[Alcohol consumption : from epidemiology to prevention]. / La consommation d'alcool : de l'épidémiologie à la prévention.

The epidemiological data about alcohol consumption show that the current preventive measures have their limits. Worryingly, the morbidity and mortality associated remain significant in the world. Two main types of preventive approaches, based on individual affect exist: the negative approach based on fear and threat and the so-called Social Norm Approach (SNA). The last original and more positive approach has been used across the Atlantic for thirty years and shows to be efficient. It aims to reduce an individual's consumption of addictive substance by confronting his own social norm (what he thinks people drink, quantities generally overestimated) to the real norm of consumption by a reference social group. A cross-border project is currently evaluating the feasibility of this approach in the Euregio Meuse-Rhin.

Les données épidémiologiques de la consommation d'alcool les plus récentes montrent que les mesures préventives actuelles connaissent leurs limites. De façon inquiétante, la morbidité et la mortalité qui lui sont associées restent importantes dans le monde. Deux grands types d'approches préventives ciblant directement les affects des individus existent : l'approche négative basée sur la peur et la menace et l'approche dite par la norme sociale (SNA pour Social Norm Approach). Cette dernière approche originale et plus positive de la santé est utilisée depuis une trentaine d'années outre-Atlantique et montre une certaine efficacité. Elle vise à réduire la consommation d'une substance addictive par un individu en confrontant sa norme sociale (ce qu'il pense que les gens boivent, quantités généralement surestimées) à la norme réelle de consommation du groupe social de référence. Un projet transfrontalier évalue actuellement la faisabilité de ce genre d'approche dans l'Eurégio Meuse-Rhin.

One-year prevalence of migraine using a validated extended French version of the ID Migraine™: A Belgian population-based study.

BACKGROUND: Country-specific prevalence data on migraine and comorbidities are vital to assess the public health burden of migraine and the corresponding resources required for proper management. Considering the absence of reliable statistics, this study aimed to estimate the one-year prevalence of migraine in Wallonia (Belgium) in relation to socio-demographic factors and several health indicators. METHODS: Among the 1071 people aged 20-69 years who participated in the NESCaV survey, 751 (70.1%) were screened for one-year migraine attacks using the "ef-ID Migraine", a validated, extended French version of the self-administered ID Migraine™ questionnaire. Socio-demographic and health data were collected with a self-administered questionnaire and a physical examination. RESULTS: The overall one-year prevalence of migraine was 25.8%; 40.8% of migraineurs reported visual symptoms compatible with an aura. The prevalence was higher in women than in men (33.9% vs. 17.9%, P<0.0001) and declined markedly after the age of 50 (P=0.005). Importantly, migraine was associated with the subjective feeling of poorer health (P=0.0004). No other socio-demographic factor or health indicator studied was significantly correlated with migraine. CONCLUSIONS: High prevalence of migraine and strong association with feeling of poor health should incite health authorities to institute more active public health and management policies with regards to the migraine problem.

High dose vitamin E therapy in amyotrophic lateral sclerosis as add-on therapy to riluzole: results of a placebo-controlled double-blind study.

UNLABELLED: Increasing evidence has suggested that oxidative stress may be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). The antioxidant vitamin E (alpha-tocopherol) has been shown to slow down the onset and progression of the paralysis in transgenic mice expressing a mutation in the superoxide dismutase gene found in certain forms of familial ALS. The current study, a double blind, placebo-controlled, randomised, stratified, parallel-group clinical trial, was designed to determine whether vitamin E (5000 mg per day) may be efficacious in slowing down disease progression when added to riluzole. METHODS: 160 patients in 6 German centres with either probable or definite ALS (according to the El Escorial Criteria) and a disease duration of less than 5 years, treated with riluzole, were included in this study and were randomly assigned to receive either alpha-tocopherol (5000 mg per day) or placebo for 18 months. The Primary outcome measure was survival, calculating time to death, tracheostomy or permanent assisted ventilation, according to the WFN-Criteria of clinical trials. Secondary outcome measures were the rate of deterioration of function assessed by the modified Norris limb and bulbar scales, manual muscle testing (BMRC), spasticity scale, ventilatory function and the Sickness Impact Profile (SIP ALS/19). Patients were assessed at entry and every 4 months thereafter during the study period until month 16 and at a final visit at month 18. Vitamin E samples were taken for compliance check and Quality Control of the trial. For Safety, a physical examination was performed at baseline and then every visit until the treatment discontinuation at month 18. Height and weight were recorded at baseline and weight alone at the follow-up visits. A neurological examination as well as vital signs (heart rate and blood pressure), an ECG and VEP's were recorded at each visit. Furthermore, spontaneously reported adverse experiences and serious adverse events were documented and standard laboratory tests including liver function tests performed. For Statistical Analysis, the population to be considered for the primary outcome measure was an "intent-to-treat" (ITT) population which included all randomised patients who had received at least one treatment dose (n = 160 patients). For the secondary outcome measures, a two way analysis of variance was performed on a patient population that included all randomised patients who had at least one assessment after inclusion. RESULTS: Concerning the primary endpoint, no significant difference between placebo and treatment group could be detected either with the stratified Logrank or the Wilcoxon test. The functional assessments showed a marginal trend in favour of vitamin E, without reaching significance. CONCLUSION: Neither the primary nor the secondary outcome measures could determine whether a megadose of vitamin E is efficacious in slowing disease progression in ALS as an add-on therapy to riluzol. Larger or longer studies might be needed. However, administration of this megadose does not seem to have any significant side effects in this patient population.

