Real-life impact of early interferon beta therapy in relapsing multiple sclerosis.

OBJECTIVE: Recent findings support greater efficacy of early vs. delayed interferon beta (IFNbeta) treatment in patients with a first clinical event suggestive of multiple sclerosis (MS). We aimed to evaluate the effectiveness of early IFNbeta treatment in definite relapsing-remitting MS (RRMS) and to assess the optimal time to initiate IFNbeta treatment with regard to the greatest benefits on disability progression. METHODS: A cohort of 2,570 IFNbeta-treated RRMS patients was prospectively followed for up to 7 years in 15 Italian MS Centers. A Cox proportional hazards regression model adjusted for propensity score (PS) quintiles was used to assess differences between groups of patients with early vs. delayed IFNbeta treatment on risk of reaching a 1-point progression in the Expanded Disability Status Scale (EDSS) score, and the EDSS 4.0 and 6.0 milestones. A set of PS-adjusted Cox hazards regression models were calculated according to different times of treatment initiation (within 1 year up to within 5 years from disease onset). A sensitivity analysis was performed to assess the robustness of findings. RESULTS: The lowest hazard ratios (HRs) for the three PS quintiles-adjusted models were obtained by a cutoff of treatment initiation within 1 year from disease onset. Early treatment significantly reduced the risk of reaching a 1-point progression in EDSS score (HR = 0.63; 95% CI = 0.48-0.85; p < 0.002), and the EDSS 4.0 milestone (HR = 0.56; 95% CI = 0.36-0.90; p = 0.015). Sensitivity analysis showed the bound of significance for unmeasured confounders. INTERPRETATION: Greater benefits on disability progression may be obtained by an early IFNbeta treatment in RRMS.

Effect of a full-grown vegetative filter strip on herbicide runoff: maintaining of filter capacity over time.

Narrow vegetative filter strips (VFS) proved to effectively reduce herbicide runoff from cultivated fields mainly due to the ability of vegetation to delay surface runoff, promote infiltration and adsorb herbicides. Since VFS are dynamic systems, their performance would not remain constant over the years indicating the need to define suitable buffer management. In order to evaluate the performance of different five and six year-old VFS, the runoff of the herbicides metolachlor and terbuthylazine was monitored in 2002 and 2003 in an experimental site in northern Italy. The structure of the herbaceous cover in the buffers changes over time. When rows of trees are present, the grass cover is decreased by the shading action of the trees, but the leaf litter gains importance. In VFS with grass cover only, the cover composition changes because of the substitution of grass by broadleaf species. Six metres wide VFS are very effective in reducing runoff volume and concentration during both wet and dry years. Classification analysis showed that runoff concentration and volume are linked to the characteristics of the rainfall event, buffer, source of herbicides and time after application. Regression analysis showed that the significant predictors for runoff volume are rainfall amount and intensity, total vegetal cover in the VFS, crop leaf area index and time after treatment; for concentration they are rainfall intensity, crop leaf area index and total vegetal cover in the VFS. The role of VFS is complex, so appropriate management is required to maintain its increasing filtering capacity over time.

A New Provocative Test for Glaucoma.

