Comparative genome analysis with the human genome reveals chicken genes associated with fatness and body weight.

The selection of meat-type chickens (broilers) for rapid growth has been accompanied by excessive fat deposition. In this study, we analysed 53 candidate genes that are associated with obesity and obesity-related traits in humans, for which we found chicken orthologues by BLAST searches. We have identified single nucleotide polymorphisms (SNPs) with significant differences in allele frequencies between broilers and layers in each of the following six candidate genes: adrenergic, beta-2-, receptor, surface (ADRB2); melanocortin 5 receptor (MC5R); leptin receptor (LEPR), McKusick-Kaufman syndrome (MKKS), milk fat globule-EGF factor 8 protein (MFGE8) and adenylate kinase 1 (AK1). To examine associations with fatness and/or body weight, we used birds of extreme phenotypes in F(2) and backcross populations with varying levels of abdominal fat weight per cent (%AFW) and body weight. We then assessed the level of gene expression by real-time PCR. In two genes, ADRB2 and MFGE8, we found significant association with %AFW. The ADRB2 gene was found to have a significantly higher expression in the liver of lean chickens compared with those of the fat individuals. We believe that this approach can be applied for the identification of other quantitative genes.

[Fertility preservation in cancer women: a multidisciplinary approach]. / Préservation de la fertilité féminine en cas de cancer : intérêt d'une prise en charge pluridisciplinaire.

Over the past two decades, major advances in diagnostic modalities and treatment have markedly improved rates of cure for adult cancers. As a consequence, the number of long-term survivors is increasing, and fertility preservation has become a major issue for young patient about to start treatment for cancer. Whether fertility preservation is a promising option, most of the technologies currently used are far from being well established or are even still experimental. Patients should be aware that no method guarantees success. Psychological and ethical impacts of fertility preservation are major concerns and should be included in the multidisciplinary approach of the patients.

[In vitro maturation of oocytes: an option for fertility preservation in women]. / Préservation de la fertilité féminine: place de la maturation ovocytaire in vitro.

Although female cancer incidence may be on rise, antineoplastic regimens have become more successful. As a result, an increasing number of women with cancer survive to endure the long-term consequences of chemotherapy. One of the most important long-term consequences of cancers treatments in young female is premature ovarian failure and infertility. Because of the increasing survival rates, many of these young women are seeking methods to preserve their fertility. Currently, embryo/oocytes cryoporeservation obtained after ovarian stimulation appears to provide the best fertility preservation option. However, patients may not have sufficient time to undergo ovarian stimulation prior to chemotherapy and/or the hormones used in ovarian stimulation are contra-indicated for estrogen-dependant tumors. In vitro maturation of oocytes (IVM) has been suggested to avoid ovarian stimulation and time requirement in patients with cancer, and can be combined with ovarian tissue cryobanking. In this review, we will discuss the position of IVM in the strategy of fertility preservation in young women.

Anti-tumour necrosis factor treatment in patients with refractory systemic vasculitis associated with rheumatoid arthritis.

OBJECTIVE: To assess anti-tumour necrosis factor (anti-TNF) agents in patients with refractory systemic rheumatoid vasculitis (SRV). METHODS: 1200 rheumatologists and internists were asked to provide medical files for patients with anti-TNF agents given as a second-line treatment for active SRV refractory to cyclophosphamide and glucocorticoids. RESULTS: We identified nine cases in which anti-TNF drugs were given for active SRV, despite previous treatment with a mean cumulative dose of 8.4 g of cyclophosphamide in association with high-dose glucocorticoids. The mean prednisone dose before anti-TNF therapy was 29.6 mg/day. After 6 months, six patients were in remission (complete in five, partial in one). The treatment failed in one patient and two patients stopped taking the anti-TNF treatment due to side-effects. Mean prednisone dose was reduced to 11.2 mg/day. Severe infection occurred in three patients. Relapses were observed in two patients. Remission was re-established by reintroducing anti-TNF therapy in one case and increasing the dose in the other. CONCLUSIONS: This study provides evidence of efficacy of anti-TNF therapy in adjunct to glucocorticoids for treating active refractory SRV. Remission was achieved in two-thirds of patients, with a significant decrease in prednisone dose, although there was a high rate of infection in these severely ill patients.

