Perampanel during pregnancy: Description of four cases.

Perampanel (PER) is approved in Italy as an adjunctive treatment for focal-onset seizures (FOS) and generalized tonic-clonic seizures (GTCs), and it could be an alternative to valproate in young women diagnosed with idiopathic generalized epilepsy. Nevertheless, clinical data about the outcome of pregnancies in women exposed to PER are lacking. Here, we report retrospectively collected data from four women suffering from FOS who were exposed to PER during pregnancy. Three pregnancies were carried out with PER as add-on therapy during the entire gestation (8 mg/day in two patients and 6 mg/day in one), without seizure frequency variations. The fourth patient started PER 2 mg/day as monotherapy during the 13th week of pregnancy due to seizure relapse and continued it until delivery with complete seizure control. All pregnancies showed good outcomes, and their newborns did not possess major congenital malformations. Apgar scores and auxological parameters at birth were normal. Fetal pathology in follow-up during pregnancies was absent in all cases. In our patients PER was well tolerated and appeared safe for the fetuses and did not result in major malformations or adverse events at birth. Nevertheless, this is a report involving a small number of patients and it does not suggest the general use of PER is safe during pregnancy.

Eyelid myoclonia with absences, intellectual disability and attention deficit hyperactivity disorder: a clinical phenotype of the RORB gene mutation.

Eyelid myoclonia with absences is recently included in the category of childhood epileptic syndromes. It is clinically characterized by brief seizures of eyelid myoclonia, sometimes followed by absences, and it is associated to EEG generalized discharges of polyspikes or polyspike-waves, which are triggered by eyes closure in a well-lit room. This epileptic syndrome probably has a genetic origin, as well as other genetic generalized epilepsies, in particular photosensitive epilepsies. We describe the case of a patient affected by eyelid myoclonia with absences, intellectual disability, and attention deficit hyperactivity disorder (ADHD), with a de novo mutation of the RORB gene (retinoid-related orphan receptor ß); this gene is involved in vivo in different neuronal processes among which are migration and differentiation. We suggest that its mutation in our patient can be considered the cause of the aberrant functioning of the cerebral cortex, which is clinically expressed by epilepsy and neurodevelopment disorders.

Insight into epileptic and physiological déjà vu: from a multicentric cohort study.

BACKGROUND AND PURPOSE: The presence of a continuum between physiological déjà vu (DV) and epileptic DV is still not known as well as epidemiological data in the Italian population. The aim was to identify the epidemiological distribution of DV in Italy, and secondly to look for specific features of DV able to discriminate between epileptic and non-epileptic DV. METHODS: In all, 1000 individuals, 543 healthy controls (C) (313 women; age 40 ± 15 years) and 457 patients with epilepsy (E) (260 women; age 39 ± 14 years), were prospectively recruited from 10 outpatient neurological clinics throughout Italy. All populations were screened using the Italian Inventory for Déjà Vu Experiences Assessment (I-IDEA) test and E and pairwise C underwent a comprehensive epilepsy interview. RESULTS: Of E, 69% stated that they experienced 'recognition' and 13.2% reported that this feeling occurred from a few times a month to at least weekly (versus 7.7% of the control group). Furthermore, a greater percentage of E (6.8% vs. 2.2%) reported that from a few times a month to at least weekly they felt that it seemed as though everything around was not real. In E, the feeling of recognition raised fright (22.3% vs. 13.2%) and a sense of oppression (19.4% vs. 9.4%). A fifth of E felt recognition during epileptic seizures. CONCLUSION: Only E regardless of aetiology firmly answered that they had the feeling of recognition during an epileptic seizure; thus question 14 of the I-IDEA test part 2 discriminated E from C. Paranormal activity, remembering dreams and travel frequency were mostly correlated to DV in E suggesting that the visual-memory network might be involved in epileptic DV.

Validation of the Hamilton Rating Scale for Depression in adults with epilepsy.

