Uveitis occurrence in early inflammatory back pain. Five years data from the prospective French nationwide DESIR cohort

ObjectiveUveitis is a frequent extra rheumatological manifestation in axial Spondyloarthritis (SpA). The aim of study was to evaluate the prevalence and incidence of uveitis over the first five years of a prospective nationwide cohort of patients with high suspicion of early axial SpA, and to evaluate its associated factors.MethodsDESIR is a prospective observational cohort of patients with recent onset inflammatory back pain (more than 3 months, less than 3 years), suggestive of axial SpA, All available factors in the database were compared between patients with and without uveitis at 5 years, by uni and then multivariate analysis. Baseline factors associated with new cases of uveitis occurrence over the 5 years were also analyzed. Significance: P less than 0.05.ResultsAfter 5 years, 91 patients (out of 480 with complete follow-up) had at least one uveitis episode, giving an estimated prevalence of 18.9% [95% CI: 15.4–22.4]. In multivariate analysis, uveitis was significantly associated with dactylitis, and elevated ESR. New incident uveitis occurred in 31 cases over 5 years, giving an estimated incidence rate of 1.29 [0.84–1.74]/100 patient-years. Incidence of new uveitis was associated in multivariate analysis with baseline factors: diagnosis of SpA, sacro iliac MRI inflammatory SPARCC score, dactylitis, syndesmophyte score. No significant association was found with HLA-B27, DMARDs, BASDAI, ASDAS, BASFI.ConclusionFive-years data of the DESIR cohort allowed an estimation of incidence rate of uveitis of 1.3/100p-y; over five years, uveitis was associated with dactylitis, biologic and sacro iliac MRI inflammation.     

Feasibility of health-related quality of life (HRQoL) assessment for cancer patients using electronic patient-reported outcome (ePRO) in daily clinical practice

Quality of Life Research - Routine Electronic Monitoring of Health-Related Quality of Life (HRQoL) (REMOQOL) in clinical care with real-time feedback to physicians could help to enhance...     

Cyclosporin A drug interactions. Screening for inducers and inhibitors of cytochrome P-450 (cyclosporin A oxidase) in primary cultures of human hepatocytes and in liver microsomes

In previous papers we demonstrated that cyclosporin A (CsA) was specifically oxidized in rabbit and human liver by cytochrome P-450IIIA. We therefore anticipated that any drug that is an inducer or an inhibitor of this cytochrome should lead to interaction with CsA when given in association with it. In order to confirm this hypothesis, primary cultures of human hepatocytes and human liver microsomes were used to "reproduce" in vitro clinically significant interactions observed between CsA and drugs known either as specific inducers (i.e., rifampicin) or as specific inhibitors (i.e., erythromycin) of P-450IIIA. Our results were in close agreement with the clinical reports. Human hepatocytes maintained in primary cultures for 72 hr in the presence of 50 microM rifampicin exhibited increased levels of P-450IIIA, determined by Western blot using specific antibodies, and concomitant increase in CsA oxidase activity, determined by HPLC analysis of extra and intracellular media. Conversely, these cultures exhibited erythromycin concentration-dependent decreases in CsA oxidase activity when incubated in the presence of 5, 20, and 100 microM erythromycin. In addition, a Lineweaver-Burk analysis of the erythromycin-mediated inhibition of CsA oxidase activity in human liver microsomes revealed competitive inhibition (with Ki of 75 microM) as expected, this macrolide being a specific substrate of P-450IIIA. Using this experimental approach, 59 molecules representative of 17 different therapeutic classes were screened for inducers and inhibitors of CsA oxidase activity. Our results allowed us to elucidate the molecular mechanism of previously observed, but unexplained, drug interactions involving CsA, and to detect drugs that should interfere with CsA metabolism as inducers or inhibitors. Drugs detected as potential inducers of CsA oxidase included: rifampicin, sulfadimidine, phenobarbital, phenytoin, phenylbutazone, dexamethasone, sulfinpyrazone, and carbamazepine. Drugs detected as potential competitive inhibitors included: triacetyloleandomycin, erythromycin, josamycin, midecamycin, ketoconazole, miconazole, midazolam, nifedipin, diltiazem, verapamil, nicardipine, ergotamine, dihydroergotamine, glibenclamide, bromocriptine, ethynylestradiol, progesterone, cortisol, prednisone, prednisolone, and methylprednisolone. Finally, cefoperazone, cefotaxime, ceftazidime, isoniazide, doxycycline, spiramycin, sulfamethoxazole, norfloxacin, pefloxacin, vancocin, trimethoprim, amphotericin B, valproic acid, quinidine, cimetidine, ranitidine, omeprazole, diclofenac, aspirin, paracetamol, debrisoquine, guanoxan, captopril, furosemide, acetazolamide, sparteine, gliclazide, and imipramine were found not to interfere with the hepatic metabolism of CsA.     