PURPOSE: To compare the effects of the water-drinking test (WDT) with the 30° inverted body position test on intraocular pressure (IOP) in normal patients, suspected glaucoma patients and glaucoma patients. MATERIALS AND METHODS: Based on clinical evaluation of the optic disk, IOP, and standard achromatic perimetry (SAP) of 71 eyes, 18 were "normal" (normal SAP and optic disk evaluation, and IOP < 21 mm Hg), 30 were "glaucoma suspect" (GS; normal SAP, cup/disk (C/D) ratio > 0.5 or asymmetry > 0.2 and/or ocular hypertension), and 31 had "early glaucoma" (MD < -6 dB, glaucomatous optic neuropathy). Standard achromatic perimetry was performed with the Octopus 3.1.1 Dynamic 24-2 program. Patients fasted before the WDT, and four measurements were performed at basal, 15', 30, and 45' after drinking 1 liter of water (WDT) in 5 minutes. In the 30° inverted position, IOP measurement with Perkins applanation tonometer was taken after 5 minutes lying down. RESULTS: There was a statistical difference in all groups between the basal IOP and peak IOP during the WDT (p < 0.001) and in the inverted position IOP (p < 0.001). Controls (p = 0.50), suspects (p = 0.41) and glaucoma patients (p = 1.0) did not exhibit a difference between WDT-IOP and inverted position IOP. CONCLUSION: The 30° inverted position test was as efficient as WDT in detecting peak IOP. This new provocative test is easier, faster and more comfortable for both patients and doctors. How to cite this article: Kanadani FN, Moreira TCA, Campos LF, Vianello MP, Corradi J, Dorairaj SK, Freitas ALA, Ritch R. A New Provocative Test for Glaucoma. J Curr Glaucoma Pract 2016;10(1): 1-3.

Diurnal Curve of the Ocular Perfusion Pressure.

PURPOSE: To describe the diurnal variation of the ocular perfusion pressure (OPP) in normal, suspects and glaucoma patients. MATERIALS AND METHODS: Seventy-nine subjects were enrolled in a prospective study. The diurnal curve of intraocular pressure (IOP) was performed and blood pressure measurements were obtained. Each participant was grouped into one of the following based upon the clinical evaluation of the optic disk, IOP and standard achromatic perimetry (SAP): 18 eyes were classified as normal (normal SAP, normal optic disk evaluation and IOP < 21 mm Hg in two different measurements), 30 eyes as glaucoma suspect (GS) (normal SAP and mean deviation (MD), C/D ration > 0.5 or asymmetry > 0.2 and/or ocular hypertension), 31 eyes as early glaucoma (MD < -6 dB, glaucomatous optic neuropathy and SAP and MDs on SAP. Standard achromatic perimetry was performed with the Octopus 3.1.1 Dynamic 24-2 program. Intraocular pressure and blood pressure measurements were taken at 6 am, 9 am, 12, 3 and 6 pm. The patients stayed in the seated position for 5 minutes prior to blood pressure measurements. RESULTS: The mean IOP values in all groups did not follow any regular pattern. The peak IOP was found to be greater in suspect [18.70 ± 3.31 (mm Hg ± SD)] and glaucoma (18.77 ± 4.30 mm Hg) patients as compared to normal subjects (16.11 ± 2.27 mm Hg). In studying the diurnal variation of the OPP, we found lower values at 3 pm in normals (34.21 ± 2.07 mm Hg), at 9 am in suspects (54.35 ± 3.32 mm Hg) and at 12 pm in glaucoma patients (34.84 ± 1.44 mm Hg). CONCLUSION: Each group has a specific OPP variation during the day with the most homogeneous group being the suspect one. It is important to keep studying the IOP and OPP variation for increased comprehension of the pathophysiology of glaucomatous optic neuropathy. How to cite this article: Kanadani FN, Moreira TCA, Bezerra BSP, Vianello MP, Corradi J, Dorairaj SK, Prata TS. Diurnal Curve of the Ocular Perfusion Pressure. J Curr Glaucoma Pract 2016;10(1):4-6.

Free DNA in urine: a new marker for bladder cancer? Preliminary data.

The aim of the present preliminary study was to investigate the presence of free DNA (FDNA) in urine as a possible marker for the diagnosis of bladder cancer. Naturally voided morning urine specimens were collected from 57 patients with suspected bladder cancer before cystoscopy. A standard urine test was performed; the specimens were then processed in order to obtain a quantitative evaluation of the presence of free DNA in the urine. Twenty-two patients were excluded from the study because they had leukocyturia and/or bacteriuria. Free DNA concentrations higher than 250 ng/mL were found in all 16 patients showing bladder cancer at cystoscopy and in seven (36.8%) of the 19 patients with negative cystoscopy. Urinary FDNA seems to have an excellent sensitivity: we observed no false negative cases and 36.8% false positive cases. By contrast, only 6.25% of the bladder cancer patients had positive urine cytology. Our results seem promising, although further studies and larger numbers are needed to define urinary free DNA as a reliable marker of bladder cancer.