PURPOSE: Mood disorders represent a frequent psychiatric comorbidity among patients with epilepsy, having a major impact on their quality of life and contributing considerably to the global burden of the disease. The availability of standardized clinical instruments validated in populations with epilepsy has important implications in terms of diagnosis and treatment. This aimed to validate the Hamilton Rating Scale for Depression (HRSD) in adult patients with epilepsy. METHODS: A consecutive sample of 120 adult outpatients with epilepsy was assessed using the Mini International Neuropsychiatric Inventory (MINI) Plus version 5.0.0 and the HRSD. RESULTS: Cronbach's alpha coefficient was 0.824 for the 17-item version and 0.833 for the 21-item version. Receiver operating characteristic analysis showed an area under the curve of 0.896 and 0.899, respectively, for the two versions. However, the HRSD-17 demonstrated the best psychometric properties compared to the HRSD-21 and, with a cutoff score of 6, showed a sensitivity of 94%, a specificity of 80%, a positive predictive value of 46%, and a negative predictive value of 99%. CONCLUSIONS: The HRSD proved to be reliable and valid in the epilepsy setting and will stimulate further research in this area.

Anti-TNF-α and risk of infections: the experience in one center.

AIM: In the last years there is an increasing interest for the question of whether patients treated with antitumour necrosis factor-α (TNF-α) agents are at increased risk of infections. We aim to assess the possible role of anti-TNF-α treatment in the increase of the risk of infections in a population of patients affected by rheumatoid arthritis or psoriatic arthritis. METHODS: We analyzed data of patients affected by chronic arthritis treated with anti-TNF-α to investigate the risk of infections. Statistical analysis was done using STATA software. RESULTS: The odds ratio for patients treated with anti-TNF-α who developed infections was 1.61 (CI: 0.88, 2.92, P<0.11). We found an odds ratio of 1.41 (CI: 0.74, 2.68, P<0.29) in patients treated with anti-TNF-α who developed urinary tract infection, and an odds ratio of 2.63 (CI: 0.31, 22.19, P<0.37) in patients treated with anti-TNF-α who developed herpes zoster. DISCUSSION: These results seems to indicate a role of anti-TNF-α treatment in the risk of infection. Nevertheless, our results are not statistically significant probably because the sample sizes are too small and the time of observation among patients is variable. Moreover, other confounding factors may be gender, age and the different degrees of disease activity and comorbidity. In conclusion, limitations in the study size and design preclude definitive conclusions about the question of whether patients treated with anti-TNF-α agents are at increased risk of infections. The performance of additional research are needed to answer this question.

Effect of endothelin inhibition on lung fibroblasts on patients with systemic sclerosis.

AIM: The aim of the study was to investigate the effect of selective ETRA Sitaxsentan on viability and differentiation into myofibroblasts of lung fibroblasts derived from SSc-ILD patients and the ability of this drug to modify the lung fibroblast synthesis of VEGF, type I collagen and fibronectin. METHODS: Primary human lung fibroblast cultures were obtained from BAL of SSc-ILD patients. Cell cultures were exposed for 48 h to crescent concentrations of Sitaxsentan (10 -6M to 10 -4M). In these experimental conditions we evaluated cell viability through crystal violet staining, the production and mRNA expression of VEGF, fibronectin and type I collagen respectively through ELISA and real-Time PCR. Further, we detected alpha-Smooth Muscle Actin (α-SMA) through immunocytochemical assay. RESULTS: The lowest concentration of sitaxsentan (10-6M) did not affect fibroblasts viability; conversely at higher concentrations, sitaxsentan induced a significant inhibition of cell viability. Synthesis and mRNA expression of VEGF, type 1 collagen and fibronectin were significantly reduced in treated lung fibroblasts compared to the untreated ones, in a dose-dependent manner. At higher concentrations, Sitaxsentan reduced the expression of α-SMA. CONCLUSION: The results of this study show that sitaxentan is able in vitro to reduce both cell viability than production of VEGF and extra-cellular matrix components in SSc lung fibroblasts, confirming the anti-fibrotic potential of ETRA in SSc. The decreased expression of α-SMA in treated cells indicate that sitaxsentan may inhibit the fibroblast differentiation toward a myo-fibroblast phenotype and further support the hypothesis that the selective ETRAs may be beneficial in patients with SSc-ILD as anti fibrotic agents.

