A Comparative Study of Laser In Situ Keratomileusis Flaps Created Using Single-Functional Versus Multifunctional Femtosecond Laser for Refractive Surgery.

PURPOSE: To compare laser in situ keratomileusis flaps created at the programmed target thickness of 120 µm using the LenSx multifunctional and the FS200 single-functional femtosecond lasers as evaluated by anterior segment optical coherence tomography (AS-OCT). METHODS: This was a prospective, comparative, consecutive, blinded, nonrandomized study. Patients with stable refraction for over a year were consecutively allocated to the LenSx group or the FS200 group (n = 66; 33 patients in each group). All the patients underwent refractive surgery in both eyes. Previous eye surgery, ocular pathology associated with refractive errors, pregnancy, breastfeeding, and use of medication that causes ocular adverse effects constituted the exclusion criteria. Corneal topography, corneal tomography, dilated fundoscopy, applanation tonometry, ultrasonic pachymetry, dynamic and static refraction, visual acuity, and AS-OCT were evaluated before and after surgery. AS-OCT flap thickness was measured at 20 points on each cornea. RESULTS: In the LenSx group, AS-OCT flap thickness differed significantly from the target thickness at 2 of 20 points (mean differences of 2.106 and 1.803 µm). In the FS200 group, 6 of 20 measurements differed significantly (mean differences ranging from 1.121 to 2.121 µm). The 2 lasers were similarly successful in creating regular and uniform flaps. The agreement between the 2 blinded examiners regarding the AS-OCT flap thickness measurements was excellent (intraclass correlation coefficient >0.75) in both groups. CONCLUSIONS: Both femtosecond lasers were safe and capable of creating highly reproducible, uniform, and regular flaps at the target preoperative thickness of 120 µm. The LenSx multifunctional femtosecond laser offers the advantage of allowing both cataract and corneal surgeries.

Reproducibility of laser in situ keratomileusis flap thickness using a new multifunctional femtosecond laser platform and correlation with clinical preoperative measurements.

PURPOSE: To analyze the reproducibility of laser in situ keratomileusis (LASIK) flap thickness (target 120 µm) using the multifunctional femtosecond laser (Lensx) and correlate postsurgical measurements with preoperative factors. SETTING: Hospital Oftalmológico Visão Laser, Santos, São Paulo, Brazil. DESIGN: Prospective case series. METHODS: Patients with stable refraction for over a year were evaluated. Patients who submitted to refractive surgery with -1.25 to -6.00 diopters (D), with or without astigmatism up to -4.00 D, and corneal curvature of 40.00 to 47.00 D were included. At 100 days postoperatively, an independent examiner performed 4 high-resolution tomographic sections of the cornea for each eye at 45- to 225-degree, 90- to 270-degree, 135- to 315-degree, and 0- to 180-degree meridians. Two masked experienced observers analyzed each section using measuring points located at the center of the cornea (0.0 mm), 2.0 mm to the left and to the right of the center, and 4.0 mm to the left and to the right of the center. RESULTS: The study comprised 33 patients (63 eyes), aged 21 to 50 years. A significant difference from the target flap thickness (120 µm) was found in 2 of 20 measurements; however, the actual difference was approximately 2.2 µm. Interrater reliability was excellent (ICC > 0.75), with an interrater bias close to 0. Clinical measurements were not predictive of the set of 20 postoperative measurements. CONCLUSION: Reproducibility of the multifunctional femtosecond laser was good for LASIK flap creation and no predictive correlation was found with preoperative clinical factors.

Previous infection and the risk of ischaemic stroke in Italy: the IN2 study.

