Adrenocorticotropic hormone, but not trilostane, causes severe adrenal hemorrhage, vacuolization, and apoptosis in rats.

Adrenal necrosis has been reported as a complication of trilostane application in dogs with hyperadrenocorticism. One suspicion was that necrosis results from the increase of adrenocorticotropic hormone (ACTH) during trilostane therapy. The aim of the current study was to assess the effects of ACTH and trilostane on adrenal glands of rats. For experiment 1, 36 rats were divided into 6 groups. Groups 1.1 to 1.4 received ACTH in different doses (60, 40, 20, and 10 µg/d) infused subcutaneously with osmotic minipumps for 16 wk. Group 1.5 received saline, and group 1.6 received no therapy. For experiment 2, 24 rats were divided into 3 groups. Group 2.1 and 2.2 received 5 and 50 mg/kg trilostane/d orally mixed into chocolate pudding for 16 wk. Eight control rats received pudding alone. At the end of the experiments, adrenal glands were assessed for necrosis by histology and immunohistochemistry; levels of endogenous ACTH and nucleosomes were assessed in the blood. Rats treated with 60 µg ACTH/d showed more hemorrhage and vacuolization and increased numbers of apoptotic cells in the adrenal glands than rats treated with 20 or 10 µg ACTH/d, trilostane, or control rats. Rats treated with 60 µg ACTH/d had a higher amount of nucleosomes in the blood compared with rats treated with 10 µg ACTH/d, trilostane, or saline. We conclude that in healthy rats ACTH, but not trilostane, causes adrenal degeneration in a dose-dependent manner. Results of this study support the hypothesis that adrenal gland lesions seen in trilostane-treated dogs are caused by ACTH and not by trilostane.

[Sexually transmitted diseases and sexual contamination with human immunodeficiency virus in the French Forces in 2006]. / Infections sexuellement transmissibles et contaminations sexuelles par le virus de l'immunodéficience humaine dans les armées françaises en 2006.

BACKGROUND: Servicemen constitute a group at risk for exposure to sexually transmitted diseases (STD) and for this reason specific surveillance of STD and human immunodeficiency virus (HIV) seroconversion has been conducted in the French Armed Forces since 1996. METHODS: All cases of STD and HIV seroconversion occurring in military personnel and corresponding to the notification criteria are reported by a military doctor, wherever the diagnosis is made. Incidence rates are calculated based on numbers of military personnel provided by the Ministry of Defence Social Observatory. RESULTS: In 2006, 67 cases of STD and 10 of HIV seroconversion due to sexual contamination were reported in the French Forces. The incidence of STD and HIV seroconversion was respectively 19.2 and 2.8 cases per 100,000. Gonorrhoea was the principal notified STD, with half of the cases of HIV seroconversion involving acute HIV infection. 59.7% of STD and 70.0% of HIV seroconversion were contracted in metropolitan France. DISCUSSION: STD and HIV seroconversion remain a subject of concern for the French Medical Forces despite low rates of incidence.

Cancer risk after cessation of asbestos exposure: a cohort study of Italian asbestos cement workers.

OBJECTIVES: We aimed to study mortality for asbestos related diseases and the incidence of mesothelioma in a cohort of Italian asbestos cement workers after cessation of asbestos exposure. METHODS: The Eternit factory operated from 1907 to 1986. The cohort included 3434 subjects active in 1950 or hired in 1950-86, ascertained from company records, without selections. Local reference rates were used for both mortality and mesothelioma incidence. RESULTS: Mortality was increased in both sexes for all causes (overall 1809 observed (obs) vs 1312.3 expected (exp); p<0.01), pleural (135 obs vs 3.6 exp; p<0.01) and peritoneal (52 vs 1.9; p<0.01) malignancies and lung cancer (249 vs 103.1; p<0.01). In women, ovarian (9 vs 4.0; p<0.05) and uterine (15 vs 5.8; p<0.01) malignancies were also in excess. No statistically significant increase was found for laryngeal cancer (16 obs vs 12.2 exp). In Poisson regression analyses, the RR of death from pleural neoplasm linearly increased with duration of exposure, while it showed a curvilinear increase with latency and time since cessation of exposure. RR for peritoneal neoplasm continued to increase by latency, duration and time since cessation of exposure. RR for lung cancer showed a reduction after 15 years since cessation of exposure and levelled off after 40 years of latency. CONCLUSION: This study of a cohort of asbestos exposed workers with very long follow-up confirmed the reduction in risk of death from lung cancer after the end of exposure. It also suggested a reduction in risk for pleural mesothelioma with over 40 years of latency, while risk for peritoneal mesothelioma showed a continuing increase.

