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2.
Heliyon ; 7(7): e07397, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34286116

ABSTRACT

Currently, due to the increasing importance of recommender systems (RSs), especially in the fields of social networking and e-commerce, these systems represent one of the most interesting subjects in computer programming. Although many research reports have previously been published in this subject area, because of lack of clarity regarding their algorithms or limited comparisons with the literature, most of them are difficult to extend for similar applications in the future. Therefore, in the present study, we have attempted to improve two novel RS evaluation measures (variety and newness) developed from previous evaluator rules (namely, diversity and novelty) based on human behavior so as to be more reliable and compatible with various developments in RSs. The new rules provide higher weighting for suggestions and respect for users' behavior and can be used in place of diversity and novelty rules with better precision and centralization, by 22.54% for variety and by 14.84% for newness. In addition, we aim to use the developed measures to improve new RSs and support better comparative analyses in this field in the future. This contribution is expected to facilitate better RS research and competition, especially in the social networking domain.

4.
Internet resource in Spanish | LIS -Health Information Locator | ID: lis-34512

ABSTRACT

En el siglo XVII fue fabricada la primera cámara fotográfica y a partir de entonces, la fotografía experimentó una evolución gracias al trabajo de científicos e investigadores. Actualmente existen en el mercado cámaras digitales que igualan o superan a las cámaras profesionales convencionales, son fáciles de manejar y de gran utilidad en odontología. El odontólogo general puede aprovechar las ventajas de esta nueva tecnología para: captar, visualizar, analizar, recortar, duplicar y archivar imágenes con gran facilidad; lo que enriquece el diagnóstico y el seguimiento de los casos clínicos. Además, las fotografías mejoran la comunicación con los pacientes y los laboratorios; permiten ser instrumentos legales; facilitan el mercadeo y la promoción de nuevos tratamientos dentales.Este artículo expone las ventajas y aplicaciones de la fotografía clínica digital, también clasifica en forma sencilla los tipos de fotografías clínicas odontológicas y describe cuáles deben ser los criterios para que las fotografías clínicas adquieran validez documental. Tomando en cuenta las ventajas expuestas, sería muy acertado incluir este aprendizaje como parte de la formación integral del odontólogo general y que no sea sólo conocimiento de especialistas, ya que, debe ser parte del trabajo diario en el ambiente clínico. (AU)


Subject(s)
Photography, Dental
5.
Neurology ; 75(17): 1548-54, 2010 Oct 26.
Article in English | MEDLINE | ID: mdl-20975055

ABSTRACT

OBJECTIVE: In some 5% of patients with facioscapulohumeral muscular dystrophy (FSHD), no D4Z4 repeat contraction on chromosome 4q35 is observed. Such patients, termed patients with FSHD2, show loss of DNA methylation and heterochromatin markers at the D4Z4 repeat that are similar to patients with D4Z4 contractions (FSHD1). This commonality suggests that a change in D4Z4 chromatin structure unifies FSHD1 and FSHD2. The aim of our study was to critically evaluate the clinical features in patients with FSHD2 in order to establish whether these patients are phenotypically identical to FSHD1 and to establish the effects of the (epi-) genotype on the phenotype. METHODS: This cross-sectional study studied 33 patients with FSHD2 from 27 families, the largest cohort described to date. All patients were clinically assessed using a standardized clinical evaluation form. Genotype analysis was performed by pulsed field gel electrophoresis and PCR; D4Z4 methylation was studied by methylation-sensitive Southern blot analysis. RESULTS: FSHD2 is identical to FSHD1 in its clinical presentation. Notable differences include a higher incidence (67%) of sporadic cases and the absence of gender differences in disease severity in FSHD2. Overall, average disease severity in FSHD2 was similar to that reported in FSHD1 and was not influenced by D4Z4 repeat size. In FSHD2, a small effect of the degree of hypomethylation on disease severity was observed. CONCLUSIONS: Clinically, patients with FSHD2 are indistinguishable from patients with FSHD1. The present data suggest that FSHD1 and FSHD2 are the result of the same pathophysiologic process.


