A prospective randomized multicentre phase III trial of fotemustine plus whole brain irradiation versus fotemustine alone in cerebral metastases of malignant melanoma

The main objective of this prospective multicentre randomized phase III study was to compare a combined regimen of fotemustine plus whole brain irradiation with fotemustine alone in terms of cerebral response and time to cerebral progression in patients with melanoma cerebral metastases. Seventy-six patients were randomized to receive either fotemustine (arm A, n = 39) or fotemustine plus whole brain irradiation (arm B, n = 37). Fotemustine was administered intravenously at 100 mg/m(2) on days 1, 8 and 15, followed by a 5 week rest period, then every 3 weeks in non-progressive patients. In arm B, concomitant whole brain irradiation was performed at a total dose of 37.5 Gy (2.5 Gy/day on days 1-5 for three consecutive weeks). Although patients who received fotemustine alone had worse prognostic factors, there was no significant difference in cerebral response (arm A, 7.4%, arm B, 10.0%) or control rates (objective responses plus stable disease) after 7 weeks (arm A, 30%; arm B, 47%) or in overall survival (arm A, 86 days; arm B, 105 days). However, there was a significant difference in favour of arm B for the time to cerebral progression (P = 0.028, Wilcoxon test). In conclusion, fotemustine plus whole brain irradiation delayed the time to cerebral progression of melanoma cerebral metastases compared with fotemustine alone but without a significant improvement in terms of objective control or overall survival.     

Informing patients about serious side effects of drugs. A 2001 survey of 341 French rheumatologists

OBJECTIVES: In May 2001, we surveyed French rheumatologists to determine how they inform their patients about serious side effects of drugs. RESULTS: Of the 600 rheumatologists invited to participate in the study, 341 completed and returned the questionnaire. Most respondents believed that full information on patients would become the rule (mean, 62.1 +/- 28.3, the items being scored on a 100-point scale where 0 was "not at all" and 100 "absolutely"). The answer to this item varied little across age groups. Respondents felt that patient information fell primarily on the physician, (78 +/- 23), followed by pharmaceutical companies (64 +/- 32) and pharmacists (46 +/- 33). The respondents believed that full information of patients about side effects would primarily benefit physicians (51 +/- 32), followed by pharmaceutical companies (43 +/- 30) and patients (38 +/- 28). The reaction of patients to information on drug-related risks was described as "always favorable" by 2% of the respondents and as "fairly often favorable" by 55%. Among respondents, 9% always gave information on serious side effects, 66% fairly often, and 4% never; 2% always communicated information on the approximate frequency of serious adverse events, 21% fairly often, and 33% never. Similarly, 3% of the respondents always warned their patients of lethal risks, 11% fairly often, and 44% never. When evaluated on a 100-point scale (0, not at all knowledgeable; 100, very knowledgeable), knowledge of serious side effects of drugs for musculoskeletal conditions was 73 +/- 23, whereas knowledge of the frequency of these effects was only 52 +/- 22. Eight percent of the respondents always recommended that patients read the package insert, 27% fairly often, and 32% never. Conversely, the possible adverse effects of not taking the treatment were always specified by 21% of the respondents and fairly often by 88%.     

Treatment of Old World cutaneous leishmaniasis by pentamidine isethionate. An open study of 11 patients

BACKGROUND: Pentavalent antimonial derivatives (PAD), especially meglumine antimoniate (Glucantime((R))), are usually considered as the first-line drugs for Old World leishmaniasis, but their potential toxicity and the number of required injection, either intralesional or intramuscular, prompt to search for alternative treatments. OBJECTIVE: To evaluate the efficiency and tolerance of pentamidine isethionate in Old World leishmaniasis. METHODS: An open pilot study included 11 patients from two regional academic centers, with varied parasitological forms of Old World leishmaniasis, treated with three strictly intramuscular injections of 4 mg/kg of base-pentamidine every other day. RESULTS: Tolerance was good overall, and 8/11 (73%) of patients responded well with a quick healing of their lesions, little scarring and no relapse. CONCLUSION: Pentamidine isethionate is a safe and effective first-line treatment for Old World leishmaniasis. Larger-scale prospective studies comparing several dosage regimens of pentamidine and pentamidine isethionate to PAD are warranted.     