Species of Anopheles (Culicidae, Anophelinae) in a malaria-endemic area, Maranhão, Brazil

INTRODUCTION: The study of the seasonal fluctuation, nocturnal activity, relative abundance and the richness of Anopheles species in anthropic environment is essential to the understanding of the their bioecology and to the surveillance program of malaria control. METHODS: The Anopheles species were studied from 6 P.M. to 6 A.M., once a month, for one year, from October 1996 to September 1997, in the municipal district of Raposa, of the S?o Luís island, Maranh?o state. The basic method was the capture of female specimens on human baits in peri and intradomicile sites by means of aspiration tube and guided luminous focus. RESULTS: A total of 1.407 specimens were collected and distributed as follow: Anopheles aquasalis (82% of the sample), Anopheles galvaoi (10,2%), Anopheles albitarsis (6,4%), Anopheles evansae, Anopheles nuneztovari, and Anopheles triannulatus davisi (the last three represented together 1, 4%). The anophelines occurred all year round, mainly in the rainy period, being more frequent in the intra (75,3%) than in the peridomicile site (24,7%), showing a clear preference to suck blood in the evening. CONCLUSION: The behavioural variation of Anopheles shows that the different species are becoming adapted to closeness to human habitations, in the rural zone of the S?o Luis island.     

Dentate gyrus-selective colchicine lesion and disruption of performance in spatial tasks: difficulties in "place strategy" because of a lack of flexibility in the use of environmental cues?

The effects of intradentate colchicine injections on the performance of tasks requiring spatial working and reference memory are controversial. Multiple-site colchicine injections (7 microg/microl; via a drawn micropipette) throughout the dentate gyrus (DG) of rats (nine sites in each hemisphere, 0.06 microl at each site) selectively destroy about 90% of the DG granule cells, as revealed by quantitative stereological estimates; stereology also revealed minor neuronal losses in the CA4 (33%) and CA1 (23%) subfields, but lack of damage to the CA3 hippocampal subfield. Spatial reference and working memory were assessed in Morris' water maze; in the reference memory task, the rats were required to learn a single, fixed location for the platform over several days of training; in the working memory task, animals were required to learn a new platform location every day, in a matching-to-place procedure. Compared to sham-operated controls, lesioned rats showed significant disruption in acquisition of the reference memory water maze task; however, the data reveal that these rats did acquire relevant information about the task, probably based on guidance and orientation strategies. In a subsequent probe test, with the platform removed, lesioned rats showed disruption in precise indexes of spatial memory (e.g., driving search towards the surroundings of the former platform location), but not in less precise indexes of spatial location. Finally, the lesioned rats showed no improvement in the match-to-place procedure, suggesting that their working memory for places was disrupted. Thus, although capable of acquiring relevant information about the task, possibly through guidance and/or orientation strategies, DG-lesioned rats exhibit a marked difficulty in place strategies. This is particularly evident when these rats are required to deal with one-trial place learning in a familiar environment, such as in the working memory version of the water maze task, which requires flexibility in the use of previously acquired information.     

Participation factors in a occupational health colorectal cancer screening program

A colorectal cancer screening campaign by Hemoccult test was carried out from January 1993 to December 1994 in collaboration with the company doctors of employees ages 45 and older in the companies of the Lot department of France. Of the 1311 employees to whom the test was offered, 811 actually had the test done, representing a rate of participation of 61.9%. Participation varied from 48.1% to 72.7% depending on the company doctor, and was higher for large companies. Managers participated less than other employees. People who never visit a dentist, who had not seen their doctor for over a year or who never give blood participated less than others. Thus, even though company doctors can play a true role by favouring the participation of general employees, their action is limited by the weak participation of people who already have little contact with the health care system.     

