Brain MRI findings in children and adolescents with Fabry disease.

OBJECTIVE: To evaluate the presence of white matter and hemorrhagic lesions in brain MRI of children and adolescents with Fabry disease (FD). METHODS: Brain MRI studies in 44 consecutive children and teenagers (20 boys, mean age 14.6 years, range 7-21 years) were evaluated using classic sequences as well as, GRE-weighted images, for white matter lesions (WML) and chronic microbleed detection. All patients lacked history of stroke or TIA. Brain MRI findings in 46 consecutive children and adolescents without FD, referred for the evaluation of headaches (36 females, mean age 14.1 years, range 7-21 years) were evaluated as a control group. Additionally, we assessed the clinical manifestations of FD. RESULTS: Seven children (15.9%) with FD had brain MRI evidence of asymptomatic WML (5 girls, mean age 14.8 years, range: 13-20 years) compared with 3 children (6.5%) in the control group (p = 0.01). Brain abnormalities in patients with FD revealed WML, deep gray matter and infratentorial involvement. Three patients presented two lesions each. None of the children showed microbleeds. Regarding clinical manifestations, 90.9% of the patients had signs or symptoms of FD. CONCLUSION: We identified asymptomatic white matter brain lesions in 15.9% of children with FD without clinical history of stroke. FD is a treatable disorder that should be routinely included in the differential diagnosis of both symptomatic and asymptomatic brain lesions in children and adolescents. The detection of brain lesions may foster earlier treatment.

[Psoriatic patients: Analysis of patients dissatisfied with their management]. / Patients atteints de psoriasis : analyse de la population insatisfaite de sa prise en charge.

BACKGROUND: The French are frequently regarded as grouchy. In a recent study, we observed a high proportion of patients initially consulting for psoriasis because they were dissatisfied with their previous therapy. We analyzed the characteristics of these patients. PATIENTS AND METHODS: This was a cross-sectional multicenter study in 40 centers belonging to the ResoPso (psoriasis treatment network) multicenter study group, with consecutive inclusions over a period of 11months in 2014. All adults (age>18 years) consulting for the first time for psoriasis at a center were included in the study. RESULTS: Among patients, 1205 were included, of whom 249 (20.3%) were consulting because of their dissatisfaction with treatment. In the univariate analysis, these patients were younger (P=0.02) and presented psoriasis that had begun earlier in life (P<0.0001). It consisted mostly of generalized plaque psoriasis (P=0.047) and more severe forms of psoriasis (PASI and/or DLQI score>10, P<0.02). There were fewer cases of psoriatic arthritis (P=0.01). The "dissatisfied" patients reported significantly more frequent use of topical treatments (P<0.0001) and alternative medicines (P=0.02), and more infrequent use of biologics (P=0.006) as well as longer treatment periods (P=0.0005). They consulted at hospitals (P=0.01) and had previously seen more GPs and dermatologists (P≤0.0008). There was no impact of gender on the dissatisfaction profile by either comorbidities (metabolic, blood pressure, alcohol and tobacco consumption, and depression), or socio-economic data. In the multivariate analysis, DLQI>10 (P=0.01; 95% CI: 1.01-1.07) and longer duration of care (P=0.004; 95% CI: 1.23-2.99) were associated with dissatisfaction. CONCLUSION: Twenty percent of our psoriatic patients seem dissatisfied with their treatment. It is difficult to draw a specific demographic and socioeconomic profile of dissatisfied patients. Only disease severity and possibly inadequate treatment at the initial consultation are associated with patient dissatisfaction. Explanations related to the individual patients and doctors may be proposed. Finally, while the French may be considered grouchy, the frequency of patient dissatisfaction seen in our study does not appear to be any greater than that observed in other countries.

