Compression of the spinal cord revealing a seronegative rheumatoid arthritis

INTRODUCTION: Craniocervical junction damages may result in a compression of the spinal cord. They may be caused by infectious, tumoral or inflammatory processes. Rheumatoid arthritis is probably among rheumatic diseases the most frequent cause of atlantoaxial arthritis. Nevertheless involvement of the craniocervical junction as the presenting symptom of rheumatoid arthritis is a very rare feature. EXEGESIS: We report the case of a 61 years old woman who presented with atlantoaxial involvement and spinal cord compression one year before the diagnosis of a seronegative rheumatoid arthritis. CONCLUSION: Symptomatic craniocervical junction damages may appear. Patients with damages of the craniocervical junction and negative investigations should be followed long-term; an underlying inflammatory disease may become evident after significant delay.     

Isolated systolic hypertension: data on a cohort of young subjects from a French working population (IHPAF)

Elderly patients with isolated systolic hypertension (ISH)--systolic blood pressure (SBP) > or =140 mmHg and diastolic blood pressure (DBP) <90 mmHg--have increased mortality and morbidity. The aim was to study the incidence of ISH in a younger population of between 15 and 60 years of age, and to measure pulse pressure (PP), mean arterial pressure (MAP) and heart rate (HR) in these subjects. The study population consisted of 27 783 subjects, aged 15-60 years, untreated for hypertension (HT) from a cohort of employees formed to study the incidence of HT in the French working population (AIHFP). BP and HR were measured with a validated, automatic device after 5, 6 and 7 min at rest. The prevalence of ISH was 6.9% in men, 2.3% in women. This prevalence was over 5% in young men and increased at 40-44 years; it was negligible in young women, but increased at 50-54 years to about 10% (ie to the same level as in men of the same age): PP in subjects with ISH (46.9 mmHg) was significantly higher than in the normotensive group (NT-40.9 mmHg); it was comparable in both young men (65.5 mmHg) and older men (66 mmHg); it was higher in men (63.1 mmHg) than in women (61.5 mmHg). HR was higher in ISH than in NT and it was higher in women ( approximately 5 bpm) in whom it decreased with age. The prevalence of ISH is not negligible in HT (30% men, 25% women), with a high prevalence in young subjects and elevated PP, MAP and HR values. These data should be taken into account as elevated ISH, PP and HR are considered as cardio-vascular risk factors.     

Trace fear conditioning involves hippocampal alpha5 GABA(A) receptors

The heterogeneity of gamma-aminobutyric acid type A (GABA(A)) receptors contributes to the diversity of neuronal inhibition in the regulation of information processing. Although most GABA(A) receptors are located synaptically, the small population of alpha5GABA(A) receptors is largely expressed extrasynaptically. To clarify the role of the alpha5GABA(A) receptors in the control of behavior, a histidine-to-arginine point mutation was introduced in position 105 of the murine alpha5 subunit gene, which rendered the alpha5GABA(A) receptors diazepam-insensitive. Apart from an incomplete muscle relaxing effect, neither the sedative, anticonvulsant, nor anxiolytic-like activity of diazepam was impaired in alpha5(H105R) mice. However, in hippocampal pyramidal cells, the point mutation resulted in a selective reduction of alpha5GABA(A) receptors, which altered the drug-independent behavior. In line with the role of the hippocampus in certain forms of associative learning, trace fear conditioning, but not delay conditioning or contextual conditioning, was facilitated in the mutant mice. Trace fear conditioning differs from delay conditioning in that the conditioned and unconditioned stimulus are separated by a time interval. Thus, the largely extrasynaptic alpha5GABA(A) receptors in hippocampal pyramidal cells are implicated as control elements of the temporal association of threat cues in trace fear conditioning.     

The serotonin-N-acetylserotonin–melatonin pathway as a biomarker for autism spectrum disorders

Elevated whole-blood serotonin and decreased plasma melatonin (a circadian synchronizer hormone that derives from serotonin) have been reported independently in patients with autism spectrum disorders (ASDs). Here, we explored, in parallel, serotonin, melatonin and the intermediate N-acetylserotonin (NAS) in a large cohort of patients with ASD and their relatives. We then investigated the clinical correlates of these biochemical parameters. Whole-blood serotonin, platelet NAS and plasma melatonin were assessed in 278 patients with ASD, their 506 first-degree relatives (129 unaffected siblings, 199 mothers and 178 fathers) and 416 sex- and age-matched controls. We confirmed the previously reported hyperserotonemia in ASD (40% (35–46%) of patients), as well as the deficit in melatonin (51% (45–57%)), taking as a threshold the 95th or 5th percentile of the control group, respectively. In addition, this study reveals an increase of NAS (47% (41–54%) of patients) in platelets, pointing to a disruption of the serotonin-NAS–melatonin pathway in ASD. Biochemical impairments were also observed in the first-degree relatives of patients. A score combining impairments of serotonin, NAS and melatonin distinguished between patients and controls with a sensitivity of 80% and a specificity of 85%. In patients the melatonin deficit was only significantly associated with insomnia. Impairments of melatonin synthesis in ASD may be linked with decreased 14-3-3 proteins. Although ASDs are highly heterogeneous, disruption of the serotonin-NAS–melatonin pathway is a very frequent trait in patients and may represent a useful biomarker for a large subgroup of individuals with ASD.     

