Mycophenolate mofetil in multiple sclerosis: a multicentre retrospective study on 344 patients.

OBJECTIVES: Mycophenolate mofetil (MMF) is an immunosuppressive agent, sometimes used as a disease-modifying therapy for multiple sclerosis (MS). Several studies have reported the relative safety of this treatment but, to date, its efficacy has rarely been described. We performed a retrospective study to assess the safety and efficacy of MMF in patients with MS. METHODOLOGY: Three French MS centres included all of their patients treated by MMF. The main outcome criterion was annualised relapse rate (ARR) in the 1 year period after onset of MMF compared with the 1 year control period. Treatment with another immunosuppressive drug, such as mitoxantrone or cyclophosphamide, in the 2 years preceding initiation of MMF was included in a subgroup analysis. MMF safety and progression of the Expanded Disability Status Scale (EDSS) score were also assessed. RESULTS: 344 patients were included; 149 patients were previously treated with another immunosuppressant (IS group). Mean MMF treatment duration was 25.3±1.1 months. During the 1 year control period, ARR was 1.11±0.08, and for the 1 year treatment period, ARR was reduced significantly to 0.35±0.05 (p<0.0001, Wilcoxon paired test). Adverse events (occurring in 11% of patients) were mainly digestive disorders, benign infections, asthenia and transitory lymphopenia. Concerning the progression of disability, in the subgroup of patients without previous immunosuppressant treatment, EDSS remained stable between initiation and 1 year after the beginning of MMF. INTERPRETATION: Our results suggest that MMF can improve or stabilise MS patients and can be used as an alternative therapy.

[Management of labial incompetence and gummy smile using profiloplasty]. / Apport de la profiloplastie dans le traitement du sourire gingival et de l'incompétence labiale.

INTRODUCTION: Gummy smile and labial incompetence are frequent for consultation in plastic surgery. We wanted to show that rhinoplasty and genioplasty should correct these anomalies. PATIENTS AND METHODS: Profiloplasty was performed on 20 patients. Aesthetic and functional items were evaluated. RESULTS: There is a correlation between aesthetic and functional results. Results seem to be better for patients having an important labial incompetence without gummy smile. CONCLUSION: Those results are based on anatomical and surgical considerations. Some non surgical procedures do exist to treat this problem. It should be a challenge to find the place for each procedure.

[T1-T2 NO hypopharyngeal cancers treated with surgery alone. A GETTEC study (French Neck Study Group)]. / Cancers de l'hypopharynx T1-T2 "N0" traités par chirurgie exclusive. Etude GETTEC.

OBJECTIVE: Consider whether surgery alone in the treatment of early cancers of the hypopharynx can give identical or better results in terms of survival and local control than radiotherapy. METHODS: Forty-five patients were operated on during the years 1991-2004. Surgical treatment consisted in a resection by the transoral approach in four patients and 41 patients had a partial pharyngolaryngectomy. An elective neck dissection was performed on 43 patients. RESULTS: The 1-, 3-, and 5-year overall survival rates were 100, 95, and 75%. The 1-, 3-, and 5-year locoregional control rates were 93, 88, and 82% and were influenced by the presence of dysplasia on surgical margins (p=0.027). The oncological occurrences observed were five local recurrences, two nodal recurrences, ten second primary cancers, and two metastases. Five locoregional failures out of seven were controlled after a second treatment. CONCLUSION: Surgery alone gives completely satisfactory results in terms of survival and locoregional control. In case of recurrence, this makes it possible to operate on patients in nonirradiated areas with lower morbidity and mortality and better results. These results must be confirmed by a randomized trial.

Yeast mitochondria contain a linear RNA strand complementary to the circular intronic bI1 RNA of cytochrome b.

bI1 RNA (excised from the first intron of the long form of the cytochrome b gene of Saccharomyces cerevisiae mitochondria) hybridizes with the two strands of a Bg/II-MboI DNA segment from this region. This fraction is resistant to digestions by DNase I and RNase T1 and disappears completely upon alkali hydrolysis. Strand-specific labeling of an intronic DNA fragment, cloned in pBR322 plasmid, was accomplished through the use of a T4 DNA polymerase. The purity of the probes was demonstrated by cloning an exon-intron fragment and labeling it by the same procedure; mRNA and pre-mRNA bands hybridized only with the transcribed DNA strand whereas bI1 RNA hybridized with the two strands under the stringent washing conditions employed (tm + 20 degrees C). Several experimental results argue against the possibility that the observation of two complementary bI1 RNA strands results from a partial self-complementarity of the RNA. A pre-mRNA intermediate from a box8 (G5046) mutant, still containing this intron, hybridizes only with the transcribed DNA strand of the pure intronic probe. The amount of the non-sense bI1 RNA strand is very low, in cells from two wild-type strains, relative to the sense RNA strand during the early stages of growth on glucose. It increases as the cells are released from glucose repression. bI1 RNA is resistant to RNase. Very little self-complementarity is seen by computer analysis of the sequence. Purified bI1 RNA is seen by electron microscopy under non-denaturing conditions as a mixture of double-stranded circular and linear molecules thus confirming the existence of the two complementary strands. The disappearance of all material following alkali hydrolysis demonstrates that these are indeed two RNA strands. Under fully denaturing conditions a mixture of single-stranded circular and linear molecules is seen as reported previously (Cell, 19, 321-329, 1980). We conclude that yeast mitochondria contain the two complementary bI1 RNA strands, one circular and the other linear. Considering a largely asymmetrical transcription of the mitochondrial genome in yeast and assuming that circularization of some intronic RNAs is part of RNA processing, we do not believe that the two strands are each a mixture of linear and circular molecules. The ratio of non-sense to sense bI1 RNA in a cytoplasmic petite mutant, A1B1, also varies according to growth conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

A low-molecular-weight RNA species in yeast mitochondria arising from a 3' end trimming of cytochrome b pre-mRNA.

Immobilization of yeast mitochondrial RNA on nitrocellulose filters without prior alkali treatment revealed a low-MW RNA species (integral of 300 bases) which hybridizes specifically to the RNA coding strand of a DNA fragment BglII-HinfI at the 3' end of the COB-BOX gene. This RNA species (often a doublet) was found in several independent preparations of wild-type mtRNA and even in box- mutants blocked in the earliest steps of mRNA maturation (e.g. box 8-1). It may, therefore, result from an endonucleolytic cut similar to that which precedes the addition of a poly-A tail in other systems.

[Red cell autoimmunization in a "normal" population. 63 cases (author's transl)]. / Auto-immunisation érythrocytaire dans la population "normale". 63 observations.

Anti-red auto-antibodies were found in 69 out of 892 000 blood donors aged between 20 and 60 years, 63 of whom were followed for up to five years. This would suggest an overall incidence of 1 in 13 000 members of a "normal" population. Uncontrolled methyl-dopa treatment could be incriminated in 25% of cases. Only 10% of autoimmune subjects had slight confirmed anaemia, but 72% had biological evidence of red cell destruction (i.e. hyper-reticulocytosis, elevated serum bilirubin levels and shortened red cell life span), which demonstrates the presence of subclinical autoimmune haemolytic disease in apparently normal people. The anti-red cell auto-antibodies were of the IgG type in 97% of the subjects and were associated with various anti-tissue antibodies in 41%, thus pointing to a multisystem autoimmune disorder. In most cases the abnormality persisted or spontaneously regressed during the observation period, but long-term follow-up is required to determine whether asymptomatic red cell autoimmunization is harmless or potentially dangerous.