A longitudinal study of the SF-36 version 2 in Friedreich ataxia.

OBJECTIVES: The Medical Outcomes Study 36 item Short-Form Health Survey (SF-36) is one of the most commonly used patient reported outcome measure. This study aimed to examine the relationship between SF-36 version 2 (SF-36V2) summary scores and Friedreich ataxia (FRDA) clinical characteristics, and to investigate the responsiveness of the scale, in comparison with the Friedreich Ataxia Rating Scale (FARS), over 1, 2 and 3 years. MATERIALS AND METHODS: Descriptive statistics were used to examine the characteristics of the cohort at baseline and years 1, 2 and 3. Correlations between FRDA clinical characteristics and SF-36V2 summary scores were reported. Responsiveness was measured using paired t tests. RESULTS: We found significant correlations between the physical component summary (PCS) of the SF-36V2 and various FRDA clinical parameters but none for the mental component summary. No significant changes in the SF-36V2 were seen over 1 or 2 years; however, PCS scores at Year 3 were significantly lower than at baseline (-3.3, SD [7.6], P=.01). FARS scores were found to be significantly greater at Years 1, 2 and 3 when compared to baseline. CONCLUSIONS: Our findings suggest that despite physical decline, individuals with FRDA have relatively stable mental well-being. This study demonstrates that the SF-36V2 is unlikely to be a useful tool for identifying clinical change in FRDA therapeutic trials.

The Italian version of the Mouth Handicap in Systemic Sclerosis scale (MHISS) is valid, reliable and useful in assessing oral health-related quality of life (OHRQoL) in systemic sclerosis (SSc) patients.

In systemic sclerosis (SSc), mouth and face involvement leads to problems in oral health-related quality of life (OHRQoL). Mouth Handicap in Systemic Sclerosis scale (MHISS) is a 12-item questionnaire specifically quantifying mouth disability in SSc, organized in 3 subscales. Our aim was to validate Italian version of MHISS, by assessing its test-retest reliability and internal and external consistency in Italian SSc patients. Forty SSc patients (7 dSSc, 33 lSSc; age and disease duration: 57.27 ± 11.41, 9.4 ± 4.4 years; 22 with sicca syndrome) were evaluated with MHISS. MHISS was translated following a forward-backward translation procedure, with independent translations and counter-translation. Test-retest reliability was evaluated, comparing the results of two administrations, with intraclass correlation coefficient (ICC). Internal consistency was assessed by Cronbach's α and external consistency by comparison with mouth opening. MHISS has a good test-retest reliability (ICC: 0.93) and internal consistency (Cronbach's α:0.99). A good external consistency was confirmed by correlation with mouth opening (rho: -0,3869, p: 0.0137). Total MHISS score was 17.65 ± 5.20, with scores of subscale 1 (reduced mouth opening) of 6.60 ± 2.85 and scores of subscales 2 (sicca syndrome) and 3 (aesthetic concerns) of 7.82 ± 2.59 and 3.22 ± 1.14. Total and subscale 2 scores are higher in dSSc than in lSSc. This result may be due to the higher presence of sicca syndrome in dSSc than in lSSc (p = 0.0109). Our results support validity and reliability in Italian SSc patients of MHISS, specifically measuring SSc OHRQoL.

The efficacy of the Rességuier method in the treatment of fibromyalgia syndrome: a randomized controlled trial.

OBJECTIVES: In fibromyalgia syndrome (FMS) defined rehabilitation guidelines are yet to be validated. Our aim is to evaluate the efficacy of the Rességuier method (RM) in FMS. METHODS: Forty-one patients were randomly assigned to Interventional (22 pts) and Observational (19 pts) Group (IG and OG). The study lasted 8 months. Patients were assessed at baseline (T0) after a 2-month rehabilitation (T1) and at a 6-month follow-up (T2) (only IG) with SF-36 Physical (PSI) and Mental Synthetic Index (MSI), Regional Pain Scale (RPS), Fibromyalgia Impact Questionnaire (FIQ), Number Rating Scales 0-10 to measure pain, movement quality, sleep, relax ability, analgesics number/per week. OG patients maintained their lifestyle for the duration of the study. RM aims to obtain patient awareness and control of bodily perceptions, thus reaching a modulation of responses to pain. Therapist controls patient attention and perception by verbal and manual contacts and leads them to perform bodily and respiratory active and conscious movements. RESULTS: In IG, at T1 all items were improved: PSI and MSI (p<0.001 and =0.001), FIQ (p<0.0001), RPS (p<0.001), pain (p<0.0001), movement quality (p=0.001), relax ability (p<0.0001), sleep (p<0.001); analgesics number/per week was reduced (p<0.001). All results obtained at T1, except FIQ, were maintained at T2. In OG at T1 versus T0, no difference in any of the assessed parameters was observed. CONCLUSION: In FMS patients, the rehabilitation with RM improves HRQoL, FMS-related disability and perceived pain, thus reducing the assumption of analgesics.

