Early posterior vitreous detachment is associated with LAMA5 dominant mutation

Background: Extracellular matrix molecular components, previously linked to multisystem syndromes include collagens, fibrillins and laminins. Recently, we described a novel multisystem syndrome caused by the c.9418G>A p.(V3140M) mutation in the laminin alpha-5 (LAMA5) gene, which affects connective tissues of all organs and apparatus in a three generation family. In the same family, we have also reported a myopic trait, which, however, was linked to the Prolyl 4-hydroxylase subunit alpha-2 (P4HA2) gene. Results of investigation on vitreous changes and their pathogenesis are reported in the present study.Materials and Methods: Nineteen family individuals underwent complete ophthalmic examination including best-corrected visual acuity (BCVA), fundus examination, fundus photography, intraocular pressure measurement, axial length measurement using ocular biometry, Goldmann visual field examination, standard electroretinogram, SD-OCT. Segregation analysis of LAMA5 and P4HA2 mutations was performed in enrolled members.Results: The vitreous alterations fully segregated with LAMA5 mutation in both young and adult family members. Slight reduction of retinal thickness and peripheral retinal degeneration in only two patients were reported.Conclusions: In this work we showed that PVD is a common trait of LAMA5 multisystem syndrome, therefore occurring as an age-unrelated trait. We hypothesize that the p.(V3140M) mutation results in a reduction of retinal inner limiting membrane (ILM) stability, leading to a derangement in the macromolecular structure of the vitreous gel, and PVD. Further investigations will be necessary to elucidate the role of wild type and mutated LAMA5 in the pathogenesis of PVD.     

Pseudomembranous colitis caused by antibiotic therapy during aorto-iliac surgery

Pseudomembranous colitis is not a rare complication of antibiotic therapy. 2000 surgical procedures with implantation of grafts in the aorto-iliac region were performed from 1974 through 1988; during this period 11 cases of CMP were observed. The Authors report their experience in regard to the various antibiotics administered.     

Soluble factors levels in the initial staging of high-grade non-Hodgkin's lymphomas.

Plasma levels of several soluble factors were assayed in 31 untreated patients with high-grade non-Hodgkin's lymphomas (NHL). The results showed statistically significant higher average levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-2 receptor (IL-2r) and transferrin receptor (TF-r) in NHL patients compared to controls (p = 0.045, p = 0.047, p = 0.020, p = 0.026 and p = 0.033 respectively). IL-2, IL-2r and TF-r levels were found more elevated in Stages III/IV than in Stages I/II (p = 0.031, p = 0.016 and p = 0.048 respectively), whereas IL-6 concentrations were higher in patients presenting B symptoms (p = 0.011). Significant correlations were found between the erythrocyte sedimentation rate (ESR) and IL-6 (r = 0.681), and between beta 2 microglobulin (B2-m) and IL-2r (r = 0.622).     

Transesophageal echocardiography-guided cardioversion of atrial fibrillation. Selection of a low-risk group for immediate cardioversion.

INTRODUCTION: In patients (pts) with atrial fibrillation (AF) of more than 48 hours' duration, electrical cardioversion (ECV) should only be performed after 3 weeks of effective anticoagulation. Transesophageal echocardiography (TEE) allows earlier ECV; however, despite exclusion of thrombi in the atrium and left atrial appendage (LAA), cases of thromboembolism related to ECV have been documented in AF. To define a low-risk group for cardioversion without previous anticoagulation, pts were selected for immediate ECV if no thrombi or dynamic spontaneous echo contrast (auto-contrast) were found after TEE and if LAA velocity was more than 0.25 m/sec. METHODS AND RESULTS: We performed TEE in 31 consecutive pts referred for ECV for AF of more than 48 hours' duration and without previous anticoagulation. After TEE the pts eligible for immediate ECV began anticoagulation with low molecular weight heparin (enoxaparin), subcutaneously in therapeutic doses, together with warfarin immediately before cardioversion. Enoxaparin was continued until an INR of over 2 was reached. Based on the TEE findings, the pts were divided in 2 groups: immediate ECV, group A, 20 pts with a mean age of 62 +/- 13 years, 6 female; and conventional therapy with warfarin before ECV, group B, 11 pts, mean age of 67 +/- 10 years (p < 0.05), 2 female. None of the pts in either group had mitral stenosis or previous episodes of thromboembolism. The mean transverse diameter of the left atrium in the 31 pts was 47 +/- 4.5 mm, without statistically significant differences between the 2 groups. Of the 11 pts in group B, 3 had a thrombus in the LAA, 6 dynamic spontaneous echo contrast and the remainder LAA velocities of less than 0.25 m/sec. ECV was achieved in all the pts, with no complications. Oral anticoagulation was maintained for at least a month. At one month, sinus rhythm was maintained in 75% of group A and 45% of group B (p < 0.01). CONCLUSION: In pts with AF of more than 48 hours' duration and no previous history of thromboembolism, the use of our exclusion criteria during TEE enabled stratification of a low-risk population for immediate ECV, which was accomplished effectively and safely in 2/3 of the pts. This strategy is associated with early symptomatic improvement, and may contribute to maintenance of sinus rhythm after one month, which was significantly better than in the pts who had prolonged therapy with warfarin before ECV, despite the differences found in age and left ventricular function.     

