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.

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.

Efficacy and tolerability of a new formulation of oral tiludronate (tablet) in the treatment of Paget's disease of bone.

We sought to assess efficacy and safety of a new oral formulation (tablet) of tiludronate in Paget's disease of bone. We studied 128 patients with Paget's disease in an open-label uncontrolled trial. Patients received a daily dose of 400 mg oral tiludronate (two tablets). Treatment was for 6 months. Serum alkaline phosphatase activity (SAP) and fasting urinary excretion of hydroxyproline/creatine (OH/Cr) were measured every 3 months, as were biochemical parameters reflecting renal, hepatic, and hematologic functions. Analgesic efficacy was self-evaluated from a visual analog scale (VAS). Statistical analysis revealed a significant reduction from baseline in SAP and OH/Cr levels, as well as VAS scores. In the whole population with evaluation under treatment, there was a reduction in initial SAP activity after 3 months (47.2 +/- 2.2%, mean +/- SEM) and 6 months (58.3 +/- 2.3%). In the population with SAP levels above twice the upper limit at inclusion and with evaluation at month 3 and month 6 (n = 96), the reduction in SAP levels was 49.3 +/- 2.4% after 3 months and of 59.5 +/- 2.6% after 6 months (ANOVA time effect, p = 0.0001). Aside from mild gastrointestinal disturbances, as experienced with other oral bisphosphonates, clinical tolerance was good. Exhaustive biochemical investigation failed to reveal significant toxicity of tiludronate tablets at the dose of 400 mg/day. The dose of 400 mg daily of this new formulation appears to be a satisfactory tiludronate regimen for the treatment of Paget's disease of bone.

Do Selye's mammalian "GAS" concept and "co-stress" response exist in plants?

Converging data indicate the possible existence of a general adaptation syndrome (GAS) in which different types of stress evoke identical coping mechanisms. In Selyean terms, this implies a "co-stress" response whereby one type of stress resistance may impart co-resistance to others. Common coping denominators may be physiological or morphological. The former include oxy-free radical scavenging, osmoregulation, ABA, jasmonates, chaperones, HSPs, and phytochelatins. Morphological GAS adaptations include leaf pubescence, movements and stance, and rooting characteristics. The feasibility, with certain reservations, of the GAS hypothesis is discussed here.

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.

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.

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.

Influence of biological variables upon pharmacokinetic parameters of intramuscular methotrexate in rheumatoid arthritis.

The pharmacokinetics of methotrexate were studied in 22 patients receiving 5-15 mg per week in a single i.m. administration for rheumatoid arthritis. The data consisted of 3 plasma levels per patient, taken at 2, 6, and 12 hours after the administration. The concentration of methotrexate was determined by fluorescence polarization immunoassay. The pharmacokinetic parameters of a 2-compartment model were determined by Bayesian estimation using the population values of Bressolle et al. [1996]. The fitted parameters were: total plasma clearance of methotrexate (CL), first-order absorption constant (ka), volume of central compartment (V1), and transfer constants between the 2 compartments (k12 and k21). Additional parameters were derived from the fitted ones: maximal concentration (Cmax), time to maximum (tmax), volume of distribution at steady-state (Vss), and terminal half-life (t1/2). Twenty-one biological covariates were considered to explain the interpatient variability. The relationships between these covariates and the pharmacokinetic parameters were investigated by principal component analysis and multiple regression analysis. About 90% of the variability of CL were explained by 4 variables (sex, age, height and serum creatinine). About 50%-70% of the variability of the other pharmacokinetic parameters were explained by a set of covariates including age, height, creatinine, creatinine clearance, and dose. The effect of dose was noticed mainly on k12, Vss, and t1/2, thus suggesting that the transfer of the drug from plasma to tissues may be nonlinear. The possibility of predicting CL with a good precision would facilitate the computation of dosage regimens in these patients.

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.

Intradiscal injection of triamcinolone hexacetonide for acute, subacute, and chronic sciatica. Results at 3 months an open-prospectus study of 30 cases and review of the literature.

The authors report an open study of 30 cases of intradiscal injection of triamcinolone hexacetonide in the treatment of sciatica. The patients were monitored at months 1 and 3. The results were judged to be good in 36.6% of the cases, moderate in 36.6% and poor in 26.7% of the cases. Two adverse effects were reported: 1 case of reversible urinary retention and 1 case of deficiency of the dorsiflexor muscles of the foot. The good results reported in previous series were only found in this study when the indications were restricted to certain favourable prognostic factors: duration of sciatica less than 6 months and CAT-scan appearance of discal hernia. This technique has the advantage of being simple, economical and nonallergic. On the basis of the encouraging results of the initial series, this technique should be considered as an interesting therapeutic alternative in sciatica. Larger series and double-blind studies, however, are necessary to confirm the initial results.

Adolescent osteoporosis disclosing familial osteopenia.

The observations of familial juvenile osteoporosis, presumably of genetic origin are exceptional. The authors report the observation of a 16-year old adolescent suffering from osteoporosis, confirmed by histomorphometry and decrease in bone density (lumbar vertebrae 0.79 g/cm2 and femoral neck 0.88 g/cm2: LUNAR DPX). We prescribed fluorine and calcium therapy. Lumbar bone density increases by 11% and bone density of the thighbone neck by 7.6%. We cannot rule out growth as a factor in the changes observed, given that the propositus is only 16. A densitometric investigation performed in 4 of his 12 brothers shows a decrease in the lumbar bone mineral content (from 61 to 94% expressed as Z score). A genotypic origin seems to be conceivable, especially since no other cause could be considered (endocrinal, alimentary...). On the other hand, there is no argument in favour of osteogenesis imperfecta disease. The bone densitometry is a useful diagnostic means to detect familial forms of osteoporosis.

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.

[Vitamin B in rheumatic diseases: critical review]. / Vitamines B dans les maladies rheumatologiques: revue critique.

Vitamin B1, B6 and B12 are frequently prescribed in rheumatic diseases as analgesic drugs. If some fundamental data suggest their analgesic potential, especially in animal models, there are very few clinical trials in human demonstrating their efficacy in rheumatology. Looking at these data from the literature, we should reconsider our prescription of vitamin B.

[Do some drugs have adverse effects on cartilage?]. / Existe-t-il des effets indésirables des médicaments sur le cartilage?

The potential chondrotoxicity of drugs is very difficult to appreciate because of the difficulties involved in evaluating the evolution of cartilage in human beings. This article attempts to summarize the data from the literature concerning the hypothetical chondrotoxicity of non steroidal anti-inflammatory drugs, fluoroquinolones, intra-articular injections of corticosteroids, and other drugs.

[Methotrexate and non-steroidal anti-inflammatory agent combination in rheumatoid arthritis]. / Association méthotrexate et anti-inflammatoire non stéroïdien au cours de la polyarthrite rhumatoïde.

It is well known that methotrexate (MTX), used at high dosage in cancer patients, must not be combined with a non-steroidal anti-inflammatory drug (NSAID) because of high risk of side effects; prescribed at low dosage (< or = 15 mg per week) in rheumatoid arthritis patients, MTX is often combined with an NSAID. Some cases reported in the literature underline the potential toxicity of the association of low dose MTX with an NSAID, but most of the pharmacological studies do not confirm this hypothesis. Except for salicylates, NSAIDs do not affect the absorption, distribution, protein binding, area under the curve, half-life, or the elimination of MTX. Therefore, if necessary, MTX (< or = 15 mg per week) can be combined with an NSAID during the treatment of rheumatoid arthritis.

[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.

[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.