Anti-platelets in diabetes management.

This study aimed to determine the prevalence of anti-platelet use, and the extent to which contraindications to anti-platelet therapy prevent its use, in 726 diabetic patients attending a private clinic. Among those who reported a history of cardiovascular disease (CVD), 87.1% were on anti-platelet therapy. Of those without prior CVD but with at least one CVD risk factor, 59.8% were not on anti-platelet therapy, but only 7.1% of these had a contraindication to anti-platelet therapy. This study showed that high usage of anti-platelet therapy in diabetic patients with prior CVD is achievable, and that contraindications did not explain low use in those without prior CVD.

Efficacy of a tailored rehabilitation program for systemic sclerosis.

INTRODUCTION: Rehabilitation may contribute to the management of Systemic Sclerosis (SSc) dealing with disabilities due to skin and joint involvement. AIM: to evaluate the efficacy of a district specific and global rehabilitation program tailored for SSc patients. MATERIALS AND METHODS: 20 SSc patients were enrolled and randomly assigned to 2 groups. Interventional group (10 pts) was treated that included hand and face specific rehabilitation and at least a global rehabilitation technique such as hydrokinesytherapy or land-based program, also comprising respiratory exercises. Hand lymphatic drainage was added when necessary. Observational group (10 patients) was only provided with educational advices and medical information about SSc. Patients were evaluated at baseline (T0) and after the 9 weeks treatment period (T1). Interventional group was also assessed after a 9 weeks follow-up (T2). Patients were evaluated by SF-36, HAQ and a purpose-built-questionnaire for global health condition and with Hamis test, Duruöz scale, range of motion, water volumetric test, mouth opening and a purpose-built-questionnaire for hand and face involvement. RESULTS: At the end of the treatment, patients of interventional group improved in all the parameters evaluated. At follow-up, mouth mobility and functionality such as global health status was partially lost, only hand mobility and functionality parameters were maintained. No changes were observed in controls. CONCLUSION: The association and of district-specific and global rehabilitative techniques conceived and tailored for SSc patients improves disability, HRQoL, hand and face disability and functionality, with its effects partially maintained at the follow-up.

Two regulators of Ste12p inhibit pheromone-responsive transcription by separate mechanisms.

The yeast Saccharomyces cerevisiae transcription factor Ste12p is responsible for activating genes in response to MAP kinase cascades controlling mating and filamentous growth. Ste12p is negatively regulated by two inhibitor proteins, Dig1p (also called Rst1p) and Dig2p (also called Rst2p). The expression of a C-terminal Ste12p fragment (residues 216 to 688) [Ste12p(216-688)] from a GAL promoter causes FUS1 induction in a strain expressing wild-type STE12, suggesting that this region can cause the activation of endogenous Ste12p. Residues 262 to 594 are sufficient to cause STE12-dependent FUS1 induction when overexpressed, and this region of Ste12p was found to bind Dig1p but not Dig2p in yeast extracts. In contrast, recombinant glutathione S-transferase-Dig2p binds to the Ste12p DNA-binding domain (DBD). Expression of DIG2, but not DIG1, from a GAL promoter inhibits transcriptional activation by an Ste12p DBD-VP16 fusion. Furthermore, disruption of dig1, but not dig2, causes elevated transcriptional activation by a LexA-Ste12p(216-688) fusion. Ste12p has multiple regions within the C terminus (flanking residue 474) that can promote multimerization in vitro, and we demonstrate that these interactions can contribute to the activation of endogenous Ste12p by overproduced C-terminal fragments. These results demonstrate that Dig1p and Dig2p do not function by redundant mechanisms but rather inhibit pheromone-responsive transcription through interactions with separate regions of Ste12p.

IL-4 and prostaglandin E2 inhibit hypomethylation of the 5' regulatory region of IFN-gamma gene during differentiation of naive CD4+ T cells.

