A large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72, a gene located on chromosome 9p21, has been recently reported to be responsible for ~40% of familial amyotrophic lateral sclerosis cases of European ancestry. The aim of the current article was to describe the phenotype of amyotrophic lateral sclerosis cases carrying the expansion by providing a detailed clinical description of affected cases from representative multi-generational kindreds, and by analysing the age of onset, gender ratio and survival in a large cohort of patients with familial amyotrophic lateral sclerosis. We collected DNA and analysed phenotype data for 141 index Italian familial amyotrophic lateral sclerosis cases (21 of Sardinian ancestry) and 41 German index familial amyotrophic lateral sclerosis cases. Pathogenic repeat expansions were detected in 45 (37.5%) patients from mainland Italy, 12 (57.1%) patients of Sardinian ancestry and nine (22.0%) of the 41 German index familial amyotrophic lateral sclerosis cases. The disease was maternally transmitted in 27 (49.1%) pedigrees and paternally transmitted in 28 (50.9%) pedigrees (P = non-significant). On average, children developed disease 7.0 years earlier than their parents [children: 55.8 years (standard deviation 7.9), parents: 62.8 (standard deviation 10.9); P = 0.003]. Parental phenotype influenced the type of clinical symptoms manifested by the child: of the 13 cases where the affected parent had an amyotrophic lateral sclerosis-frontotemporal dementia or frontotemporal dementia, the affected child also developed amyotrophic lateral sclerosis-frontotemporal dementia in nine cases. When compared with patients carrying mutations of other amyotrophic lateral sclerosis-related genes, those with C9ORF72 expansion had commonly a bulbar onset (42.2% compared with 25.0% among non-C9ORF72 expansion cases, P = 0.03) and cognitive impairment (46.7% compared with 9.1% among non-C9ORF72 expansion cases, P = 0.0001). Median survival from symptom onset among cases carrying C9ORF72 repeat expansion was 3.2 years lower than that of patients carrying TARDBP mutations (5.0 years; 95% confidence interval: 3.6-7.2) and longer than those with FUS mutations (1.9 years; 95% confidence interval: 1.7-2.1). We conclude that C9ORF72 hexanucleotide repeat expansions were the most frequent mutation in our large cohort of patients with familial amyotrophic lateral sclerosis of Italian, Sardinian and German ancestry. Together with mutation of SOD1, TARDBP and FUS, mutations of C9ORF72 account for ~60% of familial amyotrophic lateral sclerosis in Italy. Patients with C9ORF72 hexanucleotide repeat expansions present some phenotypic differences compared with patients with mutations of other genes or with unknown mutations, namely a high incidence of bulbar-onset disease and comorbidity with frontotemporal dementia. Their pedigrees typically display a high frequency of cases with pure frontotemporal dementia, widening the concept of familial amyotrophic lateral sclerosis.

Sardinia is a high-risk area for multiple sclerosis (MS), with prevalence rates of 150 per 100,000 population. The study included 689 MS patients (female-male ratio 2.6) with disease onset between 1965 and 1999 in the province of Sassari. The mean annual incidence rate increased significantly from 1.1 per 100,000 population in 1965–1969 to 5.8 in 1995–1999, with no significant difference for gender and province sub-areas. The mean age at onset increased significantly during the same period from 25.7 to 30.6 years, while the proportion of patients with progressive initial course declined over time. The marked increase of MS incidence and the change of MS clinical phenotype over time cannot be explained by ascertainment bias only, thus pointing to a corresponding change in the distribution of exogenous risk factors in this highly genetically stable population.

Aims-To identify and determine antibiotic susceptibility of coagulase negative staphylococci (CoNS) isolated from patients with chronic blepharitis, purulent conjunctivitis, and suppurative keratitis. Methods-A retrospective review of all culture positive cases of chronic blepharitis, purulent conjunctivitis, and suppurative keratitis between July 1995 and December 1996 was performed. Cases in which CoNS were the sole isolates were analysed. Species identification was performed by using a commercially available standardised biochemical test system. Antibiotic susceptibility to penicillin, gentamicin, tetracycline, erythromycin, ciprofloxacin, and teicoplanin was determined by agar disc diVusion (KirbyBauer method). Teicoplanin resistance was confirmed by agar dilution. Results-42 Staphylococcus epidermidis, four S warneri, three S capitis, two S hominis, one each of S xylosus, S simulans, S equorum, and S lugdunensis were identified. 37 CoNS were penicillin resistant, 12 gentamicin resistant, 28 tetracycline resistant, 18 erythromycin resistant, four ciprofloxacin resistant, and one teicoplanin resistant (MIC, 32 µg/ml). In total, 16 strains were resistant to three or more antibiotics. Conclusion-Species of CoNS apart from S epidermidis may be isolated from patients with corneal and external infection. Antibiotic susceptibility of CoNS is unpredictable and multiresistant strains are common. As a result, antibiotic susceptibility testing should be performed in all cases of clinically significant ocular infections caused by CoNS. (Br J Ophthalmol 1999;83:771-773)

