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1.
J Hosp Infect ; 124: 56-66, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35307506

ABSTRACT

BACKGROUND: Multi-drug-resistant organisms (MDROs) (meticillin-resistant Staphylococcus aureus, vancomycin-resistant enterococcus, MDR Acinetobacter spp., extended-spectrum beta-lactamase-producing Gram-negative organisms), Clostridioides difficile, viral respiratory pathogens and healthcare-associated infections (HAIs) are major concerns in medical facilities. AIMS: To assess environmental service workers' (ESWs) training, workload, numbers of surfaces and pieces of medical equipment cleaned per shift, how long they worked on each surface, how they cleaned, supervision, MDRO and HAI status, and measurement of effectiveness in reducing MDROs and HAIs in patients and on surfaces. METHODS: CINAHL, Cochrane CENTRAL Register of Controlled Trials, EMBASE, Medline and Scopus were searched from inception to 28th June 2021 (no language/date limits). Searches combined terms from three themes: (a) hospitals and acute/long-term care facilities (e.g. assisted living, long-term care facilities, nursing homes); (b) disinfectants (e.g. antisepsis, bleach, cleaning, copper plating of surfaces and copper impregnation of textiles, disinfection, decontamination, hydrogen peroxide, quaternary ammonium disinfectants, and ultraviolet rays); and (c) randomized controlled trials (RCTs). FINDINGS AND CONCLUSIONS: Fourteen cluster RCTs provided data on a series of interventions. Ten trials focused on reducing patient infections from MDROs/HAIs, and four found significant reductions in patient infection rates with strategies including bleach, quaternary ammonium detergents, ultraviolet light and hydrogen peroxide vapour. Minimal information was provided on ESW numbers, MDRO/HAI status, workload, numbers of surfaces and objects cleaned per shift, and effects of training on improving effectiveness. The findings suggest that there is a need for detailed evaluations of the effects of training and disinfection activities for individuals and teams of ESWs.


Subject(s)
Ammonium Compounds , Cross Infection , Disinfectants , Copper , Cross Infection/prevention & control , Disinfectants/pharmacology , Disinfection , Hospitals , Humans , Hydrogen Peroxide , Long-Term Care , Nursing Homes
3.
J Hosp Infect ; 122: 9-26, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34998912

ABSTRACT

BACKGROUND: Multiply drug-resistant organisms (MDROs) in hospitals and long-term care facilities (LTCFs) of particular concern include meticillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus, multidrug-resistant Acinetobacter species, and extended-spectrum ß-lactamase-producing organisms. Respiratory viruses include influenza and SARS-CoV-2. AIM: To assess effectiveness of cleaning and disinfecting surfaces in hospitals and LTCFs. METHODS: CINAHL, Cochrane CENTRAL Register of Controlled Trials, Embase, Medline, and Scopus searched inception to June 28th, 2021, no language restrictions, for randomized controlled trials (RCTs), cleaning, disinfection, hospitals, LTCFs. Abstracts and titles were assessed and data abstracted independently by two authors. FINDINGS: Of 14 cluster (c)-RCTs in hospitals and LTCFs, interventions in ten were focused on reducing patient infections of four MDROs and/or healthcare-associated infections (HAIs). In four c-RCTs patient MDRO and/or HAI rates were significantly reduced with cleaning and disinfection strategies including bleach-, quaternary ammonium detergent-, ultraviolet irradiation-, hydrogen peroxide vapour- and copper-treated surfaces or fabrics. Of three c-RCTs focused on reducing MRSA rates, one had significant results and one on Clostridioides difficile had no significant results. Heterogeneity of populations, methods, outcomes and data reporting precluded meta-analysis. Overall risk of bias assessment was low but high for allocation concealment, and GRADE assessment was low risk. No study assessed biofilms. CONCLUSION: Ten c-RCTs focused on reducing multiple MDROs and/or HAIs and four had significant reductions. Three c-RCTs reported only patient MRSA colonization rates (one significant reductions), and one focused on C. difficile (no significant differences). Standardized primary and secondary outcomes are required for future c-RCTs including detailed biofilm cleaning/disinfection interventions.


