmation panels.

CTX-M extended-spectrum beta-lactamases (ESBLs) have emerged as the most common type of ESBL globally, their incidence easily surpassing those of SHV and TEM ESBLs in most locales. This study compared the performance of two MicroScan dried panels with CLSI reference broth microdilution and disk diffusion methods on a collection of genetically characterized ESBL-producing isolates. These included 64 Enterobacteriaceae isolates that produced CTX-M8, -14, -15, or -16 according to PCR and sequencing of the bla gene, 17 isolates that produced a SHV or TEM ESBL, and 19 that produced both CTX-M and SHV ESBLs. Each isolate was tested by a frozen reference microdilution panel, the MicroScan ESbetaL plus confirmation panel, and a routine dried panel containing streamlined ESBL confirmation dilutions (MicroScan Neg MIC panel type 32) that included cefotaxime and ceftazidime tested alone or with a fixed concentration of 4 microg/ml of clavulanate. Each isolate was also tested by the standard CLSI double-disk confirmation tests. The disk diffusion method detected all ESBL-producing isolates, the frozen reference panel detected 90% of isolates (10 out of 100 could not be analyzed because of off-scale MICs that exceeded the clavulanate combination concentrations in the panel), the ESbetaL plus panel detected 98% (1 missed and 1 off scale), and the streamlined ESBL panel detected 95% (5 off scale). Very high MICs for a few strains that produced SHV or both CTX-M and SHV ESBLs precluded noting the required three twofold-dilution differences with clavulanate needed to confirm an ESBL primarily in the reference panel and the Neg type 32 panel.

[The communication of chronically III patients in an internet chat for aftercare of inpatient psychosomatic treatment]. / Die Kommunikation von Patienten mit einer chronischen Erkrankung in einem Internet-Chat zur Nachsorge einer stationären psychosomatischen Behandlung.

AIM: E-Health applications open new avenues for seamless care of patients with a chronic disease. This study examines the demand and the usage pattern of an Internet-assisted aftercare group-treatment following inpatient treatment. METHODS: The analysis uses data from telephone interviews which were conducted 12 months after discharge. 168 study participants of the prospective controlled effectiveness study (73.7%) participated. The frequency and the time of beginning an outpatient psychotherapy are compared between controls and chat participants. Computerized text-analyses of the chat-scripts are used to examine the usage pattern of the chat-aftercare. Statements of the patients with chronic symptoms at the beginning and at the end of their chat participation are quoted for illustration of the contents of the group therapy sessions. RESULTS: Patients with chronic course of illness utilize the online-based aftercare more frequently and more actively than patients with short durations of illness. Words indicating cognitive processes are used more frequently by chat participant with chronic illness. Chat participants with chronic course of illness who are receiving no additional outpatient psychotherapy, relapse considerably less frequently than controls without any psychotherapeutic support. CONCLUSION: Patients with chronic course of illness use online aftercare treatment to sustainably improve their health status.

Coordinating bracket torque and incisor inclination : Part 2: Reproducibility and statistical measures of the torque coordination angle (TCA).

PURPOSE: To determine the reproducibility and statistical measures of the torque coordination angle (TCA). METHODS: A total of 107 final cephalograms and corresponding casts were included, all reflecting treatment outcomes that met high qualitative standards, one of them being a Peer Assessment Rating (PAR) score of ≤3. Based on these records, the TCA was measured as a parameter to identify differences related to tooth morphology and bracket position between the torque-relevant reference plane at the bracket base and the long axis of a tooth. All measurements were performed on upper and lower central incisors (U1 and L1). RESULTS: Several reproducibility assessments for the TCA measurements yielded good results, including objectivity at 1.26 ± 0.81° (U1) or 1.41 ± 1.18° (L1), examiner reliability at 1.30 ± 0.97° (U1) or 1.25 ± 0.82° (L1), and method reliability at 1.80 ± 1.13° (U1) or 1.53 ± 1.07° (L1). The statistical measures revealed a high degree of interindividual variability. With bracket placement 4.5 mm (U1) or 4.0 mm (L1) above the incisal edge, the differences between the maximum and minimum TCA values were similarly large in both jaws (21.0° for U1 or 20.0° for L1), given mean TCA values of 24.6 ± 3.6° (U1) or 22.9 ± 4.3° (L1). Moving the bracket placement from 3.5 to 5.5 mm (U1) or from 3.0 to 5.0 mm (L1) changed the mean TCA values by 4.5° (U1) or 3.2° (L1). CONCLUSIONS: The TCA is a suitable cephalometric parameter to identify differences related to tooth morphology and bracket placement. Given its high interindividual variability, the fixed torque value of a specific bracket system should not be expected to produce the same incisor inclinations across patients.