Biodiversity of 20 chicken breeds assessed by SNPs located in gene regions.

Twenty-five single nucleotide polymorphisms (SNPs) were analyzed in 20 distinct chicken breeds. The SNPs, each located in a different gene and mostly on different chromosomes, were chosen to examine the use of SNPs in or close to genes (g-SNPs), for biodiversity studies. Phylogenetic trees were constructed from these data. When bootstrap values were used as a criterion for the tree repeatability, doubling the number of SNPs from 12 to 25 improved tree repeatability more than doubling the number of individuals per population, from five to ten. Clustering results of these 20 populations, based on the software STRUCTURE, are in agreement with those previously obtained from the analysis of microsatellites. When the number of clusters was similar to the number of populations, affiliation of birds to their original populations was correct (>95%) only when at least the 22 most polymorphic SNP loci (out of 25) were included. When ten populations were clustered into five groups based on STRUCTURE, we used membership coefficient (Q) of the major cluster at each population as an indicator for clustering success level. This value was used to compare between three marker types; microsatellites, SNPs in or close to genes (g-SNPs) and SNPs in random fragments (r-SNPs). In this comparison, the same individuals were used (five to ten birds per population) and the same number of loci (14) used for each of the marker types. The average membership coefficients (Q) of the major cluster for microsatellites, g-SNPs and r-SNPs were 0.85, 0.7, and 0.64, respectively. Analysis based on microsatellites resulted in significantly higher clustering success due to their multi-allelic nature. Nevertheless, SNPs have obvious advantages, and are an efficient and cost-effective genetic tool, providing broader genome coverage and reliable estimates of genetic relatedness.

Characterization and Inheritance of a New Source of Resistance to Fusarium oxysporum f. sp. melonis Race 1.2 in Cucumis melo.

Four physiological races (0, 1, 2, and 1.2) of Fusarium oxysporum f. sp. melonis, causal agent of Fusarium wilt in melons, have been described. Whereas resistance against each of the races 0, 1, and 2 is encoded by a single dominant R-gene, resistance against the fourth race, FOM 1.2, is polygenically inherited and was recently characterized in the cultivar Isabelle. In the present study, we report on an independently derived source of resistance to race 1.2, the Israeli breeding line BIZ. The disease response of BIZ seedlings was compared with two susceptible genotypes, Line 33 and PI 414723, and the partially resistant genotype, Isabelle, at increasing concentrations of inoculum. BIZ exhibited near-complete resistance to race 1.2, even at inoculum levels of 106 spores per ml and root wounding, indicating that such resistance is stronger than that in Isabelle. Although in previous studies the F1 hybrids between BIZ and the sensitive lines displayed full resistance in the field, in the present study they were susceptible under artificial inoculation conditions that involve high inoculum concentrations of 106 spores per ml and root wounding; under intermediate inoculum levels (105 and 5 × 105 spores per ml) they were partially resistant. Segregation of the resistance response in the F2 and back-cross-1 progeny from a cross between BIZ and PI 414723 supported a model in which two complementary, recessive genes are required to obtain full resistance. While the fungus was shown to colonize root tissue of both resistant and susceptible lines, colonization was markedly lower in the resistant plants, and the fungus was nearly absent from upper stem segments.

[Dupuytren's disease]. / La malattia di Dupuytren.

Dupuytren's disease is a contracture of the hand derived from the retractile fibrosis of the palmar aponeurosis, that leads to a progressive deformity in flexion of fingers. It has been named from the French surgeon Guillaume Dupuytren (1777-1835), that described it in 1831. In this note it is sketched a short biography of Dupuytren and the main clinical features of the disease are described, underlining some particular aspects of therapy.