Subject(s)
Muscular Dystrophy, Facioscapulohumeral/genetics , Muscular Dystrophy, Facioscapulohumeral/physiopathology , Nuclear Proteins/genetics , Adolescent , Adult , Child , Child, Preschool , Chromosomes, Human, Pair 4 , Cohort Studies , Cross-Sectional Studies , DNA Methylation/genetics , DNA Repeat Expansion/genetics , Family Health , Female , Genotype , Humans , Infant , Infant, Newborn , Male , Microfilament Proteins , Middle Aged , Phenotype , Polymorphism, Genetic/genetics , RNA-Binding Proteins , Young Adult
6.
Neurology ; 74(10): 833-8, 2010 Mar 09.
Article in English | MEDLINE | ID: mdl-20211907

ABSTRACT

BACKGROUND: In spinal muscular atrophy (SMA), weakness, decreased endurance, and fatigue limit mobility. Scales have been developed to measure function across the wide spectrum of disease severity. However, these scales typically are observer dependent, and scores are based on sums across Likert-scaled items. The Six-Minute Walk Test (6MWT) is an objective, easily administered, and standardized evaluation of functional exercise capacity that has been proven reliable in other neurologic disorders and in children. METHODS: To study the performance of the 6MWT in SMA, 18 ambulatory participants were evaluated in a cross-sectional study. Clinical measures were 6MWT, 10-m walk/run, Hammersmith Functional Motor Scale-Expanded (HFMSE), forced vital capacity, and handheld dynamometry. Associations between the 6MWT total distance and other outcomes were analyzed using Spearman correlation coefficients. A paired t test was used to compare the mean distance walked in the first and sixth minutes. RESULTS: The 6MWT was associated with the HFMSE score (r = 0.83, p < 0.0001), 10-m walk/run (r = -0.87, p < 0.0001), and knee flexor strength (r = 0.62, p = 0.01). Gait velocity decreased during successive minutes in nearly all participants. The average first minute distance (57.5 m) was significantly more than the sixth minute distance (48 m) (p = 0.0003). CONCLUSION: The Six-Minute Walk Test (6MWT) can be safely performed in ambulatory patients with spinal muscular atrophy (SMA), correlates with established outcome measures, and is sensitive to fatigue-related changes. The 6MWT is a promising candidate outcome measure for clinical trials in ambulatory subjects with SMA.


Subject(s)
Exercise Test/methods , Fatigue/diagnosis , Fatigue/etiology , Muscular Atrophy, Spinal/complications , Walking/physiology , Adolescent , Adult , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Muscle Strength Dynamometer , Retrospective Studies , Statistics, Nonparametric , Vital Capacity/physiology , Young Adult
7.
Neurology ; 68(8): 578-82, 2007 Feb 20.
Article in English | MEDLINE | ID: mdl-17229919

ABSTRACT

BACKGROUND: In the majority of facioscapulohumeral muscular dystrophy (FSHD) cases, the molecular basis of the disease is due to loss of subtelomeric D4Z4 repeat units at 4q35. Occasionally, an apparent absence of the contracted D4Z4 repeat is associated with FSHD. One explanation for this finding is a deletion in the region proximal to the D4Z4 repeat array that encompasses the p13E-11 (D4F104S1) probe-binding site used in the DNA diagnosis. The frequency of such proximally extended deletions is unknown, and to date, few patients have been described due to the difficulties in the molecular identification of such cases. METHODS: We describe a family (DUK 2531) in which a contracted D4Z4 allele and a large proximal deletion of approximately 75 kb are segregating to 11 individuals. This is the largest deletion identified to date. Family DUK 2531 was initially thought to have normal D4Z4 fragment size and therefore unlinked to the 4q35 region (FSHD1B). RESULTS: Further molecular analysis of DUK 2531 reveals the presence of 10 repeat units (33 kb). The extended deletion includes the probe p13E-11 and B31 binding sites, the inverted repeat D4S2463, and genes FRG2 and TUBB4Q. CONCLUSION: Despite the length of the proximal deletion in this family, the range and severity of the clinical manifestations are typical for the disorder. Because such deletions can lead to misinterpretation in the diagnostic setting, this suggests the need for additional diagnostic tests in facioscapulohumeral muscular dystrophy.