SULFATION PATHWAYS: Formation and hydrolysis of sulfonated estrogens in the porcine testis and epididymis.

Boars exhibit high concentrations of sulfonated estrogens (SE) mainly originating from the testicular-epididymal compartment. Intriguingly, in porcine Leydig cells, sulfonation of estrogens is colocalized with aromatase and steroid sulfatase (STS), indicating that de novo synthesis of unconjugated estrogens (UE), their sulfonation and hydrolysis of SE occur within the same cell type. So far in boars no plausible concept concerning the role of SE has been put forward. To obtain new information on SE formation and hydrolysis, the porcine testicular-epididymal compartment was screened for the expression of the estrogen-specific sulfotransferase SULT1E1 and STS applying real-time RT-qPCR, Western blot and immunohistochemistry. The epididymal head was identified as the major site of SULT1E1 expression, whereas in the testis, it was virtually undetectable. However, SE tissue concentrations are clearly consistent with the testis as the predominant site of estrogen sulfonation. Results from measurements of estrogen sulfotransferase activity indicate that in the epididymis, SULT1E1 is the relevant enzyme, whereas in the testis, estrogens are sulfonated by a different sulfotransferase with a considerably lower affinity. STS expression and activity was high in the testis (Leydig cells, rete testis epithelium) but also present throughout the epididymis. In the epididymis, SULT1E1 and STS were colocalized in the ductal epithelium, and there was evidence for their apocrine secretion into the ductal lumen. The results suggest that in porcine Leydig cells, SE may be produced as a reservoir to support the levels of bioactive UE via the sulfatase pathway during periods of low activity of the pulsatile testicular steroidogenesis.

SULFATION PATHWAYS: Expression of SULT2A1, SULT2B1 and HSD3B1 in the porcine testis and epididymis.

In the porcine testis, in addition to estrogen sulfates, the formation of numerous sulfonated neutral hydroxysteroids has been observed. However, their functions and the underlying synthetic pathways are still widely unclear. To obtain further information on their formation in postpubertal boars, the expression of sulfotransferases considered relevant for neutral hydroxysteroids (SULT2A1, SULT2B1) was investigated in the testis and defined segments of the epididymis applying real-time RT-qPCR, Western blot and immunohistochemistry (IHC). Sulfotransferase activities were assessed in tissue homogenates or cytosolic preparations applying dehydroepiandrosterone and pregnenolone as substrates. A high SULT2A1 expression was confirmed in the testis and localized in Leydig cells by IHC. In the epididymis, SULT2A1 expression was virtually confined to the body. SULT2B1 expression was absent or low in the testis but increased significantly along the epididymis. Immunohistochemical observations indicate that both enzymes are secreted into the ductal lumen via an apocrine mechanism. The results from the characterization of expression patterns and activity measurements suggest that SULT2A1 is the prevailing enzyme for the sulfonation of hydroxysteroids in the testis, whereas SULT2B1 may catalyze the formation of sterol sulfates in the epididymis. In order to obtain information on the overall steroidogenic capacity of the porcine epididymis, the expression of important steroidogenic enzymes (CYP11A1, CYP17A1, CYP19, HSD3B1, HSD17B3, SRD5A2) was monitored in the defined epididymal segments applying real-time RT-qPCR. Surprisingly, in addition to a high expression of SRD5A2 in the epididymal head, a substantial expression of HSD3B1 was detected, which increased along the organ.

[Lutetium-177-PSMA radioligand therapy : Consensus within the framework of GKV-funded care between the university hospitals in Aachen, Bonn, Düsseldorf, Essen, and Cologne and the MDK Nordrhein]. / Lutetium-177-PSMA-Radioligandentherapie : Konsensus im Rahmen der GKV-finanzierten Versorgung zwischen den Hochschulkliniken in Aachen, Bonn, Düsseldorf, Essen und Köln und dem MDK Nordrhein.

