RESUMO
BACKGROUND: The benefits of extensive lymph node dissection as performed in complete mesocolic excision are still debated, although recent studies have shown an association with improved long-term outcomes. However, none of these studies had an intention-to-treat design or aimed to show a causal effect; therefore in this study, we aimed to estimate the causal oncological treatment effects of complete mesocolic excision on right-sided colon cancer. METHODS: We did a population-based cohort study involving prospective data collected from four hospitals in Denmark. We compared the oncological outcome data of patients at one centre performing central lymph node dissection and vascular division after almost complete exposure of the proximal part of the superior mesenteric vein (ie, the complete mesocolic excision group) with three other centres performing conventional resections with unstandardised and limited lymph node dissection (ie, non-complete mesocolic excision; control group). We included data for all patients in the Capital Region of Denmark undergoing elective curative-intent right-sided colon resections for stages I-III colon cancer, as categorised by the Union for International Cancer Control (UICC; 5th edition), from June 1, 2008, to Dec 31, 2013. Patients were followed-up for 5·2 years after surgery. The primary outcome was the cumulative incidence of recurrence after 5·2 years of surgery. Inverse probability of treatment weighting and competing risk analyses were used to estimate the possible causal effects of complete mesocolic excision. This study is registered with ClinicalTrials.gov, number NCT03754075. FINDINGS: 1069 patients (813 in the control group and 256 in the complete mesocolic excision group) underwent curative-intent elective surgery for right-sided colon cancer during the study period. None of the patients were lost to follow-up regarding survival or recurrence status, and consequently no patient was censored in the analyses. The 5·2-year cumulative incidence of recurrence was 9·7% (95% CI 6·3-13·1) in the complete mesocolic excision group compared with 17·9% (15·3-20·5) in the control group, and the absolute risk reduction of complete mesocolic excision after 5·2 years was 8·2% (95% CI 4·0-12·4; p=0·00015). In the control group, 145 (18%) of 813 patients were diagnosed with a recurrence and 281 (35%) died during follow-up, whereas in the complete mesocolic excision group 25 (10%) of 256 patients were diagnosed with a recurrence and 75 (29%) died during follow-up. INTERPRETATION: This study shows a causal treatment effect of central mesocolic lymph node excision on risk of recurrence after resection for right-sided colon adenocarcinoma. Complete mesocolic excision has the potential to reduce the risk of recurrence and improve long-term outcome after resection for all UICC stages I-III of right-sided colon adenocarcinomas. FUNDING: The Tvergaard Fund, Helen Rude Fund, Krista and Viggo Petersen Fund, Olga Bryde Nielsen Fund, and Else and Mogens Wedell-Wedellsborg Fund.
Assuntos
Adenocarcinoma/terapia , Colectomia , Neoplasias do Colo/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Colectomia/efeitos adversos , Colectomia/mortalidade , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Bases de Dados Factuais , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
The extent to which increased liver fat content influences differences in circulating metabolites and/or lipids between low-birth-weight (LBW) individuals, at increased risk of type 2 diabetes (T2D), and normal-birth-weight (NBW) controls is unknown. The objective of the study was to perform untargeted serum metabolomics and lipidomics analyses in 26 healthy, non-obese early-middle-aged LBW men, including five men with screen-detected and previously unrecognized non-alcoholic fatty liver disease (NAFLD), compared with 22 age- and BMI-matched NBW men (controls). While four metabolites (out of 65) and fifteen lipids (out of 279) differentiated the 26 LBW men from the 22 NBW controls (p ≤ 0.05), subgroup analyses of the LBW men with and without NAFLD revealed more pronounced differences, with 11 metabolites and 56 lipids differentiating (p ≤ 0.05) the groups. The differences in the LBW men with NAFLD included increased levels of ornithine and tyrosine (PFDR ≤ 0.1), as well as of triglycerides and phosphatidylcholines with shorter carbon-chain lengths and fewer double bonds. Pathway and network analyses demonstrated downregulation of transfer RNA (tRNA) charging, altered urea cycling, insulin resistance, and an increased risk of T2D in the LBW men with NAFLD. Our findings highlight the importance of increased liver fat in the pathogenesis of T2D in LBW individuals.
Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Recém-Nascido , Masculino , Humanos , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/etiologia , Diabetes Mellitus Tipo 2/complicações , Lipidômica , Recém-Nascido de Baixo Peso , LipídeosRESUMO
BACKGROUND: Intranasal esketamine demonstrates rapid improvement of depressive symptoms. However, transient adverse effects (dissociation, sedation and dizziness) may occur, which could impact driving performance. AIMS: To evaluate the effects of 84 mg intranasal esketamine on driving performance in unipolar major depressive disorder (MDD) or persistent depressive disorder (PDD) patients. METHODS: The study consisted of two parts. Part A was a single-blind, double-dummy, randomized three-period, cross-over study to compare effects of esketamine versus placebo on next morning driving, 18 ± 2 h post-treatment. Alcohol was administered to demonstrate assay sensitivity. In Part B, same-day driving, 6 ± 0.5 hours post-treatment, was assessed during twice weekly esketamine administration for 3 weeks. Twenty-seven patients with mild-to-moderate MDD or PDD without psychotic features completed a 100 km on-the-road driving test on a public highway in normal traffic. The primary outcome was standard deviation of lateral position (SDLP; cm; weaving of car). RESULTS: In Part A, alcohol impaired driving performance compared to placebo: Least-square means (95% CI), p-value for delta SDLP (cm) compared with placebo: (ΔSDLP = + 1.83 (1.03; 2.62), p < 0.001), whereas esketamine did not: (ΔSDLP = -0.23 (-1.04; 0.58), p = 0.572). In Part B, weekly driving tests showed no differences between placebo baseline SDLP and after esketamine administration over 3 weeks: Day 11: (ΔSDLP = -0.96 (-3.72; 1.81), p = 0.493), Day 18: (ΔSDLP = -0.56 (-3.33; 2.20), p = 0.686) and Day 25: (ΔSDLP = -1.05 (-3.82; 1.71), p = 0.451). CONCLUSIONS: In this study, esketamine did not impair on-road driving performance the next morning following a single dose, or on same day after repeated administration.
Assuntos
Condução de Veículo , Transtorno Depressivo Maior , Antidepressivos/efeitos adversos , Estudos Cross-Over , Transtorno Depressivo Maior/tratamento farmacológico , Método Duplo-Cego , Humanos , Ketamina , Desempenho Psicomotor , Método Simples-CegoRESUMO
INTRODUCTION: In this study we describe the clinical and molecular characteristics of limb-girdle muscular dystrophy (LGMD) due to LAMA2 mutations. METHODS: Five patients clinically diagnosed with LGMD and showing brain white matter hyperintensities on MRI were evaluated using laminin α2 genetic and protein testing. RESULTS: The patients had slowly progressive, mild muscular dystrophy with various degrees of CNS involvement. Epilepsy was observed in 2, and subtle symptoms of CNS involvement (mild deficit in executive functions and low IQ scores) were noted in 3 patients. Novel LAMA2 mutations were identified in all patients. The amount of laminin α2 protein in the muscle biopsies ranged from trace to about 50% compared with controls. CONCLUSIONS: This study represents the largest series of LGMD laminin α2-deficient patients and expands the clinical phenotype associated with LAMA2 mutations. The findings suggest that brain MRI could be included in the diagnostic work-up of patients with undiagnosed LGMD.
Assuntos
Laminina/genética , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/patologia , Mutação/genética , Adolescente , Idoso , Processamento Alternativo , Sequência de Bases , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Distrofia Muscular do Cíngulo dos Membros/metabolismo , Mutagênese Insercional , Fenótipo , Sítios de Splice de RNA , Adulto JovemRESUMO
This study investigated immunological changes during an alcohol hangover, and the possible difference between hangover-resistant and hangover-sensitive drinkers in terms of immune reactivity. Using a semi-naturalistic design, N = 36 healthy social drinkers (18 to 30 years old) provided saliva samples on a control day (after drinking no alcohol) and on a post-alcohol day. Hangover severity was rated directly after saliva collection. Cytokine concentrations, interleukin (IL)-1ß, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α, and hangover severity were compared between both test days and between hangover-sensitive and -resistant drinkers. Data from N = 35 drinkers (17 hangover-sensitive and 18 hangover-resistant) were included in the statistical analyses. Relative to the control day, there were significant increases in saliva IL-6 and IL-10 concentrations on the post-alcohol day. No significant differences in cytokine concentrations were found between hangover-sensitive and hangover-resistant drinkers, nor did any change in cytokine concentration correlate significantly with hangover severity. In line with previous controlled studies assessing cytokines in blood, the current naturalistic study using saliva samples also demonstrated that the immune system responds to high-level alcohol intake. However, further research is warranted, as, in contrast to previous findings in blood samples, changes in saliva cytokine concentrations did not differ significantly between hangover-sensitive and hangover-resistant drinkers, nor did they correlate significantly with hangover severity.