Cytoprotection and iron mobilization in rat hepatocyte cultures by a new synthetic dihydroxamate chelator

The cytoprotection and iron mobilization effect of a new dihydroxamate chelator 1,1 bis [(11-N-hydroxy)-2,5,11-triaza-1,6,10-trioxo dodecanyl] ethane or KD was studied in primary rat hepatocyte cultures exposed to iron-citrate. Lactate dehydrogenase (LDH) release and malondialdehyde (MDA) production were measured as indexes of cytotoxicity. Cell viability was evaluated using the [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyl tetrazolium bromide] (MTT) reduction test. To demonstrate that this chelator was able to decrease iron uptake or increase iron release from the hepatocytes, labelled cells were obtained by maintaining the cultures in the presence of 0.02 microM 55Fe-citrate. The efficacy of KD was compared to desferrioxamine B (DFO) at stoechiometry concentrations. After 24 h of exposure to 50 microM of iron-citrate, a significant release of LDH and MDA was observed. Cell viability was also significantly decreased. When 100 microM of KD were added at the same time as iron, LDH and MDA release was decreased and cell viability was improved. In the presence of the same chelator concentration, a net decrease of iron uptake by the cells was observed as attested by the low intracellular 55Fe level. Moreover, in the 55Fe loaded hepatocytes, the chelator increased the iron extracellular level indicating its iron release effect from the cells. In all tested experimental conditions, the efficacy of 100 microM of the dihydroxamate chelator KD was close to that of 50 microM of the trihydroxamate chelator DFO. In conclusion, KD is effective at a level comparable to DFO in protecting rat hepatocytes against the toxic effect of iron-citrate by decreasing the uptake of the metal and increasing its release from the cells. This synthetic compound appears to have some potential therapeutical interest and the results obtained encourage the synthesis of new hydroxamate ligands.     

Delays in diagnosis and melanoma prognosis (II): the role of doctors

A prospective survey was conducted to assess physician responsibility in melanoma prognosis. Consecutive patients with primary melanoma were interviewed and examined using a standardized questionnaire. Main outcome measures were medical components of the delay before tumor resection and tumor thickness. Of 590 melanomas, 29.1% were coincidentally detected by physicians and their tumor depth was lower than in melanomas detected by patients (p < 0.001). Physician sensitivity for melanoma diagnosis was evaluated at 86%. Median time intervals to propose resection and to perform removal of melanoma were short: 0 (mean 103) and 7 (mean 68) days, respectively. Melanomas were managed in an inappropriate way in 14.2% of cases. Location on acral areas and absence of pigmentation were associated with longer medical delays and more frequent inappropriate medical attitudes. Melanomas located on hardly visible areas were less frequently detected by physicians than those on visible areas. Medical delays were shorter, doctor's attitude was more frequently appropriate, and melanoma thickness was lower (p < 0.001) when the patient visited a dermatologist (54.7%) than when he or she visited a general practitioner (33.4%). Our study shows that doctor responsibility accounts for only a small part of the total delay before melanoma removal. However, systematic total examination and better training of doctors, especially about unusual forms of melanoma, could still improve melanoma detection.     

Genetic susceptibility associated with rare HRAS1 variable number of tandem repeats alleles in Spanish non-small cell lung cancer patients.

The highly polymorphic HRAS1 variable number of tandem repeats (VNTR), which maps 1 kb downstream from the human H-ras1 gene, has been described as an inherited predisposing factor in many human cancers. Here, we investigated the association between the presence of rare HRAS1 minisatellite alleles and lung cancer in the population studied. Four hundred sixty-six HRAS1 VNTR alleles from 233 lung cancer patients and 892 alleles from 446 unaffected controls were typed using PCR-long agarose gel electrophoresis assay of peripheral blood lymphocyte DNA. Rare alleles were differentiated from common alleles (a1, a2, a3, and a4) by shifts in electrophoretic mobility. Odds ratio was calculated to evaluate increased risk of lung cancer associated to the presence of rare HRAS1 alleles. A higher percentage of rare HRAS1 VNTR alleles in lung cancer patients than in unaffected controls (32.7 versus 21.9%) was confirmed. The presence of rare alleles was associated with an increased risk of lung cancer (odds ratio = 1.68; P < or = 0.0001), indicating a genetic predisposition to lung cancer. No differences based on other clinicopathological variables were observed. Furthermore, a meta-analysis showed a higher distribution of rare alleles in our study of Caucasian Spaniards than was found in other studies of American and Northern European Caucasian populations. We conclude that the presence of rare HRAS1 VNTR alleles may be an inherited predisposing factor in lung cancer. This presence can be easily determined from peripheral blood samples by PCR-based methods. Furthermore, interracial variations in allele frequencies and variations between Caucasian subpopulations suggest that genetic variations may be involved in susceptibility to lung oncogenesis, especially in certain ethnic populations.     