Subject(s)
Chromosomes, Human, Pair 4/genetics , Gene Deletion , Genetic Predisposition to Disease/genetics , Muscular Dystrophy, Facioscapulohumeral/genetics , Muscular Dystrophy, Facioscapulohumeral/physiopathology , Mutation/genetics , Adult , Chromosome Aberrations , DNA Mutational Analysis , Female , Gene Dosage/genetics , Gene Frequency/genetics , Genetic Testing , Genotype , Humans , Male , Muscle Weakness/diagnosis , Muscle Weakness/genetics , Muscle Weakness/physiopathology , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Muscular Dystrophy, Facioscapulohumeral/diagnosis , Pedigree , Phenotype
8.
Neurology ; 68(8): 569-77, 2007 Feb 20.
Article in English | MEDLINE | ID: mdl-17151338

ABSTRACT

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is caused by deletions within a tandem array of D4Z4 repeats on chromosome 4q35. In addition to muscle degeneration, most patients with FSHD develop abnormalities of the retinal vasculature. Previous work has suggested that muscle degeneration in FSHD results from increased expression of genes proximal to the deletion, including FRG1. OBJECTIVES: To reexamine this mechanism and identify pathways that are abnormally regulated early in the disease process. METHODS: We prospectively studied gene expression in skeletal muscle in patients with FSHD (n = 19) vs healthy individuals (n = 30) and patients with myotonic dystrophy type 1 (n = 12). We used oligonucleotide microarrays for global analysis of gene expression and reverse transcriptase-PCR (RT-PCR) to assess expression or alternative splicing for particular genes. RESULTS: Expression of FRG1 was not increased in patients with FSHD, either by microarray analysis or quantitative RT-PCR. Among genes on 4q35, only LRP2BP showed upregulation that was specific to FSHD. However, neither LRP2BP nor FRG1 showed imbalance of allelic expression by RT-PCR. After filtering out genes that showed similar dysregulation in other forms of muscular dystrophy, only 44 genes were specifically upregulated early in FSHD. Among these, 34 genes were characterized or partially characterized, of which 11 (32%) had a role in vascular smooth muscle or endothelial cells. CONCLUSION: Expression of genes on chromosome 4q35 was normally regulated in the early stages of facioscapulohumeral muscular dystrophy. Our results support a possible link between muscular dystrophy and retinal vasculopathy in facioscapulohumeral muscular dystrophy.


Subject(s)
Genetic Linkage/genetics , Genetic Predisposition to Disease/genetics , Muscular Dystrophy, Facioscapulohumeral/complications , Muscular Dystrophy, Facioscapulohumeral/genetics , Retinal Diseases/complications , Retinal Diseases/genetics , Adolescent , Adult , Aged , Chromosomes, Human, Pair 4/genetics , DNA Mutational Analysis , Female , Gene Expression Profiling , Gene Expression Regulation/genetics , Genetic Testing , Humans , Male , Middle Aged , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Muscular Dystrophy, Facioscapulohumeral/physiopathology , Mutation/genetics , Oligonucleotide Array Sequence Analysis , Prospective Studies , Retinal Artery/metabolism , Retinal Artery/pathology , Retinal Artery/physiopathology , Retinal Diseases/physiopathology
9.
Immunopharmacol Immunotoxicol ; 28(4): 621-31, 2006.
Article in English | MEDLINE | ID: mdl-17190739