Management of osteoarthritis (OA) with an unsupervised home based exercise programme and/or patient administered assessment tools. A cluster randomised controlled trial with a 2x2 factorial design.

BACKGROUND: Diary recording of pain and disabling activities in osteoarthritis (OA) is widely recommended, but, to our knowledge, its impact on symptoms has not been investigated. Exercise programmes have been shown to be effective when patients are closely supervised by nurses or physiotherapists; however, data are lacking on the efficacy of an unsupervised home based exercise regimen in patients with OA. OBJECTIVES: To evaluate the clinical efficacy of patient administered assessment tools and an unsupervised home based exercise programme alone or in combination in patients with OA. METHODS: The study was a 24 week, open cluster randomised controlled trial with a factorial design. Rheumatologists (n = 867) were assigned to four groups according to the treatment given: standardised tools (ST; n = 220), exercises (EX; n = 213), both tools and exercises (ST+EX; n = 213), or usual care (n = 221). Each rheumatologist was to enroll four patients who met the American College of Rheumatology criteria for OA (three with knee OA, one with hip OA). "Tools" consisted of weekly recording of pain and disabling activities in a diary. A home based exercise programme was performed daily at least four times per week with the aid of videotape and booklet. In addition to exercise and assessment, all patients received 12.5 mg or 25 mg of the non-steroidal anti-inflammatory drug rofecoxib once daily. Outcome variables were: pain (measured on a visual analogue scale, 0-100); Western Ontario and McMaster Universities Osteoarthritis Index, function subscale (0-100); and patient assessment of the quality of care (0-100). RESULTS: Overall, 2957 patients with OA (2216 knee, 741 hip) were included. After 24 weeks, both pain and function improved in the ST, EX, ST+EX, and usual care groups (mean (SD) -17 (27), -20 (29), -15 (27), -19 (29); and -11 (19), -12 (19), -10 (19), -11 (20), respectively), without significant differences between groups. However, patients in the EX and ST+EX groups were more likely to agree that their rheumatologist had done his best to preserve their functional and physical activities. CONCLUSION: Although patients' assessments favoured the exercise programme, results from this study failed to demonstrate a short term symptomatic effect of the two non-pharmacological treatments (weekly recording of condition and exercise) in patients with OA concurrently receiving nonsteroidal anti-inflammatory drugs.

[Obligatory information of patients with rheumatic illness (300 cases)]. / Contribution au devoir d'information au patient en rhumatologie à propos de 300 cas.

Since 1997, legal judgments in France have revolutionized the concept of patient information. Medical information must now be clear and include all serious risks of investigations and therapies. We evaluated patients' opinions after their medical examination and scrutiny of information cards prepared by the French Society of Rheumatology. A questionnaire was used to assess the effectiveness and comprehension of the cards, and their potential to induce anxiety. Written informed consent was provided by the majority of patients. The medical information was well received, especially in oral form, and was considered comprehensible but relatively stressful. Anxiety was significantly higher among female patients and patients who had never had medical examinations or procedures.

Intra-articular injections of hylan G-F 20 in patients with symptomatic hip osteoarthritis: an open-label, multicentre, pilot study.

OBJECTIVE: To obtain prospective data on feasibility and safety of intra-articular injections of hylan G-F20 in patients with symptomatic hip osteoarthritis (OA). METHODS: Fifty-seven patients with primary hip OA, Kellgren-Lawrence grade II-III, aged > or = 40 and walking pain 50-90 mm on a visual analogue scale (VAS) were enrolled in an open-label, multicentre pilot trial. Hylan G-F20 (2 ml) was injected intra-articularly (IA) in the hip under fluoroscopy at D0, and follow-up visits were performed at D7-30-60-90. The possibility of a second injection at D30-60 or 90 was considered if the reported pain level was equivalent to baseline. Adverse events, walking pain (VAS), WOMAC index, patient and physician's global assessment were recorded at each visit. RESULTS: Twenty-five patients 1 injection and 32 received 2 injections. Transient hip pain was reported following 10.1% of injections, but no patient withdrew from the study because of this. Two mild synovial fluid aseptic effusions occurred after the first injection. No systemic device-related adverse event was reported. Walking pain decreased from 69.3 mm at entry to 39.5 mm at the end point (p < 0.0001). All other outcome measures decreased significantly. CONCLUSION: Viscosupplementation with hylan G-F20 is feasible, easy to perform and well-tolerated in hip OA. A double-blind, controlled study should be performed to confirm data on its efficacy.