BACKGROUND AND PURPOSE: There is an increasing interest in new risk factors for ischaemic stroke. Acute and chronic infections could contribute to different aetiological mechanisms of atherosclerosis that lead to cerebrovascular disease. The aim of this study was to investigate the hypothesis that previous infections and Chlamydia pneumoniae in particular increase the risk of ischaemic stroke in the population. METHODS: This was a prospective case-control study involving 11 Italian stroke units. Controls were age- and sex-matched with cases, represented by patients admitted to hospital for acute ischaemic stroke. For each participant classical vascular risk factors and previous inflammatory and infectious events up to 1 month before were registered. Blood samples were collected to analyse inflammatory markers and titres of antibodies against C. pneumoniae. RESULTS: A total of 1002 participants were included (mean age 69 years) with 749 ischaemic stroke patients. Infections occurred within 1 month previously in 12% of the entire sample with a higher prevalence in the case group (14.4% vs. 3.9%). At multivariate analysis of the seropositivity of IgA antibodies against C. pneumoniae increased the risk of stroke significantly (relative risk 2.121; 95% confidence interval 1.255-3.584) and an early previous infection (up to 7 days before the event) contributed to a rise in probability of acute cerebral ischaemia (relative risk 3.692; 95% confidence interval 1.134-6.875). CONCLUSIONS: Early previous infections and persistent chronic infection of C. pneumoniae could contribute to increase the risk of ischaemic stroke significantly, in the elderly especially.

Pattern of care and effectiveness of treatment for glioblastoma patients in the real world: Results from a prospective population-based registry. Could survival differ in a high-volume center?

BACKGROUND: As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. METHODS: Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. RESULTS: Two hundred sixty-seven GBM patients (median age, 64 y; range, 29-84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2-12.4). The 139 patients ≤aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0-18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248-0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388-0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328-0.986; P = .0446). CONCLUSIONS: The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged ≤70 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor.

Analysis of MGMT promoter methylation status on intraoperative fresh tissue section from frameless neuronavigation needle biopsy of 25 patients with brain tumor.

Formalin fixation under conditions that adversely affected the quality of the DNA, or indeterminant assay, or extensive tumor necrosis can compromise the genetic analysis of a brain bioptic sample. The success of DNA extraction and Methyl Guanine Methyl Transferase (MGMT) promoter methylation testing could be improved by freezing of fresh tumor tissue at the moment of biopsy. To ensure an increased concentration of the DNA samples the withdrawal should be performed in an area with high probability of neoplastic cells. From May 2007 to January 2011 fifty-two frameless neuronavigation brain needle biopsy were performed at the Neurosurgery Unit of the "Arcispedale Santa Maria Nuova" City Hospital of Reggio Emilia. The "image-guided" neuronavigated protocol sampling provided withdrawal specimens highly correlated with neuroimaging characteristics of the lesions. In this study the Authors report the genetic analysis on 24 cases of freezing fresh tissue from brain needle bioptic sample starting from July 2008. The molecular determination of MGMT promoter was assessed with the Nested-Methylation Specific-Polymerase Chain Reaction on fresh or cryopreserved needle bioptic tissue. The genetic characterization was feasible in all the bioptic samples. The MGMT promoter was methylated in eleven patients, including a brain infection. The diagnostic yield of brain biopsy could be increased by the neuronavigated trajectories and the intraoperative frozen sections. In the future the availability of the molecular-genetic characterization of a brain tumor before open surgery will provide important information for the optimal treatment. The MGMT promoter status analysis on needle bioptic fresh tissue could be available also for that patient not eligible for surgical remotion of the tumor.

Detection of IDH1 mutations and the status of MGMT promoter on intraoperative fresh tissue section from frameless neuronavigation needle biopsy. Analysis on 17 patients with brain glial tumor ineligible for craniotomy and tumor resection.

It is well known that primary and secondary glioblastomas are histologically largely indistinguishable. Therefore, the detection of IDH1 mutations or the status of the MGMT promoter on a simple bioptic sample could be one of major diagnostic and prognostic importance for glial patients that complements clinical criteria for distinguishing secondary from primary glioblastomas and to predict a more favourable prognosis. Currently, biopsy is the method of choice to obtain tissue from intracranial lesions with uncertain neurodiagnostic findings or in deep locations, with a minimal invasive approach. The needle biopsy with frameless neuronavigation could provide a sampling with elevated diagnostic yield and high concentration of DNA, due to the "image-guided" computer assisted technique of needle insertion through the most neurodiagnostic representative tumor area. The freezing of fresh tumor tissue at biopsy could greatly improve the success of DNA extraction. The concentration of the DNA samples can also improved from a withdrawal in an area with high probability of neoplastic cells. The present study reports the results of 17 patients who had undergone frameless image-guided intracranial needle biopsy from April 2008 until July 2010 at Neurosurgery Unit of the "Arcispedale Santa Maria Nuova" of Reggio Emilia. For these patients the molecular determination of MGMT promoter was assessed with the Nested-Methylation Specific-Polymerase Chain Reaction and the screening of mutations in IDH1 e IDH2 genes was performer by polymerase chain reaction (PCR) and direct sequencing on fresh or cryopreserved needle bioptic tissue.