In the last 3 years, Lutetium-177 prostate-specific membrane antigen radioligand therapy (Lu-177-PSMA-RLT) has received increasing attention in nuclear medicine as a new form of treatment for castration-resistant metastatic prostate cancer. This therapy combines the radionuclide Lutetium-177, which has been therapeutically used in nuclear medicine for many years, with a molecular target of the transmembrane prostate-specific membrane antigen expressed by prostate cancer cells. Since there are no prospective randomized studies on Lu-177-PSMA-RLT and the question of reimbursement has repeatedly been the subject of review by the MDK Nordrhein (Medischenische Dienst der Krankenversicherung), there was a desire because of the increasing number of patients being treated to clarify under which circumstances Lu-177-PSMA-RLT can be reimbursed by German statutory health insurance. The goals of this article are to help treating physicians understand how this new therapy option works, to integrate it in the overall therapy concept for castration-resistant metastatic prostate cancer, and, above all, to use Lu-177-PSMA-RLT-based on the current data-at the right place in the therapy sequence of castration-resistant metastatic prostate cancer.

Lovastatin increases arachidonic acid levels and stimulates thromboxane synthesis in human liver and monocytic cell lines.

The effect of lovastatin (LOV), the inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, on linoleic acid (LA, 18:2n-6) metabolism was examined in human monocytic Mono Mac 6 (MM6) and hepatoma Hep G2 cells. The desaturation of LA was examined after LOV (72 h, 10 microM) or dimethylsulfoxide (LOV carrier, < 0.1%) and [14C]LA (last 18 h, 0.3 microCi, 5 microM). In both cell lines, LOV reduced the percentage of 14C label associated with LA and increased the percentage of label in the 20:4n-6 and the 22:5n-6 fractions. In Hep G2 but not MM6 cells, this effect was fully reversible by means of coincubation with mevalonic acid (500 microM), but not with cholesterol or lipoproteins. In both cell lines, the LOV-mediated increase in LA desaturation resulted in dose-dependent reductions of LA and elevations of AA in cellular phospholipids. The lipids secreted by LOV-treated Hep G2 cells were also enriched in arachidonic acid (AA). In the MM6 cells, LOV increased release of thromboxane upon stimulation with the calcium ionophore A23187. In summary, our findings of higher LA desaturation and AA enrichment of lipids secreted by the Hep G2 cells suggest that LOV treatment may increase the delivery of AA from the liver to extrahepatic tissues. The changes in membrane fatty acid composition can influence a variety of cellular functions, such as eicosanoid synthesis in monocytic cells. The mechanism appears to be related to the reduced availability of intermediates of cholesterogenesis.

Docosahexaenoic acid inhibits PAF and LTD4 stimulated [Ca2+]i-increase in differentiated monocytic U937 cells.

We investigated the effects of different polyunsaturated fatty acids (PUFAs) of the n-6 and n-3 family on the PAF and LTD4 stimulated increase in cytosolic free Ca(2+)-concentration [Ca2+]i in retinoic acid (RA) differentiated, human monocytic U937 cells. Docosahexaenoic acid (10 microM DHA) reduced the PAF induced increase in [Ca2+]i from 455 +/- 25 nM to 319 +/- 24 nM (P less than 0.01). DHA also significantly attenuated the LTD4 induced increase in [Ca2+]. However [Ca2+]i-increase stimulated by f-MLP, ATP, or ionophore A 23187 was not affected by DHA. Other PUFAs like eicosapentaenoic acid (EPA), alpha-linolenic acid (LnA), arachidonic acid (AA) or gamma-linoleic acid (LA) were ineffective. Cellular differentiation as assessed by nitrobluetetrazolium reduction and enhanced expression of specific PAF binding sites in RA treated cells were not altered by DHA. Fatty acid composition in cellular phospholipids revealed effective incorporation of each PUFA. The DHA-effect on [Ca2+]i was time dependent and occurred at 48 h, whereas the DHA-content in phospholipids reached a plateau already at 24 h. The antioxidant vitamin E, the lipoxygenase inhibitor NDGA and the cytochrome P-450 inhibitor SKF 525A completely prevented the DHA induced reduction of PAF stimulated [Ca2+]i-increase. In contrast, the cyclooxygenase inhibitor indomethacin had no effect. Our results indicate that DHA selectively reduces intracellular [Ca2+]i-increases induced by PAF and LTD4 in RA-treated U937 cells, presumably involving an oxidative modification of DHA.

Single, sequential, and multiple alkylating agent therapy for multiple myeloma: a CALGB Study.