RESUMO
BACKGROUND: Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurodegenerative disorders characterised by progressive spasticity and weakness in the lower limbs. Mutations in PLP1 on the X chromosome cause spastic paraplegia type 2 (SPG2) or the allelic Pelizaeus-Merzbacher Disease (PMD). The PLP1 protein is a major myelin protein involved in stabilisation and maintenance of the myelin sheath. The function of the protein has been studied in the rumpshaker mouse, which is a model of SPG2/PMD. OBJECTIVE: To characterise the phenotype of patients with the 'rumpshaker mutation.' PATIENTS: A family with HSP caused by the 'rumpshaker mutation.' RESULTS: The patients showed nystagmus during infancy and had early onset of HSP. They had normal cognition, and cerebral MRI showed relatively unspecific white matter abnormalities on T2 sequences without clear progression. Urinary urgency was reported among the female carriers. MRS of both patients showed increased myo-inositol in the white matter, while decreased N-acetylaspartate was found exclusively in the oldest patient. All evoked potential examinations were compatible with severe central demyelination, while no signs of peripheral demyelination or axonal degeneration were found. (18)F-FDG-PET scans were normal. CONCLUSION: The phenotypes of the patients reported here are the mildest described to be caused by the rumpshaker mutation and represent the mildest form among the spectrum of PLP1 related disorders. No definite symptoms in the female carriers could be ascribed to the mutation. These data suggest the pathology to be an underlying dysmyelinating disorder in combination with a central axonal degeneration.
Assuntos
Proteína Proteolipídica de Mielina/genética , Mutação Puntual/genética , Paraplegia Espástica Hereditária/genética , Idoso , Alelos , Cromossomos Humanos X/genética , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Análise Mutacional de DNA , Primers do DNA/genética , Potenciais Evocados Visuais/fisiologia , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Nistagmo Congênito , Linhagem , Fenótipo , Índice de Gravidade de Doença , Paraplegia Espástica Hereditária/epidemiologiaRESUMO
BACKGROUND: Prior studies failed to detect significant association between hypoalbuminemia and small intestinal lesions. HYPOTHESIS: Use of pictorial templates will enhance consistency of interpathologist interpretation and identification of intestinal lesions associated with hypoalbuminemia. ANIMALS: Tissues from 62 dogs and 25 cats examined as clinical cases at 7 referral veterinary practices in 4 countries. METHODS: Retrospective, observational study. Histopathology slides from sequential cases undergoing endoscopic biopsy were examined by 4 pathologists by pictorial templates. Changes for 9 microscopic features were recorded as normal, mild, moderate or severe, and 2- and 4-point scales were tested for consistency of interpretation. Logistic regression models determined odds ratios (OR) of histologic lesions being associated with hypoalbuminemia while kappa statistics determined agreement between pathologists on histologic lesions. RESULTS: There was poor agreement (kappa = -0.013 to 0.3) between pathologists, and institution of origin of slides had effect (kappa = 1.0 for 3 of 4 lesions on slides from Institution 5) on agreement between pathologists on selected histologic features. Using 2 point as opposed to 4-point grading scale increased agreement between pathologists (maximum kappa = 0.69 using 4-point scale versus maximum kappa = 1.0 using 2-point scale). Significant association (P = .019- .04; 95% OR = 3.14-10.84) between lacteal dilation and hypoalbuminemia was found by 3 pathologists. CONCLUSIONS AND CLINICAL IMPORTANCE: Substantial inconsistency between pathologists remains despite use of pictorial template because of differences in slide processing. Distinguishing between mild and moderate lesions might be important source of the disagreement among pathologists.
Assuntos
Biópsia/veterinária , Doenças do Gato/patologia , Doenças do Cão/patologia , Endoscopia/veterinária , Gastroenteropatias/veterinária , Manejo de Espécimes/veterinária , Animais , Doenças do Gato/diagnóstico , Gatos , Doenças do Cão/diagnóstico , Cães , Gastroenteropatias/diagnóstico , Gastroenteropatias/patologiaRESUMO
OBJECTIVE: We followed up patients with facioscapulohumeral muscular dystrophy (FSHD) with sequential examinations over 2 years to investigate whether inflammatory lesions always precede fat replacement, if inflammation can be resolved without muscle degeneration, and if inflammatory lesions in muscle are always followed by fat replacement. METHODS: In this longitudinal study of 10 sequential MRI assessments over 2.5 years, we included 10 patients with FSHD. We used MRI with short TI inversion recovery to identify regions of interest (ROIs) with hyperintensities indicating muscle inflammation. Muscle T2 relaxation time mapping was used as a quantitative marker of muscle inflammation. Dixon sequences quantified muscle fat replacement. Ten healthy controls were examined with a magnetic resonance scan once for determination of normal values of T2 relaxation time. RESULTS: We identified 68 ROIs with T2 elevation in the patients with FSHD. New ROIs with T2 elevation arising during the study had muscle fat content of 6.4% to 33.0% (n = 8) and 47.0% to 78.0% lesions that resolved (n = 6). ROIs with T2 elevation had a higher increase in muscle fat content from visits 1 to 10 (7.9 ± 7.9%) compared to ROIs with normal muscle T2 relaxation times (1.7 ± 2.6%; p < 0.0001). Severe T2 elevations were always followed by an accelerated replacement of muscle by fat. CONCLUSIONS: Our results suggest that muscle inflammation starts in mildly affected muscles in FSHD, is related to a faster muscle degradation, and continues until the muscles are completely fat replaced. CLINICALTRIALSGOV IDENTIFIER: NCT02159612.
