Fatigue in patients with spinal muscular atrophy type II and congenital myopathies: evaluation of the fatigue severity scale.

PURPOSE: The aim of this study was to evaluate whether the fatigue severity scale (FSS) is an appropriate instrument to assess fatigue in patients with spinal muscular atrophy type II (SMA II) and congenital myopathies (CM). METHODS: FSS and visual analog scale (VAS) were administered to 33 SMA II- and 72 CM patients. The psychometric properties of the FSS were evaluated by means of classical test theories for each of the disease groups. If abnormal fatigue was present in the disease group, the construct of fatigue was evaluated by means of focus group interviews. RESULTS: Fatigue was rare in SMA II patients, but very frequent in patients with CM. The cut-off score designating abnormal fatigue (FSS score ≥ 4) was exceeded by 10% of the SMA II patients in contrast to 76% of the CM patients, of whom 52% suffered from severe fatigue (FSS score ≥ 5). Focus group interviews demonstrated that fatigue had an adverse effect on motor function, level of energy, social relations, and identity, four themes that could be captured by the FSS. The FSS and VAS were strongly correlated in SMA II patients, but only moderately in CM patients. The psychometric properties indicated that the original FSS with nine items measures more than one construct of fatigue, eliminating the first two items improved scale properties. CONCLUSION: This study demonstrates that fatigue is characteristic in patients with CM, but not in patients with SMA II, in whom fatigue does not seem to impact daily life. While fatigue in CM and SMA II can be captured by FSS, omitting the first two items of the scale will improve its properties and content validity, along with comprehension of the scale itself.

Co-purified gelatinases alter the stability and biological activities of human plasma fibronectin preparations.

BACKGROUND AND OBJECTIVE: Fibronectin (FN) is an important cell adhesion molecule that is used widely to characterize cell behavior. Preparations of FN purified from human plasma by gelatin-Sepharose affinity chromatography typically also contain gelatin-binding gelatinases that may cleave FN, reduce its stability and alter its biological activities. Available methods for separating gelatinases from FN are resource demanding. Therefore, our objective was to devise a time- and cost-efficient protocol for purification of gelatinase-free FN. MATERIAL AND METHODS: Experiments tested the elution profiles for FN and gelatinases from gelatin-Sepharose using a concentration range (1-7%) of dimethyl sulfoxide (DMSO) and 4 m urea as eluants. Subsequently, we explored the sequential application of those eluants for differential elution of gelatinases and FN using a single affinity column. Finally, experiments characterized the stability of purified FN with or without contaminating gelatinases, as well as the effects of FN degradation on cell attachment and migration. RESULTS: Assay optimization demonstrated that pre-elution with 3% DMSO efficiently eliminated gelatinases but not FN from gelatin-Sepharose, whereas subsequent elution with 4 m urea released FN. Sequential elutions with DMSO and urea produced gelatinase-free FN, which was more stable than FN eluted by urea only. Fibronectin degradation did not affect human gingival fibroblast attachment, but increased cell migration significantly. CONCLUSION: The present experiments devised a time- and cost-efficient protocol for eliminating gelatinases during purification of human plasma FN. Gelatinase-free FN preparations had greater stability, which may be essential for experiments because FN fragments have altered biological activities compared with intact FN.

Family History of MI, Smoking, and Risk of Periodontal Disease.

