RESUMO
BACKGROUND AND AIMS: Quality monitoring has great relevance in stroke care. The Project "How to guarantee adherence to effective interventions in stroke care" aimed to estimate adherence to acute-phase guidelines in stroke care in Italy. METHODS: A prospective observational study was performed in 27 hospitals of 13 Italian Regions. Adherence to 15 process indicators was evaluated, comparing also stroke units (SU) with conventional wards. An overall score of care, defined as the sum of achieved indicators, was calculated. A multilevel hierarchical model described performance at patient, hospital and regional level. RESULTS: Overall, 484 consecutive stroke patients (mean age, 73.4 years; 52.7 % males) were included. Total score ranged from 2 to 15 (mean 8.5 ± 2.4). SU patients were more often evaluated with the National Institutes of Health Stroke Scale (NIHSS) within 24 h, had more frequently an assessment of pre- and post-stroke disability, and a CT scan the same or the day after admission. Regional-hospital- and patient-level variability explained, respectively, 25, 34, and 41 % of total score variance. In multivariate models, patients >80 years vs. younger showed a change in total score of -0.45 (95 % CI -0.79 to -0.12), and those with NIHSS ≥14 vs. ≤5 of -0.92 (95 % CI -1.53 to -0.30). A negative change means a worse adjusted average adherence to process indicators. SU admission increased total score of 1.55 (95 % CI 0.52-2.58). CONCLUSIONS: Our data confirm the need of quality monitoring in stroke care. Although SU patients showed a better adherence to quality indicators, overall compliance was unsatisfactory.
Assuntos
Indicadores de Qualidade em Assistência à Saúde , Acidente Vascular Cerebral/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais/normas , Hospitais/estatística & dados numéricos , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Análise Multivariada , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Padrão de Cuidado , Acidente Vascular Cerebral/diagnósticoRESUMO
Chronic intestinal pseudo-obstruction is a life-threatening condition of unknown pathogenic mechanisms. Chronic intestinal pseudo-obstruction can be a feature of mitochondrial disorders, such as mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a rare autosomal-recessive syndrome, resulting from mutations in the thymidine phosphorylase gene. MNGIE patients show elevated circulating levels of thymidine and deoxyuridine, and accumulate somatic mitochondrial DNA (mtDNA) defects. The present study aimed to clarify the molecular basis of chronic intestinal pseudo-obstruction in MNGIE. Using laser capture microdissection, we correlated the histopathological features with mtDNA defects in different tissues from the gastrointestinal wall of five MNGIE and ten control patients. We found mtDNA depletion, mitochondrial proliferation, and smooth cell atrophy in the external layer of the muscularis propria, in the stomach and in the small intestine of MNGIE patients. In controls, the lowest amounts of mtDNA were present at the same sites, as compared with other layers of the gastrointestinal wall. We also observed mitochondrial proliferation and mtDNA depletion in small vessel endothelial and smooth muscle cells. Thus, visceral mitochondrial myopathy likely causes gastrointestinal dysmotility in MNGIE patients. The low baseline abundance of mtDNA molecules may predispose smooth muscle cells of the muscularis propria external layer to the toxic effects of thymidine and deoxyuridine, and exposure to high circulating levels of nucleosides may account for the mtDNA depletion observed in the small vessel wall.
Assuntos
DNA Mitocondrial/genética , Gastroenteropatias/fisiopatologia , Motilidade Gastrointestinal/fisiologia , Encefalomiopatias Mitocondriais/fisiopatologia , Deleção de Sequência , Adulto , Células Endoteliais/patologia , Esôfago/patologia , Feminino , Gastroenteropatias/patologia , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/patologia , Humanos , Masculino , Microdissecção , Encefalomiopatias Mitocondriais/patologia , Miócitos de Músculo Liso/patologia , Mutação Puntual/genéticaRESUMO
Ocular involvement is a prevalent feature in mitochondrial diseases. Leber's hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA) are both non-syndromic optic neuropathies with a mitochondrial etiology. LHON is associated with point mutations in the mitochondrial DNA (mtDNA), which affect subunit genes of complex I. The majority of DOA patients harbor mutations in the nuclear-encoded protein OPA1, which is targeted to mitochondria and participates to cristae organization and mitochondrial network dynamics. In both disorders the retinal ganglion cells (RGCs) are specific cellular targets of the degenerative process. We here review the clinical features and the genetic bases, and delineate the possible common pathomechanism for both these disorders.
