Inter-laboratory comparison of qualitative and quantitative detection of hepatitis C (HCV) virus RNA in diagnostic virology: a multicentre study (MS) in Italy

BACKGROUND: The importance of the standardisation of nucleic acid amplification technology (NAT) assays for the detection of hepatitis C virus RNA is well known today, as many studies carried out in different European countries attest. The results of a previous study performed in Italy (J. Clin. Virol. 1 (2003) 83) by the Italian Society of Clinical Microbiology (AMCLI) showed that the use of external reference standards and of multicentre collaborative studies significantly improves laboratory performance for the qualitative evaluation of HCV RNA. OBJECTIVES: the AMCLI organised a new study on the standardisation of both the qualitative and the quantitative evaluation of HCV RNA with NAT in order to improve the implementation of the diagnostic methods for HCV RNA detection. STUDY DESIGN: seventeen diagnostic centres of major Italian Hospitals participated in this quality control study. The study consisted of testing three panels, each made up of 10 coded samples including negative and positive samples. Positive samples contained four levels of HCV RNA (genotype 1). RESULTS AND CONCLUSION: Seven out of 510 qualitative results obtained were incorrect (1.4%), two false negative and five false positive. The results gave a sensitivity of 99.5% and a specificity of 95.8%. Regarding quantitative tests, the geometric mean (GM) and standard deviation (S.D.) could be calculated only for the three highest HCV RNA levels. The percentage of results within the range of GM +/- 0.5 log(10) varied from 91% to 100%. Some laboratories had some difficulty in the exact quantification of the lowest (3.00 log IU/ml) as well as of the highest viral levels (6.35 log IU/ml) values, very near to the limits of the dynamic range of the assays. The comparison of the results of this study with that previously carried out one confirms that a regular participation in external quality assessment (EQA) assures the achievement of a high proficiency level in the diagnosis of HCV infection.     

Cost-effectiveness of community psychiatric nurse or out-patient psychiatrist care of neurotic patients

In a prospective controlled investigation chronic patients, the majority with neurotic conditions, were randomly allocated either to community psychiatric nurses (CPN) as the main therapist or to routine out-patient psychiatrist follow-up. There was no statistically significant difference in the mean public expenditure for the two modes of care. The direct costs of psychiatric care comprised a small proportion of total public expenditure and were initially greater in the nursing group. Subsequently, and over the whole 18-month study period, nursing was the cheaper option in terms of these direct costs. Clinical and social outcomes were comparable in both follow-up groups. Consumer satisfaction was significantly greater among CPN patients. On balance, these results confirm the benefit of community psychiatric nursing for this patient group.     

Three new families with arterial tortuosity syndrome

Arterial tortuosity syndrome (ATS) is a rare condition with autosomal recessive inheritance characterized by connective tissue abnormalities. The most specific clinical findings are cardiovascular anomalies including tortuosity, lengthening, aneurysm, and stenosis formation of major arteries. Also ventricular hypertrophy is frequently present. Other anomalies are skin hyperextensibility and cutis laxa, joint laxity or contractures of the joints, and inguinal herniae. Histology shows disruption of elastic fibers of the media. These features suggest that ATS is a connective tissue disorder. A biochemical or molecular defect has not yet been identified. We describe here nine additional ATS patients from three consanguineous Moroccan families and review a total of 35 patients with this uncommon condition.     

Polyglutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2 chaperone

Spinal bulbar muscular atrophy is a neurodegenerative disorder caused by a polyglutamine expansion in the androgen receptor (AR). We show in transiently transfected HeLa cells that an AR containing 48 glutamines (ARQ48) accumulates in a hormone-dependent manner in both cytoplasmic and nuclear aggregates. Electron microscopy reveals both types of aggregates to have a similar ultrastructure. ARQ48 aggregates sequester mitochondria and steroid receptor coactivator 1 and stain positively for NEDD8, Hsp70, Hsp90 and HDJ-2/HSDJ. Co-expression of HDJ-2/HSDJ significantly represses aggregate formation. ARQ48 aggregates also label with antibodies recognizing the PA700 proteasome caps but not 20S core particles. These results suggest that ARQ48 accumulates due to protein misfolding and a breakdown in proteolytic processing. Furthermore, the homeostatic disturbances associated with aggregate formation may affect normal cell function.     

