Polylactic acid vs. polyacrylamide hydrogel for treatment of facial lipoatrophy: a randomized controlled trial [Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS) 132 SMILE].

OBJECTIVES: The aim of the study was to demonstrate the noninferiority of polyacrylamide hydrogel (PH) vs. polylactic acid (PLA) for the treatment of facial lipoatrophy in HIV-infected adults. METHODS: A randomized, blinded, multicentre, noninferiority 96-week study was carried out. Patients with facial lipoatrophy were randomly assigned to receive intradermal injections with PH or PLA, and were blinded to the filler. The primary efficacy endpoint was patient satisfaction at week 48 assessed using a visual analogue scale score (VAS). Secondary efficacy end-points included cheek thickness and skin-fold, lipoatrophy grading and quality of life. Safety was assessed by the reporting of adverse events. RESULTS: A total of 148 patients were included in the study; 93% were men, the median age was 47 years, the median CD4 count was 528 cells/µL, and the median duration of antiretroviral therapy was 12 years. Mean VAS increased from 2.8 at baseline to 7.1 and 7.5 in the PLA and PH arms, respectively, at week 48 (P=0.0002 for noninferiority) and was sustained at week 96 (6.7 and 7.9 in the PLA and PH arms, respectively; P=0.003 for noninferiority). Cheek thickness and skin-fold increases and lipoatrophy improvement were similar in the two arms. Quality of life remained unchanged or improved depending on the questionnaire used. In injected patients, subcutaneous nodules emerged in 28 (41%) and 26 (37%) patients in the PLA and PH arms, respectively (P=0.73). Four patients in the PH arm developed severe inflammatory nodules, a median of 17 months after the last injection. CONCLUSIONS: PH and PLA have similar efficacies in the treatment of facial lipoatrophy, but PH may be associated with more delayed inflammatory nodules.

Proteolipid/DM-20 proteins bearing the paralytic tremor mutation in peripheral nerves and transfected Cos-7 cells.

Paralytic tremor (Plp-pt) is a missense mutation of the myelin proteolipid gene (Plp) in rabbits. The myelin yield in the Plp-pt brain is reduced and the protein and lipid composition of central nervous system (CNS) myelin is abnormal. We studied the intracellular transport of the normal and Plp-pt mutant PLP and DM-20 in transiently transfected Cos-7 cells. While the mutant PLP accumulates in the rough endoplasmic reticulum and does not reach the plasma membrane, the spliced isoform of PLP, mutant DM-20, is normally transported to the cell surface and integrated into the membrane. Analysis of rabbit sciatic nerves revealed that concentration of peripheral nervous system (PNS) myelin proteins is normal in Plp-pt myelin. In the PNS like in the CNS, the level of Plp gene products is subnormal. But this does not affect myelination in the PNS where PLP, present in low concentration, is not a structural component of compact myelin. The normal level of Plp gene expression in Schwann cells is low and these results suggest that, in the Plp-pt PNS, Schwann cell function is not affected by the deficiency in PLP and/or the impairment of intracellular PLP transport.

Paralytic tremor (pt): a new allele of the proteolipid protein gene in rabbits.

Paralytic tremor (pt) is a sex-linked mutation in rabbit that affects myelination of the CNS. Myelin in the pt brains represents approximately 30% of the normal levels. Previously we showed that the pt mutation affects primarily proteolipid protein (Plp) gene expression. In the present study we investigated the relative effect of the pt mutation on two distinctive Plp gene products, PLP- and DM-20-specific messenger RNAs. Our results showed that both PLP and DM-20 are affected and that the ratio DM-20/PLP was higher in pt rabbits than in age-matched controls. We sequenced normal rabbit PLP cDNA and characterized pt mutation at the DNA level. Rabbit PLP sequence, deduced from cDNA, differs from the human protein only at Thr198. Sequence analysis of the mutant cDNA revealed a transversion T-->A in exon 2 of the Plp gene. This point mutation, which is placed at the end of the first potential transmembrane domain, results in a substitution of His36 by a glutamine. This transversion abolishes a restriction site that enabled us to screen a large number of animals and observe a perfect correlation between the pt allele and the abnormal phenotype.