The spectrum of antineuronal autoantibodies in a series of neurological patients.

The aim of the present study is to identify the range of neurological disorders expressing antineuronal antibodies, evaluate the number of different patterns of reactivity that can be detected, and analyse the contribution of these studies to the identification of subgroups of patients. The records of 882 patients were reviewed and their sera and cerebrospinal fluids tested for antineuronal antibodies. Patients were initially divided into four groups according to suspected clinical diagnosis. Autoantibodies were detected by immunohistochemistry, Western blot of gradient-separated neuronal and recombinant proteins and by RIA. Cerebellar degeneration and sensory neuropathies were the most common neurological disorders in which paraneoplastic-related anti-neuronal antibodies were detected. However, in addition to PCA1/anti-Yo and ANNA1/anti-Hu antibodies, we found other reactivities in six patients with cerebellar degeneration: anti-GAD in three females and atypical in the other cases. The widest range of different anti-neuronal antibodies was detected in patients with peripheral sensory neuropathy. Few patients with Stiff-Person syndrome, temporal lobe epilepsy and myoclonus harboured anti-GAD antibodies. Atypical antibodies were detected in single cases with motor neuron disorder and multiple system atrophy. No anti-neuronal antibodies were detected in patients with neurological complications of connective tissue disorders other than Sjögren's syndrome, or in neurological diseases other than motor neuron disease and multiple system atrophy. Our study shows that the spectrum of neurological disorders in which anti-neuronal antibodies can be detected is wider than previously thought. In addition, we found patterns of neuronal staining and Western blot reactivity that differed from those so far reported. This may permit identification of subgroups of patients in whom strategies directed at removing and/or suppressing antibody production could be of some benefit.

Microwave-assisted extraction by fast sample preparation for the systematic analysis of additives in polyolefins by high-performance liquid chromatography.

This paper presents a new approach for complete and systematic analysis of organic additives in polyolefins. The proposed procedure is a convenient combination of sample preparation, performed by microwave-assisted extraction (MAE), and direct chromatographic evaluation of extract by high-performance liquid chromatography coupled with ultraviolet and evaporative light scattering detection. In particular two microwave-assisted processes are reported and discussed: the one-step MAE, useful for additives with low-medium dipolarity (like stabilizers, flame retardant, antistatics, slip and processing agents), and the two-step MAE, useful for additives with either high dipolarity (like organic salts, antigasfading, antiacid, nucleating agent) or high molecular mass (like polymeric hindered amine light stabilizers). Both the proposed processes have been tested on representative additives in five commercially common polymeric matrices, demonstrating their satisfactory analytical results, in terms of repeatability and percentage recoveries, and their good performances, in terms of safety and time/solvent consumption, in comparison with those of traditional extraction methods.

Migration of antioxidant additives from various polyolefinic plastics into oleaginous vehicles.

The migration of the antioxidant additives pentaerythrityl tetrakis(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (Irganox 1010) and tris(2,4-di-tert-butylphenyl)phosphite (Irgafos 168) from polyolefinic packaging into oily vehicles was investigated. The polyolefins included in the study were from the following classes: isotactic polypropylene homopolymer (PP), ethylene-co-propylene random copolymer (RACO), ethylene-propylene heterophasic copolymer and ethylene-propylene amorphous copolymer blend (EP) and high-density polyethylene (HDPE). Each polymer was additioned with Irganox 1010 (0.15%, w/w) and Irgafos 168 (0.15%, w/w) and processed into blown bottles. To study the antioxidant release process, plastic sheets were cut from the bottles and dipped for various time intervals into a mixture of five oils (caprylic/capric triglyceride, cyclomethicone, dicaprylyl ether, isohexadecane and C(12-15) alkyl benzoate) representative of lipophilic excipients used in pharmaceutical and cosmetic formulations. After exposure to the oil medium, the non-migrated Irganox 1010 and Irgafos 168 were recovered from the polymeric matrices using microwave-assisted extraction with ethyl acetate-hexane and assayed by HPLC. The leaching of the two antioxidants varied remarkably depending on the polyolefin crystallinity and structure. The amount of Irganox 1010 transferred into the contact medium at 25 degrees C decreased in the order EP>RACO>PP>HDPE. The same polyolefin ranking was observed in the case of Irgafos 168, except for PP and HDPE which exhibited similar depletion of this additive. Migration of Irgafos 168 was greater than that of Irganox 1010 and the release of both antioxidants increased at higher temperature (50 degrees C). The obtained data are useful for the selection of polyolefinic matrices as raw-materials for the production of pharmaceutical and cosmetic containers.