Subject(s)
COVID-19 , Cross Infection , Methicillin-Resistant Staphylococcus aureus , Virus Diseases , COVID-19/prevention & control , Cross Infection/prevention & control , Drug Resistance, Multiple, Bacterial , Hospitals , Humans , Long-Term Care , SARS-CoV-2
4.
Ann Ig ; 30(4): 285-296, 2018.
Article in English | MEDLINE | ID: mdl-29895046

ABSTRACT

INTRODUCTION: In the Azienda Ospedaliera Universitaria Policlinico Umberto I in Rome, the Hospital Social Services (HSS) is located within the Directorate of Health, reporting directly to the Chief Medical Officer, providing counselling and supporting clinical services. The HSS is part of a network with its own technical, professional and assessment independence. It often serves as liaison between the hospital and the territory, facilitating the development of services and contributing to public health recovery and maintenance, therefore improving the citizens' standard of living thanks to aid projects and specific interventions. METHODS: The present Report is based on two different studies carried out in 2008 and 2014, both examining the work of the Hospital Social Service in the "Azienda Ospedaliera Universitaria Policlinico Umberto I" in Rome. The purpose is to compare these surveys and work out the results. The data collection is based on a number of social records from the HSS archives (814 records in 2008 and 790 in 2014). The research project followed subsequent stages: planning a draft of the research, where ethnomethodology was used as empirical evaluation technique; collecting data from the HSS's paper and file archives (biographical, clinical and social data); revising, analysing and elaborating the data which showed relevant changes leading to interesting conclusions. RESULTS AND CONCLUSIONS: The comparative analysis of data showed a higher demand of HSS healthcare services, despite a smaller number of beds and hospitalisations available in standard regime. Also, it indicated an increase of patients below 18 years and a decrease of the over-65s age group. As for the geographical origin of patients reported to the HSS, there was a decrease in the percentage of Italian citizens, while the percentage of irregular non-EU and EU patients increased by over 5%. Significant results were found comparing the days between the report to the HSS and patient discharge. Data concerning the 'more than 7 days' group was steady over the years, being more consistent for both the variables considered and increasing in 2014. In the comparative analysis, the interventions with more significant differences were those aimed at promoting homecare and entering sheltered housing. In the former cases, a considerable decrease was observed, if compared to the activation of the integrated health and social homecare services, while there were more requests for homecare assistance; in the latter ones the analysis highlighted a sharp decrease in the percentage of the variable called "assessment to enter Extended Care Units". The causes of these changes are remarkable and have to be found in the political, historical and cultural scenario: - a first factor is the increase in the more recent migratory flow from non-EU countries to Italy, which could explain the rising percentage of foreigners taken over by the HSS; - regional policies, economic cuts imposed on healthcare and higher income limits in order to calculate the patient's economic participation in the costs of institutionalisation have affected the above-mentioned changes; - the innovations in the regulatory field of Latium Region have brought structural changes in long-term care facilities and in the level of care in Extended Care Units (ECU).


Subject(s)
Hospitalization/statistics & numerical data , Personnel, Hospital , Social Work Department, Hospital/organization & administration , Social Work/organization & administration , Adolescent , Adult , Age Factors , Aged , Child , Child, Preschool , Emigrants and Immigrants/statistics & numerical data , Female , Humans , Infant , Infant, Newborn , Italy , Male , Middle Aged , Rome , Social Work/trends , Social Work Department, Hospital/trends , Surveys and Questionnaires , Time Factors , Young Adult
5.
BMC Emerg Med ; 17(1): 35, 2017 11 28.
Article in English | MEDLINE | ID: mdl-29183276