Validation of the Italian version of the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E).

The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) was developed for the rapid detection of a major depressive episode in people with epilepsy. It has been proven to be a user-friendly screening instrument. This study describes the development, validation, and psychometric properties of the Italian version of the NDDI-E. A consecutive sample of 120 outpatients with epilepsy has been assessed using the M.I.N.I. Plus version 5.0.0 and the NDDI-E. All patients had no major difficulties in understanding or answering the questions of the Italian version. Cronbach's alpha coefficient was 0.851. Receiver operating characteristic analysis showed an area under the curve of 0.943 (CI95%=0.902-0.985; SE 0.021; p<0.001), a cut off score of 13, a sensitivity of 86.2%, a specificity of 89%, a positive predictive value of 71.4%, and a negative predictive value of 95.3%.

Osteocytes: central conductors of bone biology in normal and pathological conditions.

Osteocytes are the most abundant and longest-living cells in the adult skeleton. For a long time, osteocytes were considered static and inactive cells, but in recent years, it has been suggested that they represent the key responder to various stimuli that regulate bone formation and remodelling as well as one of the key endocrine regulators of bone metabolism. Osteocytes respond to mechanical stimuli by producing and secreting several signalling molecules, such as nitric oxide and prostaglandin E(2) , that initiate local bone remodelling. Moreover, they can control bone formation by modulating the WNT signalling pathway, an essential regulator of cell fate and commitment, as they represent the main source of sclerostin, a negative regulator of bone formation. Osteocytes can also act as an endocrine organ by releasing fibroblast growth factor 23 and several other proteins (DMP-1, MEPE, PHEX) that regulate phosphate metabolism. It has been demonstrated that various bone diseases are associated with osteocyte abnormalities, although it is not clear if these changes are the direct cause of the pathology or if they are secondary to the pathological changes in the bone microenvironment. Thus, a better understanding of these cells could offer exciting opportunities for new advances in the prevention and management of different bone diseases.

Incidence and predictors of acute symptomatic seizures after stroke.

OBJECTIVE: To assess incidence and predictors of acute symptomatic seizures in a prospective cohort of patients with first stroke. METHODS: Patients with first stroke hospitalized in 31 Italian centers were recruited. Relevant demographic data, disease characteristics, and risk factors were collected. Acute symptomatic seizures (≤7 days) were recorded and correlated to age, gender, family history of epilepsy, and vascular risk factors. RESULTS: A total of 714 patients (315 women, 399 men; age 27-97 years) were enrolled. A total of 609 (85.3%) had cerebral infarction (32 cerebral infarction with hemorrhagic transformation [CIHT]) and 105 (14.7%) primary intracerebral hemorrhage (PIH). A total of 141 (19.7%) had a large lesion (>3 cm) and 296 (41.5%) cortical involvement. Twelve patients reported family history of seizures. Forty-five patients (6.3%) presented acute symptomatic seizures, 24 with cerebral infarction (4.2%), 4 with CIHT (12.5%), and 17 (16.2%) with PIH. In multivariate analysis, compared to cerebral infarction, PIH carried the highest risk (odds ratio [OR] 7.2; 95% confidence interval [CI] 3.5-14.9) followed by CIHT (OR 2.7; 95% CI 0.8-9.6). Cortical involvement was a risk factor for PIH (OR 6.0; 95% CI 1.8-20.8) and for CI (OR 3.1; 95% CI 1.3-7.8). Hyperlipidemia (OR 0.2; 95% CI 0.03-0.8) was a protective factor for IPH. CONCLUSION: The incidence of acute symptomatic seizures is the highest reported in patients with first stroke with prospective follow-up. Hemorrhagic stroke and cortical lesion were independent predictors of acute symptomatic seizures. Hyperlipidemia was a protective factor for hemorrhagic stroke.