Dubreuilh melanoma: and epidemiologic and prognostic study

BACKGROUND: Lentigo maligna melanoma is a specific histoclinical type of melanoma. We studied the epidemiologic features of lentigo maligna melanoma (Dubreuilh's melanoma) and compared prognosis with other types of melanoma. PATIENTS AND METHODS: A retrospective review of 516 cases of cutaneous melanomas, seen from 1985 to 1997, identified 29 cases of lentigo maligna melanoma. Epidemiologic, clinical and prognostic data were collected using a common scoring system for all patients. The chi-squared test, univariate log rank analysis, Cox multiple regression model for multivariate analysis, and actuarial survival curves were applied. RESULTS: The 29 cases of lentigo maligna melanoma (16 women, 13 men) accounted for 5.9 p. 100 of all melanomas. Mean age at diagnosis was 73 years compared with 54 years for others melanomas. Predominant localization was head and neck. There was no prior history of nevi compared with 50 p. 100. Mean delay to diagnosis was 4 years versus 1 year. All patients have had an occupation with to sun exposure. Mean tumoral thickness was 2 mm. Survival was the same as for extensive superficial melanomas and better than for nodular melanomas. Multivariate analysis showed that prognosis was not better in case of lentigo maligna melanoma. Tumoral thickness was the main prognosis factor. DISCUSSION: Our findings confirmed the specific nature of lentigo maligna melanoma and suggested that sun exposure plays an important role. Multivariate analysis did not show that prognosis was any better in case of lentigo maligna melanoma than in other types of melanoma. The thickness of the tumor must be taken into account as for other melanomas.     

Tatouages lombaires et anesthésie périmédullaire : enquête de pratique dans les maternités du Languedoc-Roussillon

To determine neuraxial anesthesia practices in obstetric departments in Languedoc-Roussillon in parturient with large lumbar tattoo covering the puncture area. “A prospective anonymous survey was sent to anaesthesiologists” including a clinical case scenario with a tattooed woman. Questionnaire included items on neuraxial anaesthesia in various circumstances, reasons for the decision process, and “consensus management” or not “within the unit”. Fifty-four anaesthesiologists answered (response rate: 57%). Fifty-seven percent would perform an epidural anaesthesia (EA) through the tattoo. Thirty-nine percent would not; among which two third only would propose an alternative for EA. Elective or emergency caesarean section would prompt most of the anaesthesiologists to perform a spinal anaesthesia, especially in parturients with Mallampati Class III (93%) versus Class I (70%) airway. Seventy percent of responders reported no consensual management in their unit. Our study illustrates this lack of consensus in obstetrical units and among anaesthesiologists along with a variable attitude linked with the obstetrical and anaesthesiological situation.     

Trisomie 21 et autisme : double diagnostic, évaluation et intervention

Autism is recognized as an additional diagnosis possible in people with Down syndrome. This pathology is still rarely detected and treated in this population in France. This article is a review of the English literature and of studies led during the last fifteen years. Studies have identified the expression of autism clinical signs in children with Down syndrome and the sensitivity and specificity of diagnostic instruments for autism in this population despite their cognitive impairments. This paper emphasizes authors’ recommendations about intervention taking into account the dual diagnosis: they encourage the identification of autism as well as early and appropriate intervention for those children whose needs differ from their peers without comorbid disorder. These results show the need to educate professionals about the importance of the detection of autism in children with Down syndrome, and the prevention that could follow.