ABSTRACT

BACKGROUND: The optimal prehospital fluid for the treatment of hypotension is unknown. Hypertonic fluids may increase circulatory volume and mute the pro-inflammatory response of the body to injury and illness. The purpose of this systematic review is to determine whether in patients presenting with hypotension in the prehospital setting (population), the administration of hypertonic saline (intervention), compared to an isotonic fluid (control), improves survival to hospital discharge (outcome). METHODS: Searches were conducted in Medline, Embase, CINAHL, and CENTRAL from the date of database inception to November, 2016, and included all languages. Two reviewers independently selected randomized control trials of hypotensive human participants administered hypertonic saline in the prehospital setting. The comparison was isotonic fluid, which included normal saline, and near isotonic fluids such as Ringer's Lactate. Assessment of study quality was done using the Cochrane Collaborations' risk of bias tool and a fixed effect meta-analysis was conducted to determine the pooled relative risk of survival to hospital discharge. Secondary outcomes were reported for fluid requirements, multi-organ failure, adverse events, length of hospital stay, long term survival and disability. RESULTS: Of the 1160 non-duplicate citations screened, thirty-eight articles underwent full-text review, and five trials were included in the systematic review. All studies administered a fixed 250 ml dose of 7.5% hypertonic saline, except one that administered 300 ml. Two studies used normal saline, two Ringer's Lactate, and one Ringer's Acetate as control. Routine care co-interventions included isotonic fluids and colloids. Five studies were included in the meta-analysis (n = 1162 injured patients) with minimal statistical heterogeneity (I 2  = 0%). The pooled relative risk of survival to hospital discharge with hypertonic saline was 1.02 times that of patients who received isotonic fluids (95% Confidence Interval: 0.95, 1.10). There were no consistent statistically significant differences in secondary outcomes. CONCLUSIONS: There was no significant difference in important clinical outcomes for hypotensive injured patients administered hypertonic saline compared to isotonic fluid in the prehospital setting. Hypertonic saline cannot be recommended for use in prehospital clinical practice for the management of hypotensive injured patients based on the available data. PROSPERO registration # CRD42016053385 .


Subject(s)
Emergency Medical Services , Hypotension/therapy , Saline Solution, Hypertonic/therapeutic use , Wounds and Injuries/therapy , Emergency Medical Services/methods , Fluid Therapy/methods , Humans , Hypotension/etiology , Treatment Outcome , Wounds and Injuries/complications
6.
Neurology ; 73(2): 89-97, 2009 Jul 14.
Article in English | MEDLINE | ID: mdl-19439720

ABSTRACT

BACKGROUND: Among patients with a patent foramen ovale (PFO) and a prior cryptogenic ischemic stroke or TIA, the absolute and relative risk of recurrent events is unclear. METHODS: We conducted a systematic review and meta-analysis of clinical studies in any language published up to February 2008. We included studies reporting original data on recurrent cerebrovascular events in patients with prior cryptogenic stroke or TIA and PFO. Two authors independently extracted data and evaluated study quality. RESULTS: We identified 15 eligible studies, four with a non-PFO comparison group. In these four studies, the pooled relative risk (RR) for recurrent ischemic stroke or TIA in patients with vs without a PFO was 1.1 (95% confidence interval [CI] 0.8 to 1.5). For ischemic stroke, the pooled RR was 0.8 (95% CI 0.5 to 1.3). We tabulated the absolute rate of recurrent events in all 15 studies. The pooled absolute rate of recurrent ischemic stroke or TIA in patients with PFO was 4.0 events per 100 person-years (95% CI 3.0 to 5.1) while the rate of recurrent ischemic stroke was 1.6 events per 100 person-years (95% CI 1.1 to 2.1). CONCLUSIONS: In medically treated patients with prior cryptogenic stroke, while the absolute rate of recurrent events is variable, available evidence does not support an increased relative risk of recurrent ischemic events in those with vs without a patent foramen ovale. Patent foramen ovale closure in these patients cannot be recommended until the results of ongoing clinical trials are reported.