ABSTRACT

Nerve fibers and sensory neuropeptides substance P and calcitonin gene-related peptide (CGRP) have been reported to be involved in allergic contact dermatitis (ACD). In the present study, we investigated the general innervation (using antibody against protein gene product 9.5, PGP 9.5), axonal growth (using antibody against growth associated protein, GAP-43), CGRP, and substance P with its receptor neurokinin 1 (NK1), in positive epicutaneous reactions to nickel sulphate from nickel-allergic patients, at the peak of inflammation, 72 hr after challenge with the antigen. There was an increased (p < 0.01) number of GAP-43 positive fibers in the eczematous compared with control skin, indicating an increased axonal growth already at 72 hr postchallenge. Double staining revealed a coexpression of CGRP and GAP-43 on dermal nerve fibers. There was no difference in the number of substance P and CGRP positive nerve fibers between eczematous and control skin. However, semiquantification analyses showed an increased expression of substance P positive inflammatory cells, being CD3, CD4, or CD8 positive, and NK1R positive inflammatory cells, being tryptase or CD3 positive. These results indicate a contribution of regenerating nerve fibers and substance P to the contact allergic reaction.


Subject(s)
Axons/physiology , Dermatitis, Allergic Contact/metabolism , Dermatitis, Allergic Contact/physiopathology , Receptors, Neurokinin-1/biosynthesis , Substance P/biosynthesis , Up-Regulation/physiology , Calcitonin Gene-Related Peptide/biosynthesis , GAP-43 Protein/biosynthesis , Humans , Immunohistochemistry , Inflammation/pathology , Microscopy, Fluorescence , Skin/pathology , Skin Tests , Tryptases/biosynthesis , Ubiquitin Thiolesterase/biosynthesis
10.
Neurology ; 67(10): 1887-9, 2006 Nov 28.
Article in English | MEDLINE | ID: mdl-17130433

ABSTRACT

Obstetric risk in facioscapulohumeral muscular dystrophy (FSHD) is not known. We surveyed 38 women with FSHD reporting 105 gestations and 78 live births. Review of medical records showed that pregnancy outcomes were generally favorable. The rates for low birth weight and total operative deliveries were statistically higher than the national rates in the general population. Worsening of FSHD was reported in 24% of gestations and did not usually resolve after delivery.


Subject(s)
Birth Injuries/epidemiology , Muscular Dystrophy, Facioscapulohumeral/epidemiology , Pregnancy Complications/epidemiology , Adolescent , Adult , Cesarean Section/statistics & numerical data , Comorbidity , Cross-Sectional Studies , Disease Progression , Female , Fetal Distress/epidemiology , Humans , Infant, Low Birth Weight/physiology , Infant, Newborn , Infections/epidemiology , Muscle Weakness/epidemiology , Pregnancy , Surveys and Questionnaires
11.
Brain ; 129(Pt 1): 8-17, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16195244

ABSTRACT

Periodic paralyses (PPs) are rare inherited channelopathies that manifest as abnormal, often potassium (K)-sensitive, muscle membrane excitability leading to episodic flaccid paralysis. Hypokalaemic (HypoPP) and hyperkalaemic PP and Andersen-Tawil syndrome are genetically heterogeneous. Over the past decade mutations in genes encoding three ion channels, CACN1AS, SCN4A and KCNJ2, have been identified and account for at least 70% of the identified cases of PP and several allelic disorders. No prospective clinical studies have followed sufficiently large cohorts with characterized molecular lesions to draw precise conclusions. We summarize current knowledge of the clinical diagnosis, molecular genetics, genotype-phenotype correlations, pathophysiology and treatment in the PPs. We focus on unresolved issues including (i) Are there additional ion channel defects in cases without defined mutations? (ii) What is the mechanism for depolarization-induced weakness in Hypo PP? and finally (iii) Will detailed electrophysiological studies be able to correctly identify specific channel mutations? Understanding the pathophysiology of the potassium-sensitive PPs ought to reduce genetic complexity, allow subjects to be stratified during future clinical trials and increase the likelihood of observing true clinical effects. Ideally, therapy for the PPs will prevent attacks, avoid permanent weakness and improve quality of life. Moreover, understanding the skeletal muscle channelopathies will hopefully lead to insights into the more common central nervous system channel diseases such as migraine and epilepsy.