Murine gammaherpesvirus 68 cyclin D homologue is required for efficient reactivation from latency.

Murine gammaherpesvirus 68 (MHV68) is a gammaherpesvirus that was first isolated from murid rodents. MHV68 establishes a latent infection in the spleen and other lymphoid organs. Several gammaherpesviruses, including herpesvirus saimiri, human herpesvirus 8, and MHV68, encode proteins with extensive homology to the D-type cyclins. To study the function of the cyclin homologue, a recombinant MHV68 has been constructed that lacks the cyclin homologue and expresses beta-galactosidase as a marker (MHV68(cy-)). MHV68(cy-) grows in vitro with kinetics and to titers similar to those of the wild type. BALB/c mice infected with mixtures of equivalent amounts of the wild type and MHV68(cy-) show deficient growth of the MHV68(cy-) in an acute infection. Infection of SCID mice with virus mixtures also showed decreased MHV68(cy-) virus growth, indicating that the deficiency is not mediated by T or B cells. Although mice infected with mixtures containing 100 times as much MHV68(cy-) had greater splenic titers of the mutant virus than wild-type virus in acute infection, at 28 days postinfection splenocytes from these mice reactivated primarily wild-type virus. Quantitative PCR data indicate that equivalent genomes were present in the latent state. Reinsertion of the cyclin homologue into the cyclin-deleted virus restored the wild-type phenotype. These results indicate that the MHV68 cyclin D homologue mediates important functions in the acute infection and is required for efficient reactivation from latency.

The murine Fhit gene is highly similar to its human orthologue and maps to a common fragile site region.

The human FHIT gene is a putative tumor suppressor gene that maps to human chromosome band 3p14.2 in a region that is frequently deleted in cancers. It exhibits both genomic deletions and aberrant transcripts in a variety of tumors and spans the common fragile site FRA3B. This fragile site extends over a broad region of several hundred kb within the FHIT gene and may account for its instability in tumors. As one test of this hypothesis, we isolated the murine Fhit gene and asked whether it also contains a common fragile site and if it is unstable in mouse tumors or tumor cell lines. The Fhit gene was isolated, and the sequence was found to be 87.5% identical to that of the human FHIT gene in the open reading frame. Using fluorescence in situ hybridization, Fhit was assigned to mouse chromosome band 14A2, in a region that was previously shown to contain an aphidicolin-inducible mouse fragile site. Fluorescence in situ hybridization with genomic clones containing Fhit and flanking sequences demonstrated that gaps and breaks in the fragile site occur over a broad region within and proximal to the Fhit locus. Thus, the physical relationship of Fhit to a common fragile site is similar to that observed with the orthologous human FHIT gene and FRA3B.

Intraerythrocytic inclusions associated with iridoviral infection in a fer de lance (Bothrops moojeni) snake.

Intraerythrocytic inclusions associated with infection by an iridovirus were observed in a fer de lance (Bothrops moojeni) snake that was being evaluated for the presence of renal carcinoma. The erythrocytes contained two types of inclusions, one viral and one crystalline, usually concomitantly. The snake was markedly anemic and exhibited a marked regenerative response. Ultrastructural analysis identified the virus to be an iridovirus consistent with snake erythrocyte virus and the crystalline structures to be of a different nature than hemoglobin.

A 350-kb cosmid contig in 3p14.2 that crosses the t(3;8) hereditary renal cell carcinoma translocation breakpoint and 17 aphidicolin-induced FRA3B breakpoints.