Opioid rotation in the treatment of joint pain. A review of 67 cases.

OBJECTIVE: To determine that opioid rotation can be useful for establishing a more advantageous analgesia/toxicity relationship in rheumatologic pain. METHODS: Among patients treated with opioids for rheumatologic non-malignant pain, 67 patients with opioid rotation were enrolled retrospectively. In all cases, the other analgesics had failed. The opioids used were: oral morphine, oral hydromorphone, oral buprenorphine and transdermal fentanyl. The reasons for rotation were noted and the improvement of pain was assessed by comparing baseline and post-treatment visual analog scales (VAS in mm). RESULTS: The 67 patients suffered from low back pain with sciatica in 27 cases, inflammatory arthritis in 14 cases, brachial neuralgia in six cases, osteoarthritis in eight cases and miscellaneous in 12 cases. The opioid rotations were the substitution of morphine by transdermal fentanyl, by oral hydromorphone in most of the cases. The principal reason for opioid rotation was failure of the first treatment. The mean of VAS improvement was 30 mm (P < 0.001). CONCLUSION: In rheumatologic non-malignant pain, the opioid rotation might allow the physician to bypass side effects or failure to alleviate pain in most cases.

[Preventive therapy for nausea and vomiting in patients on opioid therapy for non-malignant pain in rheumatology]. / Intérêt de la prévention des nausées et vomissements chez des patients traités par morphine pour des douleurs bénignes d'origine rhumatologique.

OBJECTIVE: To determine if systematic use of metoclopramide associated with opioids (Morphine sulfate SR) decreases the incidence of nausea and vomiting (N&V), established adverse effects of opioids. METHOD: Open randomised study with 132 patients treated for non malignant pain (71 women, 61 men, mean age 53.4 years). One group (n = 76) was treated with morphine alone; the other (n = 56) with morphine plus metoclopramide. Mean duration of therapy: 6 days; mean dosage: 60 mg/d RESULTS: In the 2 groups, N&V were present in the first 72 hours. The frequency of N&V in the morphine group was 38.1% (conform with the literature). The systematic use of metoclopramide decreases the frequency of N&V: p < 0.005. However the use of morphine > 60 mg/d decreases N&V: p = 0.036. High dosages of morphine can have an antiemetic effect by interaction with the mu receptors in the antiemetic center and not in the trigger zone which has an emetic effect. CONCLUSION: The systematic use of metoclopramide with opioid therapy for non malignant pain in rheumatology decreases the risk of nausea and vomiting.

Resistance gene homologues in melon are linked to genetic loci conferring disease and pest resistance.

Genomic and cDNA fragments with homology to known disease resistance genes (RGH fragments) were cloned from Cucumis melo using degenerate-primer PCR. Fifteen homologues of the NBS-LRR gene family have been isolated. The NBS-LRR homologues show high divergence and, based on the partial NBS-fragment sequences, appear to include members of the two major subfamilies that have been described in dicot plants, one that possesses a TIR-protein element and one that lacks such a domain. Genomic organization of these sequences was explored by DNA gel-blot analysis, and conservation among other Cucurbitaceae was assessed. Two mapping populations that segregate for several disease and pest resistance loci were used to map the RGH probes onto the melon genetic map. Several NBS-LRR related sequences mapped to the vicinity of genetic loci that control resistance to papaya ringspot virus, Fusarium oxysporum race 1, F. oxysporum race 2 and to the insect pest Aphis gossypii. The utility of such markers for breeding resistant melon cultivars and for cloning the respective R-genes is discussed.