Assuntos
Doenças Mitocondriais/patologia , Atrofia Óptica Autossômica Dominante/patologia , Atrofia Óptica Hereditária de Leber/patologia , Doenças do Nervo Óptico/patologia , Apoptose/genética , Apoptose/fisiologia , DNA Mitocondrial/genética , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Humanos , Doenças Mitocondriais/genética , Doenças Mitocondriais/metabolismo , Modelos Biológicos , Mutação , Atrofia Óptica Autossômica Dominante/genética , Atrofia Óptica Autossômica Dominante/metabolismo , Atrofia Óptica Hereditária de Leber/genética , Atrofia Óptica Hereditária de Leber/metabolismo , Doenças do Nervo Óptico/genética , Doenças do Nervo Óptico/metabolismoRESUMO
BACKGROUND & AIMS: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disease clinically defined by gastrointestinal dysmotility, cachexia, ptosis, ophthalmoparesis, peripheral neuropathy, white-matter changes in brain magnetic resonance imaging, and mitochondrial abnormalities. Loss-of-function mutations in thymidine phosphorylase gene induce pathologic accumulations of thymidine and deoxyuridine that in turn cause mitochondrial DNA (mtDNA) defects (depletion, multiple deletions, and point mutations). Our study is aimed to define the molecular basis of gastrointestinal dysmotility in a case of MNGIE. METHODS: By using laser capture microdissection techniques, we correlated histologic features with mtDNA abnormalities in different tissue components of the gastrointestinal wall in a MNGIE patient and ten controls. RESULTS: The patient's small intestine showed marked atrophy and mitochondrial proliferation of the external layer of muscularis propria. Genetic analysis revealed selective depletion of mtDNA in the small intestine compared with esophagus, stomach, and colon, and microdissection analysis revealed that mtDNA depletion was confined to the external layer of muscularis propria. Multiple deletions were detected in the upper esophagus and skeletal muscle. Site-specific somatic point mutations were detected only at low abundance both in the muscle and nervous tissue of the gastrointestinal tract. Analysis of the gastrointestinal tract from 10 controls revealed a non-homogeneous distribution of mtDNA content; the small intestine had the lowest levels of mtDNA. CONCLUSION: Atrophy, mitochondrial proliferation, and mtDNA depletion in the external layer of muscularis propria of small intestine indicate that visceral myopathy is responsible for gastrointestinal dysmotility in this MNGIE patient.
Assuntos
Caquexia/genética , DNA Mitocondrial/genética , Gastroenteropatias/genética , Motilidade Gastrointestinal/fisiologia , Intestino Delgado/metabolismo , Encefalomiopatias Mitocondriais/genética , Timidina Fosforilase/genética , Adulto , Caquexia/patologia , Deleção de Genes , Humanos , Intestino Delgado/patologia , Masculino , Microdissecção , Encefalomiopatias Mitocondriais/patologia , Mutação PuntualRESUMO
A novel mitochondrial DNA nucleotide transversion, C14482A (M64I), different from the previously reported C14482G (M64I), was found to cause Leber's hereditary optic neuropathy with visual recovery in an Italian family. These equivalent changes are the fifth pathogenic mutation for pure Leber's hereditary optic neuropathy. This confirms that the ND6 gene of complex I is a mutational hot spot and suggests that different amino acid substitutions at residue 64, as induced by C14482G or C14482A (M64I) and the common T14484C (M64V) mutations, are associated with visual recovery.
Assuntos
DNA Mitocondrial/genética , Mutação , NADH NADPH Oxirredutases/genética , Atrofia Óptica Hereditária de Leber/genética , Adolescente , Adulto , Criança , Complexo I de Transporte de Elétrons , Feminino , Humanos , Itália , Masculino , Atrofia Óptica Hereditária de Leber/fisiopatologia , Linhagem , Polimorfismo de Fragmento de Restrição , Campos VisuaisRESUMO
PURPOSE: To describe the ocular features of a patient with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) due to a homozygous G1443A mutation in the thymidine-phosphorylase gene. METHODS: A case report with extensive ophthalmological investigation over a 9-year period, until death at age 38 years. Measures used included standard ophthalmological examination, visual field examination and optical coherence tomography (OCT). RESULTS: Ptosis and external ophthalmoplegia progressively worsened during the follow-up, as did the neurological and general status. Corneal and optic disc alterations were also observed at the last visit. Glaucomatous changes of the optic disc were confirmed by the visual field examination and OCT. CONCLUSION: In addition to previously described alterations such as ptosis and external ophthalmoplegia, MNGIE may be associated with glaucomatous-like optic neuropathy.