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1.
Vet Clin Pathol ; 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34628677

RESUMO

BACKGROUND: Canine stomatocytosis is a well-recognized rare erythrocyte disorder characterized by nonsyndromic forms with selective erythroid involvement, syndromic forms with extra-hematologic disease, and acquired forms. OBJECTIVES: We describe serial clinicopathologic changes in two dogs with stomatocytosis of breeds that are different from those previously reported. METHODS: Blood samples were obtained from a 12-year-old female neutered Australian Cattle Dog and a 12-year-old male neutered Beagle for hematologic and biochemical analyses, including a morphologic examination of peripheral blood films. Serial clinicopathologic data were reviewed, including CBCs performed by the referring veterinary surgeons. RESULTS: Serial CBC data in both cases reported a variable decrease in RBC numbers commonly associated with a normal hematocrit, macrocytosis, hypochromasia, changes in red cell distribution width parameters including marked histogram abnormalities in volume distribution of the RBC population, and mildly increased or normal reticulocyte counts. Morphologic examination of peripheral blood films identified variable numbers of stomatocytes, knizocytes (Case 1, Day 1, Day 4), mild anisocytosis, mild macrocytosis, and mild polychromasia. CONCLUSIONS: In both cases, the changes exhibited in the erythrogram raise suspicion for an RBC membrane disorder with cell volume dysregulation and stomatocytosis, although they did not appear to cause clinically relevant hemolysis.

2.
Int J Mol Sci ; 22(9)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34063036

RESUMO

Urinary extracellular vesicles (EVs) and their RNA cargo are a novel source of biomarkers for various diseases. We aimed to identify the optimal method for isolating small (<200 nm) EVs from human urine prior to small RNA analysis. EVs from filtered healthy volunteer urine were concentrated using three methods: ultracentrifugation (UC); a precipitation-based kit (PR); and ultrafiltration (UF). EVs were further purified by size-exclusion chromatography (SEC). EV preparations were analysed with transmission electron microscopy (TEM), Western blotting, nanoparticle tracking analysis (NTA) and an Agilent Bioanalyzer Small RNA kit. UF yielded the highest number of particles both before and after SEC. Small RNA analysis from UF-concentrated urine identified two major peaks at 10-40 nucleotides (nt) and 40-80 nt. In contrast, EV preparations obtained after UC, PR or SEC combined with any concentrating method, contained predominantly 40-80 nt sized small RNA. Protein fractions from UF+SEC contained small RNA of 10-40 nt in size (consistent with miRNAs). These data indicate that most of the microRNA-sized RNAs in filtered urine are not associated with small-sized EVs, and highlights the importance of removing non-vesicular proteins and RNA from urine EV preparations prior to small RNA analysis.


Assuntos
Cromatografia em Gel , Vesículas Extracelulares/genética , MicroRNAs/urina , Sistema Livre de Células , Vesículas Extracelulares/ultraestrutura , Humanos , Ultracentrifugação , Ultrafiltração
3.
J Vet Intern Med ; 35(3): 1333-1341, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33955592

RESUMO

BACKGROUND: Serum bile acids (SBAs) are frequently measured in dogs. However, there is limited data comparing SBAs in different liver diseases diagnosed according to standardized histological criteria. OBJECTIVES: To compare resting and postprandial SBAs, and determine their sensitivity and specificity, for various liver diseases in dogs. ANIMALS: Three hundred and forty-one client-owned dogs with suspected liver disease that had a liver biopsy and SBAs measured. METHODS: Multicenter retrospective study. Cases were classified according to standardized histological criteria. The sensitivity and specificity of resting and postprandial SBAs for the diagnosis of each liver disease, and all liver diseases combined, were calculated. RESULTS: The median resting SBAs were highest in dogs with cirrhosis (98.8 µmol/L; range, 6-135) and congenital circulatory anomalies (CCa; 79.45 µmol/L; 0.3-705). The highest median postprandial concentrations were found in CCa (126 µmol/L; 0-726) and chronic hepatitis (CH; 54.3 µmol/L; 0-260). Using the cut-off value of 10 µmol/L, the highest sensitivities of resting SBAs were recorded in dogs with CCa (87.5%; 95% confidence interval, 76.8-94.4) and CH (81.1%; 71.5-88.6). The sensitivities of postprandial SBAs were the highest in cholangitis (100%; 47.8-100.0) and CCa (91.1%; 78.8-97.5). The specificities of resting and postprandial SBAs for all diseases were 49.3% (37.6-61.1) and 29.7% (15.9-47.0), respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Postprandial SBAs are more sensitive but less specific than resting SBAs for the diagnosis of liver disease. There were dogs in all categories of liver disease with resting SBAs <10 and >90 µmol/L. Therefore, careful interpretation of both normal and elevated values is required.