Lithium carbonate in amyotrophic lateral sclerosis: lack of efficacy in a dose-finding trial.

BACKGROUND: A neuroprotective effect of lithium in amyotrophic lateral sclerosis (ALS) has been recently reported. We performed a multicenter trial with lithium carbonate to assess its tolerability, safety, and efficacy in patients with ALS, comparing 2 different target blood levels (0.4-0.8 mEq/L, therapeutic group [TG], vs 0.2-0.4 mEq/L, subtherapeutic group [STG]). METHODS: The study was a multicenter, single-blind, randomized, dose-finding trial, conducted from May 2008 to November 2009 in 21 Italian ALS centers. The trial was registered with the public database of the Italian Agency for Drugs (http://oss-sper-clin.agenziafarmaco.it/) (EudraCT number 2008-001094-15). RESULTS: As of October 2009, a total of 171 patients had been enrolled, 87 randomized to the TG and 84 to the STG. The interim data analysis, performed per protocol, showed that 117 patients (68.4%) discontinued the study because of death/tracheotomy/severe disability, adverse events (AEs)/serious AEs (SAEs), or lack of efficacy. The Data Monitoring Committee recommended stopping the trial on November 2, 2009. CONCLUSIONS: Lithium was not well-tolerated in this cohort of patients with ALS, even at subtherapeutic doses. The 2 doses were equivalent in terms of survival/severe disability and functional data. The relatively high frequency of AEs/SAEs and the reduced tolerability of lithium raised serious doubts about its safety in ALS. CLASSIFICATION OF EVIDENCE: The study provides Class II evidence that therapeutic (0.4-0.8 mEq/L) vs subtherapeutic (0.2-0.4 mEq/L) lithium carbonate did not differ in the primary outcome of efficacy (survival/loss of autonomy) in ALS. Both target levels led to dropouts in more than 30% of participants due to patient-perceived lack of efficacy and AEs.

Ethical issues in end of life treatments for patients with dementia.

Dementia is a terminal disease, associated with great suffering and difficult decisions in the severe stage. The decision-making process is characterized by uncertainty because of lack of scientific evidence in treatments and by the need to reconcile conflicting points of view. In intercurrent diseases, aggressive interventions are used without consideration of its futility; in comparison with cancer, several consequences of physicians' attitude not to consider dementia as a terminal disease have been reported, especially concerning pain relief. Lack of evidence of artificial nutrition and hydration effectiveness makes advance care planning relevant.

Safe implementation of thrombolysis in stroke-monitoring study in Italy.

BACKGROUND AND PURPOSE: The safe implementation of thrombolysis in stroke-monitoring (SITS-MOST) study was an unique opportunity to test in Italy, where only few centres were expert in thrombolytic treatment before, safety and efficacy of i.v. alteplase within 3 h of ischaemic stroke outside the setting of clinical trials. METHODS: In Italy to participate in the study the clinical centres had to possess organizational and structural characteristics certified by Regional Health Authorities. RESULTS: Seventy-one centres were activated, 56 (79%) treated patients of which 41 (73%) had never used thrombolysis before the study. Globally, 586 patients were included. Baseline median National Institute of Health Stroke Scale of Italian patients was 13 vs. 12 in other European centres (P = 0.0001). Symptomatic intracerebral haemorrhage as per the NINDS/Cochrane definition, mortality and independence (modified Rankin Scale 0-2) rates at 3 months occurred respectively in 6.7% (95% CI: 4.8-9.1), 11.7% (9.2-14.6) and 51.6% (47.4-55.7) of Italian patients compared with 7.3% (6.7-8.0) (P = 0.56), 11.2% (10.4-12.1) (P = 0.75) and 55.1% (53.8-56.4) (P = 0.09) in the European patients and in 8.6% (40/65; 6.3-11.6), 17.3% (14.1-21.1) and 50.1% (44.5-54.7) of the patients treated in the pooled randomized controlled trials. CONCLUSIONS: The SITS-MOST study showed that in Italy i.v. alteplase is safe and effective in routine clinical use also in non-expert centres.