Subject(s)
Paralyses, Familial Periodic , Animals , Carbonic Anhydrase Inhibitors/therapeutic use , Genotype , Humans , Ion Channel Gating , Mice , Mice, Knockout , Models, Animal , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Mutation , Paralyses, Familial Periodic/diagnosis , Paralyses, Familial Periodic/drug therapy , Paralyses, Familial Periodic/genetics , Phenotype , Potassium/metabolism , Potassium/therapeutic use , Potassium Channels/genetics , Potassium Channels/metabolism , Sodium Channels/genetics , Sodium Channels/metabolism
13.
Neurology ; 63(9): 1647-55, 2004 Nov 09.
Article in English | MEDLINE | ID: mdl-15534250

ABSTRACT

BACKGROUND: Periodic paralyses and paramyotonia congenita are rare disorders causing disabling weakness and myotonia. Mutations in sodium, calcium, and potassium channels have been recognized as causing disease. OBJECTIVE: To analyze the clinical phenotype of patients with and without discernible genotype and to identify other mutations in ion channel genes associated with disease. METHODS: The authors have reviewed clinical data in patients with a diagnosis of hypokalemic periodic paralysis (56 kindreds, 71 patients), hyperkalemic periodic paralysis (47 kindreds, 99 patients), and paramyotonia congenita (24 kindreds, 56 patients). For those patients without one of the classically known mutations, the authors analyzed the entire coding region of the SCN4A, KCNE3, and KCNJ2 genes and portions of the coding region of the CACNA1S gene in order to identify new mutations. RESULTS: Mutations were identified in approximately two thirds of kindreds with periodic paralysis or paramyotonia congenita. The authors found differences between the disorders and between those with and without identified mutations in terms of age at onset, frequency of attacks, duration of attacks, fixed proximal weakness, precipitants of attacks, myotonia, electrophysiologic studies, serum potassium levels, muscle biopsy, response to potassium administration, and response to treatment with acetazolamide. CONCLUSIONS: Hypokalemic periodic paralysis, hyperkalemic periodic paralysis, and paramyotonia congenita may be distinguished based on clinical data. This series of 226 patients (127 kindreds) confirms some clinical features of this disorder with notable exceptions: In this series, patients without mutations had a less typical clinical presentation including an older age at onset, no changes in diet as a precipitant, and absence of vacuolar myopathy on muscle biopsy.


Subject(s)
Hypokalemic Periodic Paralysis/diagnosis , Myotonic Disorders/diagnosis , Paralysis, Hyperkalemic Periodic/diagnosis , Adolescent , Adult , Child , Child, Preschool , DNA Mutational Analysis , Female , Genotype , Humans , Hypokalemic Periodic Paralysis/genetics , Male , Middle Aged , Myotonic Disorders/genetics , NAV1.4 Voltage-Gated Sodium Channel , Paralysis, Hyperkalemic Periodic/genetics , Phenotype , Potassium Channels, Inwardly Rectifying/genetics , Potassium Channels, Voltage-Gated/genetics , Sodium Channels/genetics
14.
Cochrane Database Syst Rev ; (2): CD002276, 2004.
Article in English | MEDLINE | ID: mdl-15106171