Periodontal disease (PD) shares common risk factors with cardiovascular disease. Our hypothesis was that having a family history of myocardial infarction (FamHxMI) may be a novel risk factor for PD. Risk assessment based on FamHxMI, conditional on smoking status, was examined given the strong influence of smoking on PD. Exploratory analysis with inflammatory biomarkers and genetic determinants was conducted to understand potential mechanistic links. The Women's Genome Health Study (WGHS) is a prospective cohort of US female health care professionals who provided blood samples at baseline in the Women's Health Study, a 2 × 2 factorial clinical trial investigating vitamin E and aspirin in the prevention of cardiovascular disease and cancer. PD was ascertained via self-report over 12 y of follow-up. Prevalence (3,442 cases), incidence (1,365 cases), and survival analysis of PD were investigated for associations of FamHxMI as well as in strata of FamHxMI by smoking. Kruskal-Wallis, chi-square tests, multivariate regression, and Cox proportional hazard models were used for the analyses. In the WGHS, women with FamHxMI showed higher risk of ever having PD. A particularly high-risk group of having both FamHxMI and smoking at baseline was highlighted in the prevalence and risk of developing PD. PD risk increased according to the following strata: no FamHxMI and nonsmokers (reference), FamHxMI and nonsmokers (hazard ratio [HR] = 1.2, 95% CI = 1.0 to 1.5), smokers without FamHxMI (HR = 1.3, 95% CI = 1.2 to 1.5), and smokers with FamHxMI (HR = 1.5, 95% CI = 1.2 to 1.8). An independent analysis by the dental Atherosclerosis Risk in Communities study ( N = 5,552) identified more severe periodontitis cases among participants in the high-risk group (smokers with FamHxMI). Further examination of interactions among inflammatory biomarkers or genetic exploration with FamHxMI did not explain the risk increase of PD associated with FamHxMI in the WGHS. Future efforts based on an integrative-omics approach may facilitate validation of these findings and suggest a mechanistic link between PD and FamHxMI.

Alpha 5 integrin subunit expression changes during myogenesis.

Fibronectin and its cellular receptor, the alpha 5 beta 1 integrin, are involved in the transmembrane signalling events that control muscle cell differentiation. In this study, the expression of the alpha 5 integrin subunit was followed by reverse transcription-polymerase chain reaction (RT-PCR) to determine alterations during myogenesis. In studies of murine muscle, we found a 90% reduction in the level of the alpha 5 integrin subunit mRNA during early postnatal development. Concurrently, the fibronectin alternative splicing pattern changed markedly in the EIIIB and V exons. In-vitro analyses of these molecules during myoblast differentiation revealed changes that followed trends similar to those observed in vivo, although of lesser magnitude. These observations imply an important role of fibronectin and the alpha 5 integrin subunit in muscle development.

[Evolution of functional capacity, assessed with the Egen Klassifikation scale, in the Spanish population with spinal muscular atrophy or Duchenne muscular dystrophy. A three year longitudinal study]. / Evolucion de la capacidad funcional valorada con la escala Egen Klassifikation en personas afectas de atrofia muscular espinal o distrofia muscular de Duchenne de la poblacion española: estudio longitudinal de tres años.

INTRODUCTION: Spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are two neuromuscular diseases which evolve with a progressive loss of muscle strength and, therefore, the loss of functional capacity. The valuation measurement scales are used to understand better and to quantify this involution as well as making treatment to anticipate problems and improve the quality of life of people suffering from these diseases. AIM: To study the changes in the functional capacity of a group of patients with SMA and DMD, over a period of three years. PATIENTS AND METHODS: Nineteen individuals of the Spanish population affected with SMA and DMD, which were assessed with the Egen Klassifikation scale twice, with a time interval of three years. RESULTS: The results show a decrease in the functional capacity of these persons during this time period, with a significant difference in the total amount of the scale (p = 0.003). All scale items showed lower valuations after three years, reaching statistical significance during the assessment, containing the ability to move his hands and coughing. CONCLUSION: The functional capacity of patients with SMA and DMD decreases significantly within three years.

TITLE: Evolucion de la capacidad funcional valorada con la escala Egen Klassifikation en personas afectas de atrofia muscular espinal o distrofia muscular de Duchenne de la poblacion española: estudio longitudinal de tres años.Introduccion. La atrofia muscular espinal (AME) y la distrofia muscular de Duchenne (DMD) son dos enfermedades neuromusculares que evolucionan con perdida progresiva de la fuerza muscular y, en consecuencia, perdida de la capacidad funcional. La valoracion con escalas de medicion permite conocer mejor y cuantificar esta involucion, asi como tomar decisiones terapeuticas para anticiparse a los problemas y mejorar la calidad de vida de las personas afectas de estas patologias. Objetivo. Estudiar los cambios de la capacidad funcional de un grupo de pacientes con AME y DMD en un periodo de tres años. Pacientes y metodos. Diecinueve personas de la poblacion española afectas de AME o DMD, a las que se valoro con la escala Egen Klassifikation en dos ocasiones, en un periodo de tres años. Resultados. Los resultados obtenidos reflejan una disminucion de la capacidad funcional de estas personas durante este periodo de tiempo, con una diferencia significativa en la suma total de la escala (p = 0,003). Todos los items de la escala tuvieron valoraciones inferiores despues de tres años, y se llego a la significacion estadistica en la valoracion de la capacidad de mover las manos y de toser. Conclusion. La capacidad funcional de los pacientes con AME y DMD disminuye de forma significativa en tres años.