Rôle du foie dans le métabolisme des nutriments en nutrition artificielle

The liver is a prominent organ in nutritional homeostasis. Due to unique metabolic properties, it plays a main role in the metabolism of the three macronutrients ‘as well as the micronutrients’ (vitamins and minerals) storage. Although it represents only 2.5% of the body mass, it consumes 20% of total resting energy expenditure and a similar percentage of the amino acid mixture absorbed via the gut during and after a meal. Due to a peculiar vascularization (portal vein, the entire gastrointestinal venous flux is directed towards the liver with all hydrosoluble nutrients, only water-unsoluble lipids being excluded from this obligatory ‘first-pass mechanism’). Since it is the location for glycogen storage, VLDL synthesis and ketogenesis, the liver is crucial in the fed-to-fasted metabolic alternation. While fat is not physiologically stored in the liver, it is a very important organ in lipid metabolism. Except immunoglobulins, all plasma proteins are synthetised by the liver together with the constitutive proteins, explaining that it is a very powerful organ for protein synthesis. Finally, due to a very active amino acid metabolism, the liver can reshape the amino acid-mixture coming from the gut in the absorptive state. Such a phenomenon has a major implication in the nutritional physiology of amino acid metabolism according to the route: enteral or parenteral. Indeed, in the latter case the remodelling by the liver does not occurs.     

Pulmonary gas exchange capacity is reduced during normovolaemic haemodilution in healthy human subjects

Purpose

To test the hypothesis that a physiological compensatory mechanism maintains respiratory gas exchange during normovolaemic haemodilution.

Methods

Pulmonary gas exchange capacity was evaluated in seven healthy subjects by measuring the lung diffusion of carbon monoxide (DLCO). During the measurement, various breath-holding times, inspiratory volumes, and sitting or supine positions, were randomly selected in an attempt to alter pulmonary capillary perfusion. KCO was calculated as the percentage of theoretical values of the ratio of DLCO by alveolar volume and normalized by sex, age, and height. Normovolaemic haemodilution (NH) was performed by bleeding an average blood volume of 1 L with simultaneous Dextran 60 replacement to obtain an haematocrit below 35%.

Results

After NH, haemoblogin concentration [Hb] decreased from 14.94 ± 0.96 to 12.5 ± 0.98 g · dl^?1 (P < 0.001). KCO decreased (P < 0.02) but remained closely correlated to [Hb] at every lung volume (< 0.02). Breathholding time and body position had no effect.

Conclusion

Moderate NH impairs pulmonary gas exchange capacity in awake, resting healthy subjects. There is no evidence of any compensatory mechanism since the KCO vs [Hb] relationship is unchanged.     

Consequences of renal insufficiency on the hepatic clearance of some drugs

There have been numerous investigations into the effect of kidney or liver diseases on the renal or hepatic elimination of drugs, but little is known about the possible consequences of renal insufficiency on the hepatic clearance of medicinal agents. The first reports of diminished presystemic elimination of drugs in renal failure were presented by Bianchetti in 1976 for propranolol and by Levy in 1979 for dextropropoxyphene. We confirmed the fact that the hepatic presystemic elimination of drugs might be diminished by kidney diseases. We studied this phenomenon with the beta-blocking agents tolamolol, bufuralol and oxprenolol. Tolamolol is eliminated from the body mainly by aromatic hydroxylation and, for bufuralol, aliphatic hydroxylation also plays an important role, whereas, for oxprenolol, glucuroconjugation of the unchanged compound is an important route of elimination. After oral administration, the areas under the plasma/blood concentration curves were markedly increased in patients with renal insufficiency as compared to healthy subjects. The clearance approach of Rowland and Tozer led to the conclusion that decrease of the presystemic hepatic elimination might be the main reason for this finding. Cefoperazone is a cephalosporin eliminated to 75% by the biliary route under normal conditions. In a study in which the drug was intravenously infused to both healthy volunteers and patients with renal insufficiency, we found that in some patients the extrarenal clearance was markedly reduced. It is probable that in this situation the patients also suffered from a slight hepatic insufficiency, as sometimes observed in the case of kidney disease associated with a poor physical condition. It is well-known that in patients with terminal liver failure, the kidney may also be involved, producing a condition known as the "hepato-renal" syndrome. We feel that there is evidence to support the hypothesis that renal failure can disturb the pharmacokinetics of drugs by processes other than merely reducing their renal excretion. The precise causes of the decreased hepatic elimination found in renal patients remains, however, to be determined.