ABSTRACT

BACKGROUND: Facioscapulohumeral muscular dystrophy is a progressive muscle disease which has no agreed treatment. Early suggestions that corticosteroids might be helpful were not supported by a subsequent open label study. The beta 2 adrenergic agonist albuterol, also known as salbutamol, is known to have anabolic effects which might be beneficial for facioscapulohumeral muscular dystrophy. Creatine has been used as a muscle performance enhancer by athletes and it might be helpful in muscular dystrophies including facioscapulohumeral muscular dystrophy. OBJECTIVES: The objective of the review was to determine whether there is any drug treatment which alters the progression of facioscapulohumeral muscular dystrophy. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group specialised register (searched August 2003), MEDLINE (January 1966 to August 2003) and EMBASE (January 1980 to August 2003) for any references to facioscapulohumeral muscular dystrophy. Abstracts from the major neurological meetings and trial bibliographies were also searched for further references to trials. Experts were contacted for information regarding unpublished trials or trials in progress. SELECTION CRITERIA: We included all randomised or quasi-randomised trials of any drug treatment for facioscapulohumeral muscular dystrophy, in adults with a recognised diagnosis of facioscapulohumeral muscular dystrophy. Trials had to include an assessment of muscle strength at one year. DATA COLLECTION AND ANALYSIS: All identified trials were independently assessed by both reviewers to ensure that they fulfilled the selection criteria and were then rated for their quality. Trial data were extracted and entered by one reviewer and checked by the other. If appropriate data existed a weighted treatment effect was to be calculated across trials using the Cochrane statistical package, Review Manager. The results were to have been expressed as relative risks and 95% confidence intervals and risk differences and 95% confidence intervals for dichotomous outcomes, and weighted mean differences and 95% confidence intervals for continuous outcomes. MAIN RESULTS: Two published high quality randomised controlled trials fulfilled the selection criteria. One compared creatine supplementation with placebo and the other compared high and low-dose albuterol with placebo. A further unpublished randomised controlled trial of albuterol in facioscapulohumeral muscular dystrophy was identified. The creatine trial showed a non-significant difference in favour of creatine. The albuterol trial showed no significant difference in muscle strength at one year but some secondary measures such as lean body mass and handgrip strength did improve. REVIEWERS' CONCLUSIONS: There is no evidence from randomised controlled trials to support any drug treatment for facioscapulohumeral muscular dystrophy but only two randomised controlled trials have been published.


Subject(s)
Adrenergic beta-Agonists/therapeutic use , Albuterol/therapeutic use , Creatine/therapeutic use , Muscular Dystrophy, Facioscapulohumeral/drug therapy , Humans , Randomized Controlled Trials as Topic
15.
Neurology ; 60(11): 1811-6, 2003 Jun 10.
Article in English | MEDLINE | ID: mdl-12796536

ABSTRACT

BACKGROUND: Mutations in KCNJ2, the gene encoding the inward-rectifying K+ channel Kir2.1, cause the cardiac, skeletal muscle, and developmental phenotypes of Andersen-Tawil syndrome (ATS; also known as Andersen syndrome). Although pathogenic mechanisms have been proposed for select mutations, a common mechanism has not been identified. METHODS: Seventeen probands presenting with symptoms characteristic of ATS were evaluated clinically and screened for mutations in KCNJ2. The results of mutation analysis were combined with those from previously studied subjects to assess the frequency with which KCNJ2 mutations cause ATS. RESULTS: Mutations in KCNJ2 were discovered in nine probands. These included six novel mutations (D71N, T75R, G146D, R189I, G300D, and R312C) as well as previously reported mutations R67W and R218W. Six probands possessed mutations of residues implicated in binding membrane-associated phosphatidylinositol 4,5-bisphosphate (PIP2). In total, mutations in PIP(2)-related residues accounted for disease in 18 of 29 (62%) reported KCNJ2 -based probands with ATS. Also reported is that mutation R67W causes the full clinical triad in two unrelated males. CONCLUSIONS: The novel mutations corresponding to residues involved in Kir2.1 channel-PIP2 interactions presented here as well as the overall frequency of mutations occurring in these residues indicate that defects in PIP2 binding constitute a major pathogenic mechanism of ATS. Furthermore, screening KCNJ2 in patients with the complex phenotypes of ATS was found to be invaluable in establishing or confirming a disease diagnosis as mutations in this gene can be identified in the majority of patients.