Assuntos
Doenças do Cão , Hepatopatias , Animais , Ácidos e Sais Biliares , Doenças do Cão/diagnóstico , Cães , Cirrose Hepática/veterinária , Hepatopatias/veterinária , Estudos Retrospectivos
4.
Vet Clin Pathol ; 50(2): 236-239, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33797110

RESUMO

Currently, canine soft tissue sarcoma (STS) grading is based on histopathology. In humans, several studies have demonstrated concordance between cytologic grading systems for STS and histologic grade. The aim of this study was to correlate several cytologic parameters (smear cellularity, anisokaryosis, nucleolar malignancy score, multinucleation, and the number of mitotic figures per 200 cells) that form part of a human STS cytologic grading system, with histologic grades of canine cutaneous and subcutaneous STS. Three observers (blinded) reviewed the cytologic preparations independently from cases with confirmed histologic diagnoses of STS. A cytologic grading score was assigned for each parameter. Correlations between cytologic grading scores (averaged between observers) and histologic grades were assessed using Spearman's correlation coefficient, with statistical significance defined as P < .05. Twenty-one cases were included in the study (10 Grade I STS, nine Grade II STS, and two Grade III STS). The number of mitotic figures (≥3) per 200 cells was the only parameter that showed a significant but weak, positive correlation with histologic grade (rs  = .469; P = .032). No Grade I tumors had ≥3 mitotic figures per 200 cells; however, ≥3 mitotic figures per 200 cells were only observed in 33% of Grade II tumors and 50% (one out of two) of the Grade III tumors. This pilot study suggests that an increased number of mitotic figures seen on cytology might correlate with higher grade STS; however, the sensitivity of this parameter for grading STS appears to be low.


Assuntos
Doenças do Cão , Sarcoma , Neoplasias de Tecidos Moles , Animais , Citodiagnóstico/veterinária , Doenças do Cão/patologia , Cães , Projetos Piloto , Sarcoma/patologia , Sarcoma/veterinária , Pele/patologia , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/veterinária
5.
Vet Clin Pathol ; 48(3): 413-418, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31401808

RESUMO

BACKGROUND: Salivary urea concentrations correlate with serum urea concentrations in dogs and humans. Salivary urea concentrations can now be determined semi-quantitatively using a salivary urea test strip method that has been validated for use in humans. OBJECTIVES: We aimed to evaluate the repeatability of the salivary urea test strip score, and the correlation between the salivary urea test strip scores and serum urea concentrations in dogs. METHODS: Intra-run and inter-run variabilities were determined (n = 10 in triplicate). Correlations between salivary urea test strip scores and serum urea concentrations in dogs were assessed using the Spearman's correlation coefficient. Receiver operator curve analysis was used to evaluate the diagnostic performance of the salivary urea test strip score to identify dogs with serum urea concentration >7.4 mmol/L (upper limit of laboratory RI). RESULTS: The intra-run repeatability was good (28/30 concordant results) whereas the inter-run repeatability was moderate (23/30 concordant results). Salivary and serum urea concentrations showed a moderately positive correlation (rs  = .63, n = 33; P < .0001). A salivary urea test strip score ≥4 was 57% sensitive and 96% specific for detecting a serum urea concentration >7.4 mmol/L. CONCLUSIONS: Uremia can be detected using salivary urea test strips in dogs. Based on our preliminary data, salivary urea test strip scores of 1 or 2 might exclude clinically relevant uremia in most cases; however, it is recommended that the salivary urea test be repeated in dogs with a test strip score of 3. Dogs with a salivary urea test strip score of ≥4 would likely require additional investigations.