Four intravenous (IV) alkylating agent regimens were tested in 615 previously untreated patients with multiple myeloma. Patients were randomized to receive melphalan, cyclophosphamide, and carmustine in combination (MCBP), sequentially (Seq-MCBP), or in combination with doxorubicin (MCBPA). The fourth group received IV melphalan (MP) as the only alkylating agent. All groups received a tapering dose of prednisone. Toxicity was similar for all regimens although the nadir of cytopenia was reached more quickly for the regime including melphalan only. Response as measured by reduction in myeloma protein or other parameters were similar for the four treatments. Survival was significantly poorer for the group receiving the alkylating agents in sequence. The survival of high tumor cell load patients who were azotemic was better in the groups treated with IV MP or with the combination of IV MCBP. In view of the simplicity and probable cost savings attached to single-agent treatment, a melphalan/prednisone regimen should be considered as initial therapy for all patients with myeloma.

A randomized trial of anticoagulation with warfarin and of alternating chemotherapy in extensive small-cell lung cancer by the Cancer and Leukemia Group B.

The Cancer and Leukemia Group B (CALGB) conducted a prospective randomized trial to evaluate the role of warfarin and alternating chemotherapy in extensive small-cell lung cancer (SCCL). After stratification for sex and performance status, patients were randomly assigned to receive chemotherapy with methotrexate, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH), cyclophosphamide, and lomustine (CCNU) (MACC), or MACC plus warfarin (MACC + W), or mitomycin, etoposide, cisplatin, and hexamethylmelamine alternating with MACC (MEPH/MACC). Warfarin was given continuously to maintain a prothrombin time of one and one half to twice the control values. A total of 328 patients were enrolled, and 294 were evaluable. There was a statistically significant advantage in objective response rates (complete [CR] and partial responses [PR], respectively) for MACC + W (17% and 50%) as compared with MACC alone (8% and 43%) or MEPH/MACC (10% and 38%) (P = .012). Both failure-free survival (P = .054 Wilcoxon test) and overall survival (P = .098 Wilcoxon test) were higher on MACC + W (median, 6.6 months and 9.3 months, respectively), as compared with MACC (5.0 months and 7.9 months) and MEPH/MACC (5.0 months and 7.9 months). Toxicity was comparable among the three arms, except for increased hemorrhagic events on MACC + W, which were life-threatening in four patients (4%), and lethal in two others (2%). These data support the role of warfarin in the treatment of SCCL, but do not establish its mechanism of action. Warfarin deserves further studies in SCCL, particularly in patients with limited disease.

Prognostic factors in small-cell carcinoma of the lung: an analysis of 1,521 patients.

Cancer and Leukemia Group B (CALGB) accrued 1,745 patients with limited (LD) or extensive (ED) small-cell lung cancer (SCCL) to five separate trials between 1972 and 1986. We reviewed these data to evaluate the impact of pretreatment prognostic factors on outcome. In multivariate analysis, female gender was predictive of improved response (LD, P = .01; ED, P = .04) and survival (LD, P = .01; ED, P = .02). A performance status of 0 or 1 was associated with improved response rates in both subsets, but was statistically significant (P = .04) only for overall objective response in LD patients. Performance status was a highly significant predictor of survival in both LD and ED groups (P less than .001). Supraclavicular lymph node involvement, while still LD, had a borderline unfavorable impact on survival (P = .06) compared with a lesser extent of LD involvement. In ED patients, a decrease in survival rates was associated with an increased number of metastatic sites (P = .01). Changes in the patient population were noted with time: the percentage of women increased from 21% to greater than 35%; an increased number of metastatic sites was identified among ED patients; mean performance status improved for both LD and ED subsets. These trends reflect the changing demographics of lung cancer, improved lung cancer staging, and probably lead-time bias. Response rates, overall survival, and long-term (greater than 2-year) survival varied significantly among the five protocols, both before and after multivariate correction for identified prognostic variables. However, the changing character of the study population limits the ability to determine retrospectively how much improvements in therapy contributed to the positive changes in failure-free survival, overall survival, and long-term survival observed in our sequentially studied population.

Sleep deprivation as a probe in the elderly.

Decreased slow-wave sleep (SWS) and sleep continuity are major effects of healthy aging and of associated psychopathological states. Using sleep deprivation, we studied the extent to which age- and psychopathology-related sleep "decay" is reversible in aged normal, depressed, and demented subjects. Depression or probable Alzheimer's dementia compromised the augmentation of sleep continuity and SWS seen in healthy elderly following sleep deprivation. Rapid eye movement (REM) latency decreased during recovery sleep in the controls but increased in both patient groups. Compared with demented patients, depressed elderly had greater severity of sleep continuity disturbance both before and after sleep deprivation, a more protracted course of recovery sleep, and increased slow-wave density in the second non-REM (NREM) sleep period (during recovery). The REM sleep time was diminished in dementia compared with depression both at baseline and during recovery sleep. These differential effects of age, health, and neuropsychiatric disease on recovery from sleep loss are relevant to recovery or reversal theories of sleep and have implications for daytime well-being in the elderly.

