Intra-articular morphine and clonidine produce comparable analgesia but the combination is not more effective

Both intra-articular morphine and clonidine produce analgesia. This study was designed to compare the analgesic effects of the two drugs, used separately and in combination. We studied 90 patients undergoing arthroscopy of the knee under general anaesthesia. Patients were allocated randomly to receive 20 ml of intra-articular isotonic saline solution containing morphine 2 mg, clonidine 150 micrograms or both. Pain was assessed on an visual analogue scale after operation and time for rescue medication was measured. There was no difference in VAS scores between the three groups and the time for rescue analgesic was comparable. We conclude that intra-articular morphine and clonidine have comparable analgesic effects in the doses used. The combination of both drugs did not seem to increase analgesia.      

Attributable risk in men in two French case-control studies on mesothelioma and asbestos

Pleural mesothelioma is a primary tumor of the pleura that is mainly due to asbestos exposure. To study the relationship between mesothelioma and occupational asbestos exposure in France, two case–control studies (A and B) were conducted. A substantial difference in the attributable risk in the population (AR_p) was observed among men: 44.5% (95% CI: [32.6–56.4]) in study A and 83.2% (95% CI: [76.8–89.6]) in study B. As different exposure assessment expert methods were used, the main objective of this work was to re-estimate the AR_p men in two case–control studies according to a common standardized exposure assessment by using a Job Exposure Matrix (JEM) and to assess the role of subjects’ selection. The initial observed AR_p difference was maintained: 36.3% (95% CI: [24.3–50.3]) in study A and 69.7% (95% CI: [51.7–83.2]) in study B. Further investigations highlighted the potential selection bias introduced in both studies, especially among controls. The AR_p could be underestimated in study A and overestimated in study B. After weighting subjects according to distribution of socio-economic status in the general population for controls and according to distribution of socio-economic status of cases registered by the French National Mesothelioma Surveillance Program, re-estimated AR_p values were 52.4% in study A and 70.2% in study B. These results provide additional information to describe the relationship between pleural mesothelioma and occupational asbestos exposure, but also confirm the importance of subjects’ recruitment in case control studies, particularly control selection.     

Tumour-derived and host-derived nitric oxide differentially regulate breast carcinoma metastasis to the lungs

To study the role of nitric oxide (NO) in lung metastasis of breast carcinoma, we isolated two cell clones (H and J) from the parental EMT-6 murine breast carcinoma cell line, based on their differential NO production. In vitro, EMT-6 J cells, but not EMT-6H cells, constitutively expressed inducible NO synthase (NOS II) and secreted high levels of NO. IL-1beta increased NO production in both clones, and TNF-alpha had a synergistic effect on IL-1beta-induced NO production, but NO production by EMT-6 J cells was always higher than by EMT-6H cells. Proliferation, survival and adhesion to lung-derived endothelial cells of both clones were similar and were not affected by NO. In vivo, both clones similarly located in the lungs of syngeneic mice 48 h after injection. However, EMT-6H cells were significantly more tumorigenic than EMT-6 J cells as assessed at later time points. Injection of EMT-6 J cells and simultaneous treatment of mice with aminoguanidine (AG), a NOS II inhibitor, significantly increased tumour formation. Injection of EMT-6H and EMT-6 J cells into NOS II-deficient mice resulted in a significant survival increase as compared with wild-type animals. Simultaneous administration of AG increased the death rate of NOS II-deficient mice injected with EMT-6 J cells. These results demonstrate that: (i) NO does not influence the early stages of tumour metastasis to the lungs and (ii) NOS II expression in tumour cells reduces, while NOS II expression in host cells enhances, tumour nodule development. In conclusion, the cellular origin and the local NO production are critical in the metastatic process.     

To stimulate or to inhibit nitric oxide production in mammary tumors?