Dose-dependent metabolic effect of zoledronate on primary human osteoblastic cell cultures.

OBJECTIVES: To evaluate the in vitro effect of the bisphosponate zoledronate on metabolic activity, proliferation and viability of human osteoblasts. METHODS: Primary human osteoblasts cultures were obtained from cancellous bone of healthy subjects undergoing bone marrow biopsy. Cell cultures were treated with crescent concentrations of zoledronate (10⁻¹°to 10⁻³), with and without 1,25(OH)2 vitamin D3. In these experimental conditions we evaluated cells viability and proliferation using the MMT colorimetric test, cell apoptosis by measurement of Caspase 3 activity and metabolic cell activity through alkaline phosphatase activity and osteocalcin production. RESULTS: Osteocalcin and alkaline phosphatase synthesis was significantly enhanced by 10⁻¹° M to 10⁻5 M zoledronate concentrations, whereas was dramatically decreased by higher drug concentrations. Vitamin D3 enhanced the positive metabolic effect of zoledronate. The effect of zoledronate on cell proliferation was variable and dose-dependent. While no effect was observed with lower drug concentrations (10⁻¹° M to 10⁻8 M), zoledronate 10⁻7 M increased cell proliferation. Conversely, concentrations higher than 10⁻7 M significantly reduced cell proliferation, in a dose-dependent manner. Osteoblast apoptosis was enhanced after treatment with the highest zoledronate concentrations. The maximum positive effect on osteoblasts metabolic activity and proliferation was observed with the zoledronate concentrations corresponding to those theoretically reached in bone microenvironment when zoledronate is used in clinical practice for post-menopausal osteoporosis treatment. CONCLUSIONS: The results of this study confirm that bisphosphonates exert different cellular biochemical effects depending on dosage and support the hypothesis that their positive effect on bone mineral density could be partially due to an anabolic action on bone forming cells.

Frequency of human papillomavirus infection and genotype distribution among women with known cytological diagnosis in a Southern Italian region.

INTRODUCTION: In the Puglia region (South Italy) about 200 new hospitalizations for cervical cancer are registered every year. The study investigated the frequency of Human Papillomavirus (HPV) infection and the genotype distribution of HPV in a sample of women with known cytology attending the outpatient clinics of four Gynecological Departments of the University of Bari over a four-year period (2005-2008). METHODS: Cervical samples from 1,168 women were analyzed for the presence of HPV-DNA through Polymerase Chain Reaction (PCR) in L1 region and reverse hybridization. The cytological results were associated with HPV positivity and type-specific prevalence. RESULTS: Overall, HPV infection was found in 355 (30.4%) women. HPV-DNA was found in 34.4% of women with a cytological diagnosis of ASCUS, in 46.8% of women with Low-grade Squamous Intraepithelial Lesion (LSIL) and in 87.0% of women with High-grade Squamous Intraepithelial Lesion (HSIL)/carcinoma. Also 16.0% of women with normal Pap smear were found to be HPV-DNA positive. The most common HPVgenotype was type 16 found in 27.3% of positives, followed by type 53 (11.5%), type 66 (9.2%) and type 31 (9.0%). HPV genotype 18 was found in 6.4% of positives. Types 16 or 18 were detected in about 34% (120/355) of all infected women, in about 33% of LSIL and in 60% of HSIL/ carcinoma HPV-positive women. Among low risk (LR) genotypes, type 61 was found in 10.7% of HPV positive women, type 62 in 8.4%, type 42 in 8.1% and type CP6108 in 7.8%. DISCUSSION AND CONCLUSIONS: The findings of the study give evidence that HPV infection is frequent in the studied cohort of women. The most widespread genotypes found were 16 and 53. These data may represent a benchmark for future evaluation after the recent introduction of vaccination against HPV in 12-year-old girls.

Evaluation of toxic chemical parameters and ecotoxicity levels in bottled mineral waters.