Reliable discrimination of elderly depressed and demented patients by electroencephalographic sleep data.

Using electroencephalographic sleep data from a sample of 235 elderly subjects, discriminant function analyses of sleep alterations in depression and dementia were performed. Overall, 80% of patients were correctly classified using a backward discriminant function analysis, and 81% with a general stepwise discriminant function analysis. Four measures contributed to the separation of depressed and demented patients: rapid eye movement (REM) sleep latency (lower in depressives); REM sleep percent (higher in depressives); indeterminate non-REM sleep percent (higher in demented patients, reflecting greater loss of spindles and K complexes); and early morning awakening (more marked in depressives). When both discriminant functions were subjected to cross-validation in independent subsamples, both procedures correctly identified 78% of patients. The classification functions derived from nondemented depressed and nondepressed demented patients were applied to a mixed-symptom group (n = 42). Overall, 27 patients (64%) with either depressive pseudodementia or dementia with depressive features were correctly classified using the same four predictor variables. These findings suggest that sleep physiological alterations of depression and dementia reflect between-group differences in sleep continuity, sleep architecture, and REM sleep temporal distribution, and that the differences are statistically reliable, in both diagnostically pure and mixed clinical presentations. These findings are discussed in the context of current hypotheses of sleep regulation and its mechanisms.

[The situation of patients with dementia may be rectified by Ginkgo biloba. Results of a health services research study concerning the ability of patients with dementia, quality of life of the nursing family members and total treatment costs]. / Versorgungssituation von Demenzkranken kann durch Ginkgo biloba verbessert werden. Ergebnisse einer Studie zur Versorgungsforschung hinsichtlich der Leistungsfähigkeit der Demenzkranken, der Lebensqualität der Pflegenden und der Gesamtkosten der Behandlung.

UNLABELLED: BACKGROUND AND ISSSUES: Ginkgo biloba-extracts are often used in therapy of patients with dementia. In this study, benefit and structure of Ginkgo biloba-extract EGb 761 in treatment of patients with dementia was examined. PATIENTS AND METHODS: For the assessment of quality of life of care-taking relatives and patients as well as treatment costs were documented. The study was conducted as a non-randomised, two-armed cohort study with an open design for 683 slightly or moderately demented patients, aged between 65 and 80 years. Society's perspective was taken. Barthel-Index and MMST were also documented. Because of significant differences at inclusion of both cohorts, a matched-pairs-analysis and multiple regression analysis conducted. RESULTS: According to PLC a significant improvement in quality-of-life of care-taking relatives (p < 0.001) and patients (positive mood p = 0.018, negative mood p < 0.001) was only observed in the Ginkgo-cohort. Also Barthel-Index indicated an improvement in the Ginkgo-cohort (p < or = 0,001). MMST-scores increased significantly only in the Ginkgo-cohort (p < 0.001). Average total cost per patient amounted to 3.614,75 euro in the standard-cohort, whereas these costs per patient in the Ginkgo-cohort amounted to 3.031,78 euro (p = 0.067). Results were confirmed by matched-pairs-analysis. RESULTS: Ginkgo treatment has a valid place in caretaking structure of health services. Gingko attributes to a higher quality of life for both care-takers and patients, the progression of disease is slowed down and treatment costs are lower.

EEG sleep in elderly depressed, demented, and healthy subjects.

In a prospective study of EEG sleep patterns in 25 elderly depressives, 25 elderly demented patients, and 25 healthy, elderly control subjects, the sleep of depressives was characterized by reduced REM sleep latency, increased REM percent and first REM period density, and altered temporal distribution of REM sleep, as well as by diminished sleep maintenance (correlated significantly with Hamilton ratings of depression: multiple R = -0.42, p less than 0.05). In contrast, the sleep of demented patients showed reduced REM sleep percent, but normal REM temporal distribution, increased loss of spindles and K-complexes (the latter correlating significantly with severity of cognitive impairment as measured by the Folstein score: multiple R = -0.59, p less than 0.01), and less severe sleep maintenance difficulty than for depressives. An examination of REM latency demonstrated a skewed distribution in depression (i.e., 42% of nights with sleep-onset REM periods), but a normal distribution in the controls and demented subjects. A REM latency cut-off score of 30 min correctly classified 68% of all patients (kappa = 0.36; p less than 0.005), compared with 78% correctly identified in our retrospective study (Reynolds et al. 1983).