Assuntos
Fitas Reagentes , Saliva/química , Ureia/análise , Animais , Cães , Feminino , Masculino , Ureia/sangue
6.
J Vet Intern Med ; 32(5): 1629-1636, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30133945

RESUMO

BACKGROUND: Chronic hepatitis (CH) occurs commonly in dogs but is associated with a variable and largely unpredictable prognosis. p21, a cell-cycle inhibitor and marker of cellular senescence, is upregulated in human liver disease and is a better prognostic marker than histological or clinical scoring systems. OBJECTIVE: To quantify hepatocyte p21 immunopositivity in histopathology samples from dogs with CH and determine its association with outcome. ANIMALS: Twenty-six client-owned dogs with histologically confirmed CH, and 15 dogs with normal liver histology. METHODS: Medical records and liver histopathology samples were retrospectively reviewed to identify cases of CH. Immunohistochemistry for p21 was performed on all samples and hepatocyte immunopositivity was visually quantified. Relationships between p21 and dog age and dog survival time were statistically evaluated. RESULTS: Hepatocyte p21 immunopositivity in dogs with CH was high (median percentage of positive hepatocytes: 90%, range: 20%-98%) and exceeded 70% in 23/26 cases with no association with age. In control dogs, p21 immunopositivity was low (≤15% positive hepatocytes in 12/15 cases) and was positively correlated with age (rs = 0.63; P = .011). Dogs with p21 immunopositivity exceeding 91.8% (upper tercile) had significantly shorter survival compared to dogs with less than 88.9% immunopositivity (lowest tercile; 218 versus 874 days, P = .006). Increasing hepatocyte p21 immunopositivity was significantly negatively associated with survival time (HR 4.12; 95% CI 1.34-12.63; P = .013). CONCLUSIONS AND CLINICAL IMPORTANCE: Marked p21 immunopositivity in dogs with CH might be indicative of widespread hepatocellular senescence. A significant association with survival time also suggests a potential value for p21 quantification in determining prognosis.


Assuntos
Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Doenças do Cão/metabolismo , Hepatite Animal/metabolismo , Hepatócitos/metabolismo , Animais , Biomarcadores , Inibidor de Quinase Dependente de Ciclina p21/genética , Doenças do Cão/patologia , Cães , Feminino , Regulação da Expressão Gênica , Hepatite Animal/patologia , Fígado/patologia , Masculino , Estudos Retrospectivos
7.
Vet Rec Open ; 5(1): e000270, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29868172

RESUMO

The objectives of this study were fourfold: technical validation of a commercial canine 1,2-o-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin) ester (DGGR) lipase assay, to calculate a reference interval for DGGR lipase by the indirect a posteriori method, to establish biological validity of the assay, and to assess agreement between DGGR lipase and specific canine pancreatic lipase (Spec cPL) assays. Dogs with histologically confirmed acute pancreatitis (n=3), chronic pancreatitis (n=8) and normal pancreatic tissue (n=7) with stored (-80°C) serum samples were identified. Relevant controls were selected. Precision, reproducibility and linearity of DGGR lipase, and the effect of sample haemolysis and freezing, were assessed. Sensitivity and specificity of DGGR lipase and Spec cPL were determined. Agreement between these two parameters was calculated using Cohen's kappa coefficient (κ). The DGGR lipase assay demonstrated excellent precision, reproducibility and linearity. Sample haemolysis and storage at -80°C for 12 months did not influence the assay. DGGR lipase (>245IU/l) and Spec cPL (>400µg/l) both showed poor sensitivity but excellent specificity for acute pancreatitis, and poor to moderate sensitivity but excellent specificity for chronic pancreatitis. Substantial agreement (κ=0.679) was found between DGGR lipase and Spec cPL. The validated DGGR lipase assay had similar sensitivity and specificity for the diagnosis of acute and chronic pancreatitis to Spec cPL. DGGR lipase is a reliable alternative to Spec cPL for the diagnosis of pancreatitis.