Post-marketing of disease modifying drugs in multiple sclerosis: an exploratory analysis of gender effect in interferon beta treatment.

BACKGROUND: There are a few and conflicting results from randomised controlled trials (RCTs) pertaining to the influence of gender in response to currently used disease modifying drugs in Multiple Sclerosis (MS). Observational studies may be especially valuable for answering effectiveness questions in subgroups not studied in RCTs. OBJECTIVE: To conduct a post-marketing analysis aimed to evaluate the gender effect on Interferon beta (IFNbeta) treatment response in a cohort of relapsing (RR) MS patients. METHODS: A cohort of 2570 IFNbeta-treated RRMS was prospectively followed for up to 7 years in 15 Italian MS Centers. Cox proportional hazards regression models were used to assess gender differences for risk of reaching 1st relapse and risk of progression by 1 point on Expanded Disability Status Scale (EDSS) score. Gender effects were also explored by a propensity score (PS) matching algorithm, and a tree-growing technique. RESULTS: The multivariate Cox Regression analyses showed that male patients had a significant (p=0.0097) lower risk for 1st relapse and a trend (p=0.0897) for a higher risk to reach 1 point EDSS progression than females. The PS matched multivariate Cox Regression confirmed these results. The RECPAM analysis showed that male sex conferred a significant reduction in the risk for 1st relapse (HR=0.86; 95% CI=0.76-0.98; p=0.0226) in the subgroup with a low pre-treatment number of bouts, and a significant increase in the risk for 1 point EDSS progression (HR=1.33; 95% CI: 1.00-1.76; p<0.05) in the subgroup with a delayed treatment, but a still young age at the start of treatment. CONCLUSION: The results of this exploratory analysis seem to suggest that male patients do not respond to IFNbeta treatment in the same way of females.

Antigenic differences between neurological and diabetic patients with anti-glutamic acid decarboxylase antibodies.

Antibodies to glutamic acid decarboxylase (GADAb) are found in Stiff-Person syndrome, type 1 diabetes, cerebellar ataxia and other neurological disorders (such as epilepsy and myoclonus) involving the GABAergic ways. GADAb are usually detected by immunohistochemistry (IHC), radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA). This study analysed the serum of 14 patients with neurological disorders who were positive by IHC for GADAb. The performance of a commercial RIA was compared with in-house immunoblotting and ELISA methods using recombinant GAD65 (rGAD65). RIA was positive in 14 of 14, immunoblotting was positive in seven of 14 and ELISA in 12 of 14. There was no correlation between the RIA result and the ELISA optical densities. Using a sodium thiocyanate chaotrope system with ELISA to determine antibody affinity, we found no significant correlation between antibody affinity and the RIA result. A consensus should be defined concerning which assay could be used as the gold standard for detecting GADAb. The most intriguing finding was that GAD antibodies from uncomplicated diabetics do not appear to recognize GAD in frozen sections from the rat cerebellum, whereas GAD antibodies from neurologically compromised diabetics do. A working proposal is therefore that type 1 diabetic patients with unusual neurological symptoms should be tested for GADAb both by RIA and IHC.