The Duchenne muscular dystrophy population in Denmark, 1977-2001: prevalence, incidence and survival in relation to the introduction of ventilator use.

Mechanical ventilation of patients with Duchenne muscular dystrophy continues to be a subject of study. The purpose was to estimate prevalence, incidence, mortality and use of mechanical ventilation in the total Duchenne muscular dystrophy population in Denmark between 1977 and 2001 and further, to reconstruct the introduction of mechanical ventilation to assess the role of the patient organization. Study objects were collected from five sources and verifiable cases identified. Negotiations between health authorities and the patient organization constituted main empirical data for the reconstruction. While overall incidence remained stable at 2.0 per 10(5), prevalence rose from 3.1 to 5.5 per 10(5), mortality fell from 4.7 to 2.6 per 100 years at risk and prevalence of Duchenne muscular dystrophy ventilator users rose from 0.9 to 43.4 per 100. We conclude that survival of Duchenne muscular dystrophy patients has increased and ventilator use is probably a main reason. The patient organization exercised a key role but acted upon preconditions created by other players.

A randomized comparative study of two methods for controlling Tendo Achilles contracture in Duchenne muscular dystrophy.

A 30-month prospective randomized study of 27 Scandinavian boys with confirmed diagnosis of Duchenne muscular dystrophy was done to compare the effect of passive stretching combined with the use of night splints (group A) or passive stretching (group B) on the evolution of Tendo Achilles contractures. Assessments were based on the methodology of Scott et al. (Muscle Nerve 1982;5:291-301)Analysis of the pattern and mechanism of dropout was done to eliminate bias between the two groups. Logistic regression showed that Tendo Achilles contracture was the most important variable (P=0.0020) for dropout. Methods of statistical analysis for longitudinal data avoiding induced serial correlations were used in the analysis. The expected annual change in Tendo Achilles contracture was found to be 23% less in group A than in group B after equalization for total muscle strength (%MRC).

Longitudinal data analysis: an application to construction of a natural history profile of Duchenne muscular dystrophy.

A 30-month prospective study of 27 Scandinavian boys with confirmed diagnosis of Duchenne muscular dystrophy was carried out to construct profiles of the natural history of the disease. Assessments which included measures of voluntary muscle strength and function were done at 3 monthly intervals except for the first and second which were separated by 1 month. Recently developed statistical methods for analysis of longitudinal data with repeated observations on the same individual were used avoiding the problem of induced serial correlations. This allowed for the construction of both reference and prediction profiles for the variables %MRC, motor ability, walking time for 10 m and the sum of myometry of seven muscle groups.

Indicators of need for mechanical ventilation in Duchenne muscular dystrophy and spinal muscular atrophy.

STUDY OBJECTIVES: The purpose was to investigate a possible relationship between different parameters of physical function, spirometric measurements, and the approaching need for mechanical ventilation. DESIGN: A nonrandomized, prospective, descriptive study of 11 patients with spinal muscular atrophy type II (SMA-II) and 14 patients with Duchenne muscular dystrophy (DMD). At a home visit, the anthropometric indices of age, height, and weight were recorded, the degree of disability was scored, and measurement of the strength of eight muscle groups and spirometry was performed. The interdependence of the variables was analyzed and the intergroup differences evaluated. Eighteen months later, it was found that one of the authors (B.J.), who was blind to the results of the first examination had instituted home mechanical ventilation on seven of the patients. The data were analyzed retrospectively for their predictive value as indicators of approaching ventilator dependency. RESULTS: The seven patients who needed mechanical ventilation were the patients with DMD with the highest disability score (Egen Klassifikation [EK] sum > 20) and the smallest values for FVC < 1.2 L (FVC% < 30). We found a significant correlation (p = 0.002) between FVC% and the EK sum at the first examination and between the FVC% and the time until treatment with mechanical ventilation was instituted (p = 0.023). Although 7 of the 11 patients with SMA type II had FVC below 1.2 L and some of them had an EK sum score higher (indicating more disability) than some patients with DMD who needed mechanical ventilation, none of them required mechanical ventilation. CONCLUSION: In this investigation, a combination of EK sum and FVC% provided a better indication of the approaching need for mechanical ventilation in the patients with DMD than the variables separately.