We have previously shown that prostaglandin E2 (PGE2) and IL-4 inhibit the priming of IFN-gamma-production during the differentiation of naive CD4+ T cells from human cord blood by different signal-transducing mechanisms. To compare and analyse the molecular mechanisms by which PGE2 and IL-4 inhibit the priming of IFN-gamma production, we investigated the effects of PGE2 and IL-4 on the methylation of the IFN-gamma gene during the in vitro differentiation of naive CD4+ T cells. In human naive CD4+ T cells, which produce primarily IL-2 and a little amount of IFN-gamma, the IFN-gamma gene was methylated. After stimulation via TCR, CD4+ T cells produced IFN-gamma and the CpG dinucleotide contained within the TATA proximal regulatory element of the IFN-gamma gene was partially hypomethylated. Both IL-4 and PGE2 inhibited the hypomethylation of this site and the acquisition of IFN-gamma-producing ability. In contrast to the SnaBI site in the TATA proximal regulatory element, the HpalI site in the first intron of the IFN-gamma gene of the CD4+ T cells from cord blood was completely methylated even after stimulation via TCR. 5-azacytidine restored the IFN-gamma-producing ability of these cells treated with IL-4 and PGE2. These findings suggest that, although the signal transduction that inhibits the priming of IFN-gamma-production is different for each reagent, the protection from hypomethylation of the regulatory region of the IFN-gamma gene is involved in the molecular mechanisms by which these reagents inhibit the priming of IFN-gamma-production during the differentiation of human naive CD4+ T cells.

Case report: coincident granular cell tumour of the breast with invasive ductal carcinoma.

Granular cell tumours of the breast are rare lesions which are almost always benign. They are of interest because their clinical, radiological and pathological appearances often closely resemble those of malignancy. A case is described in which screening mammography in an asymptomatic woman led to the diagnosis of simultaneous invasive intraductal carcinoma in one breast and benign granular cell tumour in the other. Granular cell tumour of the breast coincident with other breast tumours is very rarely described and an association with breast carcinoma is unknown.

Outbreak of suspected trichinosis among travelers returning from a neighboring island.

BACKGROUND: An outbreak of trichinosis involving a cohort of 33 returning travelers from a resort island in a neighboring country was suspected, beginning with 2 initial cases who were hospitalized with a syndrome of fever, myalgia and eosinophilia. METHOD: At the initial visit, a full history was obtained and a physical examination was performed for each individual. Also, blood was drawn for full blood count, blood film for malaria parasites and Trichinella serology. Extensive epidemiological investigations identified a total of 84 returning travelers from 6 separate groups, of which 58 (69%) were subjected to a detailed interview, including the kinds of meat consumed on the island. RESULTS: Twenty-five of these 33 persons (75.7 %) fulfilled clinical or serological case definition criteria for trichinosis. IgG antibody for Trichinella spiralis was detected in 8 out of 32 persons who had the test done (25%). Symptoms were generally mild, with only one patient (3%) requiring steroids for prolonged myositis. CONCLUSION: We suspect this outbreak to be due to trichinosis although the source could not be identified. Extensive epidemiological investigations identified a total of 84 returning travelers from 6 separate groups, of which 58 (69%) were subjected to a detailed interview, including the kinds of meat consumed on the island, but the source of the outbreak could not be identified.

Genotypic variability and mode of action of Colorado potato beetle (Coleoptera: Chrysomelidae) resistance in seven Solanum species.

Accessions from seven wild Solanum species were evaluated in the field for resistance to the Colorado potato beetle, Leptinotarsa decemlineata (Say). The multivariate insect population density data were analyzed using factor analysis. The factors extracted corresponded to relevant phases of the insect's life cycle and provided information on the mode of resistance (antixenosis and antibiosis) of the plant species. S. berthaultii, S. capsicibaccatum, S. jamesii, S. pinnatisectum, and S. trifidum demonstrated both antixenosis and antibiosis but expressed different levels of resistance. The mode of resistance of S. polyadenium seemed to be antibiosis and that of S. tarijense antixenosis. Genetic variability and heritability of insect resistance traits within accessions was trivial or inconsistent for all Solanum species studied.

A comparison of three measures of upper limb function in Friedreich ataxia.

