Natural history of young-adult amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) affects people of all ages, but whether the wide range of age at onset is due to distinct diseases or merely reflects phenotypic variability of the same disorder is still unknown. The purpose of this study is to describe clinical and prognostic features of young-adult ALS, with onset before age 40 years, and to compare them with features of the common adult-onset type. METHODS: We analyzed clinical features and long-term follow-up of 57 young-adult ALS patients, with disease onset between 20 and 40 years, and compared them with 450 patients affected by adult-onset ALS. RESULTS: We found that the majority of young-adult patients showed a predominant upper motor neuron (p-UMN) ALS, characterized by marked spastic paraparesis, with lower motor neuron signs confined to the upper limbs. The proportion of patients with p-UMN ALS phenotype was 59.6% in the young-adult patients and 17.4% in the adult-onset form (p < 0.0001). Young-adult ALS with p-UMN phenotype had longer survival than did the classic phenotype: median survival was 74 months (range 10-226, 95% CI 60.61-87.38) in the former and 56 months (range 6-106, 95% CI 48.65-63.34) in the latter (p = 0.03). In the young-adult patients, a marked male excess was observed in the p-UMN ALS group (5.8:1), whereas the ratio of men to women was 1.1:1 in the classic phenotype (p = 0.01). CONCLUSIONS: Our findings show that young-adult amyotrophic lateral sclerosis with the predominant upper motor neuron phenotype represents a distinctive clinical variant characterized by a unique clinical pattern, longer survival, and male prevalence.

An Italian experience of sequential intravenous and oral azithromycin plus intravenous ampicillin/sulbactam in hospitalized patients with community-acquired pneumonia.

The efficacy and safety of intravenous (i.v.) azithromycin followed by the oral form, given in addition to i.v. ampicillin-sulbactam, were evaluated in 151 patients hospitalized due to community-acquired pneumonia (CAP). Azithromycin 500 mg i.v. once daily plus ampicillin/sulbactam 3 g i.v. twice daily were administered for 2-5 days, then followed by oral azithromycin 500 mg once daily plus the same i.v. ampicillin/sulbactam regimen for a total of 7-10 days of treatment. The clinical response at day 14 was defined as cure, improvement or failure (with the addition of relapse at follow-up at day 30). The other efficacy measures included microbiological (eradication, presumed eradication, persistence, relapse, superinfection) and radiological (resolution, improvement, failure) findings, and outcome of signs and symptoms. Adverse events, vital signs and routine laboratory tests were the safety variables. The number and rate of patients with a positive clinical outcome at day 14 (cured + improved) in the intention-to-treat (ITT) analysis (n = 138) were 119 (86.2%), while 118 (87.4%) were cured or improved in the per-protocol population (PP) subset (n = 135). The rate of success at day 14 was slightly lower in the treated population (78.8%), which included all patients discontinued due to any cause. Clinical failures in the ITT population were 19 (13.8%) at day 14 and 1 (0.9%) at day 30, while 4 patients (3.6%) relapsed at day 30. Signs and symptoms of CAP improved from baseline to endpoint. The results in patients with a pathogen isolated at baseline in the cultures of respiratory tract secretions showed that 17 patients (77.3%) had eradication and 5 (22.7%) had presumed eradication (i.e. absence of adequate sputum for culture) at day 14, with no cases of persistence or superinfection. In the X-ray exam at day 30, 96 patients (85.0%) had resolution, 11 (9.7%) had improvement and 4 (3.5%) had failure. Treatment-related adverse events were reported in 10 patients (6.6%) and caused study discontinuation in 5 of them (one case of angioedema and one case of anaphylactic reaction were serious). No abnormal changes from baseline were found in laboratory parameters. Azithromycin i.v. followed by oral form given in addition to i.v. ampicillin/sulbactam was effective and well tolerated in patients with CAP who required hospital care.

A novel microdeletion syndrome with loss of the MSH2 locus and hereditary non-polyposis colorectal cancer.

Constitutional chromosome deletions can predispose to the development of cancer with the phenotypic characteristics of inherited cancer syndromes, when the deleted region encompasses a tumour suppressor gene. Examples of such conditions are represented by the cytogenetic deletions associated with retinoblastoma, Wilms tumour and familial adenomatous polyposis. So far, no constitutional deletions involving the genes implicated in hereditary non-polyposis colorectal cancer (HNPCC) have been identified. This may be at least partially because of the lack of distinctive phenotypic manifestations in HNPCC. We describe the first case of a constitutional microdeletion associated with HNPCC. Suspicion of a microdeletion was prompted by the association of mental retardation, postnatal growth deficiency, minor congenital anomalies and early onset (37 years) sporadic colon cancer. The patient was found to harbour a microdeletion within chromosome 2p16-p21, including the MSH2 gene. Since there are very few reports of deletions of the 2p16-p21 region, our observation sets the grounds for the definition of a novel multiple congenital anomaly/mental retardation/cancer microdeletion syndrome.

Multicenter comparative evaluation of six commercial systems and the national committee for clinical laboratory standards m27-a broth microdilution method for fluconazole susceptibility testing of Candida species.

Fluconazole susceptibility among 800 clinical Candida isolates (60% C. albicans) and two control strains (C. krusei ATCC 6258 and C. parapsilosis ATCC 22019) was tested with the NCCLS M27-A method (gold standard) and six commercial products (Candifast, disk, Etest, Fungitest, Integral System Yeasts, and Sensititre YeastOne). Results were classified as susceptible, susceptible-dose dependent, or resistant using M27-A breakpoints or, for Fungitest, Integral System Yeasts, and Candifast, as susceptible, intermediate, or resistant, according to the manufacturers' instructions. Concordance with NCCLS M27-A results was analyzed with the chi(2) test. Intra- and interlaboratory reproducibility was also evaluated. NCCLS M27-A (90.1%), Etest (93.1%), Sensititre YeastOne (93.1%), disk (96.7%), Fungitest (92.6%), Integral System Yeasts (40.6%), and Candifast (6.0%) classified the indicated percentages of C. albicans isolates as susceptible. Among non-C. albicans strains, the percentages of susceptible isolates were as follows: NCCLS M27-A, 74.0%; Etest, 83.8%; Sensititre YeastOne, 64.1%; disk, 60.6%; Fungitest, 76.6%; Integral System Yeasts, 28.3%; and Candifast, 27.4%. All methods except Candifast and Integral System Yeasts showed good agreement with NCCLS M27-A results for both C albicans and non-C. albicans isolates. Intralaboratory reproducibility was excellent for NCCLS M27-A, Etest, Sensititre YeastOne, disk, and Fungitest (88 to 91%). Similar results emerged from the interlaboratory reproducibility evaluation. Our findings indicate that some commercial methods can be useful for fluconazole susceptibility testing of clinical Candida isolates. Those characterized by a lack of medium standardization and/or objective interpretative criteria should be avoided. Particular caution is necessary when testing is being done for clinical and epidemiological purposes.