Nucleophile-Catalyzed Additions to Activated Triple Bonds. Protection of Lactams, Imides, and Nucleosides with MocVinyl and Related Groups

Additions of lactams, imides, (S)-4-benzyl-1,3-oxazolidin-2-one, 2-pyridone, pyrimidine-2,4-diones (AZT derivatives), or inosines to the electron-deficient triple bonds of methyl propynoate, tert-butyl propynoate, 3-butyn-2-one, N-propynoylmorpholine, or N-methoxy-N-methylpropynamide in the presence of many potential catalysts were examined. DABCO and, second, DMAP appeared to be the best (highest reaction rates and E/Z ratios), while RuCl3, RuClCp*(PPh3)2, AuCl, AuCl(PPh3), CuI, and Cu2(OTf)2 were incapable of catalyzing such additions. The groups incorporated (for example, the 2-(methoxycarbonyl)ethenyl group that we name MocVinyl) serve as protecting groups for the above-mentioned heterocyclic CONH or CONHCO moieties. Deprotections were accomplished via exchange with good nucleophiles: the 1-dodecanethiolate anion turned out to be the most general and efficient reagent, but in some particular cases other nucleophiles also worked (e.g., MocVinyl-inosines can be cleaved with succinimide anion). Some structural and mechanistic details have been accounted for with the help of DFT and MP2 calculations.

Family Alliance as a Moderator of the Link Between Maternal Postpartum Depression and Child Symptoms Assessed by Both Parents

We investigated the moderating effect of family relationships on the links between maternal postpartum depression and child symptoms in a low-risk community sample of families with 3-month-old infants (n = 57). The level of maternal depression was assessed by the Montgomery-Asberg Depression Rating Scale from a clinical interview, child symptoms by the Symptom Check List completed by both parents, and family relationships by direct observation of father-mother-baby interactions (Lausanne Trilogue Play). Families were categorized as high coordination or low coordination from their overall coordination level throughout the play. Results showed no significant links between maternal depression level and child symptoms reported by both parents. Mothers with a high depressive level in high coordination families tended to report more symptoms in their child than did mothers with lower depressive scores, whereas this link was not found in low coordination families. Prevention perspectives and clinical implications of these results are discussed.

Specificities of defense mechanisms in bipolar affective disorder: relations with symptoms and therapeutic alliance.

Defense mechanisms as a central notion of psychoanalysis have inspired various levels of interest in research in psychotherapy and psychopathology. Defense specificities have only recently been investigated systematically with regard to several clinical diagnoses, such as affective and personality disorders. For the present study, 30 inpatients diagnosed with Bipolar Affective Disorder I (BD) were interviewed. An observer-rater method, the Defense Mechanisms Rating Scales (DMRS), applied to session-transcripts, of assessment of defenses was used. A matched, nonclinical control group was introduced. Defense specificities in BD encompass a set of 5 immature defenses, of which omnipotence is linked with symptom level. The level of the therapeutic alliance is predicted by mature defenses. These results are discussed with regard to the psychological vulnerability of BD, and treatment implications for psychodynamic psychotherapy with such challenging patients are evoked.

Superiority of the Triple Combination of Bortezomib-Thalidomide-Dexamethasone Over the Dual Combination of Thalidomide-Dexamethasone in Patients With Multiple Myeloma Progressing or Relapsing After Autologous Transplantation: The MMVAR/IFM 2005-04 Randomized Phase III Trial From the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

PURPOSE This prospective multicenter phase III study compared the efficacy and safety of a triple combination (bortezomib-thalidomide-dexamethasone [VTD]) versus a dual combination (thalidomide-dexamethasone [TD]) in patients with multiple myeloma (MM) progressing or relapsing after autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS Overall, 269 patients were randomly assigned to receive bortezomib (1.3 mg/m(2) intravenous bolus) or no bortezomib for 1 year, in combination with thalidomide (200 mg per day orally) and dexamethasone (40 mg orally once a day on 4 days once every 3 weeks). Bortezomib was administered on days 1, 4, 8, and 11 with a 10-day rest period (day 12 to day 21) for eight cycles (6 months), and then on days 1, 8, 15, and 22 with a 20-day rest period (day 23 to day 42) for four cycles (6 months). Results Median time to progression (primary end point) was significantly longer with VTD than TD (19.5 v 13.8 months; hazard ratio, 0.59; 95% CI, 0.44 to 0.80; P = .001), the complete response plus near-complete response rate was higher (45% v 25%; P = .001), and the median duration of response was longer (17.2 v 13.4 months; P = .03). The 24-month survival rate was in favor of VTD (71% v 65%; P = .093). Grade 3 peripheral neuropathy was more frequent with VTD (29% v 12%; P = .001) as were the rates of grades 3 and 4 infection and thrombocytopenia. CONCLUSION VTD was more effective than TD in the treatment of patients with MM with progressive or relapsing disease post-ASCT but was associated with a higher incidence of grade 3 neurotoxicity.

Working alliance in communication skills training for oncology clinicians: A controlled trial.

OBJECTIVE: The aim of this study was to evaluate the impact of communication skills training (CST) on working alliance and to identify specific communicational elements related to working alliance. METHODS: Pre- and post-training simulated patient interviews (6-month interval) of oncology physicians and nurses (N=56) who benefited from CST were compared to two simulated patient interviews with a 6-month interval of oncology physicians and nurses (N=57) who did not benefit from CST. The patient-clinician interaction was analyzed by means of the Roter Interaction Analysis System (RIAS). Alliance was measured by the Working Alliance Inventory - Short Revised Form. RESULTS: While working alliance did not improve with CST, generalized linear mixed effect models demonstrated that the quality of verbal communication was related to alliance. Positive talk and psychosocial counseling fostered alliance whereas negative talk, biomedical information and patient's questions diminished alliance. CONCLUSION: Patient-clinician alliance is related to specific verbal communication behaviors. PRACTICE IMPLICATIONS: Working alliance is a key element of patient-physician communication which deserves further investigation as a new marker and efficacy criterion of CST outcome.