Friedreich Ataxia (FRDA) is the commonest inherited ataxia. Clinical trials of pharmaceuticals are increasingly being conducted in this condition. This requires the most accurate outcome measures to enable trials to be conducted with a minimum number of subjects in the shortest time frame and to minimize the risk of false negative results. Upper limb function is a major area of morbidity in FRDA. We therefore have compared the performance of three tests of upper limb function in FRDA: the Nine Hole Peg Test (9HPT), Box and Blocks Test (BBT) and Jebsen Taylor Hand Function Test (JTHFT). This study was undertaken to ascertain the best test for inclusion in a Friedreich Ataxia Functional Composite (FAFC) test for use in clinical studies and therapeutic trials. The three tests were administered to the dominant and non-dominant upper limbs of 38 individuals with genetically proven FRDA on two occasions, 12 months apart. The results of testing were correlated with the following disease parameters; age at disease onset, disease duration and score for the Friedreich Ataxia Rating Scale (FARS). The responsiveness to change of each test was assessed by measuring the effect size and calculations of the number of subjects required for similarly powered therapeutic trials. Results for all tests correlated significantly with disease duration and FARS score. The only test scores that changed significantly over 12 months were those for the non-dominant 9HPT and BBT. Scores for these two tests also had the largest effect sizes and required the fewest subjects for similarly powered therapeutic trials. We conclude, therefore, that the non-dominant 9HPT and BBT are the best tests for inclusion in a FAFC. Since the 9HPT has already been suggested for inclusion in a FAFC, we recommend that this test is used but that it is the non-dominant limb that is tested.

A method to construct confidence interval for expected response to multi-trait selection.

Confidence intervals are constructed for the expected responses to three types of multi-trait selection. The influence of numbers of replicates and genotypes used in a progeny test experiment on the precision of response of multi-trait selection is discussed based on the structure of the established intervals. Special attention is paid to the characteristics of the intervals constructed for the conventional least square selection indices.

An interval estimation of expected response to selection.

A method is presented here for obtaining an interval estimate of expected response to selection based on results of a progeny test experiment. The structure of the constructed confidence limits is then examined for the influence of the numbers of lines and replicates on the precision of predicting the expected response to selection.

A method for quantitative genetic analysis of early clonal generation seedlings of an asexual crop with special application to a breeding population of the potato (Solarium tuberosum L.).

Traditionally, the selection and breeding of asexual crops starts with a population of many thousands of seedlings derived from many crosses. Heavy screening of clones in the first field trial, sometimes up to 90% of the population, is a routine practice. The extent of such early selection pressure is questioned since plants in the early clonal generations are usually managed in an unconventional cultivation system as compared to that used in the later clonal generation trials or in the commercial practice. A method of quantitative genetic analysis is presented for analyzing data of quantitative traits which are collected from two different clonal generations. It is proposed to measure the regression type of heritability between two clonal generations in standard deviation unit and the expected response to selection in the first clonal generation with a physical unit used in the second clonal generation. Subsequently, the method was applied to a breeding population of potato. The results indicated that selection for quantitative traits in the first clonal generation was in most cases less efficient than direct selection in the second clonal generation.

A proposal to improve the efficiency of index selection by "rounding".

This paper describes a rounding procedure to improve the efficiency of index selection. The procedure involves performing canonical variate analysis on the phenotypic and genotypic variances of a group of traits estimated from a progeny test experiment. The eigenvectors corresponding to the significant eigenvalues are used to transform the original traits into a set of independent variables. The selection index is then constructed based on the new set of variables. The efficiency of the new index is expected to be improved by rounding off the variables associated with the insignificant eigenvalues.

Tuberosum x Tuberosum and Tuberosum x Andigena potato hybrids: comparisons of families and parents, and breeding strategies for Andigena potatoes in long-day temperate environments.

Tuberosum x Tuberosum families and Tuberosum x long-day adapted Andigena families are compared with each other and with their parents using multivariate analyses. The Tuberosum x Tuberosum families, representative of those used in present-day breeding programs, have lower mean tuber weights, marketable yields and total yields than their parents, and a trend towards the Andigena clones which represent their putative ancestors. The Tuberosum x Andigena families are superior to the Tuberosum x Tuberosum families in total yield and tuber number, but have reduced tuber size, later maturity and more persistent stolons. The characteristics of the Andigena parents dominate the inter-Group hybrids. The multivariate analyses facilitate the identification of superior hybrid families and superior parents. The results are discussed in the context of further Andigena selection, cytoplasmic male sterility, and reciprocal differences in inter-Group hybrid families. Future breeding strategies are proposed.