Segmental pruritus and intramedullary vascular malformation.

Pruritus remains a medical mystery. Generally related with dermatological diseases, it is rarely associated with a neurological cause. We report a case of segmental pruritus (right T2 dermatome) related to an intramedullary vascular malformation. An anatomicophysiological explanation is presented. It is the first demonstration in man that pain receptors are not involved in pruritus, and suggests pruritus is under the control of descending inhibitory pathways.

Myelin proteolipid protein mutation in the rabbit: a new model of Pelizaeus-Merzbacher disease.

Proteolipid protein (PLP) is a major myelin protein of the central nervous system. Mutations of the Plp gene are responsible for a number of sex-linked disorders in humans (Pelizaeus-Merzbacher disease) and in animals. We have identified a novel mutation of the Plp gene which gives rise to the paralytic tremor (pt) phenotype in rabbit. Pt rabbits are hypomyelinated and present very low levels of PLP protein and its mRNA. Sequence analysis revealed a single nucleotide change in exon 2 which results in the substitution of a histidine by a glutamine at position 36. Histidine36 is positioned at the boundary of the first transmembrane domain. Therefore, its position can be crucial for the efficient interaction of PLP with other proteins and lipids, and for correct incorporation into the membrane.

Paralytic tremor (pt) rabbit: a sex-linked mutation affecting proteolipid protein-gene expression.

Paralytic tremor (pt) is a neurological sex-linked recessive mutation in rabbits which is characterized by a coarse body tremor and limb paresis. Morphological studies showed that this mutation affects CNS myelination. Although the number of oligodendrocytes is not reduced, myelination is slower, irregular and defective. We have made a biochemical and molecular analysis of 4-wk-old mutant and normal rabbits. The amount of myelin in the mutant represents only approximately 25% of the normal level. Radioimmunoassay for myelin basic protein showed a reduction to approximately 40% in pt whole-brain homogenate but the difference was not significant in purified myelin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of brain homogenates followed by immunoblotting showed that all major myelin proteins are affected by the pt mutation, although to different degrees. While most of the myelin proteins are reduced to approximately 60-80% of the normal level, an important reduction to approximately 30%, was measured for the proteolipid protein (PLP). In purified myelin, the difference in PLP concentration was significant while the other specific proteins were less affected. A similar reduction in myelin-protein gene expression was detected at the mRNA level. Sex-linked transmission, low concentrations of PLP and its specific mRNA in the CNS indicate that the pt mutation primarily affects the expression of the Plp gene.

[Value of prostatic massage for detection of Chlamydia trachomatis in the male urethra]. / Intérêt du massage prostatique pour la mise en évidence de Chlamydia trachomatis dans l'urètre masculin.

The aim of this work was to evaluate prostatic massage (PM) as diagnostic method of chronic chlamydial infection (possible etiologic agent of male infertility or chronic prostatitis). 105 men were examined. One urethral swabbing and one urine sampling are done before PM. After PM, prostatic fluid is collected spontaneously and in a minimum volume of urine. Chlamydial isolation samples are treated by 3 methods: culture on HeLa 229 cells, immunoenzymology and direct immunofluorescence. Of 107 samplings, 22 were positive. In 13 patients (14 samplings) the result was positive by PM alone. In those cases, prostatic massage was the only way to establish the Chlamydial infection, when urethral swabbing, usual method, is negative. If confirmed, the interest of prostatic massage rests on detection of unknown genital Chlamydial infection, and this, by a non surgical method.

[Double-blind study versus excipient of 0.75% metronidazole gel in the treatment of rosacea]. / Etude en double insu contre excipient du métronidazole gel à 0.75 p. 100 dans le traitement de la rosacée.