Displasia cortical focal: hallazgos en imágenes de tensor de difusión

Objetivo: La displasia cortical focal (DCF) es una anomalía del desarrollo cortical. Representa una de las causas más frecuentes de epilepsia refractaria, siendo fundamental la resonancia magnética (RM) para su diagnóstico. Dada la importancia que ha cobrado la secuencia de tensor de difusión (DTI), el objetivo de este trabajo fue evaluar retrospectivamente los hallazgos en el mapa de fracción de anisotropía del DTI en pacientes con DCF. Observaciones: Se buscó retrospectivamente a pacientes con diagnóstico anatomopatológico de DCF en la base de datos de nuestro hospital. De un total de 74, se seleccionaron 8 casos con diagnóstico aislado de DCF y estudio de RM prequirúrgico con DTI. El foco de displasia se identificó en las imágenes anatómicas convencionales de la RM. Se evaluó el mapa de fracción de anisotropía (FA) y se definieron las alteraciones en la región de la DCF. Se observó una disminución de la FA en la sustancia blanca adyacente a la DCF en 7 de los 8 pacientes (87,5%). Discusión: Los hallazgos con el DTI brindan información complementaria en relación con la RM. En la mayoría de nuestros pacientes no hubo cambios de señal en la sustancia blanca en las imágenes convencionales, pero sí se identificó una disminución de la FAen el DTI. Se desconoce si esto refleja cambios estructurales o únicamente funcionales, secundarios a la lesión primaria. Creemos que el DTI puede agregar información complementaria de valor para el diagnóstico y valoración de la extensión de esta patología.

Objective: Focal cortical dysplasia (DCF) in an anomaly of cortical development. It represents one of the most frequent causes of drug resistant epilepsy and the magnetic resonance imaging (MRI) is trivial for its diagnosis. In the last years the use of diffusion tensor imaging (DTI) has increased in this kind of pathology. The purpose of this work was to evalúate retrospectively DTI findings on fractional anisotropy maps in patients with FCD. Observations: We retrospectively searched patients with confirmed anatomo-pathological diagnosis of FCD in our hospital datábase. From a total of 74, 8 patients, with isolated diagnosis of FCD and preoperative MRI with DTI, were selected. The FCD was identified in conventional anatomical MRI in all patients. Fractional anisotropy (FA) maps were evaluated and changes in the región of FCD were defined. Decreased FA was observed in white matter adjacent to the FCD, in 7 of 8 patients (87.5%). Discussion: Findings of DTI gives us complementary information to those of conventional MRI. Most of our patients showed no signal changes of white matter in conventional sequences and they presented decreased FA in DTI. We don't actually know if these DTI findings represent structural changes in white matter or just functional changes secondary to the adjacent FCD. We think DTI can give valuable complementary information for the diagnosis and determination of the extensión of this pathology.

Metabolic comorbidities and hypertension in psoriasis patients in France. Comparisons with French national databases.

INTRODUCTION: Several studies have shown a high prevalence of cardiovascular and metabolic comorbidities in psoriasis. Our study aimed to evaluate the association of psoriasis with key comorbidities such as smoking, obesity, hypertension, dyslipidaemia and diabetes comparatively with French national data. MATERIAL AND METHODS: This multicentre noninterventional observational study of adults with psoriasis was conducted in 29 dermatology centres in France. A total of 2210 patients were included. The prevalence of comorbidities in psoriatic patients was compared to data from the French national databanks "ObEpi 2012" (obesity, hypertension, dyslipidaemia and diabetes) and "Baromètre Santé 2010" (smoking). RESULTS: We reported a higher prevalence of all metabolic comorbidities and high blood pressure in psoriatic patients. Smoking: 32.5% were active smokers; the age of onset and the prevalence of familial psoriasis were significantly lower in the smoking group but the severity of psoriasis was significantly higher. The frequency of smoking was higher than in the general population, particularly among young female patients. Obesity: 24% of patients with psoriasis were obese. Multivariate analysis showed obesity to be significantly associated with other comorbidities, severity of psoriasis and psoriatic arthritis. The incidence of obesity was higher than in general population, occurring chiefly in subjects aged over 45 years. HYPERTENSION: 26% of patients with psoriasis had hypertension. The age of onset of psoriasis and the prevalence of psoriatic arthritis were significantly higher in the hypertension group, although there was less familial psoriasis. The incidence of hypertension was higher than in general population. Dyslipidaemia: 27.5% of patients with psoriasis had dyslipidaemia. The age of onset in the dyslipidaemia group was higher although there was less familial psoriasis. The incidence of dyslipidaemia was higher than in general population. Diabetes: 11.0% of patients with psoriasis had diabetes. The age of onset of psoriasis was significantly higher in the diabetes group although there was less familial psoriasis. The incidence of diabetes was higher than in general population particularly after the age of 35 years. CONCLUSION: These results confirmed that psoriasis is associated with significant metabolic comorbidities and hypertension compared to the general population in France, with certain epidemiological differences for each.