Subject(s)
Brain Ischemia/epidemiology , Brain Ischemia/etiology , Foramen Ovale, Patent/complications , Stroke/epidemiology , Stroke/etiology , Age Factors , Brain Ischemia/mortality , Brain Ischemia/therapy , Foramen Ovale, Patent/epidemiology , Foramen Ovale, Patent/mortality , Foramen Ovale, Patent/therapy , Humans , Ischemic Attack, Transient/epidemiology , Ischemic Attack, Transient/etiology , Ischemic Attack, Transient/mortality , Ischemic Attack, Transient/therapy , Recurrence , Risk , Stroke/mortality , Stroke/therapy , Treatment Outcome
7.
Cochrane Database Syst Rev ; (1): CD004493, 2007 Jan 24.
Article in English | MEDLINE | ID: mdl-17253511

ABSTRACT

BACKGROUND: There is evidence that children's decisions to smoke are influenced by family and friends. OBJECTIVES: To assess the effectiveness of interventions to help family members to strengthen non-smoking attitudes and promote non-smoking by children and other family members. SEARCH STRATEGY: We searched 14 electronic bibliographic databases, including the Cochrane Tobacco Addiction Group specialized register, MEDLINE, EMBASE, PsycINFO and CINAHL. We also searched unpublished material, and the reference lists of key articles. We performed both free-text Internet searches and targeted searches of appropriate websites, and we hand-searched key journals not available electronically. We also consulted authors and experts in the field. The most recent search was performed in July 2006. SELECTION CRITERIA: Randomized controlled trials (RCTs) of interventions with children (aged 5-12) or adolescents (aged 13-18) and family members to deter the use of tobacco. The primary outcome was the effect of the intervention on the smoking status of children who reported no use of tobacco at baseline. Included trials had to report outcomes measured at least six months from the start of the intervention. DATA COLLECTION AND ANALYSIS: We reviewed all potentially relevant citations and retrieved the full text to determine whether the study was an RCT and matched our inclusion criteria. Two authors independently extracted study data and assessed them for methodological quality. The studies were too limited in number and quality to undertake a formal meta-analysis, and we present a narrative synthesis. MAIN RESULTS: We identified 19 RCTs of family interventions to prevent smoking. We identified five RCTs in Category 1 (minimal risk of bias on all counts); nine in Category 2 (a risk of bias in one or more areas); and five in Category 3 (risks of bias in design and execution such that reliable conclusions cannot be drawn from the study). Considering the fourteen Category 1 and 2 studies together: (1) four of the nine that tested a family intervention against a control group had significant positive effects, but one showed significant negative effects; (2) one of the five RCTs that tested a family intervention against a school intervention had significant positive effects; (3) none of the six that compared the incremental effects of a family plus a school programme to a school programme alone had significant positive effects; (4) the one RCT that tested a family tobacco intervention against a family non-tobacco safety intervention showed no effects; and (5) the one trial that used general risk reduction interventions found the group which received the parent and teen interventions had less smoking than the one that received only the teen intervention (there was no tobacco intervention but tobacco outcomes were measured). For the included trials the amount of implementer training and the fidelity of implementation are related to positive outcomes, but the number of sessions is not. AUTHORS' CONCLUSIONS: Some well-executed RCTs show family interventions may prevent adolescent smoking, but RCTs which were less well executed had mostly neutral or negative results. There is thus a need for well-designed and executed RCTs in this area.


Subject(s)
Family , Smoking Prevention , Adolescent , Child , Humans , Randomized Controlled Trials as Topic , Smoking/psychology
8.
Qual Life Res ; 15(3): 377-90, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16547775

ABSTRACT

OBJECTIVE: To design a Health-related Quality of Life (HRQoL) instrument for HIV-infected people in the era of highly active antiretroviral therapy (HAART). METHODS: The self-administered questionnaire was developed by an Italian network including researchers, physicians, people living with HIV, national institutions and community-based organizations (CBO) through several steps: (1) review of existing HRQoL literature and questionnaires for HIV-infected people; (2) selection of relevant domains measuring HRQoL in HIV-infected people, and identification of new domains related to new aspects of HRQoL concerning HAART-treated individuals; (3) conduction of two pre-test analyses in independent groups of Italian HIV-positive people (n approximately =100) distributed throughout the country. The objectives of the first pre-test were to verify the usefulness of the questionnaire, to construct a form easily understandable by everyone, to define the domains and their significance; the second pre-test aimed at evaluating and reshaping the questionnaire based on a statistical analysis of the outcomes of first pre-test; (4) validation analysis. A large cohort of people with HIV infection was recruited for the last step. RESULTS: The internal consistence reliability (Cronbach's alpha) was >or=0.70 for all domains. Most domains had Cronbach's coefficient >0.80. All domains demonstrated convergent and discriminant validity. The final version of ISSQoL includes two sections: HRQoL Core Evaluation Form (9 domains) and Additional Important Areas for HRQoL (6 domains). The ISSQoL was administered together with two additional forms: a Daily Impact of Symptoms Form and a Demographic Information Form. The Additional Important Areas for HRQoL include social support, interaction with medical staff, treatment impact, body changes, life planning, and motherhood/fatherhood. CONCLUSION: The data reported in the present paper provide preliminary evidence of the reliability and validity of the ISSQoL questionnaire for the measurement of HRQoL in HIV-infected people. The direct involvement of HIV-positive people in all the phases of the project was a key aspect of our work.


Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections , Quality of Life , Surveys and Questionnaires/standards , Adult , Female , Health Surveys , Humans , Italy , Male , Middle Aged
9.
Telemed J E Health ; 10(1): 77-83, 2004.
Article in English | MEDLINE | ID: mdl-15104919

ABSTRACT

This research was undertaken to inform future telehealth policy directions regarding the socioeconomic impact of telehealth. Fifty-seven sources were identified and analyzed through a comprehensive literature search of electronic databases, the Internet, journals, conference proceedings, as well as personal communication with consultants in the field. The review revealed a focus on certain socioeconomic indicators such as cost, access, and satisfaction. It also identified areas of opportunity for further research and policy analysis and development (e.g., social isolation, life stress, poverty), along with various barriers and challenges to the advancement of telehealth. These included confidentiality, reimbursement, and legal and ethical considerations. To become fully integrated into the health care system, telehealth must be viewed as more than an add-on service. This paper offers 19 general and 20 subject-specific telehealth recommendations, as well as seven policy strategies.


Subject(s)
Health Policy , National Health Programs , Telemedicine , Alberta , Health Plan Implementation , Organizational Case Studies , Policy Making , Program Development , Socioeconomic Factors
10.
J Telemed Telecare ; 9(6): 311-20, 2003.
Article in English | MEDLINE | ID: mdl-14680514

ABSTRACT

We reviewed the socio-economic impact of telehealth, focusing on nine main areas: paediatrics, geriatrics, First Nations (i.e. indigenous peoples), home care, mental health, radiology, renal dialysis, rural/remote health services and rehabilitation. A systematic search led to the identification of 4646 citations or abstracts; from these, 306 sources were analysed. A central finding was that telehealth studies to date have not used socio-economic indicators consistently. However, specific telehealth applications have been shown to offer significant socio-economic benefit, to patients and families, health-care providers and the health-care system. The main benefits identified were: increased access to health services, cost-effectiveness, enhanced educational opportunities, improved health outcomes, better quality of care, better quality of life and enhanced social support. Although the review found a number of areas of socio-economic benefit, there is the continuing problem of limited generalizability.


Subject(s)
Telemedicine , Bias , Health Services , Humans , Patient Acceptance of Health Care , Quality of Health Care , Quality of Life , Social Support , Socioeconomic Factors , Telemedicine/economics , Telemedicine/ethics
11.
Hum Mol Genet ; 9(5): 779-85, 2000 Mar 22.
Article in English | MEDLINE | ID: mdl-10749985

ABSTRACT

To elucidate the pathophysiology of spinocerebellar ataxia type 1 (SCA1) and to evaluate repeat length instability in the context of the mouse Sca1 gene, we generated knock-in mice by inserting an expanded tract of 78 CAG repeats into the mouse Sca1 locus. Mice heterozygous for the CAG expansion show intergenerational repeat instability (+2 to -6) at a much higher frequency in maternal transmission than in paternal transmission. The majority of changes transmitted through the female germline were small contractions, as in humans, whereas small expansions occurred more frequently in paternal transmission. The frequency of intergenerational changes was age dependent for both paternal and maternal transmissions. Mice homozygous for mutant ataxin-1 on a C57BL/6J-129/SvEv mixed background performed significantly less well on the rotating rod than did wild-type littermates at 9 months of age, although they were not ataxic by cage behavior. Histological examination of brain tissue from mutant mice up to 18 months of age revealed none of the neuropathological changes observed in other transgenic models overexpressing expanded polyglutamine tracts. These data suggest that, even with 78 glutamines, prolonged exposure to mutant ataxin-1 at endogenous levels is necessary to produce a neurological phenotype reminiscent of human SCA1. Pathogenesis is thus a function of polyglutamine length, protein levels and duration of neuronal exposure to the mutant protein.


