Promotion of mindfulness in psychotherapists in training: preliminary study.

This study examined whether the promotion of mindfulness in psychotherapists in training can influence the treatment results of their patients. The therapeutic course and treatment results of 196 inpatients, who were treated during a nine week period by nine psychotherapists in training, were compared: in the first phase of the study, the treatment group without (CG, historical control group, n=55), and in the second phase the treatment group with, (MFG, n=58) therapists who were currently practicing Zen meditation. The results of treatment were examined (according to the intent-to-treat principle) with the Session Questionnaire for General and Differential Individual Psychotherapy (STEP), the Questionnaire of Changes in Experience and Behaviour (VEV) and the Symptom Checklist (SCL-90-R), and showed significantly better results in the MFG.     

Urothelial carcinoma of the upper urinary tract: inverted growth pattern is predictive of microsatellite instability

Urothelial carcinoma of the renal pelvis and ureter may develop as a manifestation of hereditary nonpolyposis colorectal cancer syndrome (HNPCC), a disorder characterized by mutation or inactivation of a number of DNA mismatch repair genes and detectable as microsatellite instability (MSI). Some urothelial carcinomas display areas of endophytic, or inverted, growth. In this study, urothelial cancers of the upper urinary tract (n = 132) from patients treated at 2 tertiary care centers were studied to identify an association between growth pattern and MSI. Thirty-five neoplasms were microsatellite unstable (26.5%), and MSI was more frequent in papillary lesions than in sessile urothelial cancers (P = .033). The amount of inverted growth was estimated as a percentage of the total tumor. The interobserver and intraobserver concordance in recognizing inverted growth was good, and 65.7% of microsatellite-unstable tumors exhibited at least 20% of an inverted growth component, compared with only 17.5% of microsatellite-stable tumors (P < .0001). In this series, inverted growth predicted MSI with a sensitivity and specificity of .82. Inverted growth in urothelial carcinomas of the upper urinary tract may serve as a marker lesion for MSI and may help identify patients who should be offered testing for HNPCC.     

Microsatellite analysis of breast carcinoma and corresponding local recurrences

Local recurrence is a serious complication of breast carcinoma that reduces quality of life and influences prognosis. The aim of this study was to determine whether local recurrences of breast carcinoma are genetically related to the primary tumours. Forty cases of locally recurrent breast carcinomas (median onset: 3.6 years after primary surgery) were analysed: 22 patients had undergone breast-conserving therapy and 18 mastectomy. Eighteen microsatellites on chromosomes 2p, 3p, 5q, 10q, 11p, 11q, 13q, 17q, 17p, 18p were amplified by PCR using fluorescent-labelled primers, automatically detected after polyacrylamide gel electrophoresis and analysed for loss of heterozygosity (LOH) or microsatellite instability (MSI). Follow-up data were available for 39 cases with a median value of 89 months. All LOH and MSI found in the primary tumours were also present in the corresponding recurrences, indicating that they are genetically related to the primary tumours and not secondary malignancies in the same breast. MSI was found in three cases, of which one harboured MSI at more than two loci. The median value of LOH per case was significantly higher in the recurrent (four per case) compared to the primary tumours (two per case; p < 0.001, Mann-Whitney test), reflecting the genotype of tumour progression. Early local recurrence was associated with specific LOH for TP53.15 (p = 0.018, log-rank test) in the primary tumours. LOH on D13S1699 or D17S855 was associated with lymph node metastases (p = 0.024 and p = 0.019, respectively; chi-square test). In addition, tumour grade, lack of oestrogen or progesterone receptor expression, young patient age and early appearance of local recurrence significantly correlated with poor survival. The development of local recurrence despite clear resection margins may result from residual DCIS distant from the invasive carcinoma, homing of circulating tumour cells, or genetically altered, histologically normal breast tissue not immediately adjacent to the invasive carcinoma.     