Fluvastatin synergistically improves the antiproliferative effect of everolimus on rat smooth muscle cells by altering p27Kip1/cyclin E expression.

Multiple intracellular signaling pathways stimulate quiescent smooth muscle cells (SMCs) to exit from G(0) and re-enter the cell cycle. Thus, a combination of two drugs with different mechanisms of action may represent a suitable approach to control SMC proliferation, a prominent feature of in-stent restenosis. In the present study, we investigated the effect of everolimus, a mammalian target of rapamycin inhibitor, in combination with fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on proliferation of rat SMCs. The antiproliferative action of everolimus was amplified by 2.5-fold by the addition of subliminal concentrations of fluvastatin (5 x 10(-7) M), lowering the IC(50) value from 2.5 x 10(-9) to 1.0 x 10(-9) M. The increased antiproliferative effect of everolimus by fluvastatin was prevented in the presence of mevalonate, farnesol, or geranylgeraniol, suggesting the involvement of prenylated proteins. Cell cycle analysis and [3H]thymidine incorporation assay demonstrated that the two drugs synergistically interfered with the progression of G(1) phase. In particular, the drug combination significantly up-regulated p27(Kip1) levels by 47.0%, suppressed cyclin E by 43.0%, and it reduced retinoblastoma (Rb) hyperphosphorylation by 79.0%, compared with everolimus alone. Retroviral overexpression of cyclin E conferred a significant resistance of rat SMCs to the antiproliferative action of the drug combination, measured by cell counting, [3H]thymidine incorporation, and cell cycle analysis, with higher levels of hyperphosphorylated form of Rb. Taken together, these results demonstrated that everolimus acts synergistically with fluvastatin to inhibit SMC proliferation by altering the expression of cyclin E and p27(kip1), which affects Rb phosphorylation and leads to G(1) phase arrest.

Pollakisuria in a dwarf goat due to pathologic enlargement of the uterus.

Pollakisuria in adult goats can be caused by diseases of the urinary tract and by distension of parts of the genital tract leading to irritation of the bladder. Hydrometra is the most common cause of uterine distension in goats and usually can be resolved by prostaglandin injections. But other pathologies of the uterus can generate a similar syndrome. A dwarf goat was presented at the clinic with a history of chronic pollakisuria and tenesm. An initial ultrasonographic examination of the abdomen led to the suspicion of hydrometra, but treatment with injections of prostaglandin were not successful. Blood samples revealed low progesterone and high oestrogen values. A laparotomy was performed and an enlarged uterus with 1.5 L of mucous content and cystic ovaries were found and partially removed. A single solid leiomyoma was diagnosed histologically in the uterine wall. Two months later the goat's condition had deteriorated and therefore she was euthanized. Necropsy and pathohistological examination revealed the presence of a metastasized adenocarcinoma of the uterus. In this case, the pollakisuria provoqued by distension of the uterus was not caused by hydrometra, but by neoplasia. The syndrome and the pathogenesis of the adenocarcinoma in consideration of the hormonal status of the patient is discussed.

[Avidity of IgG anti-Toxoplasma gondii. Study to establish a new decision tree for screening]. / Avidité des IgG anti Toxoplasma gondii. Etude en vue d'établir un nouvel arbre décisionnel dans le dépistage de la maladie.

Toxoplasmosis infection is commonly asymptomatic, but it may have severe teratogenic consequences. The authors review the literature on serologic screening in the first trimester of pregnancy.

A randomized placebo-controlled trial of fluvastatin for prevention of restenosis after successful coronary balloon angioplasty; final results of the fluvastatin angiographic restenosis (FLARE) trial.