[Mortality from pleural and peritoneal cancer in a cohort of asbestos workers, many years after start of the exposure: possible role of fibers clearance]. / Mortalità per tumore pleurico e peritoneale in una coorte di lavoratori del cemento amianto, dopo lunghi periodi di latenza: valutazione di un possibile ruolo della clearance delle fibre.

The multistage theory of carcinogenesis assumes rates of mesothelioma increasing monotonically as a function of time since first exposure (TSFE) to asbestos. However, some authors have suggested that the increase in mesothelioma rate with TSFE might be attenuated by clearance of asbestos from the lungs. We estimated mortality time trends from pleural and peritoneal cancer in a cohort of 3443 asbestos-cement workers. The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalized to include a term representing elimination over time. We observed 139 deaths from pleural and 56 from peritoneal cancer during the period 1950-2003. The rate of pleural cancer increased during the first 40 years of TSFE and reached a plateau thereafter. In contrast, the rate of peritoneal cancer increased monotonically with TSFE. The model allowing for asbestos elimination fitted the data better than the traditional model for pleural (p = 0.02) but not for peritoneal cancer (p = 0.22). The risk for pleural cancer, rather than showing an indefinite increase, might reach a plateau when a sufficiently long time has elapsed since exposure. The different trends for pleural and peritoneal cancer might be related to clearance of the asbestos from the workers' lungs.

[Contribution of the French Armed Forces Health Services to relief in Indonesia following the tsunami on December 26, 2004]. / Principales actions menées par le Service de santé des armées en Indonésie au décours du tsunami du 26 décembre 2004.

As of early January 2005, the French Armed Forces Health Services were on the ground in Indonesia to contribute to relief operations following the tsunami in Indonesia on December 26, 2004. Findings of preliminary investigation performed upon deployment of the first French elements demonstrated that a major priority was to speed up vaccination against measles in children between the ages of 6 months and 15 years. A vaccination campaign was planned in cooperation with Indonesian authorities and UNICEF. Implementation involved training of personnel and setting up vaccination clinics in refugee camps, schools, and neighborhoods in the city of Meulaboh. The vaccination campaign was hampered by a number of problems in particular involving logistics and required constant supervision. A survey to evaluate the results of the campaign in terms of vaccination coverage showed that the objective of vaccinating 70% of children in refugee camps was achieved. The survey provided other child health indicators that will be helpful to local authorities taking over after the departure of the French Armed Forces Health Services.

All-trans retinoic acid and interferon-alpha in the treatment of a patient with resistant metastatic osteosarcoma.

BACKGROUND: A boy age 14 years who was in complete remission from Stage IIB small cell osteosarcoma, which was misdiagnosed as Ewing sarcoma and consequently was treated, developed inoperable lung metastases when he was off therapy. He received second-line treatment for recurrent Ewing sarcoma, including chemotherapy and radiotherapy, and obtained only a temporary response. A compassionate treatment with all-trans retinoic acid (ATRA) and interferon-alpha (IFNalpha) was then undertaken. METHODS: The patient initially was treated according to the national SE91 protocol for nonmetastatic Ewing sarcoma. After a bilateral pulmonary recurrence, he received second-line chemotherapy and irradiation of the largest metastasis, with a temporary partial response. The patient was then treated with a combination of oral ATRA (90 mg/m(2) for 3 days per week) and subcutaneous IFNalpha (3 x 10(6) U/m(2) 5 days per week) for 4 months. The same therapy also was administered for the control of residual disease after surgery for a total duration of 1 year of ATRA/IFN treatment. During the first 3 weeks of therapy, ATRA pharmacokinetics were studied. RESULTS: After progression of the patient's disease, despite the administration of first-line and second-line chemotherapy, combined treatment with ATRA/IFNalpha yielded a partial remission, which allowed surgical resection of the largest metastasis. The same therapy was effective in preventing tumor recurrence after incomplete removal of the remaining metastases. Treatment was well tolerated, and the patient is in stable complete remission 14 months after the end of therapy. The pharmacokinetics results confirmed the indication of an intermittent schedule for oral ATRA therapy. CONCLUSIONS: ATRA/IFNalpha treatment may be considered as an alternative approach in the treatment of patients with metastatic osteosarcoma who have disease that is resistant to conventional chemotherapy and in the treatment of patients with minimal tumor residue.

