Home mechanical ventilation: a Canadian Thoracic Society clinical practice guideline.

Increasing numbers of patients are surviving episodes of prolonged mechanical ventilation or benefitting from the recent availability of userfriendly noninvasive ventilators. Although many publications pertaining to specific aspects of home mechanical ventilation (HMV) exist, very few comprehensive guidelines that bring together all of the current literature on patients at risk for or using mechanical ventilatory support are available. The Canadian Thoracic Society HMV Guideline Committee has reviewed the available English literature on topics related to HMV in adults, and completed a detailed guideline that will help standardize and improve the assessment and management of individuals requiring noninvasive or invasive HMV. The guideline provides a disease-specific review of illnesses including amyotrophic lateral sclerosis, spinal cord injury, muscular dystrophies, myotonic dystrophy, kyphoscoliosis, post-polio syndrome, central hypoventilation syndrome, obesity hypoventilation syndrome, and chronic obstructive pulmonary disease as well as important common themes such as airway clearance and the process of transition to home. The guidelines have been extensively reviewed by international experts, allied health professionals and target audiences. They will be updated on a regular basis to incorporate any new information.

Reporting diet-related health issues through newspapers: portrayal of cardiovascular disease and Type 2 diabetes.

This study identifies (i) the extent to which newsprint media communicate to their readers the lifestyle factors associated with the development of cardiovascular disease and Type 2 diabetes and (ii) newspaper portrayal of social determinants affecting onset of disease. A content analysis of five leading UK national newspapers and their Sunday equivalents was conducted over a 3-month period between January and March 2008. This study shows that cardiovascular disease had much higher press interest than Type 2 diabetes. 'Middle-market' and 'Quality' papers had higher levels of reporting than the 'Popular' press, but the patterns were more complex when the comprehensiveness of reporting was measured within each article. Social determinants affecting disease onset were poorly reported by newspapers, supporting similar research conducted in other countries. This research identifies that there is potential for newspapers to improve their reporting of lifestyle diseases, by including individual and social determinants of disease onset. Lower social classes who read the popular press receive the lowest frequency of reporting and could benefit most from this information. While the research identifies that newspapers are missing the potential to actively communicate and reinforce government health policy, it recognises that the commercial context of the print media may counter such behaviour.

Differential protein profiling as a potential multi-marker approach for TSE diagnosis.

BACKGROUND: Transmissible spongiform encephalopathy describes a family of diseases affecting both man and animals. Current tests for the diagnosis of these diseases are based on the detection of an abnormal misfolded form of the host protein PrP which is found within the central nervous and lymphoreticular systems of affected animals. Recently, concern that this marker may not be as reliable as previously thought, coupled with an urgentneed for a pre-clinical live animal test, has led to the search for alternative assays for the detection of TSE disease. METHODS: This "proof of concept" study, examines the use of differential protein expression profiling using surface enhanced laser desorption and ionisationtime of flight mass spectrometry (SELDI-TOF) for the diagnosis of TSE disease. Spectral output from all proteins selectively captured from individual murine brain homogenate samples, are compared as "profiles" in groups of infected and non-infected animals. Differential protein expression between groups is thus highlighted and statistically significant protein "peaks" used to construct a panel of disease specific markers.Studies at both terminal stages of disease and throughout the time course of disease have shown a disease specific protein profile or "disease fingerprint" which could be used to distinguish between groups of TSE infected and uninfected animals at an early time point of disease. RESULTS: Our results show many differentially expressed proteins in diseased and control animals, some at early stages of disease. Three proteins identified by SELDI-TOF analysis were verified by immunohistochemistry in brain tissue sections. We demonstrate that by combining the most statistically significant changes in expression, a panel of markers can be constructed that can distinguish between TSE diseased and normal animals. CONCLUSION: Differential protein expression profiling has the potential to be used for the detection of disease in TSE infected animals. Having established that a "training set" of potential markers can be constructed, more work would be required to further test the specificity and sensitivity of the assay in a "testing set". Based on these promising results, further studies are being performed using blood samples from infected sheep to assess the potential use of SELDI-TOF as a pre-mortem blood based diagnostic.

[Pulmonary and nonpulmonary alterations in Duchenne muscular dystrophy]. / Alteraciones pulmonares y no pulmonares en la distrofia muscular de Duchenne.