Comparison of the fertilizing capability of spermatozoa from ejaculates, epididymal aspirates and testicular biopsies using intracytoplasmic sperm injection

A prospective study was carried out to compare the fertilizing capability and pregnancy outcome following intracytoplasmic sperm injection (ICSI) using spermatozoa obtained from ejaculates, or surgically from epididymis or seminiferous tubules. A total of 77 ICSI cycles (one per patient) was included. In all, 28 patients had severe oligoasthenoteratozoospermia, 19 patients had obstructive azoospermia and 30 patients had non-obstructive azoospermia. The main outcome measures were fertilization rate per injected metaphase II oocyte and the clinical pregnancy rate per embryo transferred back to the female recipients. In patients with severe oligoasthenoteratozoospermia, the fertilization and pregnancy rates were 79 and 25 %. In patients with obstructive azoospermia, for whom epididymal spermatozoa were used, these were 75 and 28%, and in the non-obstructive group for which testicular spermatozoa were used for injection, they were 69 and 21% respectively. These rates were not significantly different in the three groups (P = 0.85 and P = 0.14 respectively), suggesting that spermatozoa from the ejaculates and epididymal or testicular biopsies are able to fertilize equally by using ICSI. Live birth per embryo transfer was significantly reduced in patients with non-obstructive azoospermia compared to the other two groups. The high abortion rate (50%) in the group in which testicular spermatozoa were used raises doubts about the developmental competence of such embryos.      

Characterization of the human jumonji gene

While constructing a cDNA library of human embryos, we have isolated a clone homologous to jumonji, a mouse gene required for neural tube formation. We have determined the complete coding sequence of the human homologue (JMJ) and deduced the amino acid sequence of the putative protein. We show here that human and mouse jumonji putative proteins are homologous and present 90% identity. During human embryogenesis, JMJ mRNAs are predominantly expressed in neurons and particularly in dorsal root ganglion cells. They are also expressed in neurons of human adult cerebral cortex. In view of these observations, we propose JMJ as a candidate gene for developmental defects of the central nervous system in the human. The human JMJ gene maps at position 6p24-6p23.      

Active music therapy in Parkinson's disease: an integrative method for motor and emotional rehabilitation

BACKGROUND: Modern management of Parkinson's disease (PD) aims to obtain symptom control, to reduce clinical disability, and to improve quality of life. Music acts as a specific stimulus to obtain motor and emotional responses by combining movement and stimulation of different sensory pathways. We explored the efficacy of active music therapy (MT) on motor and emotional functions in patients with PD. METHODS: This prospective, randomized, controlled, single-blinded study lasted 3 months. It consisted of weekly sessions of MT and physical therapy (PT). Thirty-two patients with PD, all stable responders to levodopa and in Hoehn and Yahr stage 2 or 3, were randomly assigned to two groups of 16 patients each. We assessed severity of PD with the Unified Parkinson's Disease Rating Scale, emotional functions with the Happiness Measure, and quality of life using the Parkinson's Disease Quality of Life Questionnaire. MT sessions consisted of choral singing, voice exercise, rhythmic and free body movements, and active music involving collective invention. PT sessions included a series of passive stretching exercises, specific motor tasks, and strategies to improve balance and gait. RESULTS: MT had a significant overall effect on bradykinesia as measured by the Unified Parkinson's Disease Rating Scale (p < .034). Post-MT session findings were consistent with motor improvement, especially in bradykinesia items (p < .0001). Over time, changes on the Happiness Measure confirmed a beneficial effect of MT on emotional functions (p < .0001). Improvements in activities of daily living and in quality of life were also documented in the MT group (p < .0001). PT improved rigidity (p < .0001). CONCLUSIONS: MT is effective on motor, affective, and behavioral functions. We propose active MT as a new method for inclusion in PD rehabilitation programs.