In vitro and in vivo antitumor effects of retrovirus-mediated herpes simplex thymidine kinase gene-transfer in human medulloblastoma.

Herpes simplex virus thymidine kinase gene (HSVtk) transfer together with treatment with the prodrug ganciclovir (GCV) represents the most commonly used suicide gene approach for the gene therapy of human central nervous system malignancies. Despite encouraging results reported in clinical trials conducted in adults, very little is known about the feasibility of this approach for the treatment of CNS tumors of childhood. We studied the effects of the HSVtk/GCV system on human medulloblastoma cells in vitro and in vivo. The transfer of tk gene to medulloblastoma cells was capable of mediating cell suicide in vitro and in vivo upon treatment with GCV, but the overall effect in vivo appeared to be suboptimal. The relatively low sensitivity of the medulloblastoma cells to viral infection and a limited bystander effect, coupled with a low expression of connexin-43 protein, might partially explain these results. Whether this is a peculiarity of the cell line studied or a general characteristic of medulloblastoma remains to be determined. These findings should be taken into account for the future planning of gene therapy trials for human medulloblastoma.

Expression of type I interferon receptor in solid tumors of childhood.

Interferon alpha (IFN alpha) is used as an antineoplastic agent, both in hematopoietic malignancies and in solid tumors, because of its immunomodulatory action and direct antitumor activity. IFN alpha binds to specific cell-surface receptors that mediate its biologic activity. We studied the expression of IFN alpha receptors in pediatric solid tumors by use of the monoclonal antibody IFNaR3, which specifically recognizes the alpha subunit of the IFN Type I receptor. In three cell lines derived from those tumors, we determined the structure of the receptors by affinity cross-linking and immunoprecipitation techniques, and we determined their ability to mediate an antiproliferative effect. All of the tumor specimens studied by immunocytochemical analysis, including neuroblastomas, primitive neuroectodermal tumors, and rhabdomyosarcomas, stained positive for the IFN alpha receptor antibody, although in some cases immunoreactivity was weak. The three cell lines, derived from a neuroblastoma, a primitive neuroectodermal tumor, and a Ewing's sarcoma, respectively, showed the same pattern of IFN alpha receptor expression, both by affinity crosslinking and immunoprecipitation assays. Treatment with IFN alpha of those cell lines induces growth inhibition in vitro. These results suggest that IFN Type I receptor might be expressed in most solid tumors of childhood and that its structure is identical to the receptor expressed by the majority of hematologic malignancies.

[Control of an epidemic of meningococcal meningitis in Central Africa]. / Contrôle d'une épidémie de méningite à méningocoque en Afrique centrale.

