Combination therapy with interferon beta-1b and azathioprine in secondary progressive multiple sclerosis. A two-year pilot study

Combination therapy may benefit the subgroup of patients with secondary progressive multiple sclerosis (SPMS) who do not respond to interferon beta (IFNB). We performed a two-year study of azathioprine (AZA) combined with IFNB-1b in SPMS patients who had not responded well to IFNB-1b alone. Patients with SPMS were eligible for this non-controlled prospective study if they had two or more relapses requiring corticosteroid treatment or deteriorated by at least 0.5 points on the Expanded Disability Status Scale (EDSS) while on IFNB-1b in the year preceeding the study. Patients were to continue treatment with IFNB-1b (8 MIU qod, subcutaneous) and received AZA (50 mg tid, oral). Safety was assessed in terms of adverse reactions and laboratory measures graded according to the WHO toxicity scale. Efficacy was explored by changes in relapse rate, EDSS, 9-hole peg test (9-HPT), neuropsychological scores, and magnetic resonance imaging (MRI) results. Neutralizing antibodies (NAB) were measured. Ten SPMS patients (6 females) with a median EDSS score of 4.5 were enrolled. One patient withdrew because of gastrointestinal complaints, one was withdrawn owing to poor compliance, and 8 patients completed therapy. The only frequent side effect was lymphopenia, reported at least once in all patients. Annual relapse rate was reduced by approximately 50 % in the second year. There was a significant trend for EDSS increase. Total lesion load measured by MRI decreased at 12 and 24 months; only one patient had active lesions. No changes were seen in the 9-HPT. There was a significant improvement in neuropsychological tests after 24 months (p = 0.045). One patient tested positive for NAB throughout the study, and transient NAB were detected in 4 patients. In conclusion, combination therapy with IFNB-1b and AZA was safe and generally well tolerated in patients with SPMS. Strict clinical and laboratory monitoring is recommended during this combination therapy. Received: 26 November 2001 Received in revised form: 15 February 2002 Accepted: 19 February 2002     

Functional fixation of autotransplanted tooth germs by using bioresorbable membranes

OBJECTIVE: The purpose of this study was to evaluate the contribution of a bioresorbable membrane placement to the healing of immature teeth after autotransplantation of tooth buds. STUDY DESIGN: Six cases were selected: 2 transplantations of wisdom teeth, 2 for premolar agenesis, 1 for ectopia, and 1 premolar in an incisor position. The crown of each tooth germ and the marginal alveolar bone were covered with a resorbable membrane. RESULTS: The radicular edification was nearly complete, neither ankylosis nor inflammatory resorption was observable, the pulp vitality was preserved, and the periodontal integration was identical to that of other teeth. The membrane ensured contention and stabilization of the transplant, allowed functional stimulation, permitted protection of the coagulum and periodontal cells, and kept the epithelium at a distance. CONCLUSIONS: The transplantations of immature teeth were improved by the use of a resorbable membrane, which caused an optimal functional fixation of the transplanted tooth.     

Primary graft failure following lung transplantation: predictive factors of mortality

STUDY OBJECTIVES: To assess incidence, outcome, and early predictors of mortality for patients with primary graft failure (PGF) following lung transplantation (LTx), and to develop an injury severity score able to accurately predict ICU mortality for these patients. DESIGN: Retrospective cohort analysis. SETTING: Two LTx centers in Paris. PATIENTS: Two hundred fifty-nine patients who underwent LTx over a 12-year period. MEASUREMENTS AND RESULTS: One hundred thirty-one patients (50.6%) met PGF criteria: radiographic graft infiltrate within the first 3 days following LTx associated with gas exchange impairment (PaO(2)/fraction of inspired oxygen ratio < 300 mm Hg). This syndrome was associated with an increased duration of mechanical ventilation (9.1 +/- 1 days vs 3.1 +/- 0.6 days, mean +/- SD; p < 0.001) and ICU mortality (29% vs 10.9%; p < 0.01). The patients with PGF were randomly assigned to developmental (n = 85) and validation (n = 46) samples. Using logistic regression analysis, four variables were found associated with ICU mortality in these patients: age, degree of gas exchange impairment, graft ischemic time, and severe early hemodynamic failure. An ischemia/reperfusion injury severity score was derived using these four variables. Model calibration was good in the developmental and validation samples, as was model discrimination (area under receiver operating characteristic curves, 0.93 and 0.85, respectively). CONCLUSION: PGF following LTx is a frequent event, with significant ICU morbidity and mortality. We demonstrate that four simple factors allow prediction of ICU mortality with good accuracy.     

Immune response to equine Chorionic Gonadotropin used for the induction of ovulation in goats and ewes

In dairy goats and ewes the use of equine Chorionic Gonadotropin (eCG) as a convenient hormone for the induction of ovulation is necessary for out-of-season breeding and artificial insemination (AI). Treatment for induction and synchronization of ovulation consists of a progestagen delivered by vaginal sponge, followed by an eCG injection. In some females, the first injection of eCG induces a humoral response with high concentrations of anti-eCG antibodies in contrast to other females displaying a very low concentration of anti-eCG antibodies. Females eliciting a low response were also poor responders after the following treatments. Conversely, high responders at the first treatment systematically yielded high immune responses upon the following treatment. By a molecular genetic approach using microsatellites we showed that the anti-eCG immune response phenotypes were associated with MHC class II polymorphism. Females with high residual antibody concentrations at the time of eCG injection exhibited a much lower kidding rate than other females did. Lower fertility of these females, inseminated at a fixed time after eCG treatment (43H for goats and 55H for ewes), might be due to the delay in estrus occurrence and the pre ovulatory LH surge. Consequently, under field conditions old females selected for AI are only those with low residual anti-eCG antibody concentrations and old females with high residual antibody concentration are culled from AI breeding because of their low fertility during the previous year. So we have undertaken comparative studies to establish if the anti-eCG immune response is correlated with the global immunity in animals.     

Amenorrhoea revealing an arteriovenous uterine malformation, and recovery of menses after embolization

A case is reported of secondary amenorrhoea related to an arteriovenous malformation (AVM) successfully treated with embolization, with a recovery of menstrual cycles. A 28-year-old woman presented with secondary amenorrhoea as the only clinical symptom. Although she had an eugonadic status, there was no genital withdrawal bleeding upon cessation of an oral contraceptive. Pelvic transvaginal ultrasonography revealed a pelvic mass but magnetic resonance imaging (MRI) clearly showed an AVM. Classical angiography was performed with endovascular embolization. Partial thrombosis of the lesion was assessed by magnetic resonance angiography. Recovery of menses occurred 2 months later. It is speculated that blood stolen from the endometrium by the uterine AVM could have been responsible for the amenorrhoea. It is a very unusual cause, and it can be successfully treated with embolization.     

Case report: a prenatal case of Jarcho-Levin syndrome diagnosed during the first trimester of pregnancy

The Jarcho-Levin syndrome is a specific form of spondylocostal/spondylothoracic dysostosis. There have been various classifications of this syndrome. We present the case of a severe prenatal Jarcho-Levin syndrome, diagnosed by ultrasound examination during the first trimester of pregnancy in a family with no previous medical history of an affected child. X-ray exploration, high-resolution spiral computed tomography and autopsy confirmed the diagnosis.