INTRODUCTION: The proven value of tetracyclines and metronidazole administered orally in the treatment of the chronic and recurrent disease that is rosacea is tempered by the important undesirable effects observed in long-term therapy. The purpose of this study was to test the effectiveness of an 0.75 p. 100 metronidazole gel in the treatment of rosacea. PATIENTS AND METHODS: The study involved two groups of patients: one received the metronidazole gel and the other the vehicle of the gel used as placebo. The multicentre randomized trial was conducted in the double-blind fashion by 18 private dermatologists working in the Paris region. Fifty one patients who, since more than 3 months, had been presenting with rosacea, defined as at least 4 papulopustules associated with erythema and/or telangiectasia, entered the trial. Topical treatments and systemic treatments which had shown some activity against rosacea had been interrupted for 15 days or 2 months respectively. The product (or the placebo) was applied a.m. and p.m. on the whole dry face. The patients were seen on days 0, 21 and 42. The evaluation was purely clinical, and the principal criterion of judgement was a change in the number of papulopustules between days 0 and 42. RESULTS: The metronidazole gel reduced the number of papulopustules between day 0 and day 42, and this reduction was significantly greater than that observed with the excipient alone. The active product began to be effective during the third week and remained so during the next three weeks. Both the metronidazole gel and its excipient seemed to be poorly tolerated, with frequent complaints of dry skin, but in 5 women of the metronidazole group this dryness was alleviated by application of moisturizers. CONCLUSION: This study has demonstrated that the 0.75 p. 100 metronidazole gel is effective in the treatment of the papulopustular component of rosacea.

Developmental expression of major myelin proteins in hypomyelinated pt mutant rabbit.

A term "paralytic tremor" (pt) is attributed to a neurological mutation of Chinchilla rabbits, affecting the development of the central nervous system (CNS). A quantification of myelin protein content indicates the strong CNS hypomyelination during the development (1-120 postnatal days). SDS-PAGE electrophoresis of total brain homogenates, followed by immunoblotting, shows a reduced concentration of major myelin-connected proteins. MBP deficiency corresponds approximately to the level of the hypomyelination, whereas PLP expression is drastically reduced.

Triiodothyronine has diverse and multiple stimulating effects on expression of the major myelin protein genes.

If the importance of triiodothyronine (T3) on brain development including myelinogenesis has long been recognized, its mechanism of action at the gene level is still not fully elucidated. We studied the effect of T3 on the expression of myelin protein genes in aggregating brain cell cultures. T3 increases the concentrations of mRNA transcribed from the following four myelin protein genes: myelin basic protein (Mbp), myelin-associated glycoprotein (Mag), proteolipid protein (Plp), and 2',3'-cyclic nucleotide 3'-phosphodiesterase (Cnp). T3 is not only a triggering signal for oligodendrocyte differentiation, but it has continuous stimulatory effects on myelin gene expression. Transcription in isolated nuclei experiments shows that T3 increases Mag and Cnp transcription rates. After inhibiting transcription with actinomycin D, we measured the half-lives of specific mRNAs. Our results show that T3 increases the stability of mRNA for myelin basic protein, and probably proteolipid protein. In vitro translation followed by myelin basic protein-specific immunoprecipitation showed a direct stimulatory effect of T3 on myelin basic protein mRNA translation. Moreover, this stimulation was higher when the mRNA was already stabilized in culture, indicating that stabilization is achieved through mRNA structural modifications. These results demonstrate the diverse and multiple mechanisms of T3 stimulation of myelin protein genes.

Post-transcriptional events are responsible for low expression of myelin basic protein in myelin deficient mice: role of natural antisense RNA.

Myelin deficient mice (mld) are characterized by tandem duplication of the gene coding for myelin basic protein (MBP). The upstream gene contains a large inversion of the 3' region which includes exons 3-7, and therefore it cannot give rise to mature mRNA and functional protein. MBP and MBP mRNA concentrations in mld brains constitute only approximately 2% of the concentrations present in normal mice. The overall transcription rate of the Mbp gene is normal. In order to explain the discrepancy between mRNA concentration and transcription rate, we studied transcription of each individual gene. The two genes were transcribed independently, although some uninterrupted transcription could not be excluded. The rate of transcription of the upstream gene was higher than that of the downstream gene. This difference was reflected in the concentration of sense and antisense RNA found in nuclei. Our results indicate that the low concentration of the mature mRNA cannot be caused by transcriptional interference. High concentration of nuclear antisense RNA strongly suggests that post-transcriptional regulation occurs in mld mice through formation of double stranded RNA.

