Systemic lupus erythematosus-associated acute transverse myelitis: manifestations, treatments, outcomes, and prognostic factors in 20 patients.

BACKGROUND: Transverse myelitis is a rare complication of systemic lupus erythematosus (SLE). This retrospective multicentre study identifies the prognostic factors in a relatively large patient series. PATIENTS AND METHODS: Twenty patients fulfilled the SLE criteria of the ACR classification and the Transverse Myelitis Consortium Working Group. A severe neurological flare was defined as muscle strength grade <3/5 in more than half the muscle groups at the motor neurological level. Inability to run or another significant ambulation-unrelated disability was considered as 'unfavourable neurological outcome'. RESULTS: Myelitis was the first SLE symptom in 12 patients; in the eight others, it occurred 8.6 years (median delay) after SLE onset. Eleven patients presented severe neurological impairments. The treatment included corticosteroids in all patients associated with intravenous cyclophosphamide in 11 and/or hydroxychloroquine in 14. Unfavourable outcomes were observed in 53% of the patients at six months and in 28% at end of follow-up (median: 5.9 years). An initial severe neurological impairment and no cyclophosphamide use were associated with unfavourable neurological outcomes at six months and at end of follow-up, respectively. CONCLUSION: Transverse myelitis may reveal SLE or occur more than 10 years after SLE diagnosis. The initial severity of the neurological flare (with paraplegia) is the main prognostic marker. The study provides arguments for cyclophosphamide use.

National cancer incidence is estimated using the incidence/mortality ratio in countries with local incidence data: is this estimation correct?

BACKGROUND: In countries with local cancer registration, the national cancer incidence is usually estimated by multiplying the national mortality by the incidence/mortality (I/M) ratio from pooled registries. This study aims at validating this I/M estimation in France, by a comparison with estimation obtained using the ratio of incidence over hospital discharge (I/HD) or the ratio of incidence over health insurance data (long-duration diseases, I/LDD). METHODS: This comparison was performed for 22 cancer sites over the period 2004-2006. In France, a longitudinal I/M approach was developed relying on incidence and mortality trend analyses; here, the corresponding estimations of national incidence were extracted for 2004-2006. The I/HD and I/LDD estimations were performed using a common cross-sectional methodology. RESULTS: The three estimations were found similar for most cancers. The relative differences in incidence rates (vs. I/M) were below 5% for numerous cancers and below 10% for all cancers but three. The highest differences were observed for thyroid cancer (up to +21% in women and +8% in men), skin melanoma (up to +13% in women and +8% in men), and Hodgkin disease in men (up to +15%). Differences were also observed in women aged over 60 for cervical cancer. Except for thyroid cancer, differences were mainly due to the smoothing performed in the I/M approach. CONCLUSION: Our results support the validity of I/M approaches for national estimations, except for thyroid cancer. The longitudinal version of this approach has, furthermore, the advantage of providing smoothed estimations and trend analyses, including useful birth-cohort indicators, and should thus be preferred.

[Diversity of incidence trend patterns: implications for carcinogenesis?]. / Diversité des modèles d'évolution des incidences: implication en cancérogenèse?

OBJECTIVE: Cancers of the ENT, oesophagus and lungs are caused mainly by alcohol and/or tobacco consumption but have potentially heterogeneous latencies and dose-incidence relationships. The incidence of cancers having the same risk factors may vary in a similar way over time and space. The aim of the study was to identify groups of cancers with similar spatio-temporal incidence trends. METHODS: Fifty thousand nine hundred and eighty cases of ten cancer types were collected between 1982 and 2002 in six French departments. The incidence levels and trends were assessed using an age-cohort random-effect model that took into account heterogeneity of incidence levels and trends between departments. RESULTS: Three groups of cancer sites/types with similar spatio-temporal incidence trends were identified: (1) oral cavity, oropharynx, hypopharynx, larynx, oesophagus, and lung squamous cell carcinomas in which the incidence decreased similarly in time and space; (2) other types of lung cancer and lung adenocarcinomas whose incidence increased similarly; and (3) lung large- and small-cell carcinomas whose incidence trends were heterogeneous. CONCLUSION: Using the tools of descriptive epidemiology different cancer groups with different temporal and spatial incidence trends were identified. This diversity suggests different latencies and different sensitivities of those groups to the main risk factors, alcohol and tobacco.