Effects of repetitive transcranial magnetic stimulation over dorsolateral prefrontal and posterior parietal cortex on memory-guided saccades

We investigated the role of the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC) in a visuospatial delayed-response task in humans. Repetitive transcranial magnetic stimulation (20 Hz, 0.5 s) was used to interfere temporarily with cortical activity in the DLPFC and PPC during the delay period. Omnidirectional memory-guided saccades with a 3-s delay were used as a quantifiable motor response to a visuospatial cue. The question addressed was whether repetitive transcranial magnetic stimulation (rTMS) over the DLPFC or PPC during the sensory of memory phase affects accuracy of memory-guided saccades. Stimulation over the primary motor cortex served as control. Stimulation over the DLPFC significantly impaired accuracy of memory-guided saccades in amplitude and direction. Stimulation over the PPC impaired accuracy of memory-guided saccades only when applied within the sensory phase (50 ms after cue offset), but not during the memory phase (500 ms after cue offset). These results provide further evidence for a parieto-frontal network controlling performance of visuospatial delayed-response tasks in humans. It can be concluded that within this network the DLPFC is mainly concerned with the mnemonic respresentation and the PPC with the sensory representation of spatially defined perceptual information. Received: 22 April 1996/Accepted: 16 June 1997     

Untersuchungen zum Problem der Mumpsimmunität

Ohne Zusammenfassung     

Plasma HIV-1 RNA decline within the first two weeks of treatment is comparable for nevirapine, efavirenz, or both drugs combined and is not predictive of long-term virologic efficacy: A 2NN substudy

BACKGROUND: The initial rate of plasma HIV-1 RNA (pVL) decline has been proposed as a marker of early efficacy of antiretroviral therapy (ART) and a possible predictor of late efficacy. We compared the rate of pVL decline in patients starting ART with nevirapine (NVP), efavirenz (EFV), or both drugs combined in addition to lamivudine (3TC) and stavudine (d4T). METHODS: Analysis of the viral decay constant (VDc) during the first 2 weeks of treatment in patients enrolled in the 2NN study who remained on allocated treatment. RESULTS: The median VDc (log10 copies per day, [interquartile range]) was similar for NVP (0.30 [0.25-0.36], EFV (0.31 [0.27-0.37]), and NVP + EFV (0.30 [0.27-0.36]). Patients with a baseline pVL >100,000 copies/mL were 8.7 (95% confidence interval [CI]: 6.2-12.3) times more likely to have a VDc >75th percentile. A high VDc was not associated with plasma drug concentration or with a decreased risk of virologic failure at week 48 after the start of therapy (hazard ratio = 0.8, 95% CI: 0.6-1.2). CONCLUSION: NVP, EFV, or NVP + EFV in combination with 3TC and d4T show similar rates of pVL decline during the first 2 weeks of treatment. The VDc with these regimens is not predictive of late virologic efficacy.     

Toll-like receptor 9 contributes to recognition of Mycobacterium bovis Bacillus Calmette-Guérin by Flt3-ligand generated dendritic cells

Recognition of mycobacteria by the innate immune system is essential for the development of an adaptive immune response. Mycobacterial antigens stimulate antigen presenting cells (APCs) through distinct Toll-like receptors (TLRs) resulting in rapid activation of the innate immune system. The role of TLRs during infection with Mycobacterium bovis Bacillus Calmette-Guérin (BCG) has been evaluated for TLR2 and TLR4 only. Surprisingly, despite the fact that immune stimulatory CpG-motifs have been originally derived from BCG, for the vaccine strain the role of TLR9 has not been addressed before. To identify the set of TLRs involved in the recognition of BCG, we infected bone marrow-derived macrophages and bone marrow-derived dendritic cells (Flt3-ligand generated DCs) from TLR2, TLR3, TLR4, TLR7, TLR9, MyD88 knockout, TLR2/4 and TLR2/4/9 multiple knockout mice. The degree of activation and stimulation was determined by TNFα, IL-6 and IL-12p40 ELISA. Activation of DCs was measured by surface expression of the costimulatory molecule CD86. We observed the most dramatic reduction of the inflammatory response for TLR2-deficient antigen presenting cells. Both macrophages and DCs produce markedly decreased amounts of TNFα and IL-6 in the absence of TLR2 whereas no significant reduction could be observed for TLR3, 4, 7, 9 single TLR-knockouts. However, IL-12 production in DCs appears not exclusively dependent on TLR2 and only in TLR2/4/9-deficient DCs BCG-induced IL-12 is reduced to background levels. Similarly, up-regulation of CD86 is abolished only in TLR2/4/9-deficient DCs supporting a role of TLR9 in the recognition of M. bovis BCG by murine dendritic cells.