Amelogenin is a cell adhesion protein.

Amelogenin, the major protein component of tooth enamel, is shown to be a cell adhesion protein. Since it had been shown that an amelogenin-containing preparation, Emdogain, possessed cell-adhesive activity, we tested the hypothesis that amelogenin was responsible for cell-adhesive activity. Recombinant amelogenin was found to promote adhesion at less than 15 micro g/60-mm plate and requires divalent cations for activity. While we found that amelogenin does not bind to collagen or heparin under physiological conditions, it was demonstrated previously that amelogenin does bind to hydroxyapatite. The cell-adhesive activity of amelogenin may play a role in development and may provide a partial explanation for the therapeutic effects of Emdogain in periodontal regeneration.

Relationship between the radiographic periodontal defect angle and healing after treatment.

This study radiographically evaluated the correlation between the changes in alveolar bone level occurring in bony defects after periodontal therapy and the corresponding pretreatment defect angles. The defect angle was defined by the bony defect surface and the root surface. The changes were determined from identically exposed and processed radiographs obtained just prior to surgery and 15 to 18 months later. The defect angle was clearly correlated to the radiographic changes in alveolar bone level. Most defects with an angle less than 45 degree showed a gain of bone while defects with the largest defect angles showed a loss. In addition, defects on root surfaces without furcations showed better healing than defects associated with furcations.

The prognosis of tunnel preparations in treatment of class III furcations. A follow-up study.

The present study evaluated the long-term prognosis of tunnel preparations performed in a large number of teeth with advanced periodontal furcation defects. One hundred seven (107) patients, in which 156 teeth had been treated by tunnel preparations, were recalled for an evaluation, which was based on a questionnaire, a clinical examination, and radiographs; 102 patients attended (149 teeth = 95%). The mean observation time per tooth was 37.5 months (range 10 to 107 months). The results showed that 10 teeth (6.7%) had been extracted and 7 teeth (4.7%) hemisected. The indication for 12 of these extractions or hemisections was root caries. Among the remaining 132 teeth, 23 (15.4%) showed initial or established caries. There was no relationship between caries development and length of the observation time. Thus, approximately 75% of the teeth were still caries-free and in function. The findings demonstrated that tunnel preparations have a considerably better prognosis than previously reported and should be considered a valid treatment alternative.

Clinical validation of a new subtraction radiography technique for periodontal bone loss detection.

BACKGROUND: Diagnostic subtraction radiography (DSR) is a new digital radiographic image subtraction method designed to enhance detection of crestal or periapical bone density changes and to help evaluate caries progression in teeth. In this clinical study, the performance of the DSR method was evaluated for its ability to detect periodontal bone loss and was compared with that of conventional evaluation of radiographs and the standardized cephalostat-guided image acquisition and subtraction technique (LRA) which served as the "gold standard." METHODS: In each of 25 subjects with alveolar crestal bone loss created by periodontal surgery, one set of DSR radiographs and one set of LRA radiographs were obtained before and after the surgery. Subtraction images were then generated by both the proprietary DSR and the LRA techniques. Four viewers evaluated the paired film sets and both subtraction image sets using a 5 point confidence scale to determine the presence or absence of crestal bone loss. Receiver operating characteristics (ROC) statistical procedures were applied to analyze the diagnostic accuracy and statistical differences between the three imaging modalities. RESULTS: The DSR subtraction viewing generated an ROC area of 0.882. For 2 of the viewers this represented a statistically significant gain (P <0.05) over the conventional viewing of the radiographs which had an average ROC area of 0.730. In comparison, the LRA method achieved an area of 0.954. The differences between the LRA and the DSR subtraction methods were not statistically significant, but the statistical power for claiming equality was low ranging from 0.2 to 0.6. CONCLUSIONS: The use of the DSR technique in clinical radiographic image acquisition and subsequent subtraction analysis clearly enhanced the accuracy of alveolar crestal bone loss detection when compared to conventional film viewing. Because this methodology is less resource demanding than LRA and the film exposure techniques and computer-based image analysis skills may be acquired with only a few hours of training, the DSR has potential in clinical practice.