8.
J Vet Intern Med ; 32(3): 1100-1108, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29572949

RESUMO

BACKGROUND: Feline morbillivirus (FeMV) is associated with the presence of tubulo-interstitial nephritis (TIN) in cats, however the seroprevalence of FeMV in the UK and the association between the presence of FeMV and renal azotemia is unknown HYPOTHESIS/OBJECTIVES: To identify whether paramyxoviruses are present in urine samples of geriatric cats and to develop an assay to assess FeMV seroprevalence. To investigate the relationship between both urinary paramyxovirus (including FeMV) excretion and FeMV seroprevalence and azotemic chronic kidney disease (CKD). ANIMALS: Seventy-nine cats (40 for FeMV detection; 72 for seroprevalence). METHODS: Retrospective cross-sectional, case control study. Viral RNA was extracted from urine for RT-PCR. PCR products were sequenced for virus identification and comparison. The FeMV N protein gene was cloned and partially purified for use as an antigen to screen cat sera for anti-FeMV antibodies by Western Blot. RESULTS: Feline morbillivirus RNA from five distinct morbilliviruses were identified. Detection was not significantly different between azotemic CKD (1/16) and nonazotemic groups (4/24; P = .36). Three distinct, non-FeMV paramyxoviruses were present in the nonazotemic group but their absence from the azotemic group was not statistically significant (P = .15). 6/14 (43%) azotemic cats and 40/55 (73%) nonazotemic cats were seropositive (P = .06). CONCLUSIONS AND CLINICAL IMPORTANCE: Feline morbillivirus was detected in cats in the UK for the First time. However, there was no association between virus prevalence or seropositivity and azotemic CKD. These data do not support the hypothesis that FeMV infection is associated with the development of azotemic CKD in cats in the UK.


Assuntos
Azotemia/veterinária , Doenças do Gato/virologia , Infecções por Morbillivirus/veterinária , Morbillivirus , Infecções por Paramyxoviridae/veterinária , Paramyxoviridae , Insuficiência Renal Crônica/veterinária , Animais , Azotemia/complicações , Azotemia/virologia , Estudos de Casos e Controles , Doenças do Gato/epidemiologia , Gatos , Estudos Transversais , Feminino , Masculino , Infecções por Morbillivirus/complicações , Infecções por Morbillivirus/diagnóstico , Infecções por Morbillivirus/epidemiologia , Infecções por Paramyxoviridae/complicações , Infecções por Paramyxoviridae/diagnóstico , Infecções por Paramyxoviridae/epidemiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/virologia , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Estudos Soroepidemiológicos , Reino Unido/epidemiologia
9.
Res Vet Sci ; 115: 412-417, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28753515

RESUMO

Our objective was to identify if changes in serum protein concentrations occur in hyperthyroidism and to assess their association with the development of azotaemia following treatment. Initially non-azotaemic hyperthyroid cats and healthy older cats were included. Serum concentrations of protein fractions were determined by agarose gel electrophoresis and compared between; hyperthyroid and control cats, initially non-azotaemic hyperthyroid cats which developed azotaemia in a 4month follow up period (masked-azotaemic) and those which remained non-azotaemic, and hyperthyroid cats before and at the time of restoration of euthyroidism. Data are presented as median [25th, 75th percentiles]. Hyperthyroid cats (n=56) had higher serum α2 globulin concentrations (12.5 [10.9, 13.1] g/L vs. 9.8 [3.0, 11.4] g/L; P<0.001) and lower serum γ globulin concentrations (11.4 [9.1, 13.3] g/L vs. 14.0 [12.4, 16.8] g/L; P=0.001) than control cats (n=26). Following treatment, serum total globulin concentration increased (from 38.6 [35.4, 42.8] g/L to 42.3 [39.0, 45.7] g/L; P<0.001), serum α2 globulin concentration decreased (from 12.5 [10.9, 13.9] g/L to 11.5 [10.1, 12.6] g/L; P<0.001) and serum γ globulin concentration increased (from 11.4 [9.0, 13.3] g/L to 14.0 [12.4, 16.8] g/L; P<0.001). Serum concentrations of total globulin or globulin fractions were not significantly different between masked-azotaemic and non azotaemic groups. In conclusion, hyperthyroidism is associated with altered serum concentrations of the α2 and γ globulin fractions, however these changes were not associated with the development of azotaemic chronic kidney disease following treatment.