The constitutive fragile site at human chromosomal band 3p14.2, FRA3B, has been described as the most active common fragile site in the human genome. FRA3B is cytologically indistinguishable from the chromosome 3 breakpoint observed in the hereditary renal cell carcinoma (hRCC) translocation t(3;8) (p14.2;q24.13). Previous work demonstrated that a 1330-kb YAC clone, YC850A6, spans both the t(3;8) translocation and FRA3B and also encompasses FRA3B-associated breakpoints induced in hamster-human hybrids. This YAC was used to construct a multi-hit cosmid library. Screening of this library resulted in a 350-kb cosmid contig that extends distally from the t(3;8) translocation breakpoint. Seventeen aphidicolin-induced 3p14. 2 breakpoints derived from hamster-human hybrids were mapped within this cosmid contig. These breakpoints were found to localize as two distinct clusters, separated by 200 kb, which lie on either side of a region of frequent breakage within FRA3B as defined by FISH analysis using cosmids from the contigs. The most proximal of the breakpoint clusters lies approximately 100 kb distal to the hRCC t(3;8) breakpoint. The distribution of these breakpoints, together with the region of frequent chromosomal breakage mapped by FISH analysis, further confirms the position of FRA3B and helps to define the extent over which its fragility is exerted. These data indicate that FRA3B comprises several hundred kilobases of DNA sequence within 3p14.2. The 350-kb contig and the cosmid library constructed from YAC YC850A6 will be essential for further characterization of the region surrounding FRA3B and in experiments to determine the molecular basis of the fragility of FRA3B.

FRA3B extends over a broad region and contains a spontaneous HPV16 integration site: direct evidence for the coincidence of viral integration sites and fragile sites.

The common fragile site at 3p14.2 (FRA3B) is the most sensitive site on normal human chromosomes for the formation of gaps and breaks when DNA replication is perturbed by aphidicolin or folate stress. Although rare fragile sites are known to arise through the expansion of CCG repeats, the mechanism responsible for common fragile sites is unknown. Beyond being a basic component of chromosome structure, no biological effects of common fragile sites have been convincingly shown, although suggestions have been made that breakage and recombination at these sites may sometimes be mechanistically involved in deletions observed in many tumors and in constitutional deletions. In an observation related to the high rate of recombination at fragile sites, a number of studies have shown a statistical association between the integration of transforming DNA viruses and chromosomal fragile sites. Using FISH analysis we recently identified a 1.3 Mb YAC spanning both FRA3B and the t(3;8) translocation associated with hereditary RCC. Here we report the further localization of FRA3B within this YAC. Using lambda subclones of the YAC as FISH probes, gaps and breaks were found to occur over a broad region of at least 50 kb. Neither CCG nor CAG repeats were found in this region suggesting a different mechanism for fragility than seen with rare fragile sites. We further show that an area of frequent gaps and breaks within FRA3B, defined by a lambda contig, coincides with a previously characterized site of HPV16 integration in a primary cervical carcinoma. The HPV16 integration event gave rise to a short chromosomal deletion limited to the local FRA3B region within 3p14.2. Interestingly, 3p14.2 lies within the smallest commonly deleted region of 3p in cervical cancers, which are often HPV16 associated. To our knowledge this is the first molecular characterization of an in vivo viral integration event within a confirmed fragile site region, supporting previous cytogenetic observations linking viral integration sites and fragile sites.

Oocistos de Cryptosporidium spp nas fezes de bovinos em Montes Claros, Minas Gerais / Oocysts of Cryptosporidium spp in the feces of bovines, in Montes Claros, MG, Brazil

In January 1990, fecal samples from two dairy and five beef cattle farms located in Montes Claros, MG, Brazil were examined by using the centrifugation-flotation method in saturated sugar solution. Thirteen (27,1 per cent), of 48 two month-old calves were positive for oocysts of Cryptosporidium muris, found in one beef cattle and two dairy farms. Six (6,6 per cent) out of 91 cows were positive for C. parvum oocysts. This species of coccidium was observed in one dairy and two beef cattle farms. All cows were negative for C. muris

Glucagonoma occurring as a large cystic abdominal mass.

We have described a 77-year-old woman with a 14 x 15 cm cystic mass arising from the head of pancreas. The serum glucagon level was elevated, and electron microscopy revealed large numbers of alpha granules within the tumor cells. Glucagonoma syndrome should be considered in the differential diagnosis of a large abdominal mass even if skin rash is minimal.

Histologic and staging classification of breast cancer: implications for therapy.