Is it possible to estimate the incidence of breast cancer from medico-administrative databases?

One approach to estimate cancer incidence in the French Départements is to quantify the relationship between data in cancer registries and data obtained from the PMSI (Programme de Médicalisation des Systèmes d'Information Médicale). This relationship may then be used in Départements without registries to infer the incidence from local PMSI data. We present here some methodological solutions to apply this approach. Data on invasive breast cancer for 2002 were obtained from 12 Départemental registries. The number of hospital stays was obtained from the National PMSI using two different algorithms based on the main diagnosis only (Algorithm 1) or on that diagnosis associated to a mention of "resection" (Algorithm 2). Considering registry data as gold standard, a calibration approach was used to model the ratio of the number of hospital stays to the number of incident cases. In Départements with registries, validation of the predictions was done through cross-validation. In Départements without registries, validation was done through a study of homogeneity of the mean number of hospital stays per patient. Cross-validation showed that the estimates predicted by the model were true with data extracted by Algorithm 1 but not by Algorithm 2. However, with Algorithm 1, there was an important heterogeneity between French Départements as to the mean number of hospital stays per patient, which had an important impact on the estimations. In the near future, the method will allow using medico-administrative data (after calibration with registry data) to estimate Départemental incidence of selected cancers.

Plasma fatty acids and lipid hydroperoxides increase after antibiotic therapy in cystic fibrosis.

The present authors investigated whether cystic fibrosis is linked to a defect in fatty acids and assessed the impact of the main patients' characteristics on the levels of several fatty acids, mostly during respiratory exacerbation and after antibiotic therapy. Fatty acid phospholipid and cholesteryl ester levels were measured in stable-state patients and controls. No differences were found concerning either the fractions of palmitic and oleic acids or the cholesteryl esters of alpha-linolenic and arachidonic acids. However, phospholipids of alpha-linolenic and arachidonic acids, as well as cholesteryl esters and phospholipids of stearic and linoleic acids, were lower in patients than in controls, but fractions of dihomo-gamma-linolenic, docosatetraenoic, docosapentaenoic, palmitoleic and eicosatrienoic acids were higher. Fatty acid levels, oxidative stress markers, nutrients, body mass index and forced expiratory volume in one second (FEV(1)) were measured in patients before and after antibiotic courses for bronchial exacerbation. After adjustments, palmitic, stearic, alpha-linolenic, linoleic, arachidonic, palmitoleic and oleic acids generally decreased during exacerbation but almost all increased after antibiotic courses. Nearly all fractions increased along with FEV(1) and a positive relationship linked fatty acids to lipid hydroperoxides. There was no general drop in fatty acids. Patients' fatty acid profiles depended on the pulmonary function and the inflammation state.

Modelling the progression towards duodenal cancer among patients with familial polyposis on the basis of two different score profiles.

The objective was to design a method that considers, on clinical arguments, the likely existence of patient subgroups with different evolution profiles. The method is applied in familial adenomatous polyposis to predict the proportion of patients that would develop duodenal cancer. A subject-specific linear mixed-effects model was elaborated to explicitly model heterogeneity in regression parameters. The estimates of the parameters were obtained by Bayesian inference using Gibbs sampling. The application concerned two potential polyposis subgroups: stable-state and progressive. Each patient's score was expressed in function of his putative subgroup, the reference subgroup mean score (intercept), the rate of change (slope), and time. The estimated proportion of stable-state patients was 35%. In progressive-state patients, the estimated annual score increase was 0.38 (95% CI: 0.27-0.48). The regression model predicted that the proportion of patients with a score > or = 9 is near 43% at age 60 (36-50%) and 50% at 70 (43-57%). The method indicates the evolution profile of each subject, which facilitates therapeutic decisions. The modelling may be extended to other more complex situations with several subgroups, with different change rates, or with various genetic or therapeutic profiles.