Clinical effects of electromagnetic stimulation as an adjunct to periodontal therapy.

The clinical effects of electromagnetic stimulation (EMS) on periodontal soft tissues and alveolar bone level were studied among 23 patients. The sides of the arch to receive EMS were randomly selected and exposed for a period of eight weeks following periodontal surgery. The contralateral control sides received surgery only. The electromagnetic signal was a multiple pulse signal with 21 asymmetrical quasirectangular pulses per burst and a burst frequency of 16.9 Hz. The peak magnetic field strength reached 0.46 Gauss. Changes from baseline in clinical attachment level, probing depth, and radiographic alveolar bone level were assessed at six, 12, and 18 months postsurgically. A greater gain of clinical attachment level following EMS was observed only for pockets with initial depth of 1 to 3 mm. There were no consistent differences between test (EMS) and control sides in the change of clinical attachment level or probing depth for pockets deeper than 4 mm. Radiographically, the test sides demonstrated statistically significant gain of alveolar bone level compared with the control sides at six months following surgery. Hereafter, the rates of change were similar in the stimulated and unstimulated sides, and the total gain of alveolar bone level remained greater in the test side throughout the observation period. Within the limitations of this study, it was concluded that electromagnetic stimulation does not promote gains in clinical attachment or alveolar bone level to the extent that it can be recommended as an adjunct to conventional periodontal therapy.

Immunohistological localization of cell adhesion proteins and integrins in the periodontium.

The distribution of the cell adhesion proteins vitronectin, fibronectin, tenascin, and laminin as well as several integrin subunits, alpha 2, alpha 5, and alpha v, was studied in primate periodontal tissues. Full baboon mandibular sections were analyzed by immunohistochemical methods in order to localize the molecules studied in both soft and hard tissues. Vitronectin was associated with the connective tissue of the marginal gingiva, the periodontal ligament, as well as the endosteum and periosteum. A notable finding was the particularly high staining intensity of vitronectin in the periodontal ligament. Fibronectin was widely distributed in the periodontal connective tissue and was also localized to the pericellular matrix of osteocytes and blood vascular elements. Epithelial basement membranes stained positively for both fibronectin and tenascin. These proteins were also expressed in the periosteal and endosteal connective tissues and the periodontal ligament. The staining intensity for tenascin was higher in zones along the cementum and bone surfaces. Laminin was, characteristically, limited to basement membranes of epithelium and endothelium. The distribution of fibronectin, tenascin, and laminin is related to previous findings in other species. The localization of the several integrin alpha-subunits is also described in full baboon mandibular sections. The vitronectin receptor (alpha v) had a uniquely strong expression in osteoclasts of the alveolar bone and was found, at lesser intensity, on periodontal ligament fibroblasts. The fibronectin receptor alpha subunit, alpha 5, was also observed on osteoclasts, and, in addition, was widely distributed on fibroblasts, cementoblasts, and osteoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Root resorptions in a patient with hemifacial atrophy.

Hemifacial atrophy (Parry-Romberg syndrome) is a rare but well-recognized condition. The developmental effects on facial and oral structures have been well documented in the literature. However, the etiology of hemifacial atrophy remains unknown. Previous reported alterations in tooth growth and development include delayed tooth eruption, abnormal root morphology, and malocclusion but not root resorption. This report presents the orofacial changes from hemifacial atrophy in a 22-yr-old woman and describes the occurrence of root resorptions in two regions affected by this condition. The concurrent presence of root resorptions in both the maxilla and mandible in the regions showing the most severe dental malformations points to root resorption as an additional complication of hemifacial atrophy.

Fracture risk in patients with muscular dystrophy and spinal muscular atrophy.