Antidepressant effects of total tertiary alkaloid fraction of Cissampelos sympodialis Eichler in rodents / Efeitos antidepressivos da fração de alcalóides terciários totais de Cissampelos sympodialis Eichler em roedores

A proposta deste trabalho foi de avaliar os efeitos da fração de alcalóides terciários totais (TTAF) de Cissampelos sympodialis Eichler (Menispermaceae) em dois modelos animais de depressão: a) teste do nado forçado e b) teste da reserpina. O tratamento de camundongos com TTAF (12,5 mg/kg) reduziu o tempo total de imobilidade dos animais. Também reverteu a hipotermia induzida por reserpina, demonstrando um efeito antidepressivo nos dois modelos. Adicionalmente, o tratamento com TTAF não modificou a ambulação e o comportamento de levantar das patas dianteiras dos animais avaliados no teste do campo aberto, realizado no intuito de investigar se a redução no tempo de imobilidade apresentada no teste do nado forçado foi causada por estimulação na atividade locomotora. Como a warifteína é um dos principais alcalóides presente na TTAF da C. sympodialis, e tem atividade inibidora da enzima fosfodiesterase, ela pode ser responsável pelo efeito antidepressivo observado na fração estudada.

The purpose of the present study was to evaluate the effects of total tertiary alkaloid fraction (TTAF) of Cissampelos sympodialis Eichler (Menispermaceae) on two animal models of depression: a) forced swim test and b) reserpine test. Treatment of mice with TTAF (12.5 mg/kg) reduced the total immobility time. It also reversed the reserpine-induced hypothermia, demonstrating an antidepressant effect in both models. Additionally, TTAF treatment did not modify the ambulation and rearing evaluated in open field test in order to investigate if the immobility time reduction found in the forced swimming test was caused by locomotive activity stimulation. Since warifteine is one of the main alkaloids present in the TTAF of C. sympodialis, and it has inhibitory activity of the phosphodiesterase enzyme, it may be responsible by the antidepressant effect found in the fraction studied.

Ethical questions in the treatment of subjects with dementia. Part I. Respecting autonomy: awareness, competence and behavioural disorders.

The document deals with some ethical issues raised by the treatment of demented people. In particular the conceptual and empirical aspects of the assessment of awareness and competence of these patients are analysed, as well as the dilemmas related to the treatment of behavioral disorders.

Epidemiological survey of amyotrophic lateral sclerosis in the province of Reggio Emilia, Italy: influence of environmental exposure to lead.

We carried out a retrospective incidence, prevalence and mortality survey of amyotrophic lateral sclerosis (ALS) in the province of Reggio Emilia, northern Italy. Based on 79 patients, the mean incidence per year for the period 1980 through 1992 was 1.5 cases per 100,000. On December 31st, 1992, the prevalence rate was 5.4 per 100,000. In the 10-year period of 1983-1992 the average mortality rate was 1.3 per 100,000 per year. The average age at onset was 61.3 +/- 10.2, the average survival period thereafter was 26.3 months +/- 17.7; 27.3 +/- 17.6 for classic ALS, 19.5 +/- 8.4 for progressive bulbar palsy and 36.3 +/- 41.4 for pseudopolyneuritic ALS. The incidence rate, recorded in public health district No.12, an area with documented lead pollution since the 1970s, was standardized to the sex and age of the population of the province. Its incidence and prevalence rate were comparable to the rates found in the remaining area of the province.

Sympathetic skin response in patients with Duchenne muscular dystrophy.