Subject(s)
Nerve Tissue Proteins/genetics , Nuclear Proteins/genetics , Trinucleotide Repeats , Amino Acid Sequence , Animals , Ataxin-1 , Ataxins , Base Sequence , Brain/metabolism , Brain/pathology , DNA , Female , Genomic Imprinting , Humans , Mice , Molecular Sequence Data , Phenotype , Sequence Homology, Nucleic Acid
12.
Am J Hum Genet ; 63(4): 1060-6, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9758625

ABSTRACT

To test the hypothesis that the frequencies of normal alleles (ANs) with a relatively large number of CAG repeats (large ANs) are related to the prevalences of the dominant spinocerebellar ataxias (SCAs)-SCA types 1, 2, 3 (Machado-Joseph disease), 6, and dentatorubral-pallidoluysian atrophy (DRPLA)-we investigated the relative prevalences of these diseases in 202 Japanese and 177 Caucasian families and distributions of the number of CAG repeats of ANs at these disease loci in normal individuals in each population. The relative prevalences of SCA1 and SCA2 were significantly higher in Caucasian pedigrees (15% and 14%, respectively) than in Japanese pedigrees (3% and 5%, respectively), corresponding to the observation that the frequencies of large ANs of SCA1 (alleles >30 repeats) and of SCA2 (alleles >22 repeats) were significantly higher in Caucasians than in Japanese. The relative prevalences of MJD/SCA3, SCA6, and DRPLA were significantly higher in Japanese pedigrees (43%, 11%, and 20%, respectively) than in Caucasian pedigrees (30%, 5%, and 0%, respectively), corresponding to the observation that the frequencies of large ANs of MJD/SCA3 (>27 repeats), SCA6 (>13 repeats), and DRPLA (>17 repeats) were significantly higher in Japanese than in Caucasians. The close correlations of the relative prevalences of the dominant SCAs with the distributions of large ANs strongly support the assumption that large ANs contribute to generation of expanded alleles (AEs) and the relative prevalences of the dominant SCAs.


Subject(s)
Gene Frequency , Genes, Dominant , Spinocerebellar Degenerations/genetics , Trinucleotide Repeat Expansion , Asian People/genetics , Ataxin-1 , Ataxins , Calcium Channels/genetics , Humans , Japan , Machado-Joseph Disease/genetics , Nerve Tissue Proteins/genetics , Nuclear Proteins/genetics , Paris , Pedigree , Proteins/genetics , Spinocerebellar Degenerations/epidemiology , Texas , White People/genetics
13.
Biochemistry ; 37(8): 2701-8, 1998 Feb 24.
Article in English | MEDLINE | ID: mdl-9485421

ABSTRACT

Models for the disease-associated expansion of trinucleotide repeats involve the participation of alternative DNA structures during replication, repair, or recombination. CAT or AGG interruptions within the (CAG)n or (CGG)n repeats of SCA1 or FRAXA, respectively, confer increased genetic stability to the repeats. In this study, we report the formation of slipped strand structures (S-DNA) using genomic sequences containing pure and interrupted SCA1 and FRAXA repeats having lengths above and below the genetic stability thresholds. S-DNA forms within the repeats during annealing of complementary strands containing equal lengths of repeats. Increased lengths of pure repeats led to an increased propensity for S-DNA formation. CAT or AGG interruptions have both quantitative and qualitative effects upon S-DNA formation: they decrease the total amount of slipped structures as well as limit the specific isomers formed. This demonstrates a unifying inhibitory effect of interruptions in both (CAG)n and (CGG)n tracts. We also present transmission stability data for SCA1 and FRAXA alleles spanning the thresholds and compare these with the ability to form slipped structures. The effect of both the length and purity of the repeat tract on the propensity of slipped structure formation correlates with their effect on genetic instability and disease, suggesting that S-DNA structures may be models for mutagenic intermediates in instability.