Neuronal organization of the stapedius reflex pathways in the rat: a retrograde HRP and viral transneuronal tracing study.

The location of stapedius motoneurons in the rat was determined with horseradish peroxidase (HRP) retrograde tracing techniques. After injection of free HRP or wheat germ agglutinin-horseradish peroxidase (WGA-HRP) in the stapedius muscle on one side, labeled neurons were seen ipsilaterally in a region ventromedial to the rostral half of the facial motor nucleus (VII), extending rostrally to the caudal part of the superior olivary complex (SOC). These labeled neurons, located outside the SOC and facial motor nuclei themselves, constitute the pool of stapedius motoneurons, in agreement with previous descriptions for other species. In order to identify the origin of some inputs to the stapedius motoneurons, injections of herpes virus suis were performed in the stapedius muscle. After replication in the motoneurons, the viruses are transported transneuronally to some premotor neurons, as previously reported in other systems. The presence of the virus was detected by immunofluorescence in neurons corresponding to the stapedius motoneurons labeled with HRP or WGA-HRP. In addition, infected neurons were seen bilaterally at the level of the SOC, in the mediotrapezoid region, where no labeled cells were observed following HRP or WGA-HRP injections in the stapedius muscle. These neurons were considered as infected transneuronally and therefore providing inputs to the pool of stapedius motoneurons. No virus could be detected in cochlear nucleus neurons. These data are consistent with previous observations in the rabbit based on lesion experiments, suggesting that neurons at the level of the SOC are involved in the reflex arc of middle ear muscles.

[quot ]Apendice cecal con perdigones[quot ]. / [[quot ]Cecal appendix with pellets[quot ]]

A case is presented of caecal appendix with birdshots, in a 38 years-old male patient, with a clinical picture of biliary pathology. An elongated and [quot ]heavy[quot ] caecal appendix was palpated during cholecystectomy and removed. The pathological study showed the presence of 99 ammunitions or lead birdshots in the appendicular lumen, with a diameter of 1-5 mm, without histologic evidence of active appendicitis. The patient was fond of hunting wild animals and is used to eat them pickled. Pertinent literature is revised and works are commented in relation to the incidence of different foreign bodies in the appendix lumen, clinical picture and complications.

Apendice cecal con perdigones / Cecal appendix with pellets

Se presenta un caso de apéndice cecal con perdigones, en un paciente de sexo masculino de 38 años de edad, con cuadro clínico de patología biliar. Durante la colecistectomía se palpó apéndice cecal alargado y "pesado", procediéndose a la exéresis del mismo. La anatomía patológica reveló la presencia de 99 municiones o perdigones de plomo en la luz apendicular, de 1-5 mm. de diámetro, sin evidencias histológicas de apendicitis activa. El pacientes es aficionado a la caza de animales silvestres e ingiere los mismos en escabeche. Se revisa la literatura al respecto y se comentan trabajos en relación a la incidencia de diferentes cuerpos extraños en la luz apendicular, cuadro clínico y complicaciones (AU)

Sexual behavior and smoking: risk factor for urethritis in men.

Two hundred men who had symptoms of urethritis and 207 controls were interviewed. Because 60% of the men were of foreign nationality, the analysis of risk factors for urethritis was undertaken separately for the French and foreign subpopulations. The risk factors for urethritis were different for the French and foreign men. For the French men who had smoked, the risk of infection was 2.9 times greater than that for men who had never smoked (95% confidence interval, 1.2-7.6), after taking type of sexual behavior into account. There is a significant increase in the risk of urethritis when the amount of tobacco consumed daily increases (P less than 0.02). This finding suggests that smoking is an independent risk factor.