It has been recently reported that a large proportion of patients with familial amyotrophic lateral sclerosis (familial ALS) and frontotemporal dementia (FTD) are associated with a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72. We have assessed 1,757 Italian sporadic ALS cases, 133 from Sardinia, 101 from Sicily, and 1,523 from mainland Italy. Sixty (3.7%) of 1,624 mainland Italians and Sicilians and 9 (6.8%) of the 133 Sardinian sporadic ALS cases carried the pathogenic repeat expansion. None of the 619 regionally-matched control samples (1,238 chromosomes) carried the expansion. Twenty-five cases (36.2%) had behavioral FTD in addition to ALS. FTD or unspecified dementia was also detected in 19 pedigrees (27.5%) in first-degree relatives of ALS patients. Cases carrying the C9ORF72 hexanucleotide expansion survived one year less than cases who did not carry this mutation. In conclusion, we found that C9ORF72 hexanucloetide repeat expansions represents a sizeable proportion of apparent sporadic ALS in the Italian and Sardinian population, representing by far the commonest mutation in Italy and the second more common in Sardinia.

No abstract

IntroductionAntibiotics that suppress Propionibacterium acnes are the standard treatment for acne but are becoming less effective, due to the appearance of antibiotic-resistant strains. Many plants are known to have innate antimicrobial action and can be used as alternatives to antibiotics; thus, it is necessary to prove their effectiveness in vivo. This study aimed to evaluate the anti-acne efficacy of a new cream based on three natural extracts, comparing it to erythromycin cream and placebo.Patients and methodsSixty patients with mild to moderate acne vulgaris were randomly divided into three groups: treated with cream containing 20% propolis, 3% “tea tree oil”, and 10% “Aloe vera” (PTAC) (n=20); or with 3 % erythromycin cream (ERC) (n=20); or with placebo (n=20). At baseline, after 15 and 30 days, investigators evaluated response to treatment by counting acne lesions through noninvasive measurements and macrophotography.ResultsAll the clinical and instrumental values studied were statistically different from placebo except for sebometry, pHmetry, and erythema index values, measured on healthy skin. Unlike in the placebo group, papular and scar lesions showed high erythema reduction after 15 and 30 days of PTAC and ERC application.ConclusionThe PTAC formulation was better than ERC in reducing erythema scars, acne severity index, and total lesion count.

The pediatric MS incidence in Sardinia is estimated to be significantly higher than those reported elsewhere. The pediatric MS prevalence in Sardinia is among the highest values worldwide.

Background In the isolated population of Sardinia, a Mediterranean island, ~25% of ALS cases carry either a p.A382T mutation of the TARDBP gene or a GGGGCC hexanucleotide repeat expansion in the first intron of the C9ORF72 gene. Objective To describe the co-presence of two genetic mutations in two Sardinian ALS patients. Methods We identified two index ALS cases carrying both the p.A382T missense mutation of TARDBP gene and the hexanucleotide repeat expansion of C9ORF72 gene. Results The index case of Family A had bulbar ALS and frontemporal dementia (FTD) at 43. His father, who carried the hexanucleotide repeat expansion of C9ORF72 gene, had spinal ALS and FTD at 64 and his mother, who carried the TARDBP gene p.A382T missense mutation, had spinal ALS and FTD at 69. The index case of Family B developed spinal ALS without FTD at 35 and had a rapid course to respiratory failure. His parents are healthy at 62 and 63. The two patients share the known founder risk haplotypes across both the C9ORF72 9p21 locus and the TARDBP 1p36.22 locus. Conclusions Our data show that in rare neurodegenerative causing genes can co-exist within the same individuals and are associated with a more severe disease course.