Stronger association of drug-induced progressive multifocal leukoencephalopathy (PML) with biological immunomodulating agents

Aim  

The aim of the present study was to collect and compare cases of drug-induced PML in order to contribute to the debate about the role of the underlying diseases and/or drug immunosuppression in PML occurrence.     

Spontaneous reporting of adverse drug reactions in an Italian region: Six years of analysis and observations

Pharmacovigilance started in Italy in 1965, and from 1987 reporting of ADRs has been mandatory. Doctors have to send the filled forms on suspected ADRs to the Local Health Districts which transmit biannually all the reports to the Health Department. In a Northern Italian Region (Veneto) spontaneous reporting of adverse drug reactions (ADRs) has been studied during the period 1988–1993. This Region contributes a substantial percentage of the total Italian reports. The total number of reports was 3700, most of these (54 per cent) coming from GPs. A great variability in the reporting rate among the 36 districts of Veneto Region (range: 0–8.8 per 10,000 inhabitants per year) and an important under-reporting have been evident. Underreporting is also emphasized by the fact that in 1993 the Veneto doctors who sent at least one report were only 2.7 per cent. On the whole about 35 per cent of reports concerned minor reactions caused by drugs which have a well known toxicological profile. Comparison between reports coming from Veneto and the UK in some cases show a similar safety profile (omeprazole and simvastatin), whereas in other cases (e.g. terfenadine, glafenine, fluoxetine) no correspondence can be found. This article reveals the limits of the actual spontaneous reporting in Italy and suggests some possible measures for improving it.     

Aqueductal stenosis as isolated localization involving the central nervous system in children affected by von Recklinghausen disease

The Authors report three cases of non tumoral aqueductal stenosis associated with von Recklinghausen disease in children. Moreover, 16 similar cases collected from the literature are illustrated. The clinical features are evaluated in light of literature's data. Among all 19 cases, the median age was 19 years (range 6-46 years) and 9 patients were under the age of 13 years. In this latter group, the most represented clinical symptoms were headache and gait disturbances. As regards the neuroradiological procedures, CT scan represented the best tool in the evaluation of the ventricular size. Our own three cases underwent to ventriculo-atrial shunt procedures, followed by clinical recovery (follow-up: 3 months-5 years). In conclusion it is felt that, among all the pathological events usually described in patients affected by neurofibromatosis, aqueductal stenosis seems to belong to the natural history of this disease.     

Acute anti-inflammatory activity and gastrointestinal tolerability of diclofenac and nitrofenac

Diclofenac and its derivative nitrofenac were compared to test their anti-inflammatory efficacy and gastrointestinal toxicity in rats.A similar good anti-inflammatory activity of the two drugs was observed in carrageenan oedema and a marked gastrointestinal toxicity was induced by diclofenac, while nitrofenac failed to produce gastric damage even with very high doses (50 and 100 mg/kg).The lack of the gastric ulcers in rats treated with nitrofenac could be due to the absorption of the drug as an inactive inhibitor of PG synthesis and/or to the fact that probably nitric oxide is release in the intestine and plays an important protective role in maintaining the tissue integrity.     

Could mitochondrial haplogroups play a role in sporadic amyotrophic lateral sclerosis?

Mitochondrial impairment has been implicated in the pathogenesis of the amyotrophic lateral sclerosis (ALS). Furthermore, mitochondrial-specific polymorphisms were previously related to other neurodegenerative diseases, such as Parkinson, Friedreich and Alzheimer disease. To investigate if specific genetic polymorphisms within the mitochondrial genome (mtDNA) could act as susceptibility factors and contribute to the clinical expression of sporadic ALS (sALS), we have genotyped predefined European mtDNA haplogroups in 222 Italian patients with sALS and 151 matched controls. Individuals classified as haplogroup I demonstrated a significant decrease in risk of ALS versus individuals carrying the most common haplogroup, H (odds ratio 0.08, 95% confidence interval 0.04-0.4, p < 0.01). Further stratification of the dataset by sex, age and site of onset of disease and survival failed to reach significance for association. Our study provides evidence of the contribution of mitochondrial variation to the risk of ALS development in Caucasians. Further it may help elucidate the mechanism of the mitochondrial dysfunction detectable in ALS, and may be of relevance in development of strategies for the treatment of this disease.