Subject(s)
Abnormalities, Multiple/genetics , Arrhythmias, Cardiac/genetics , Mutation , Paralysis/genetics , Phosphatidylinositol 4,5-Diphosphate/metabolism , Potassium Channels, Inwardly Rectifying/genetics , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/pathology , Arrhythmias, Cardiac/diagnosis , Binding Sites , Female , Genetic Predisposition to Disease , Humans , Male , Muscle Weakness/genetics , Paralysis/diagnosis , Pedigree , Phenotype , Potassium Channels, Inwardly Rectifying/chemistry , Potassium Channels, Inwardly Rectifying/metabolism , Syndrome
16.
Neurology ; 57(8): 1434-40, 2001 Oct 23.
Article in English | MEDLINE | ID: mdl-11673585

ABSTRACT

BACKGROUND/OBJECTIVES: Animal and human studies suggest that beta(2)-adrenergic agonists exert anabolic effects on muscles, inducing and preventing atrophy after a variety of insults. Based on data from an open-label trial of albuterol in 15 patients with facioscapulohumeral dystrophy (FSHD), the authors conducted a randomized, double-blind, placebo-controlled trial of sustained-release albuterol in this disease. METHODS: Ninety patients were randomized to three groups: placebo; 8.0 mg albuterol twice daily; or 16.0 mg albuterol twice daily. Patients were treated for 1 year with assessments at baseline and weeks 13, 26, and 52. The primary outcome was the 52-week change in global strength by maximum voluntary isometric contraction testing (MVICT). Secondary outcomes included changes at 52 weeks in strength by manual muscle testing (MMT), grip strength, functional testing, and muscle mass assessed by dual energy x-ray absorptiometry (DEXA). RESULTS: Eighty-four patients completed the study. The mean changes in composite MVICT scores were not significantly different between the groups (mean +/- SD: placebo 0.20 +/- 0.91; low dose -0.04 +/- 0.84; high dose 0.08 +/- 0.98). Similarly, there were no differences in the mean MMT change (placebo 0.04 +/- 0.16; low dose -0.03 +/- 0.13; high dose 0.00 +/- 0.15). Grip improved in both treatment groups compared to placebo (placebo -0.53 +/- 4.13, low dose +1.90 +/- 3.34 [p = 0.02], high dose +1.70 +/- 4.13 [p = 0.03]). The high-dose group had a significant increase in lean mass by DEXA (+1.57 +/- 1.71 kg) compared to placebo (0.25 +/- 2.24; p = 0.007). Albuterol was well tolerated; side effects included cramps, tremors, insomnia, and nervousness. CONCLUSIONS: Although albuterol did not improve global strength or function in patients with FSHD, it did increase muscle mass and improve some measures of strength.


Subject(s)
Adrenergic beta-Agonists/therapeutic use , Albuterol/therapeutic use , Muscular Dystrophy, Facioscapulohumeral/drug therapy , Adult , Body Mass Index , Double-Blind Method , Female , Hand Strength , Humans , Male , Middle Aged , Placebos , Treatment Outcome
17.
Prostate ; 47(3): 194-204, 2001 May 15.
Article in English | MEDLINE | ID: mdl-11351349

ABSTRACT

BACKGROUND: Mxi1, an antagonist of c-Myc, maps to human chromosome 10q24-q25, a region altered in a substantial fraction of prostate tumors. Mice deficient for Mxi1 exhibit significant prostate hyperplasia. We studied the ability of Mxi1 to act as a growth suppressor in prostate tumor cells. METHODS: We infected DU145 prostate carcinoma cells with an Mxi1-expressing adenovirus (AdMxi1) in vitro, and measured Mxi1 expression, cell proliferation, soft agar colony formation, and cell cycle distribution. To explore mechanisms of Mxi1-induced growth arrest, we performed gene expression analysis. RESULTS: AdMxi1 infection resulted in reduced cell proliferation, reduced soft agar colony formation, and a higher proportion of cells in the G(2)/M phase of the cell cycle. This G(2)/M growth arrest was associated with elevated levels of cyclin B, and reduced levels of c-MYC and MDM2. CONCLUSIONS: The ability of AdMxi1 to suppress prostate tumor cell proliferation supports a role for Mxi1 loss in the pathogenesis of a subset of human prostate cancers. Prostate 47:194-204, 2001.