We aimed at studying fracture risk in patients with Duchenne's muscular dystrophy (DMD), Becker's muscular dystrophy (BEMD), and spinal muscular atrophy type II and III (SMA II and III). A self-administered questionnaire was mailed to 293 patients with DMD, BEMD, SMA II or SMA III of which 229 returned the questionnaire. Each respondent was compared with an age- and gender-matched control subject. The mean age was 23.9 +/- 15.9 years for the patients and 23.3 +/- 16.5 years for the controls. There were significantly more fractures among patients than controls after the diagnosis was made (RR = 1.9), but not before. The patients had more fractures of the femurs, lower legs, and upper arms than the controls. Low energy fractures were more frequent in patients than controls (9% vs 0%). Many fractures in the femurs (40%), lower legs (35%), and feet and toes (44%) led to a permanent loss of function. Loss of ambulation was the major risk factor for fractures. In conclusion, fracture risk is increased in neuromuscular disease.

Validity of the EK scale: a functional assessment of non-ambulatory individuals with Duchenne muscular dystrophy or spinal muscular atrophy.

BACKGROUND AND PURPOSE: The EK scale comprises ten categories (EK 1-10), each contributing to an overall picture of function in the non-ambulatory stage of Duchenne muscular dystrophy (DMD). The purpose of the present study was to investigate content and construct validity of the EK scale as a tool to discriminate between levels of functional ability in individuals with DMD or spinal muscular atrophy (SMA) who were non-ambulatory. METHOD: Data from a sample of 56 subjects with DMD and 38 with SMA, who were non-ambulatory, were obtained from four separate studies. The relationship of functional ability by use of the EK scale and (1) muscle strength, (2) contractures, (3) forced vital capacity and (4) years of wheelchair dependency were assessed. All items of the EK scale were used except the one representing severe hypoventilation. RESULTS: Regression analyses showed that the EK sum was the most significant explanatory variable (p < 0.05) of all variables measured to explain muscle strength in both DMD and SMA subjects. The individual categories of EK (1-10) all contributed as significant explanatory variables (p < 0.05) to the other variables measured. CONCLUSIONS: The categories and items of the EK scale were relevant and valid as means of discriminating between levels of functional performance in the population studied which was evidence of content and construct validity.

[Life quality of patients with muscular failure, using permanent respiratory support, seen from their point of view. 1. Information, choice and quality of life]. / Tilvaerelsen for permanente respiratorbrugere med muskelsvind, set med brugerøojne. 1. Information, valg og livskvalitet.

Sixteen patients with neuromuscular disease receiving long-term assisted ventilation participated in a combined questionnaire/interview investigation with the purpose of illustrating: 1. What information the patient had received prior to institution of the respirator treatment, 2. The difficult choice which had to be made, 3. Whether life as a severely disabled person with assisted ventilation is worth living, and 4. The factors on which successful respirator treatment depends. It is concluded that the general information on use of assisted ventilation should be implemented at an early stage, preferably before problems of respiratory insufficiency occur, and that information should be carried out by people other than merely professionals and be as broad and truthful as possible in order to provide the disabled person with sufficient foundation and sufficient time to consider his personal choice of potential respirator treatment. Further, it is concluded that life for these sixteen ventilator-dependent persons definitely is worth living. The fact that the respirator implies the prospect of longer life, partly freed from symptoms of hypoventilation, means that they have got strength and time for education, work, family and dreams. No correlation was found between the success of the respirator treatment and the patients' sense of achieved quality of life and factors such as age, family-/working situation, extent of disability etc., and professionals should not attach importance to such factors in the selection of "suitable" patients for assisted ventilation.

[Life quality of patients with muscular failure, using permanent respiratory support, seen from their point of view. 2. Practical requirements and problems connected with respirator treatment]. / Tilvaerelsen for permanente respiratorbrugere med muskelsvind, set med brugerøjne. 2. Praktiske krav og problemer i forbindelse med respiratorbehandling.

Sixteen patients with neuromuscular disease receiving long-term assisted ventilation participated in a combined questionnaire/interview investigation with the purpose of illustrating their situation as regards appropriate personal attention, technical aids, knowledge of respirator-technique, illness and regular hospital examinations, multidisciplinary conferences, adapted housing and speech problems connected with tracheostomy. Generally, we conclude that these practical factors and arrangements, enabling the patient to manage everyday life, were, on the whole, satisfactorily settled. Compliance with the patient's desires to the utmost extent is recommended and achievement of the optimal solutions for him, by means of teamwork. Thus one must always bear in mind that the goal of these practical arrangements for the patient (such as personal attention, technical assistance, hospital examinations etc.) apart from optimal maintenance of daily activities should be to keep the patient independent of residential care.