Heavy metals, phthalates, characterizing elements, CO2 concentrations and pH and hardness levels were measured in forty samples of bottled mineral waters. In some samples arsenic, manganese, mercury and selenium were present in higher concentrations than permitted by Italian law. No significant release of phthalates from containers in PET was observed. In the same samples, toxicity tests with Daphnia magna were carried out. Toxicity levels, expressed as % of immobile organisms, ranged from 0 to 100%; generally the highest toxicity values were found in the hardwaters.

[Epidemiology of HPV infections and cervical cancer in Apulia: a survey study and current data analysis]. / Epidemiologia delle infezioni da HPV e del cervicocarcinoma in Puglia: studi ad hoc e analisi dei dati correnti.

HPV infection is common in sexually active women and is an important risk factor for cervical cancer. The aim of this article is to describe the prevalence of HPV infection, the incidence and the mortality rates for cervical cancer and adherence to screening programs in Apulia in the light of recent introduction of anti-HPV vaccines. The prevalence of HPV was evaluated testing biological samples from 1082 women. The 33% resulted positive for HPV (80% for high-risk genotypes and 20% for low-risk genotypes). The 59% of positive samples showed only a single viral type while 37% multiple genotypes. In Apulia, from 1998 to 2005, a total of 1849 women were hospitalized for cervical cancer with a decreasing trend; the 46% had exo cervical cancer; the 22% endocervical cancer, 29% cancer of cervix without specification and 3% infiltrating cervical cancer. The mortality rate was 1,5 x 100.000. Data from PASSI study regarding cervical cancer screening showed that 62% of Apulian women 25-64 years aged had a Pap smear and 54.7% get it every three years. The viral genotypes circulating in Apulia region are present in anti-HPV vaccines; this item could give information on their introduction together with actions to implement the adherence to screening program that results lower than international standard.

Perception of visual motion coherence by rats and mice.

The coherence thresholds to discriminate the direction of motion in random-dot kinematograms were measured in rats and mice. Performance was best in the rats when dot displacement from frame-to-frame was about 2 degrees, and frame duration was less than 100 ms. Mice had coherence thresholds similar to those of rats when tested at the same step size and frame duration. Although the lowest thresholds in the rats and mice occasionally reached human levels, average rodent values ( approximately 25%) were 2-3 times higher than those of humans. These data indicate that the rodent and primate visual systems are similar in that both have local motion detectors and a system for extracting global motion from a noisy signal.

Discontinuing antiepileptic drugs in patients who are seizure free on monotherapy.

OBJECTIVES: To assess the recurrence rate of epilepsy attributable to discontinuation of treatment in seizure free patients and to identify the risk factors for recurrence. METHODS: 330 patients referred to an epilepsy centre who were seizure free for at least 2 years while on stable monotherapy were the study population. Discontinuation of antiepileptic drugs (AEDs) was proposed to all eligible patients or to their carers after discussion of the risks and benefits. Depending on whether they accepted or refused treatment withdrawal, the patients were stratified into two cohorts and followed up until seizure relapse or 31 March 1999, whichever came first. For each patient, records were taken of the main demographic and clinical variables. RESULTS: The sample comprised 225 patients who entered the discontinuation programme and 105 who decided to continue treatment. Twenty nine patients (28%) continuing treatment had a relapse, compared with 113 (50%) of those entering the withdrawal programme. For patients continuing treatment, the probability of remission was 95% at 6 months, 91% at 12 months, 82% at 24 months, 80% at 36 months, and 68% at 60 months. The corresponding values for patients discontinuing treatment were 88%, 74%, 57%, 51%, and 48%. After adjusting for the principal prognostic factors, in patients discontinuing AEDs the risk of seizure relapse was 2.9 times that of patients continuing treatment. A relation was also found between relapse and duration of active disease, number of years of remission while on treatment, and abnormal psychiatric findings. CONCLUSIONS: Seizure free referral patients on stable monotherapy who elect to withdraw drug treatment are at higher risk of seizure relapse compared with patients continuing treatment. Severity of disease and seizure free period are significant prognostic factors.