Breast cancer has 20 different histologic descriptions grouped into four categories, A, B, C, and D, based on prognosis. An analysis of 3,902 patients has revealed significant differences in outcome. Class A disease--for the most part in situ--was relatively benign, with a frequency distribution of 5%. Positive nodes were found in 1.6%, and five-year survival curves exceeded 91%. Class B (mucinous, medullary, etc) occurred in 4.1% of patients. Fewer advanced stages indicated less aggressive tumors, and survival at five years was 75%. The most common class, C (85%), had a five-year survival of 66%, closely related to stage. Class D tumors, 4.3% with ill defined, wildly infiltrative borders, and undifferentiation, were ominous with 33% demonstrating distant spread at first diagnosis. The five-year survival was only 46%. Epidemiologic findings revealed a high incidence of bilaterality and high family risk in some categories, but not in others. Mammography should be done in all class A lesions. A complete pretreatment metastatic survey is recommended for class D patients, as well as those with advanced stage II and III lesions. Indications for various surgical and adjuvant therapies are described.

Multidisciplinary approach to breast cancer control.

A multidisciplinary approach to breast cancer control was developed through a network of 22 hospitals, and data were collected over two time periods to evaluate the impact of the network. A total of 1,800 cases of female breast cancer treated during the baseline period of 1971 to 1973 were compared with 2,102 current cases treated during the 1975 to 1977 study period. These cases were compared with regard to detection, diagnosis, and primary therapy. Several improvements in the diagnosis and treatment of patients studied in the later period indicate the program has had a positive impact. Improvements include an increase in case accrual by an average of 100 cases per year; an increase in detection of early (in situ and localized) and advanced disease; an increase in the proportion of patients whose interval from first symptoms to diagnosis was less than one month; a threefold increase in the proportion of patients diagnosed before admission; the increased use of simple or modified radical mastectomy (from 11% to 25%); a reduction in the number of patients whose mastectomy was done by a physician who did five or fewer mastectomies per year; an increase in the number of patients receiving bone, liver, or spleen scans; and an improvement in the quantity and quality of information in hospital charts, such as family history of cancer, history of benign breast disease, and menstrual history. Data are also provided on primary therapy and method of detection according to stage and tumor size.

Morphologic types of breast cancer: age, bilaterality, and family history.

Morphologic type is not generally included in the study of cancer risk factors. In breast cancer, attention is being given to age at diagnosis. In this study cases were analyzed by morphologic type as well as age at diagnosis for occurrence of bilateral disease and for family history of breast cancer. Of the morphologic types which were more frequent in younger patients--lobular in situ, medullary, and intraductal comedo--only lobular in situ had an increased frequency of bilaterality (fourfold increase). Of these, only patients with intraductal comedo reported familial breast cancer more frequently than the average. Lobular infiltrating carcinoma is diagnosed more frequently in elderly patients and is associated with 2.6 times more bilaterality and increased familial risk. Diagnosis at age 45 to 54 is also associated with increased bilaterality, but the diagnosis of lobular carcinoma has much stronger association with bilaterality than early age at diagnosis. Because of the high risk of bilaterality in lobular neoplasia and in those with a family history of cancer occurring before the menopause, bilateral biopsies and subsequent screening for malignancy should be done in these women.

Antitumor antibodies in human breast cancer sera as detected by fixed cell immunofluorescence and living cell membrane immunofluorescence assays.

The reactions of patients' sera with cultured human breast cancer cells were studied by fixed cell immunofluorescence (FCF) and living cell membrane immunofluorescence (MF) tests. The results suggested that the FCF reaction detected antibodies that were cell or organ specific, whereas the MF test was more indicative of an antineoplastic immune response.

Adrenalectomy and oophorectomy plus limited-term chemotherapy in the treatment of breast cancer.

A prospective study employing adrenalectomy and oophorectomy followed by limited-term combination chemotherapy was used in the treatment of 39 patients with advanced breast cancer. Chemotherapy was abruptly stopped at 8 weeks in order to take advantage of rebound immunocompetence. Delayed hypersensitivity was tested by dinitrochlorobenzene skin tests and responses to phytohemagglutinin. There were 22 CRs among 33 patients who entered remission. Eleven patients had a PR with greater than 50% reduction of tumor. Thirteen of 20 patients with visceral disease had a CR. There was a close association between response and competence of the cell-mediated immune system. The median duration of unmaintained remission in those patients with a CR was greater than 16 months. Four of the six failures had had recent radiation therapy to the chest wall which may have influenced immunocompetence. Responses to chemotherapy appear to be additive to endocrine ablation. Rebound of immunocompetence after chemotherapeutic immunosuppression may be related to remission induction and maintenance.