The active metabolite of leflunomide,A77 1726, inhibits the production of prostaglandin E(2), matrix metalloproteinase 1 and interleukin 6 in human fibroblast-like synoviocytes

OBJECTIVES: To investigate the effects of the active metabolite of leflunomide, A77 1726, on fibroblast-like synoviocytes. In rheumatoid arthritis (RA) synoviocytes participate in tissue destruction by producing metalloproteinases (MMP), prostaglandin E(2) (PGE(2)) and interleukin (IL) 6, which are involved in extracellular matrix degradation, resorption of the mineral phase and osteoclast-mediated bone resorption. METHODS: Human synoviocytes were stimulated with IL-1alpha or tumour necrosis factor alpha (TNF-alpha) in the presence of A77 1726. Culture supernatants were analysed for production of interstitial collagenase (MMP-1), tissue-inhibitor of metalloproteinases 1 (TIMP-1), PGE(2) and IL-6. Total RNA was isolated and analysed for steady-state levels of MMP-1, cyclooxygenase-2 (COX-2) and IL-6 mRNA. RESULTS: A77 1726 inhibited the production of PGE(2) in synoviocytes activated by TNF-alpha and IL-1alpha with median inhibitory concentrations (IC(50)) of 7 and 3 microM respectively. In contrast, MMP-1 and IL-6 production was inhibited at high A77 1726 concentrations (> 10 microM), whereas TIMP-1 was not affected. The inhibition of MMP-1 and IL-6 production was due to the known inhibitory effect of A77 1726 on pyrimidine synthesis, as it was reversed by the addition of uridine. This did not apply to PGE(2) production, which was inhibited via direct action of A77 1726 on COX-2, as shown by the increasing amount of substrate (arachidonic acid) in the culture medium. CONCLUSION: This study shows that some of the beneficial effect of leflunomide in RA patients may be due to the inhibition of PGE(2), IL-6 and MMP-1 production in synoviocytes. This effect, coupled with its multiple inhibitory effects on T lymphocyte functions, might account for the significant reduction in the rate of disease progression in RA patients treated with leflunomide.     

Uterine artery embolisation to treat severe haemorrhage following legal abortion

The aim of this paper is to present a case of hemorrhagic complication following a legal abortion treated with uterine embolisation. A 45-year-old woman, with a history of one caesarean section and seven legal induced abortions, requested legal induced abortion at 12 weeks of amenorrhea. Legal induced abortion was performed as a day case using vacuum aspiration with a plastic cannula under general anaesthesia. Severe haemorrhage, with an estimated blood loss of 800 ml, occurred during the procedure. Bleeding was not related to cervical laceration, incomplete abortion, or uterine perforation. Surgical conservative procedures and intravenous use of sulprostone (Nalador) failed to control haemorrhage. The patient underwent uterine artery embolisation with Curaspon, a porcine-derived gelfoam, used for the temporary occlusion of the visceral arteries. Successful hemostasis was obtained. The patient presented no complication related to the procedure. Severe haemorrhage following legal induced procedure is rarely reported. Emergency arterial embolisation may offer an effective modality of treatment.     

Quels sont actuellement les espoirs réels de grossesse après cryoconservation ovarienne ?

Survival rates for cancers that occur in childhood and adolescence have improved over the last decades, and preservation of future fertility in these patients has become a relevant issue. Premature ovarian failure is a consequence of exposing women to chemotherapeutic drugs and ionizing radiation. Ovarian cryopreservation is an alternative to cryopreservation of embryos or oocytes for theses patients. Ovarian cryopreservation aims to reimplant ovarian tissue after complete remission into the pelvic cavity (orthotopique site) or a heterotopic site like the abdominal wall or the forearm. In vitro folliculogenesis, that aims at the maturation of ovarian cortex primordial follicles cryopreserved for a FIV, is still in an experimental research stage. In this review, the objective was to evaluate the real hopes of pregnancy after ovarian cryopreservation. Indeed, many teams offer ovarian cryopreservation at present time, although only two pregnancies have been achieved to date. In both cases, it can be discussed whether the fertilized oocyte originated from the transplant or from the native ovary. Furthermore, the potential for reintroduction of cancerous cells may limit this technique in cancers that are known to have a risk of ovarian dissemination. The hopes engendered by ovarian cryopreservation, but also its limits, must be explained to the patients before an ovarian surgery for cryopreservation.