A severe epidemic of group A meningococcal disease occurred in the northwest part of the Central African Republic from January to March 1992. The outbreak affected a large and densely populated area, with a poor road network, located 400 kilometers south of the classical meningitis belt. An initial selective vaccination campaign was carried out by the national health care service. As the epidemic was continuing, the national authorities asked for international assistance. The French participated by sending Bioforce, a medical task force designed by the Ministry of Defense, with the financial support of the Ministry of Cooperation. Neisseria meningitidis strains were isolated and identified within 36 hours by the Bioforce field laboratory. Strains from 24 patients were sent to the Pasteur Institute in Paris (Neisseria Unit) for serotyping, testing of antibiotic susceptibility, and multilocus enzyme electrophoresis. With one exception, all strains had formula A:4:P1.9. By an initial rapid assessment, the limits of the affected area and populations were determined. The weekly incidence rates observed in different areas varied within a range of 3 to 10 cases per 1,000, with fatality rates from 20 to 30 cases per 100. The spread of the epidemic was stopped by a mass vaccination campaign, which targeted the entire population (200,000 immunizations) of the affected area. The case fatality rate could not be reduced below 15%, despite antimicrobial treatments implemented as soon as possible. The optimal treatment was the standard single intramuscular injection of oily chloramphenicol. The predictive values of clinical symptoms were calculated. The efficacy of vaccination was estimated by comparison of the percentage of people immunized and the proportion of those vaccinated people who developed meningitis identified during the 3 weeks following the mass vaccination campaign. The efficacy varied between 93 to 95% according to the place. The typical weekly incidence rate of 1 case per 1,000 is not a relevant threshold to sufficiently and immediately detect a meningitis outbreak and needs to be reconsidered.

[Chemoprophylaxis of Plasmodium falciparum malaria by a combination of 100 mg of chloroquine and 200 mg of proguanil per day in a zone III of chloroquine resistance (Gabon). Study of 431 French soldiers]. / Chimioprophylaxie du paludisme à Plasmodium falciparum par une association de 100 mg de chloroquine et de 200 mg de proguanil par jour dans une zone III de chloroquino-résistance (Gabon). Etude chez 431 militaires français.

Incidence of P. falciparum malaria in french non-immune soldiers serving in Gabon for four months has increased from 21% in 1987 to 37% in 1988. Since 1989, in a first step, the personal protection measures were reinforced. Thereafter, the usual chemoprophylaxis (chloroquine 100 mg daily) was replaced by a daily association of chloroquine 100 mg and proguanil 200 mg. A 85% decrease of malaria incidence was observed in 431 soldiers. The effects of the personal protection strengthening and of the new chemoprophylaxis can be evaluated to be respectively responsible for 50% and 71% decrease. Among the secondary effects, gastric pain was the most frequent, but it was never a cause of chemoprophylaxis stopping. The mouth ulcer frequency was far lower than that elsewhere reported. No significant biological abnormalities could be related to the chloroquine-proguanil association.

[Prevention of thromboembolism in patients operated on for hip prosthesis]. / La prevenzione delle tromboembolie negli operati di artroprotesi d'anca.

The latest research into the prevention of peri- and postoperative thromboembolic disease has found orthopaedic surgery patients to be most at risk. As the genesis of deep venous thrombosis (DVT) is due to haemodynamic, hemorheologic and parietal factors, various prophylactic measures have been considered in the past, measures which have not proved able to provide satisfactory protection in orthopaedics. The results obtained with Defibrotide in a random and controlled clinical study versus calcium heparin involving 211 patients of both sexes candidates to receive total hip arthroplasty and presenting at least one major thromboembolic risk factor are reported. The patients were assigned at random to one of the following treatments: 1) Defibrotide at a dose of 400 mg b.i.d. i.v. in 50 ml phleboclysis in 5 minutes (n = 108); 2) calcium heparin at a dose of 5000 IU t.i.d. subcutaneously (n = 103). The treatment began the day before operation and continued on average up to the eighth day for the Defibrotide group. With the control group it continued until discharge (usually on the 15th day) and at home for about three weeks until the completion of the physiotherapy cycle. In the 108 patients treated with Defibrotide only one case of DVT was reported and in none of these patients were symptoms or signs of pulmonary embolism encountered. In the group treated with calcium heparin 2 cases of clinically and radiologically diagnosed pulmonary embolism and 4 cases of DVT were observed. Although the differences were not statistically significant, the tendency favours Defibrotide. Statistically significant (p less than 0.01) was the difference in postoperative bleeding evaluated with particular attention in patients of advanced age. Further, in the Defibrotide group, scarring was considered excellent in 96% of cases while in the heparin group scarring was excellent in 85% (p less than 0.05). To conclude, the sure clinical effectiveness, tolerance, handiness and lack of interference with clotting functions make Defibrotide a really useful drug for the prevention of thromboembolic episodes in patients undergoing major orthopaedic surgery.