Subject(s)
DNA/chemistry , DNA/genetics , Fragile X Syndrome/genetics , Nerve Tissue Proteins/genetics , Nuclear Proteins/genetics , Trinucleotide Repeats , Ataxin-1 , Ataxins , Base Sequence , Cloning, Molecular , DNA Primers/genetics , Humans , In Vitro Techniques , Minisatellite Repeats , Models, Genetic , Molecular Structure , Polymerase Chain Reaction , Spinocerebellar Degenerations/classification , Spinocerebellar Degenerations/genetics
14.
Neurology ; 49(4): 1009-13, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9339681

ABSTRACT

The autosomal dominant spinocerebellar ataxias (ADSCAs) are a heterogeneous group of late-onset neurodegenerative disorders with overlapping clinical features. Genetic linkage studies have identified at least seven distinct loci for the ADSCAs, allowing the genetic classification of these disorders. The spinocerebellar ataxia type 2 (SCA2) locus was mapped to chromosome 12, and a gene responsible for this disorder was recently isolated. The mutation causing SCA2 is an expansion of a trinucleotide CAG repeat contained within the coding region of a novel gene. We describe the results of genotypic analysis for the SCA2 repeat in individuals with ADSCA who were previously found negative for CAG repeat expansions in the SCA1, SCA3, or SCA6 genes. The expanded CAG repeat has been identified in 15 independent families. Repeat instability and anticipation were observed in two large kindreds. The SCA2 mutation was found in 18% of our ADSCA kindreds, confirming the high proportion of SCA2 among this group of disorders.


Subject(s)
Genes, Dominant , Proteins/genetics , Spinocerebellar Degenerations/genetics , Trinucleotide Repeats , Adolescent , Adult , Ataxins , Child , Chromosome Mapping , Cohort Studies , Genotype , Humans , Middle Aged , Mutation , Nerve Tissue Proteins , Phenotype , Prevalence , Spinocerebellar Degenerations/classification , Spinocerebellar Degenerations/epidemiology
15.
Neurology ; 46(4): 1133-7, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8780105

ABSTRACT

Hereditary neuropathy with liability to pressure palsies (HNPP) is commonly associated with a 1.5-megabase deletion on chromosome 17p11.2-12. We analyzed the phenotypic expression of the deletion in 39 HNPP patients from 16 families carrying the deletion. Two-thirds of the individuals had episodes of acute mononeuropathy, often involving nerve territories of the upper limbs or brachial plexus; however, 41% of affected subjects were unaware of their disease, and 25% were almost or totally free of symptoms; one-third complained of chronic symptoms and four older patients had a picture of polyneuropathy. Electrophysiologic abnormalities differed among affected subjects, ranging from conduction abnormalities localized at common entrapment sites to diffuse conduction slowing, usually more evident at entrapment sites; patients from one family had preeminent proximal involvement. The spectrum of phenotypic expression of deletion-associated HNPP appears to be broader than previously thought. The prevalence of the disease is probably underestimated, and the availability of molecular diagnosis should increase disease detection.


Subject(s)
Chromosomes, Human, Pair 17 , Gene Deletion , Nervous System Diseases/genetics , Paralysis/genetics , Adolescent , Adult , Aged , Electrophysiology , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Nervous System Diseases/pathology , Nervous System Diseases/physiopathology , Phenotype , Pressure
16.
Am J Hum Genet ; 56(1): 91-8, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7825607