OBJECTIVE: To describe our experience in managing patients with Duchenne muscular dystrophy. PATIENTS AND METHODS: We analyzed the following variables in a group of 27 patients with Duchenne muscular dystrophy: arterial blood gases, lung function before and after mechanical ventilation, oxygen saturation (measured by pulse oximetry), nocturnal PaCO2 (measured transcutaneously by capnography), heart function, and dysphagia. RESULTS: The mean (SD) age was 26 (6) years and the mean age at which mechanical ventilation had initiated in the patients was 21 (5) years. Sixty-two percent had undergone tracheostomy and invasive mechanical ventilation. Arterial blood gas levels returned to normal once mechanical ventilation was administered and remained so for the entire treatment period (mean duration of follow-up, 56 [49] months). Thirteen patients had cardiac symptoms and they all presented abnormal electrocardiograms and echocardiograms indicating dilated cardiomyopathy, left ventricular dysfunction, and posterior hypokinesis. Only 9 patients were receiving enteral nutrition (7 through a gastrostomy tube and 2 through a nasogastric tube). The videofluoroscopic swallowing study confirmed that dysphagia was related to neuromuscular disease rather than the presence or not of a tracheostomy. Five patients (18%), 4 of whom were receiving invasive mechanical ventilation, died during the follow-up period. Three patients had serious heart disease. CONCLUSIONS: Mechanical ventilation confers clinical benefits and prolongs life expectancy in patients with Duchenne muscular dystrophy. Heart disease and feeding difficulties are determining factors in the prognosis of these patients.

Alteraciones pulmonares y no pulmonares en la distrofia muscular de Duchenne / Pulmonary and nonpulmonary alterations in Duchenne muscular dystrophy

Objetivo: Describir nuestra experiencia en el manejo de pacientes con distrofia muscular de Duchenne (DMD). Pacientes y métodos: En 27 pacientes con DMD analizamos los gases arteriales y la función pulmonar antes y después de la ventilación mecánica (VM); la pulsioximetría (saturación de oxihemoglobina) y la capnografía (presión arterial de anhídrido carbónico por determinación transcutánea) nocturna; la función cardíaca y la evaluación de la disfagia. Resultados: Se incluyó en el estudio a 27 pacientes con una edad media ± desviación estándar de 26 ± 6 años. Todos recibían VM, que se había iniciado cuando contaban 21 ± 5 años. El 62% eran portadores de traqueostomía y VM invasiva. Una vez iniciada la VM, se observó la normalización de los gases arteriales, que se mantuvo durante todo el tiempo de tratamiento (seguimiento medio: 56 ± 49 meses). Trece pacientes presentaban síntomas cardíacos y en todos ellos se observaban anormalidades en el electrocardiograma y ecocardiograma: miocardiopatía dilatada, disfunción ventricular izquierda o hipocinesia de la pared posterior. Sólo 7 pacientes llevaban una sonda de gastrostomía para alimentación y 2 una sonda nasogástrica. El estudio con videofluoroscopia permitió afirmar que los problemas de disfagia estaban relacionados con la enfermedad neuromuscular y no con la presencia o no de traqueostomía. Durante el período de seguimiento, 5 pacientes fallecieron (18%), 4 de ellos con VM invasiva; 3 pacientes presentaban una enfermedad cardíaca grave. Conclusiones: La VM proporciona beneficios clínicos y prolonga la vida de los pacientes con DMD. Las alteraciones cardíacas y nutricionales son factores determinantes en el pronóstico de estos pacientes

Objective: To describe our experience in managing patients with Duchenne muscular dystrophy. Patients and Methods: We analyzed the following variables in a group of 27 patients with Duchenne muscular dystrophy: arterial blood gases, lung function before and after mechanical ventilation, oxygen saturation (measured by pulse oximetry), nocturnal PaCO2 (measured transcutaneously by capnography), heart function, and dysphagia. Results: The mean (SD) age was 26 (6) years and the mean age at wich mechanical ventilation had initiatid in the patients was 21 (5) years. Sixty-two percent had undergone tracheostomy and invasive mechanical ventilation. Arterial blood gas levels returned to normal once mechanical ventilation was administered and remained so for the entire treatment period (mean duration of follow-up, 56 [49] months). Thirteen patients had cardiac symptoms and they all presented abnormal electrocardiograms and echocardiograms indicating dilated cardiomyopathy, left ventricular dysfunction, and posterior hypokinesis. Only 9 patients were receiving enteral nutrition (7 through a gastrostomy tube and 2 through a nasogastric tube). The videofluoroscopic swallowing study confirmed that dysphagia was related to neuromuscular disease rather than the presence or not of a tracheostomy. Five patients (18%), 4 of whom were receiving invasive mechanical ventilation, died during the follow-up period. Three patients had serious heart disease. Conclusions: Mechanical ventilation confers clinical benefits and prolongs life expectancy in patients with Duchenne muscular dystrophy. Heart disease and feeding difficulties are determining factors in the prognosis of these patients

Microdissection: a method developed to investigate mechanisms involved in transmissible spongiform encephalopathy pathogenesis.