A single-blind comparison of three-day azithromycin and ten-day co-amoxiclav treatment of acute lower respiratory tract infections.

The efficacy and safety of a three-day regimen of azithromycin (500 mg od) and a ten-day regimen of co-amoxiclav (625 mg tid) were compared in a single-blind study in 99 patients with acute lower respiratory tract infections. Of these, 70 (71%) suffered an infective exacerbation of their chronic obstructive pulmonary disease. Nine patients had pneumonia and 19 purulent bronchitis. Treatment success, defined as cure or improvement, occurred in 43 of 48 (90%) patients in the azithromycin group, compared with 45 of 51 (88%) patients in the co-amoxiclav group. The most common isolated pathogens were Haemophilus influenzae (25 cases; MIC range of azithromycin (A) < or = 0.06-4 mg/L; for co-amoxiclav (CA) 0.25-4 mg/L; Streptococcus pneumoniae (10 cases; A: < or = 0.06- > 128; CA: < or = 0.06); and Moraxella catarrhalis (four cases; A: < or = 0.06; CA: < or = 0.06-0.25). Microbiological response rates were comparable in the two groups. In 5% of patients, serological evidence for virus or atypical pathogens was found. Thirteen (26%) patients treated with co-amoxiclav had gastrointestinal complaints (seven with diarrhoea), compared with five (10%) treated with azithromycin (P = 0.09). Additional complaints occurred in three patients treated with co-amoxiclav and in one patient treated with azithromycin. It was concluded that a three-day regimen of azithromycin was as effective, clinically and microbiologically, as a ten-day regimen of co-amoxiclav in the treatment of acute lower respiratory tract infections.

The effect of glass heat treatment on the properties of a novel polyalkenoate cement.

The effect of heat treating the glass component of a novel glass-ionomer (polyalkenoate) cement on cement properties has been determined, with specific reference to the reactivity of the glass, and the mechanical properties of the resultant cement. It has been shown that heat treatment is a suitable method of decreasing the glass reactivity and improving the handling characteristics of the mixed cement. Under some conditions, an increase in compressive strength was found, although the effect on tensile properties was not significant.

Appendiceal mucoceles and pseudomyxoma peritonei.

Mucoceles of the appendix and associated pseudomyxoma peritonei are a heterogeneous group comprising various histopathologic lesions with differing prognoses. Between 1983 and 1990, we treated eight patients with appendiceal mucocele, three cystadenomas and five cystadenocarcinomas, three of which had accompanying pseudomyxoma peritonei. All patients were more than 50 years of age. Women outnumbered men by seven to one. Preoperative diagnosis was acute appendicitis or appendiceal abscess in all instances of mucocele unaccompanied by pseudomyxoma peritonei. Ultrasound of the abdomen, together with paracentesis, diagnosed pseudomyxoma peritonei in two of three patients. Elevated carcinoembryonic antigen levels were found in six of the eight patients and monitoring of this parameter was useful in the early detection of the two recurrences observed. The three patients with cystadenomas remain free of disease after appendectomy. Of the five patients treated for cystadenocarcinoma by right colectomy, two underwent reoperation after recurrence of disease. One patient died 41 months later of intestinal obstruction caused by pseudomyxoma peritonei. Pseudomyxoma peritonei significantly decreases survival of patients with appendiceal mucocele. In these patients, aggressive initial surgical management, repeated if need be, is indicated.

Development of novel dental cements. I. Formulation of aluminoborate glasses.

Aluminoborate glasses were formulated as potential novel glass-ionomer cement components, and their reactivity with a polyalkenoic acid was assessed by means of working and setting time measurements. Of the 20 prepared formulations, some containing fluoride, eight were found to have acceptable manipulative characteristics, and three of these formed hard set materials.

Development of novel dental cements. II. Cement properties.

Following earlier work, three novel aluminoborate glasses have been studied as potential cement components. Factors studied include the effect of batch size on composition and manipulative characteristics, and the effect of tartaric acid and conditions of storage on mechanical properties. It was concluded that two materials have potential for application as dental luting agents.