NO is a molecule produced in different amounts by two types of enzymes, constitutive NO-synthases and inducible NO-synthase, the last one produce large amount of NO. In tumor outcome, its role may be either beneficial or detrimental due to its actions in the different steps of tumor growth and metastasis. This review deals with mammary tumors and the mechanisms lying behind NO effects. In human patients, increased amounts of NO were evidenced in blood, linked with the presence and activity of NO-synthase in breast tumors. Non-unequivocal correlations were established with tumor grade, invasiveness and metastatic potential. Studies in animal models have given hints to explain these discrepancies by the type of the involved NO-synthase, the amount of NO it produces, and its belonging to tumoral or stromal cells. Indeed, it was recently shown that NO produced by tumor cells inhibits, while NO produced by stromal cells facilitates tumor growth, at least in the model which was studied. On the one hand, NO toxicity against tumor cells is a well known phenomenon, but on the other hand, NO may promote tumor invasiveness due to its effect on extracellular matrix, and to its angiogenetic properties. So the role of NO in mammary tumor outcome is not clear-cut, and, at the present time, it cannot be ascribed a pronostic value in breast tumor. However, researches aimed at managing tumor cells to produce NO sufficient to induce their death may be fruitful since, be tumor targeting successful, no general toxicity would be encountered.     

Prognostic value of early 18 fluorodeoxyglucose positron emission tomography and gallium-67 scintigraphy in aggressive lymphoma: a prospective comparative study

The prognostic value of fluorodeoxyglucose positron emission tomography (FDG-PET) and gallium-67 scan (GS) performed early after chemotherapy was assessed in 40 patients with newly diagnosed aggressive lymphoma. FDG-PET and GS were performed before and after three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or two cycles of ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone), with or without rituximab. Thirty-five patients had diffuse large B-cell lymphoma (DLBCL), two had mantle-cell lymphoma and three had T-cell lymphoma. Four patients relapsed despite early negative FDG-PET and GS including all three patients with T-cell lymphoma. Nine patients stayed in remission despite positive FDG-PET and/or GS of whom five showed moderate intensity residual bone uptake. Seven of these nine early false positives had a negative exam at the end of treatment. In patients with DLBCL, the 2-year event-free survival was 85% for negative versus 30% for positive FDG-PET patients (P = 0.003) whereas it was 78% for negative versus 33% for positive GS patients (P = 0.018). Sensitivity, specificity and diagnostic accuracy of FDG-PET and GS were not significantly different: 90% versus 70%, 76 versus 80% and 80 versus 77%, respectively. We conclude that both FDG-PET and GS are valuable tools to early predict outcome in patients with DLBCL.     

Ultrasonic study of the carotid artery bifurcation. Comparative study with arteriography (50 cases)

This prospective study was initiated in March 1981 and all results were compared with arteriography. The investigations were carried out with a real time Toshiba SAL 20 equipped with a 5 MHz transducer and a DUD 400 continuous Doppler ultrasonogram with a 4 MHz transducer. All patients were referred to us from the neurological and cardiac departments of our hospital. They had a wide range of conditions varying from simple paraesthesia to massive hemiplegia or from arrhythmias to syncope. The investigation always started with classical Doppler examination (12 recording points) and was followed by real time ultrasonography of the cervical vascular axes. An improved diagnostic performance with the association of Doppler + real time B mode ultrasonography was demonstrated in a previous study. The results of this study were compared with the angiographic appearances and a close correlation was observed with normal and pathological cases. In this series of 50 cases the sensitivity was 92 p. 100 and the specificity 87 p. 100. More detailed analysis of this population showed the two false negatives to correspond to two ulcerated atheromatous plaques at the carotid bifurcation. The false positive results were more difficult to interpret and may have been due to technical artefacts. However, other workers have already encountered this difficulty with surgery demonstrating the plaques detected by ultrasound. In conclusion, real time ultrasonography and Doppler are two complementary investigations which when used by the same operator can become very sensitive and reliable methods of investigation.(ABSTRACT TRUNCATED AT 250 WORDS)