X-linked adrenoleukodystrophy with olivopontocerebellar atrophy.

X-linked adrenoleukodystrophy (X-ALD) is a rare neurological disorder characterized by adrenal, gonadal and nervous system dysfunction. Patients usually develop spinal cord degeneration with involvement of the cerebral white matter. While a spinocerebellar variant has been described, the selective involvement of cerebellar white matter is very rare. We report the case of a patient affected by X-ALD whose clinical and magnetic resonance imaging (MRI) results resembled olivopontocerebellar atrophy. He was a 29-year-old mentally retarded man, who began to complain of slowly progressive gait ataxia after an 8-year history of Addison's disease. Serial MRI revealed marked cerebellar atrophy involving the inferior cerebellar vermis and brainstem, but sparing the supratentorial white matter. The diagnosis of X-ALD was confirmed by elevated levels of very long-chain fatty acids in the serum. After 2 years follow-up, the patient developed spastic paraparesis. The patient represents an unusual clinical presentation of X-ALD, as further confirmed by the MRI results. Consequently, cerebellar symptoms should be considered as a clinical presentation of X-ALD. Early recognition of this rare disorder would be useful for genetic counselling and therapy.

Glutamic acid decarboxylase autoantibodies and neurological disorders.

Glutamic acid decarboxylase (GAD) is the enzyme that catalyses the production of GABA, a major neurotransmitter of the central nervous system. Antibodies to GAD (GAD-Ab) were first recognised in a patient affected by stiff-person syndrome; subsequently they were reported in a large number of cases with type 1 diabetes. Recently GAD-Ab have been described in a number of patients affected by chronic cerebellar ataxia, drug-resistant epilepsy and myoclonus. These cases usually harbour other autoantibodies or are affected by organ-specific autoimmune diseases. The role of GAD-Ab is still unclear; the lack of experimental models makes it difficult to investigate their potential pathogenetic role. However two mechanisms have been suggested: the reduction by GAD-Ab of GABA synthesis in nerve terminals or the interference with exocytosis of GABA.

[Trisomy of chromosome No. 10 in mosaic (author's transl)]. / Trisomie 10 en mosaique.

A case of trisomy of chromosome No. 10 in mosaic is described in a boy who died at the age of 6 months. The frequency of pathological cells is less than 30% (28% from lymphocytes, 20% from fibroblasts); it is possible, anyway, to rule out the hypothesis of a cellular cloning in vitro, since the trisomy 10 was observed in two different cultures, terminated after 48 and 72 hours. The parents' karyotype was normal, except for a litte number (6%) of cells with trisomy 10 from cultured lymphocytes of the mother. The morphological features of the present case are compared with those of the boy described by Higurashi et al. in 1969 (mosaic of trisomy 10, with a higher frequency of pathological cells).

[Chromosome aberrations studied in short and long-term cultures of lymphocytes from patients with chronic hepatitis]. / Alterazioni cromosomiche osservate nelle colture a breve e a lungo termine di linfociti di epatitici cronici.

Chromosome aberrations of short and long-term cultured lymphocytes have been studied in 12 subjects with chronic hepatitis B. Short-term cultures show "stickiness", aneuploidy, and fragmentations. Long-term cultures show minor damages, made up almost totally of "lacunae" and sporadic fragmentations. Major size chromosomes appear to be more affected, among the latter those containing sites for the interferon. This latter findings would suggest that the interferon decrease in patients might be bound, even only partially to the virus-linked chromosome alterations.

Karyotype-phenotype correlation in partial trisomy 13. Report of a case due to maternal translocation.

A partial trisomy 13q, originating from a maternal translocation, 46,XX,t(3;13) (p26;q22), occurred in a 3-month-old infant, affected by multiple congenital anomalies. A review of the previously reported cases of partial trisomy for the distal segment of the long arm of chromosome 13 is conclusive for the existence of a distinct clinical entity; however, it is difficult to assign particular malformations to specific chromosome bands.