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What’s so funny about melancholy? Iconic as Hamlet is, Shakespearean comedy showcases an extraordinary reliance on melancholy that ultimately reminds us of the porous demarcation between laughter and sorrow. This richly contextualized study of Shakespeare’s comic engagement with sadness contends that the playwright rethinks melancholy through comic theatre and, conversely, re-theorizes comedy through melancholy. In fashioning his own comic interpretation of the humour, Shakespeare distils an impressive array of philosophical discourses on the matter, from Aristotle to Robert Burton, and as a result, transforms the theoretical afterlife of both notions. The book suggests that the deceptively potent sorrow at the core of plays such as The Comedy of Errors, Twelfth Night, or The Winter’s Tale influences modern accounts of melancholia elaborated by Sigmund Freud, Judith Butler, and others. What’s so funny about melancholy in Shakespearean comedy? It might just be its reminder that, behind roaring laughter, one inevitably finds the subtle pangs of melancholy.

263 patients (median age 65+/-10 years) with multiple myeloma were treated with cyclophosphamide-prednisone. Out of this cohort, 103 patients had progressive disease and were randomly assigned to either VAD (vincristine, doxorubicin, dexamethasone; 50 cases) or VMBCP (vincristine, BCNU, cyclophosphamide, melphalan and prednisone; 53 cases). There were no statistical differences between the two groups with the respect to clinical, biological and radiological parameters. There was no difference in survival between the VAD and VMBCP groups. The 4 months response rate was similar in the two groups (50% VAD, 56% VMBCP). With multivariate analysis for survival (Cox model), two factors had a statistically significant impact: Karnofsky index (> 60) and albuminaemia ( 60 and albuminaemia > or = 34 g/l, the median survival was 29 months v 2 months with a Karnofsky index < or = 60 and albuminaemia < 34 g/l (P

Between January 1985 and July 1989 we diagnosed asymptomatic stage I multiple myeloma according to Durie and Salmon [Durie and Salmon: Cancer 36:842, 1975] in 91 patients. All patients were followed without chemotherapy. Disease progression occurred in 41 patients and the median time to progression for all patients was 48 months. In the Cox multivariate regression analysis, hemoglobin levels 25% (P or = 30 g/l for Ig G or > or = 25 g/l for Ig A (P < .01) were the only significant prognostic factors for progression. The 38 patients without any harmful factor remained free of progression for a median of more than 50 months. The 18 patients with two or three of these characteristics (high-risk group) had the shortest median time to progression of 6 months. Despite different times to progression, the response rate and survival after chemotherapy were similar for all groups of patients. Patients in the high-risk group for progression have to be frequently monitored for disease progression and might benefit from early treatment.

A randomized trial has been performed in which 91 patients with stage III myeloma and additional severe criteria were randomly allocated to either VAD or VMBCP. No significant difference was noted between these two groups using the following criteria: response rate (VMBCP: 54%; VAD: 39%), impact on symptoms, median survival (VMBCP: 14 months, VAD: 17 months). However, toxic effects and refusal to pursue treatment were more frequent with VAD than with VMBCP (12 v 6). Therefore, in this trial, VMBCP appears to be more useful than VAD.

Neurons (n = 107) were recorded, in anaesthetized rats, with extracellular micropipettes, in the nucleus centralis of the amygdala (Ce). The activity of a large majority (77%) was exclusively or preferentially affected by noxious stimuli applied in any area of the body. The rest of the neurons was not activated by any stimuli (21%) or responded only to innocuous stimuli (2%). The nociceptive neurons were classified into two groups: the neurons in the first group (34% of the whole population) were activated by mechanical and thermal noxious stimuli; the neurons in the second group (43% of the whole population) were inhibited by noxious stimuli. Neurons in two groups precisely encoded thermal stimuli in the noxious range. Transcutaneous electrical stimulation suggested that the Ce nociceptive neurons were under the influence of A delta and C fibers. These results demonstrate important nociceptive input to the Ce which according to previous studies probably relays in the pontine parabrachial nucleus. In addition, they are in good agreement with the involvement of the amygdala in emotional, autonomic and/or behavioral reactions to noxious events.

CD16, the type III receptor for IgG, is expressed on neutrophils, natural killer cells, and some T lymphocytes, mast cells, and activated monocytes but not on cells of the B-lymphocyte lineage including plasma cells. It is also produced in a soluble form found in serum. We analyzed sera from 165 multiple-myeloma patients, 29 patients with monoclonal gammopathies of unknown significance, and 20 normal disease-free donors. We found that the level of soluble CD16 was significantly decreased in sera from patients with multiple myeloma compared to sera from healthy and monoclonal gammopathies of unknown significance donors (P = 0.0001). In addition, a stage-dependent decrease in soluble CD16 was observed, with a highly significant difference (P = 0.004) between stage I and stage II+III myeloma patients. The correlation between the myeloma stage and the serum level of soluble CD16, which is related to the host response, was found to be more sensitive than that of beta 2-microglobulin, which reflects the tumor burden. The concomitant evaluation of the serum levels of these two markers allows better staging and therefore has a more precise prognostic value.

Soluble CD16 (sCD16) are soluble part of Fc receptor for IgG which control in mice, proliferation of hybridoma B cells and IgG production. The levels of sCD16 in 165 myeloma patients and 29 patients with MGUS appear significantly different: 25a.u./ml versus 144a.u./ml and values of stage I are significantly higher than those of stages II +III.sCD16 might be a prognosis factor in myeloma.

In a multicentric controlled study, 49 patients with multiple myeloma (MM) received etidronate (10 mg/kg/j), and 45 received placebo, for 4 months. No difference was found for clinical, biological and radiogical parameters. 41 MM had bone biopsy before and after treatment: bone resorption parameters decreased significantly with etidronate (p

Bernard-Becharies J.F. Le mode de vie comme production sociale de sens. In: Langage et société, supplément au n°17, 1981. Pratiques langagières et stratégies de communication. Terrains, méthodes d'enquête et d'ananlyse. pp. 39-42.