BACKGROUND: The transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases affecting both human and animals. The neuroanatomical changes which occur in the central nervous system (CNS) of TSE infected animals include vacuolation, gliosis, neuronal loss and the deposition of a disease specific protein, PrPSc. Experimental murine models of scrapie, a TSE of sheep, have revealed that pathology may be confined to specific brain areas with targeting of particular neuronal subsets depending on route of injection and scrapie isolate. To assess the biochemical changes which are taking place in these targeted areas it was necessary to develop a reliable sampling procedure (microdissection) which could be used for a variety of tests such as western blotting and magnetic resonance spectroscopy. METHODS: The method described is for the microdissection of murine brains. To assess the usefulness of this dissection technique for producing similar sample types for analysis by various down-stream biochemical techniques, the areas dissected were analysed for PrPSc by western blotting and compared to immunocytochemical (ICC) techniques. RESULTS: Results show that the method generates samples yielding a consistent protein content which can be analysed for PrPSc. The areas in which PrPSc is found by western blotting compares well with localisation visualised by immunocytochemistry. CONCLUSION: The microdisssection method described can be used to generate samples suitable for a range of biochemical techniques. Using these samples a range of assays can be carried out which will help to elucidate the molecular and cellular mechanisms underlying TSE pathogenesis. The method would also be useful for any study requiring the investigation of discrete areas within the murine brain.

Immunohistochemical comparison of anti-prion protein (PrP) antibodies in the CNS of mice infected with scrapie.

One of the pathological changes characteristic of the transmissible spongiform encephalopathies (TSEs) is the accumulation of disease-specific PrP (PrP(sc)). Immunolabeling of PrP(sc) was compared using a panel of monoclonal and polyclonal antibodies. To determine the effects of tissue fixation on immunostaining, we performed a supplementary investigation reviewing the fixatives formol saline and periodate-lysine-paraformaldehyde (PLP). The main target sites of the antibodies were similar. However the monoclonal antibodies (MAbs) 6H4, 7A12 and 8H4 revealed targeted PrP(sc) labeling with no background labeling. Although 7A12 and 8H4 did not detect early PrP deposition, we propose that during the later stages of disease 7A12 and 8H4 can be used with equal effectiveness in place of 6H4. Tissues taken during the early stages of disease that had been fixed in PLP displayed more PrP immunolabeling than tissues that had undergone formol fixation. PLP fixation on 6H4-immunostained tissue revealed interweaving granular linear PrP deposits in the hippocampus. This labeling was not observed in tissue that had undergone formol fixation, suggesting that PLP fixation might enhance the sensitivity of the immunohistochemical (IHC) detection of PrP. In the two scrapie mouse models studied here, PLP fixation and immunolabeling with the anti-PrP antibody 6H4 gave superior results.

The transmissible spongiform encephalopathies: pathogenic mechanisms and strategies for therapeutic intervention.

Primary neurodegenerative diseases tend to be intractable and largely affect the elderly. There is rarely the opportunity to identify individuals at risk and the appearance of clinical symptoms usually signifies the occurrence of irreversible neurological damage. This situation describes sporadic Creutzfeldt-Jakob disease which occurs world-wide, affecting one person per million per annum. The epidemic of bovine spongiform encephalopathy in the UK in the 1980s and the subsequent causal appearance of variant Creutzfeldt-Jakob disease in young UK residents in the 1990s has refocused attention on this whole group of diseases, known as the transmissible spongiform encephalopathies or prion diseases. The potentially lengthy incubation period of variant Creutzfeldt-Jakob disease, including perhaps an obligate peripheral phase, prior to neuroinvasion, marks variant Creutzfeldt-Jakob disease out as different from sporadic Creutzfeldt-Jakob disease. The formal possibility of detecting individuals infected with the bovine spongiform encephalopathy agent during this asymptomatic peripheral phase provides a strong incentive for the development of therapies for transmissible spongiform encephalopathies. This review focuses on recent advances in the understanding of the pathogenesis of these diseases, with particular reference to in vitro and animal model systems. Such systems have proved invaluable in the identification of potential therapeutic strategies that either specifically target the prion protein or more generally target peripheral pathogenesis. Furthermore, recent experiments in animal models suggest that even after neuroinvasion there may be pharmacological avenues to explore that might retard or even halt the degenerative process.