ABSTRACT

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder characterized by recurrent mononeuropathies. A 1.5-Mb deletion in chromosome 17p11.2-p12 has been associated with HNPP. Duplication of the same 1.5-Mb region is known to be associated with Charcot-Marie-Tooth disease type 1 (CMT1A), a more severe peripheral neuropathy characterized by symmetrically slowed nerve conduction velocity (NCV). The CMT1A duplication and HNPP deletion appear to be the reciprocal products of a recombination event involving a repeat element (CMT1A-REP) that flanks the 1.5-Mb region involved in the duplication/deletion. Patients from nine unrelated Italian families who were diagnosed with HNPP on the basis of clinical, electrophysiological, and histological evaluations were analyzed by molecular methods for DNA deletion on chromosome 17p. In all nine families, Southern analysis using a CMT1A-REP probe detected a reduced hybridization signal of a 6.0-kb EcoRI fragment mapping within the distal CMT1A-REP, indicating deletion of one copy of CMT1A-REP in these HNPP patients. Families were also typed with a polymorphic (CA)n repeat and with RFLPs corresponding to loci D17S122, D17S125, and D17S61, which all map within the deleted region. Lack of allelic transmission from affected parent to affected offspring was observed in four informative families, providing an independent indication for deletion. Furthermore, pulsed-field gel electrophoresis analysis of SacII-digested genomic DNA detected junction fragments specific to the 1.5-Mb HNPP deletion in seven of nine Italian families included in this study. These findings suggest that a 1.5-Mb deletion on 17p11.2-p12 is the most common mutation associated with HNPP.


Subject(s)
Chromosomes, Human, Pair 17/ultrastructure , Gene Deletion , Hereditary Sensory and Motor Neuropathy/genetics , Charcot-Marie-Tooth Disease/genetics , DNA Mutational Analysis , Electrophoresis, Gel, Pulsed-Field , Female , Humans , Italy , Male , Myelin Proteins/genetics , Pedigree , Polymorphism, Restriction Fragment Length , Recombination, Genetic
19.
Eur J Hum Genet ; 1(2): 133-43, 1993.
Article in English | MEDLINE | ID: mdl-7914465

ABSTRACT

We investigated linkage disequilibrium between Friedreich's ataxia (FRDA) and four tightly linked multi-allele markers in 140 families from France and Italy. These markers include three microsatellites (D9S111, D9S15 and D9S110) and one RFLP (D9S5). Their chromosomal order, D9S111-D9S15-D9S110-D9S5, had previously been established by physical mapping. Linkage disequilibrium was evaluated between each marker and FRDA and between markers. Extended haplotypes were obtained and their frequencies on FRDA and normal chromosomes were evaluated. We obtained evidence of strong allelic association of FRDA with D9S5 only. Analysis of linkage disequilibrium between markers revealed a significant decrease between D9S110 and D9S5, suggesting the presence of a recombination hot spot in the interval between these markers. Probably for this reason, no major FRDA-associated extended haplotype could be identified. Our data suggest the presence of a few common disease-causing mutations in the examined population, and indicate a putative localization for the FRDA gene. Transcribed sequences have been found in this candidate region.


Subject(s)
Friedreich Ataxia/genetics , Linkage Disequilibrium , Alleles , Base Sequence , DNA, Satellite/genetics , Friedreich Ataxia/ethnology , Haplotypes , Humans , Molecular Sequence Data , Polymerase Chain Reaction , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , White People/genetics
20.
Can J Ophthalmol ; 21(3): 96-102, 1986 Apr.
Article in English | MEDLINE | ID: mdl-3518889

ABSTRACT

The authors report six cases of lens-induced inflammations that help to illustrate the wide variability and clinical overlap of these conditions. Using cytological and histopathological findings, they attempt to clarify the confusion surrounding the terminology used to label these inflammations, and outline the immune factors responsible for them. With the recent upsurge in extracapsular cataract surgery, it is important to consider lens-induced inflammations in the differential diagnosis of any postoperative uveitis or endophthalmitis.


Subject(s)
Endophthalmitis/etiology , Lens, Crystalline/injuries , Lenses, Intraocular/adverse effects , Wounds, Penetrating , Adult , Aged , Cataract Extraction/adverse effects , Corneal Transplantation , Endophthalmitis/pathology , Eye Diseases/etiology , Female , Humans , Inflammation , Lens, Crystalline/pathology , Male , Middle Aged , Postoperative Complications , Uveitis/etiology , Vitreous Body
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