Gene differences in heading date, height, seed weight and seed yield between two pure line varieties of Triticum aestivum L.

Reciprocal sets of homozygous inbred backcross lines were developed by crossing two pure line varieties (Baart 46 and Ramona) of Triticum aestivum L., followed by two backcrosses to each of the two parent varieties, and six to eight generations of selfing. Data on each inbred backcross line was obtained from twelve plots (from replications in three years). Five genes were responsible for over 95% of the genetic variation for heading date. These genes had pleiotropic effects on plant height that were proportional to their effects on heading date. Two additional genes had detectable effects on plant height. The genes with a measurable effect on height accounted for 90% of the genetic variation in the Baart 46 genetic background. One gene affected seed weight. In the Ramona background, this gene accounted for 80% of the genetic variation in seed weight and 16% of the genetic variation in seed yield. Two genes, responsible for the earliest and latest heading date classes, had large pleiotropic effects on seed yield. They accounted for 60% of the genetic variation in yield. One gene, with no effect on heading date, caused a detectable reduction in yield of 23% in the Baart 46 inbred backcross lines. This gene had no apparent effect in the Ramona genetic background. Quantitative trait genes are sparsely distributed in the genome: fewer than one in four chromosome arms carries a gene with a detectable effect. Gene effects on quantitative traits are not small and similar. The distribution of 22 gene effects for heading date and height is slightly skewed to the right: as the magnitude of effect increases, the frequency of genes having the effect decreases.

N.m.r. spectroscopic studies of fucose-containing oligosaccharides derived from keratanase digestion of articular cartilage keratan sulphates. Influence of fucose residues on keratanase cleavage.

Keratan sulphate chains from bovine articular cartilage were fully digested with keratanase from Pseudomonas sp. and the products were reduced with alkaline borohydride. The resultant fragments were fractionated on a Nucleosil 5SB column and the earliest eluting fucose-containing oligosaccharides were isolated. Structural analysis using 1H n.m.r. spectroscopy (600 MHz) showed the two least-charged species to have the following structure: GlcNAc(6S) beta 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc(6S) beta 1- 3Gal beta 1-4GlcNAc(6S) beta 1-3Gal-ol and GlcNAc(6S) beta 1-3Gal beta 1- 4(Fuc alpha 1-3)GlcNAc(6S) beta 1-3Gal beta 1-4GlcNAc(6S) beta 1-6(Gal beta 1- 3)GalNAc-ol. Both galactoses adjacent to the fucosylated N-acetylglucosamine residue are unsulphated. Therefore, it can be deduced from these structures that the presence of fucose on N-acetylglucosamine residues in keratan sulphates protects both of the adjacent unsulphated galactose residues from keratanase cleavage. This result has implications for the interpretation of keratanase fingerprints, because in articular cartilage keratan sulphates the keratanase-resistant blocks are not solely those with fully sulphated galactose residues, but also include the fucosylated sequences, which have unsulphated galactoses. It is, therefore, not possible to estimate their galactose sulphation or the size of the fully sulphated disaccharide-repeat sequences from keratan sulphates that contain fucose.

Selective infection of astrocytes in human glial cell cultures by rubella virus.

BACKGROUND: Rubella virus (RV) can cause a wide variety of neurologic symptoms, particularly when infection occurs in utero. However, little is known about the pathogenesis of these infections and the cell types in human brain susceptible to infection have not been characterized. EXPERIMENTAL DESIGN: Cell cultures derived from human brain tissue were examined for susceptibility to two wild-type and two vaccine strains of RV. Cell types expressing viral antigen were identified by double-label immunofluorescence with monoclonal antibodies to specific cell markers and a polyclonal anti-RV antibody. Viral yield was determined by plaque assay. RESULTS: All four RV strains replicated in the brain cultures, although the titers obtained in the case of the vaccine strains were more than 100-fold lower than those found for wild-type isolates. Astrocytes appeared to be the main cell type infected, expressing large amounts of viral antigen. In contrast, oligodendrocytes were rarely productively infected, even when surrounded by infected astrocytes. Occasional neurons expressing viral antigen were also seen. CONCLUSIONS: The main cell type permissive to RV infection in developing brain tissue is the astrocyte. Although not highly cytolytic, the virus may disrupt the functioning of these cells, resulting in neurologic deficits. The restricted replication of this virus in oligodendrocytes correlates with the lack of demyelination generally reported as being typical of RV neurologic disease.