Tensor tympani reflex pathways studied with retrograde horseradish peroxidase and transneuronal viral tracing techniques.

The neural pathway involved in activation of the tensor tympani (TT) muscle was studied in the rat using retrograde HRP and transneuronal viral tracing techniques. The pool of TT motoneurons labeled with HRP was located ipsilaterally under the anterior third of the trigeminal motor nucleus and extended rostrally towards the lateral lemniscus. The origin of the inputs to these motoneurons was then determined using transneuronal viral transport: presumably transneuronally infected neurons appeared bilaterally in the vicinity of the superior olivary complex, mainly in between the two nuclei of the trapezoid body. The present data are consistent with previous conclusions based on lesion experiments that the TT reflex loop is made up of a chain of 4 neurons.

Biochemical and electrophysiological evidence of functional vasopressin receptors in the rat superior cervical ganglion.

Binding of radioactive vasopressin--but not of oxytocin--was detected by autoradiography and by labeling of membranes obtained from the rat superior cervical ganglion. In both instances binding could be displaced by V1 (smooth muscle-type) but not by V2 (kidney-type) agonists, indicating that the ganglionic vasopressin receptors are similar to those present on hepatocytes and vascular smooth muscle. In accordance with the V1 character of the receptors, vasopressin activated the turnover of membrane inositol lipids, and this effect was abolished by a structural analogue known to act as a vasopressor antagonist. A possible physiological role of vasopressin was suggested by intracellular recordings obtained from ganglion cells in vitro. Vasopressin induced a reduction in the amplitude of the fast excitatory postsynaptic potential evoked by electrical stimulation of the preganglionic nerve. This reduction in ganglionic transmission was antagonized by the same synthetic structural analogue that blocked the effect of vasopressin on inositol lipids. This study provides evidence for the presence of functional vasopressin receptors in a rat sympathetic ganglion and thus suggests that vasopressin may play a role in peripheral autonomic function.

[Treatment with ofloxacin (RU 43280) of uncomplicated bacterial urethritis in males]. / Traitement par ofloxacine (RU 43280) des uréthrites masculines bactériennes non compliquées.

Ofloxacin is a new fluoroquinolone with in vitro activity against the three main urethritis-causing pathogens: i.e. Neisseria gonorrhoeae, Chlamydia trachomatis and Ureaplasma urealyticum. 18 adult males with acute uncomplicated urethritis took 200 mg ofloxacin by mouth twice daily for 7 (non-chlamydial urethritis) or 14 (chlamydial urethritis) days. 12 patients had N. gonorrhoeae; 2 had H. parainfluenzae, 1 had E. coli and 5 had C. trachomatis. Urethral cultures were obtained before treatment and on day 7 (non-chlamydial urethritis) or 28 (chlamydial urethritis). Clinical and microbiological cure was achieved in 17 of the 18 patients. Clinical manifestations failed to resolve in one patient due to the presence of Trichomonas vaginalis recognized on day 7. No side effects were observed. According to these results, ofloxacin is effective and safe against gonococcal and chlamydial urethritis.

Neurohypophysial peptides depress cholinergic transmission in a mammalian sympathetic ganglion.

The actions of arginine-vasopressin (AVP) and oxytocin (OXT) were investigated in the rat superior cervical ganglion (SCG). At micromolar concentrations AVP decreased the amplitude of fast excitatory postsynaptic potentials (f-EPSPs) evoked by preganglionic stimulation and in many cells depolarized the postsynaptic membrane. Both effects were reversibly abolished by a potent vasopressor antagonist. The peptide decreased the frequency of spontaneous miniature EPSPs and the quantal content of the f-EPSPs without affecting the sensitivity of the ganglion cells to acetylcholine. OXT exerted the same effects as AVP but was less powerful. It was concluded that neurohypophysial peptides exert a dual pre- and post-synaptic action mediated by specific receptors.