Elevation of cyclic adenosine monophosphate levels independently down regulates IL-1, IL-2, and IL-2 receptor (CD25) syntheses.

In view of the central involvement of interleukin-1 (IL-1) in T-cell functions and the negative effects exerted by cyclic adenosine monophosphate (cAMP) on T-cell responses, we wondered whether these inhibitions rely on defects in IL-1 generation. We investigated the effect of a known cAMP elevating agent, cholera toxin (CT), on the generation of IL-1 from peripheral blood adherent cells as well as the role of IL-1 whenever IL-2 synthesis and IL-2 receptor (CD25 antigen) expression are inhibited. While augmenting intracellular cAMP concentration, CT inhibits from 20 to 40% the generation of IL-1 activity from E. coli lipopolysaccharide (LPS)-stimulated adherent cells. Theophylline (TH), a cAMP degradation blocking agent, induces the same decrease in IL-1 activity. The B chain of CT, devoid of cAMP activating potency, is not inhibitory. In systems where CT and TH dramatically inhibit the generation of IL-2 activity (80%), addition of exogenous IL-1 does not restore the ability of T-cells to produce or release IL-2. Moreover, CT- and dibutyryl (db)cAMP-induced inhibition of CD25 antigen expression is not overcome by exogenous IL-1, IL-2, nor by both interleukins. It is concluded that inhibition of IL-1 and IL-2 production are independent and that inhibition of CD25 antigen expression is independent of IL-1 and IL-2 modulation. Cholera toxin and cAMP influences on interleukin synthesis are discussed.

Elevation of 3'5' cyclic adenosine monophosphate alters CD3 and CD25 antigens expression in activated T lymphocytes.

Modulation of CD3 molecules and expression of receptors for IL-2 (CD25) are pivotal events of lymphocyte activation and proliferation. Knowing the inhibitory effect of cAMP elevating agents on T lymphocyte activation, we investigated the effect of cholera toxin (CT) and dibutyryl cyclic AMP (dbcAMP) on the modulation of the CD3/Ti complex and on the appearance of the CD25 antigen on PHA-activated human lymphocytes. Cytofluorometry analysis of indirectly anti-CD3 labelled cells showed that CT accelerated the disappearance of CD3 molecules and slowed their reappearance. CT or dbcAMP inhibited the expression of CD25 antigen. In both cases, not only the relative number of CD3+ or CD25+ cells decreased, but the number of CD3 or CD25 antigens per cell as well. Exogenous rIL-2 did not reverse the inhibition of IL-2R expression by CT, showing that this effect is independent of the inhibition of IL-2 production already demonstrated. We conclude that augmenting cAMP levels might affect early steps of activation such as antigen receptor modulation, but do affect more profoundly late IL-2 dependent steps especially the autocrine IL-2 pathway of IL-2 receptor upregulation and the production of IL-2.

Elevation of cyclic 3'5' adenosine monophosphate levels by cholera toxin inhibits the generation of interleukin 2 activity.

Several molecules can interact with membrane receptors on mononuclear cells to increase intracellular levels of cyclic adenosine monophosphate (cAMP). We used the cholera toxin (CT), a cAMP elevating agent, to study the influence of this nucleotide on the production of interleukin 2 (IL-2) by human peripheral blood mononuclear cells stimulated by phytohemagglutinin and phorbol myristate acetate. Stimulated generation of IL-2 activity was inhibited by CT but not by its B subunit. The inhibition was potentiated by addition of theophylline. Therefore the synthesis and/or release of IL-2 is controlled by intracellular cAMP levels and may be modulated by agents active on this nucleotide system, such as bacterial toxins, glycoprotein hormones, or neurotransmitters.