Piroxicam concentrations in plasma and synovial fluid after a single dose of piroxicam-beta-cyclodextrin.

AIMS: The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in rheumatic diseases depends on their concentrations within the joint. We determined piroxicam concentrations in plasma and synovial fluid (SF) after a single oral dose of 20 mg in the form of one tablet of piroxicam-beta-cyclodextrin. METHODS: 45 patients, aged 21 to 84 years, presenting with an effusion of the knee, related to degenerative or inflammatory joint disease, were included in this study after having given their written consent. One blood and one SF sample were drawn concomitantly in each patient from 0.5 to 48 h after NSAID administration. Piroxicam assays were performed by high performance liquid chromatography. Pharmacokinetic parameters were obtained from the mean plasma and synovial concentrations measured at various sampling times. RESULTS: The peak concentration was higher in plasma (2.51+/-0.25 microg/ml) than in SF (1.31+/-0.76 microg/ml), but the elimination half-life was much longer in SF (90.7 h) than in plasma (32.5 h). The SF/plasma area under the concentration-time curve ratio (evaluating the quantity of NSAID transferred from the blood to the joint) was equal to 0.39. CONCLUSIONS: Piroxicam contained in piroxicam-beta-cyclodextrin diffused well into the SF where its pharmacokinetic profile corresponded to that of a long half-life NSAID.

[Did Georges Bizet die of a acute articular rheumatism?]. / Georges Bizet est-il mort d'un rhumatisme articulaire aigu?

As perhaps in the case of Mozart (1) or Malher (2), Georges Bizet may have died of an acute articular rheumatism or of its consequences.

Drug-induced rheumatic disorders: incidence, prevention and management.

The purpose of this article is to review the causes, the clinical manifestations and the management of the more frequent drug-induced rheumatic disorders. These include: (i) articular and periarticular manifestations induced by fluoroquinolones, nonsteroidal anti-inflammatory drugs, injections of corticosteroids, and retinoids; (ii) multisystemic manifestations such as drug-induced lupus and arthritis induced by vaccination, Bacillus Calmette-Guerin therapy and cytokines; (iii) drug-induced disorders of bone metabolism (corticosteroid-induced osteoporosis, drug-induced osteomalacia and osteonecrosis); and (iv) iatrogenic complex regional pain syndromes. Disorders caused by nonpharmacological and rarely used treatments have been deliberately excluded. Knowledge of these drug-induced clinical symptoms or syndromes allows an earlier diagnosis and treatment, and earlier drug withdrawal if necessary. With the introduction of new medications such as the recombinant cytokines and antiretroviral treatments, the number of drug-induced rheumatic disorders is likely to increase.

[Aspirin, pain and inflammation]. / Aspirine, douleurs et inflammation.

SUBJECT: Acetylsalicylic acid (ASA) is among the most commonly analgesic, antipyretic and anti-inflammatory used drugs. The anti-inflammatory effects of ASA are mediated by the inhibition of cyclooxygenase enzymes with the subsequent decrease of prostaglandin synthesis. NEW DATA: However, since this discovery of Vane in 1971, much of other mechanisms of anti-inflammatory action, without relation with cyclooxygenases, have been proposed. ASA has peripheric analgesic properties by reducing prostaglandin biosynthesis. But there is evidence that the analgesic effects could be mediated by central mechanisms with changes in the monoaminergic and opioid systems. ASA is essentially used in moderate pains with an inflammatory component (rheumatological disorders, headaches, dental and postoperative pains). PERSPECTIVES: The clinical use of ASA at anti-inflammatory dose is less frequent because the other non steroidal anti-inflammatory drugs are as effective as ASA, but they are associated with less side effects. Nevertheless, the synergism of ASA and morphine association and the possible involvement of the central serotonergic and opiatergic systems in the antinociceptive activity of ASA could confer a greater role of ASA in pain management.