Assuntos
Proteínas Sanguíneas , Doenças do Gato/sangue , Hipertireoidismo/veterinária , Insuficiência Renal Crônica/veterinária , Animais , Gatos , Feminino , Hipertireoidismo/sangue , Insuficiência Renal Crônica/sangue
10.
Vet Clin Pathol ; 45(3): 444-9, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27391303

RESUMO

BACKGROUND: Pseudothrombocytopenia secondary to platelet clumping is a common cause of preanalytic error for platelet counts in dogs, cats, and horses. In human beings, it is suggested that prewarming blood samples to 37°C prior to hematology analysis will reduce platelet clumping. OBJECTIVES: The purpose of the study was to evaluate the effect of prewarming EDTA blood samples to 37°C on measured platelet counts and other hematologic variables. METHODS: The EDTA blood samples from dogs, cats and horses submitted to the clinical pathology laboratory at the University of Cambridge were included. Complete blood cell counts performed using a Sysmex XT-2000iV hematology analyzer were done on samples at room temperature (approximately 22°C) and following warming of the samples to 37°C in a water bath. The Wilcoxon signed rank test was used to compare hematologic variables, including platelet count, before and after sample warming to 37°C. Data are presented as median (25(th) , 75(th) percentile) increase. RESULTS: Blood samples from 39 dogs, 19 cats, and 10 horses were included. Sample warming to 37°C resulted in a statistically significant increase in platelet counts in dogs (11 [-2, 30] ×10(9) /L), cats (36 [14, 84] ×10(9) /L), and horses (42 [31, 79] ×10(9) /L). Sample warming did not significantly affect other hematologic variables. CONCLUSIONS: Prewarming EDTA blood samples to 37°C prior to hematologic analysis increased platelet counts overall in canine, feline, and equine blood, but did not abrogate platelet clumping and pseudothrombocytopenia fully in some cases. Furthermore, true pseudothrombocytopenia was not confirmed in these animals.


Assuntos
Gatos/sangue , Cães/sangue , Cavalos/sangue , Contagem de Plaquetas/veterinária , Animais , Ácido Edético , Contagem de Plaquetas/instrumentação , Temperatura , Trombocitopenia/veterinária
11.
Vet Clin Pathol ; 45(1): 148-53, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26840919

RESUMO

BACKGROUND: Hyperthyroidism is common in older cats, which necessitates frequent screening of serum total thyroxine (TT4) concentrations. Fast, cheap, and reliable methods to measure TT4 in cats are needed. OBJECTIVES: The purpose of the study was the validation of a human TT4 enzyme immunoassay (EIA) for use with feline serum, and derivation of a TT4 reference interval (RI) for cats aged 9 years and older. METHODS: Assay precision, reproducibility, and linearity were evaluated. Interference by hemolysis was also assessed. Method comparison studies between the human EIA and a previously validated radioimmunoassay (RIA) and chemiluminescent-enzyme immunoassay (CEIA) were performed. Healthy cats (> 9 years) were recruited from 3 UK first opinion practices. RESULTS: The human TT4 EIA demonstrated good precision and reproducibility, and adequate linearity. Hemolysis did not significantly alter measured TT4 concentrations until HGB > 8 g/L. Method comparison revealed proportional and constant errors between EIA and RIA/CEIA. The TT4 RI for cats (> 9 years) was calculated as 7.1-45.1 nmol/L (n = 49). CONCLUSIONS: The human TT4 EIA was successfully validated for use with feline serum and offers a rapid, cheap, and reliable method for determination of serum TT4 concentrations in cats.