To verify an eventual disfunction of the palmar sympathetic skin activity in Duchenne Muscular Dystrophy, we studied the sympathetic skin response (SSR) with endogenous, Deep Breathing (DB-SSR), exogenous Startle (SE-SSR) and Electric type stimuli (EE-SSR) in a group of patients and a control group. At the same time as the SSR, the heart rate (HR) and the basic R-R interval variation (RRIV) as well as the EMG diaphragmatic activity were checked. In this way, significant differences in the latency (p = 0.02) and amplitude (p = 0.009) values of the EE-SSR and in the amplitude values of the SE-SSR (p = 0.001) and of the DB-SSR (p = 0.02) were noted in the DMD group compared to the control group. In the group of patients the rise in latency of the EE-SSR correlates with the age (p = 0.0001) and with the reduction of its amplitude (p = 0.03). This last parameter correlates with the stage of the illness (p = 0.02). In the control group the mean amplitude of the EE-SSR is approximately 30% greater than that of startle and 50% of deep breathing. Although with amplitudes homogeneously reduced, these ratios are also conserved in the DMD group. Moreover the HR is greater (p = 0.0001) whilst the RRIV is reduced (p = 0.02) in the group of the patients. However these parameters do not correlated either to the cardiac involvement or to the stage of the illness. The presence of the SSR for all the modalities of stimulation indicates the substantial integrity of the afferent and the efferent paths of the ANS. The alterations in latency and amplitude of the SSR in the patients could be the consequence of a lack of dystrophin at the level of the sudoriparous myopithelium in analogy to what has been demonstrated in the mdx mouse.

Dystrophin expression in skin biopsy immunohistochemical. Localisation of striated muscle type dystrophin.

Dystrophin is normally localized in smooth muscle fibers of various organs in experimental animals, and it has been shown to be defective in the smooth muscle fibers of the mdx mouse, including the myoepithelial cell layer of the sweat glands. We investigated dystrophin localization, using three antisera raised against different domains of skeletal muscle type of dystrophin, in the smooth muscle structures of the skin, using immunohistochemical methods with monoclonal antibodies against dystrophin, in 24 patients with various neuromuscular diseases, and in a normal control. Skin biopsy showed a strong dystrophin reaction in the arrector pili muscles and in the myoepithelial cells of the sweat glands of patients with congenital muscular dystrophy, polymyositis, distal myopathy, putative Duchenne muscular dystrophy carriers, myoglobinuria, neurogenic atrophy and in a normal control. A faint positive dystrophin reaction was seen in four patients with Becker muscular dystrophy, whereas it was absent in 3 patients with Duchenne muscular dystrophy. As our data suggest that immunohistochemical dystrophin expression in smooth muscle structures of the skin is similar to that observed in striated muscle, skin biopsy may represent an alternative way to ascertain dystrophin deficiency.

[Lyme disease. Case contribution and review of the literature]. / Malattia di Lyme. Contributo casistico e revisione della letteratura.

Lyme borreliosis is a systemic disease. The etiologic agent is a tick-bite borne spirochete (Borrelia burgdorferi) of which men are casual hosts. Although the illness is reported worldwide, it is more frequent in the northern parts of Countries. Some isolated clinical pictures are reported in the past, but only in 1975 the illness was well described at Old Lyme (Connecticut, Usa) and then well defined in its pathogenesis and clinical course in three stages. Lyme disease, involving skin, heart, nervous system and joints, is frequently protean and misdiagnosed, so that it was called "the new great imitator". In Italy the first case is reported in 1985. The authors report three (3) new cases, mostly with neuro-articular signs and symptoms. Literature is partially reviewed, for a better definition and outline of some epidemiological, etiopathogenetic, historical and clinico-therapeutic aspects of Lyme disease.

[Goiter recurrences after surgical resection]. / Le recidive del gozzo dopo resezione chirurgica.

A personal experience about 135 pz. with non-toxic goitre treated by mono o bilateral thyroidectomy and followed during 5 years (2-8) to evaluate the incidence of recurrences is reported. The recurrences were 10.5%, especially after monolateral thyroidectomy (9 pz.). Therefore the authors stress the importance of a more accurate surgical indication, a wider resection of the gland and a careful follow-up to undertake opotherapy when hypofunction appears.