BACKGROUND: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors competitively inhibit biosynthesis of mevalonate, a precursor of non-sterol compounds involved in cell proliferation. Experimental evidence suggests that fluvastatin may, independent of any lipid lowering action, exert a greater direct inhibitory effect on proliferating vascular myocytes than other statins. The FLARE (Fluvastatin Angioplasty Restenosis) Trial was conceived to evaluate the ability of fluvastatin 40 mg twice daily to reduce restenosis after successful coronary balloon angioplasty (PTCA). METHODS: Patients were randomized to either placebo or fluvastatin 40 mg twice daily beginning 2-4 weeks prior to planned PTCA and continuing after a successful PTCA (without the use of a stent), to follow-up angiography at 26+/-2 weeks. Clinical follow-up was completed at 40 weeks. The primary end-point was angiographic restenosis, measured by quantitative coronary angiography at a core laboratory, as the loss in minimal luminal diameter during follow-up. Clinical end-points were death, myocardial infarction, coronary artery bypass graft surgery or re-intervention, up to 40 weeks after PTCA. RESULTS: Of 1054 patients randomized, 526 were allocated to fluvastatin and 528 to placebo. Among these, 409 in the fluvastatin group and 427 in the placebo group were included in the intention-to-treat analysis, having undergone a successful PTCA after a minimum of 2 weeks of pre-treatment. At the time of PTCA, fluvastatin had reduced LDL cholesterol by 37% and this was maintained at 33% at 26 weeks. There was no difference in the primary end-point between the treatment groups (fluvastatin 0.23+/-0.49 mm vs placebo 0.23+/-0.52 mm, P=0.95) or in the angiographic restenosis rate (fluvastatin 28%, placebo 31%, chi-square P=0.42), or in the incidence of the composite clinical end-point at 40 weeks (22.4% vs 23.3%; logrank P=0.74). However, a significantly lower incidence of total death and myocardial infarction was observed in six patients (1.4%) in the fluvastatin group and 17 (4.0%) in the placebo group (log rank P=0.025). CONCLUSION: Treatment with fluvastatin 80 mg daily did not affect the process of restenosis and is therefore not indicated for this purpose. However, the observed reduction in mortality and myocardial infarction 40 weeks after PTCA in the fluvastatin treated group has not been previously reported with statin therapy. Accordingly, a priori investigation of this finding is indicated and a new clinical trial with this intention is already underway.

Molecular analysis of Methanobacterium phage psiM2.

The methanogenic archaeon Methanobacterium thermoautotrophicum Marburg is infected by the double-stranded DNA phage psiM2. The complete phage genome sequence of 26 111 bp was established. Thirty-one open reading frames (orfs), all of them organized in the same direction of transcription, were identified. On the basis of comparison of the deduced amino acid sequences to known proteins and by searching for conserved motifs, putative functions were assigned to the products of six orfs. These included three proteins involved in packaging DNA into the capsid, two putative phage structural proteins and a protein related to the Int family of site-specific recombinases. Analysis of the N-terminal amino acid sequences of three phage-encoded proteins led to the identification of two genes encoding structural proteins and of peiP, the structural gene of pseudomurein endoisopeptidase. This enzyme is involved in the lysis of host cells, and it appears to belong to a novel enzyme family. peiP was overexpressed in Escherichia coli, and its product was shown to catalyse the in vitro lysis of M. thermoautotrophicum cells. Comparison of the phage psiM2 DNA sequence with parts of the sequence of the wild-type phage psiM1 suggests that psiM2 is a deletion derivative, which formed by homologous recombination between two copies of a direct repeat.

High-dose fluvastatin and bezafibrate combination treatment for heterozygous familial hypercholesterolemia.

This study assessed the long-term use of fluvastatin, alone or in combination with bezafibrate, in patients with severe familial hypercholesterolemia who, in a previous study, did not achieve target levels (European Atherosclerosis Society) of low density lipoprotein cholesterol (LDL-C) with fluvastatin at 60 mg/day plus bezafibrate 200 mg/day, with or without cholestyramine (CME) at 8 g/day. This open-label study comprised 3 periods: period I, 6 weeks of fluvastatin at 40 mg twice daily (at breakfast and at bedtime); period II, fluvastatin at 80 mg/day (40 mg at breakfast, 40 mg at bedtime), and bezafibrate at 200 mg/day (at lunchtime) for 6 weeks in patients not achieving LDL-C target levels; and period III, force-titration of fluvastatin to 800 mg/day (as in period II) and bezafibrate at 400 mg/day (slow release) in patients receiving combination treatment. Patients were excluded if, during the previous study, they had experienced a serious drug-related adverse event or deterioration in liver or kidney function (liver enzymes > 3 times upper limit of normal). The standard physical and laboratory evaluations were performed at regular intervals. Lipid profiles were determined from 12-hour fasting blood samples. All adverse events occurring or worsening during the study, whether spontaneously reported or elicited by questioning, and regardless of relationship to study medication, were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)