Assuntos
Doenças do Gato/diagnóstico , Hipertireoidismo/veterinária , Técnicas Imunoenzimáticas/veterinária , Tiroxina/sangue , Animais , Gatos , Feminino , Hipertireoidismo/diagnóstico , Masculino , Radioimunoensaio/veterinária , Valores de Referência , Reprodutibilidade dos Testes , Testes de Função Tireóidea/veterinária
12.
Case Rep Neurol ; 7(1): 95-100, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26327906

RESUMO

Three patients with the clinical and investigation features of facial onset sensory and motor neuronopathy (FOSMN) syndrome are presented, one of whom came to a post-mortem examination. This showed TDP-43-positive inclusions in the bulbar and spinal motor neurones as well as in the trigeminal nerve nuclei, consistent with a neurodegenerative pathogenesis. These data support the idea that at least some FOSMN cases fall within the spectrum of the TDP-43 proteinopathies, and represent a focal form of this pathology.

13.
J Dairy Sci ; 97(9): 5474-80, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24997666

RESUMO

Thromboelastography is a whole blood-based coagulation assay that can be used to investigate hypocoagulability and hypercoagulability, as seen with thromboembolic diseases and disseminated intravascular coagulation. Numerous coagulopathies due to different causes are reported in cows. The objective was to establish reference intervals for thromboelastography using the TEG 5000 (Haemonetics GmbH, Munich, Germany) with citrated whole blood samples and kaolin activation in dairy cows and to investigate possible thromboelastographic changes between cows in different lactation periods. An additional objective was to test the stability of samples for up to 100h. Sixty blood samples from healthy Holstein-Friesian cows were examined. The samples were allocated to 3 different lactation groups (≤30 d postcalving, 31-99 d postcalving, ≥100 d postcalving). Thromboelastography was performed by using the TEG 5000 analyzer with citrated whole blood samples with kaolin activation. The calculated reference intervals were as follows: reaction time=2.2 to 6.2min, coagulation time=0.8 to 2.0min, angle α=58.2 to 81.8°, maximum amplitude=64.3 to 89.2mm, and clot rigidity=9.2 to 41.2 dyn/cm(2). The 3 different lactation groups showed no significant differences in TEG parameters. No significant difference was seen in samples stored for up to 48h at room temperature, which indicates that delays in processing samples, such as those arising during transit, are not an issue.


Assuntos
Coagulação Sanguínea , Bovinos , Tromboelastografia/veterinária , Animais , Bioensaio , Ácido Cítrico/química , Feminino , Alemanha , Caulim/farmacologia , Lactação , Valores de Referência
15.
J Neurol Neurosurg Psychiatry ; 83(4): 371-6, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21849339

RESUMO

BACKGROUND: In motor neurone disease (MND), respiratory muscle weakness causes substantial morbidity, and death is usually due to respiratory failure. Non-invasive ventilation (NIV) improves symptoms, quality of life and survival, but previous surveys showed that few patients with MND received NIV. METHODS: A postal survey was conducted of the clinical application of NIV in MND among consultant neurologists in the UK. The results were compared with those of a similar survey done in 2000. FINDINGS: Over 12 months, 612 patients were referred for NIV of whom 444 were successfully established on treatment (72.5% success rate). 38% of responding neurologists assessed respiratory function at presentation and 20% routinely monitored respiratory function; 32% relied on symptoms as the only criterion for NIV referral and 43% used a combination of symptoms and physiological impairment. 75% of responding neurologists accessed specialist palliative care services for their patients towards the end of life and 69% at an earlier stage. INTERPRETATION: Compared with 2000, there has been a marked increase in the number of patients referred for, and currently using, NIV (2.6 and 3.4-fold, respectively). The proportion successfully established on NIV has also increased, suggesting more appropriate selection and/or improvement in the methods of using NIV in this challenging group of patients. However, monitoring of respiratory function is suboptimal and uncontrolled oxygen is sometimes used inappropriately before the terminal phase.


Assuntos
Doença dos Neurônios Motores/terapia , Neurologia/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Respiração Artificial/estatística & dados numéricos , Insuficiência Respiratória/prevenção & controle , Humanos , Doença dos Neurônios Motores/complicações , Cuidados Paliativos/estatística & dados numéricos , Vigilância da População , Encaminhamento e Consulta/estatística & dados numéricos , Testes de Função Respiratória/estatística & dados numéricos , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/etiologia , Inquéritos e Questionários , Reino Unido
16.
Arch Neurol ; 67(4): 455-61, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20385912

