61 research outputs found
Application of LANDSAT data and digital image processing
There are no author-identified significant results in this report
Mucopolysaccharidoses in northern Brazil: Targeted mutation screening and urinary glycosaminoglycan excretion in patients undergoing enzyme replacement therapy
Mucopolysaccharidoses (MPS) are rare lysosomal disorders caused by the deficiency of specific lysosomal enzymes responsible for glycosaminoglycan (GAG) degradation. Enzyme Replacement Therapy (ERT) has been shown to reduce accumulation and urinary excretion of GAG, and to improve some of the patients’ clinical signs. We studied biochemical and molecular characteristics of nine MPS patients (two MPS I, four MPS II and three MPS VI) undergoing ERT in northern Brazil. The responsiveness of ERT was evaluated through urinary GAG excretion measurements. Patients were screened for eight common MPS mutations, using PCR, restriction enzyme tests and direct sequencing. Two MPS I patients had the previously reported mutation p.P533R. In the MPS II patients, mutation analysis identified the mutation p.R468W, and in the MPS VI patients, polymorphisms p.V358M and p.V376M were also found. After 48 weeks of ERT, biochemical analysis showed a significantly decreased total urinary GAG excretion in patients with MPS I (p < 0.01) and MPS VI (p < 0.01). Our findings demonstrate the effect of ERT on urinary GAG excretion and suggest the adoption of a screening strategy for genotyping MPS patients living far from the main reference centers
Mucopolysaccharidosis I, II, and VI: Brief review and guidelines for treatment
Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions
Cardiac disease in patients with mucopolysaccharidosis: presentation, diagnosis and management
The mucopolysaccharidoses (MPSs) are inherited lysosomal storage disorders caused by the absence of functional enzymes that contribute to the degradation of glycosaminoglycans (GAGs). The progressive systemic deposition of GAGs results in multi-organ system dysfunction that varies with the particular GAG deposited and the specific enzyme mutation(s) present. Cardiac involvement has been reported in all MPS syndromes and is a common and early feature, particularly for those with MPS I, II, and VI. Cardiac valve thickening, dysfunction (more severe for left-sided than for right-sided valves), and hypertrophy are commonly present; conduction abnormalities, coronary artery and other vascular involvement may also occur. Cardiac disease emerges silently and contributes significantly to early mortality
Anaesthesia and airway management in mucopolysaccharidosis
Abstract This paper provides a detailed overview and dis-cussion of anaesthesia in patients with mucopolysacchari-dosis (MPS), the evaluation of risk factors in these patients and their anaesthetic management, including emergency airway issues. MPS represents a group of rare lysosomal storage disorders associated with an array of clinical mani-festations. The high prevalence of airway obstruction and restrictive pulmonary disease in combination with cardio-vascular manifestations poses a high anaesthetic risk to these patients. Typical anaesthetic problems include airway obstruction after induction or extubation, intubation diffi-culties or failure [can’t intubate, can’t ventilate (CICV)], possible emergency tracheostomy and cardiovascular and cervical spine issues. Because of the high anaesthetic risk, the benefits of a procedure in patients with MPS shoul
Review and evaluation of the methodological quality of the existing guidelines and recommendations for inherited neurometabolic disorders
Achieving the "triple aim" for inborn errors of metabolism: a review of challenges to outcomes research and presentation of a new practice-based evidence framework
Across all areas of health care, decision makers are in pursuit of what
Berwick and colleagues have called the “triple aim”: improving patient
experiences with care, improving health outcomes, and managing
health system impacts. This is challenging in a rare disease context, as
exemplified by inborn errors of metabolism. There is a need for evaluative
outcomes research to support effective and appropriate care for
inborn errors of metabolism. We suggest that such research should
consider interventions at both the level of the health system (e.g., early
detection through newborn screening, programs to provide access to
treatments) and the level of individual patient care (e.g., orphan drugs,
medical foods). We have developed a practice-
based evidence framework
to guide outcomes research for inborn errors of metabolism.
Focusing on outcomes across the triple aim, this framework integrates
three priority themes: tailoring care in the context of clinical heterogeneity;
a shift from “urgent care” to “opportunity for improvement”;
and the need to evaluate the comparative effectiveness of emerging
and established therapies. Guided by the framework, a new Canadian
research network has been established to generate knowledge that will
inform the design and delivery of health services for patients with
inborn errors of metabolism and other rare diseases.This work was supported by a CIHR Emerging Team Grant (“Emerging
team in rare diseases: acheiving the ‘triple aim’ for inborn errors
of metabolism,” B.K. Potter, P. Chakraborty, and colleagues, 2012–
2017, grant no. TR3–119195). Current investigators and collaborators
in the Canadian Inherited Metabolic Diseases Research Network
are: B.K. Potter, P. Chakraborty, J. Kronick, D. Coyle, K. Wilson, M.
Brownell, R. Casey, A. Chan, S. Dyack, L. Dodds, A. Feigenbaum, D.
Fell, M. Geraghty, C. Greenberg, S. Grosse, A. Guttmann, A. Khan,
J. Little, B. Maranda, J. MacKenzie, A. Mhanni, F. Miller, G. Mitchell,
J. Mitchell, M. Nakhla, M. Potter, C. Prasad, K. Siriwardena, K.N.
Speechley, S. Stocker, L. Turner, H. Vallance, and B.J. Wilson. Members
of our external advisory board are D. Bidulka, T. Caulfield, J.T.R.
Clarke, C. Doiron, K. El Emam, J. Evans, A. Kemper, W. McCormack,
and A. Stephenson Julian. J. Little is supported by a Canada Research
Chair in Human Genome Epidemiology. K. Wilson is supported by a
Canada Research Chair in Public Health Policy
Therapeutic targeting of HMGB1 during experimental sepsis modulates the inflammatory cytokine profile to one associated with improved clinical outcomes
Sepsis remains a significant health burden and a major clinical need exists for therapeutics to dampen the excessive and uncontrolled immune activation. Nuclear protein high mobility group box protein 1 (HMGB1) is released following cell death and is a late mediator in sepsis pathogenesis. While approaches targeting HMGB1 have demonstrated reduced mortality in pre-clinical models of sepsis, the impact of HMGB1 blockade on the complex septic inflammatory milieu and the development of subsequent immunosuppression remain enigmatic. Analysis of plasma samples obtained from septic shock patients established an association between increased HMGB1 and non-survival, higher APACHE II scores, and increased pro-inflammatory cytokine responses. Pre-clinically, administration of neutralising ovine anti-HMGB1 polyclonal antibodies improved survival in murine endotoxaemia and caecal ligation and puncture-induced sepsis models, and altered early cytokine profiles to one which corresponded to patterns observed in the surviving patient cohort. Additionally, anti-HMGB1 treated murine sepsis survivors were significantly more resistant to secondary bacterial infection and exhibited altered innate immune cell phenotypes and cytokine responses. These findings demonstrate that anti-HMGB1 antibodies alter inflammation in murine sepsis models and reduce sepsis mortality without potentiating immunosuppression.Natalie E. Stevens, Marianne J. Chapman, Cara K. Fraser, Tim R. Kuchel, John D. Hayball and Kerrilyn R. Diene
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