Subject(s)
DNA-Binding Proteins/physiology , Prostatic Neoplasms/pathology , Transcription Factors/physiology , Adenoviridae/genetics , Basic Helix-Loop-Helix Transcription Factors , Blotting, Western , Cell Division/physiology , DNA-Binding Proteins/biosynthesis , DNA-Binding Proteins/genetics , Flow Cytometry , G2 Phase/physiology , Gene Expression Profiling , Humans , Male , Microscopy, Confocal , Mitosis/physiology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Proto-Oncogene Proteins c-myc/antagonists & inhibitors , Transcription Factors/biosynthesis , Transcription Factors/genetics , Tumor Cells, Cultured , Tumor Suppressor Proteins
18.
Cell ; 105(4): 511-9, 2001 May 18.
Article in English | MEDLINE | ID: mdl-11371347

ABSTRACT

Andersen's syndrome is characterized by periodic paralysis, cardiac arrhythmias, and dysmorphic features. We have mapped an Andersen's locus to chromosome 17q23 near the inward rectifying potassium channel gene KCNJ2. A missense mutation in KCNJ2 (encoding D71V) was identified in the linked family. Eight additional mutations were identified in unrelated patients. Expression of two of these mutations in Xenopus oocytes revealed loss of function and a dominant negative effect in Kir2.1 current as assayed by voltage-clamp. We conclude that mutations in Kir2.1 cause Andersen's syndrome. These findings suggest that Kir2.1 plays an important role in developmental signaling in addition to its previously recognized function in controlling cell excitability in skeletal muscle and heart.


Subject(s)
Arrhythmias, Cardiac/genetics , Chromosomes, Human, Pair 17 , Facies , Paralyses, Familial Periodic/genetics , Potassium Channels, Inwardly Rectifying , Potassium Channels/genetics , Alleles , Amino Acid Sequence , Animals , Calcium Channels/genetics , DNA Primers , Family Health , Female , Gene Expression , Genetic Linkage , Genotype , Humans , Male , Mutation, Missense , NAV1.4 Voltage-Gated Sodium Channel , Oocytes/physiology , Patch-Clamp Techniques , Pedigree , Phenotype , Sodium Channels/genetics , Xenopus
19.
J Clin Neuromuscul Dis ; 3(1): 1-7, 2001 Sep.
Article in English | MEDLINE | ID: mdl-19078645

ABSTRACT

OBJECTIVES: To characterize clinically and molecularly a large, non-chromosome 4-linked facioscapulohumeral muscular dystrophy (FSHMD) family. METHODS: Neurological evaluations of affected (N = 55) and at-risk (N = 48) individuals were performed along with selected laboratory analyses, including creatine kinase testing, muscle biopsy, p13E-11 fragment analysis, and cytogenetic studies. Genetic analyses of the scapuloperoneal muscular dystrophy and scapuloperoneal muscular atrophy regions on chromosome 12 were performed using genetic markers flanking the intervals of interest and parametric LOD score analyses. RESULTS: Clinically, the FSHMD in individuals in this family is indistinguishable from that observed in chromosome 4-linked FSHMD. Fragment analysis with p13E-11 showed no small fragment segregating with the family and no evidence for 4:10 translocation or deletion of the p13E-11 binding site. Linkage analysis excluded the loci for autosomal-dominant scapuloperoneal muscular dystrophy and scapuloperoneal muscular atrophy. CONCLUSIONS: This family is clinically similar to patients with the chromosome 4-linked FSHMD. These data support our previous hypothesis of genetic heterogeneity within FSHMD.

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