RESUMO

OBJECTIVE: To determine the frequency of and clinicopathologic phenotypes associated with FUS/TLS mutations in a large cohort of amyotrophic lateral sclerosis (ALS) cases from the north of England. DESIGN: Genetic screening project with neuropathologic examination of postmortem tissue in selected cases. The clinical details of selected cases are also presented. SETTING: Neurology departments of 2 university teaching hospitals in the north of England. PARTICIPANTS: The 15 exons of FUS/TLS were sequenced in an initial cohort of 42 familial ALS (FALS) and 117 sporadic ALS (SALS) cases. Exons 14 and 15 were subsequently screened in a larger cohort of 431 SALS cases. Regions mutated in ALS cases were also screened in 293 controls. MAIN OUTCOME MEASURE: Evaluation of gene-sequencing chromatographs and detailed histopathologic analysis of the central nervous system. RESULTS: Four heterozygous mutations, 1 of which is novel, were identified in 6 patients with ALS (4 with FALS and 2 with SALS). Two of the substitutions were not found to be present in controls, and neuropathology in these cases revealed neuronal and/or glial cytoplasmic inclusions positive for the FUS/TLS protein. One of these cases is also the first reported SALS case with an FUS/TLS mutation. The other 2 substitutions identified were also identified in control cases. Neuropathology in these cases revealed typical SALS pathology, suggesting that they are likely to represent benign polymorphisms. CONCLUSIONS: FUS/TLS mutations represented approximately 5% of FALS cases screened. A FUS/TLS mutation was also identified in a single SALS case. Subsequent screening of this region in a larger cohort of SALS cases, however, did not reveal any additional mutations.


Assuntos
Esclerose Amiotrófica Lateral/genética , Esclerose Amiotrófica Lateral/patologia , Sistema Nervoso Central/patologia , Predisposição Genética para Doença/genética , Mutação/genética , Proteína FUS de Ligação a RNA/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Esclerose Amiotrófica Lateral/fisiopatologia , Estudos de Casos e Controles , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/fisiopatologia , Estudos de Coortes , Análise Mutacional de DNA , Éxons/genética , Feminino , Frequência do Gene/genética , Marcadores Genéticos/genética , Testes Genéticos , Genótipo , Humanos , Padrões de Herança , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética
17.
Lancet Neurol ; 5(2): 140-7, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16426990

RESUMO

BACKGROUND: Few patients with amyotrophic lateral sclerosis currently receive non-invasive ventilation (NIV), reflecting clinical uncertainty about the role of this intervention. We aimed to assess the effect of NIV on quality of life and survival in amyotrophic lateral sclerosis in a randomised controlled trial. METHODS: 92 of 102 eligible patients participated. They were assessed every 2 months and randomly assigned to NIV (n=22) or standard care (n=19) when they developed either orthopnoea with maximum inspiratory pressure less than 60% of that predicted or symptomatic hypercapnia. Primary validated quality-of-life outcome measures were the short form 36 mental component summary (MCS) and the sleep apnoea quality-of-life index symptoms domain (sym). Both time maintained above 75% of baseline (T(i)MCS and T(i)sym) and mean improvement (microMCS and microsym) were measured. FINDINGS: NIV improved T(i)MCS, T(i)sym, microMCS, microsym, and survival in all patients and in the subgroup with better bulbar function (n=20). This subgroup showed improvement in several measures of quality of life and a median survival benefit of 205 days (p=0.006) with maintained quality of life for most of this period. NIV improved some quality-of-life indices in those with poor bulbar function, including microsym (p=0.018), but conferred no survival benefit. INTERPRETATION: In patients with amyotrophic lateral sclerosis without severe bulbar dysfunction, NIV improves survival with maintenance of, and improvement in, quality of life. The survival benefit from NIV in this group is much greater than that from currently available neuroprotective therapy. In patients with severe bulbar impairment, NIV improves sleep-related symptoms, but is unlikely to confer a large survival advantage.


Assuntos
Esclerose Amiotrófica Lateral/terapia , Respiração com Pressão Positiva , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Síndromes da Apneia do Sono/etiologia , Síndromes da Apneia do Sono/terapia , Sobrevida , Resultado do Tratamento
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