Assuntos
Tecido Adiposo/diagnóstico por imagem , Inflamação/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Distrofia Muscular Facioescapuloumeral/diagnóstico por imagem , Adulto , Progressão da Doença , Feminino , Humanos , Perna (Membro) , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Força Muscular , Dinamômetro de Força Muscular , Distrofia Muscular Facioescapuloumeral/fisiopatologia , Coxa da Perna , Teste de CaminhadaRESUMO
OBJECTIVES: Brain dysfunction is a serious complication after cardiac surgery. In the Perfusion Pressure Cerebral Infarcts trial, we allocated cardiac surgery patients to a mean arterial pressure of either 70-80 or 40-50 mmHg during cardiopulmonary bypass (CPB). In this secondary analysis, we compared selected cerebral metabolites using magnetic resonance spectroscopy hypothesizing that a postoperative decrease in occipital grey matter (GM) N-acetylaspartate-to-total-creatine ratio, indicative of ischaemic injury, would be found in the high-target group. METHODS: Of the 197 patients randomized in the Perfusion Pressure Cerebral Infarcts trial, 55 and 42 patients had complete and useful data from GM and white matter (WM), respectively. Spectroscopies were done preoperatively and on postoperative days 3-6. Cognitive function was assessed prior to surgery, at discharge and at 3 months. We predefined the statistical significance level to be 0.01. RESULTS: A postoperative decrease was found in GM N-acetylaspartate-to-total-creatine ratio in the high-target group [mean difference -0.09 (95% confidence interval -0.14 to -0.04), P = 0.014]. No significant differences were found in other metabolite ratios investigated in GM or WM. No significant association was found between changes in metabolite ratios and new cerebral infarcts, WM lesion score or cognitive dysfunction. CONCLUSIONS: A higher mean arterial pressure during CPB was associated with signs of impaired cerebral metabolism, though not at the predefined significance level of 0.01. No significant association was found between metabolite ratio changes and neuroradiological pathology or change in cognitive function. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT02185885.
Assuntos
Lesões Encefálicas , Procedimentos Cirúrgicos Cardíacos , Pressão Sanguínea , Encéfalo , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Humanos , PerfusãoRESUMO
BACKGROUND: The quality of histopathology slides of endoscopic biopsies from different laboratories varies, but the effect of biopsy quality on outcome is unknown. HYPOTHESIS: The ability to demonstrate a histologic lesion in the stomach or duodenum of a dog or cat is affected by the quality of endoscopic biopsy samples submitted. More endoscopic samples are needed to find a lesion in poor-quality tissue specimens. ANIMALS: Tissues from 99 dogs and 51 cats were examined as clinical cases at 8 veterinary institutions or practices in 5 countries. METHODS: Histopathology slides from sequential cases that underwent endoscopic biopsy were submitted by participating institutions. Quality of the histologic section of tissue (inadequate, marginal, adequate), type of lesion (lymphangiectasia, crypt lesion, villus blunting, cellular infiltrate), and severity of lesion (normal, mild, moderate, severe) were determined. Sensitivity of different quality tissue samples for finding different lesions was determined. RESULTS: Fewer samples were required from dogs for diagnosis as the quality of the sample improved from inadequate to marginal to adequate. Duodenal lesions in cats displayed the same trend except for moderate duodenal infiltrates for which quality of tissue sample made no difference. Gastric lesions in dogs and mild gastric lesions in cats had the same trend, whereas the number of tissue samples needed to diagnose moderately severe gastric lesions in cats was not affected by the quality of tissue sample. CONCLUSIONS AND CLINICAL IMPORTANCE: The quality of endoscopically obtained tissue samples has a profound effect on their sensitivity for identifying certain lesions, and there are differences between biopsies of canine and feline tissues.
Assuntos
Biópsia/veterinária , Doenças do Gato/diagnóstico , Doenças do Cão/diagnóstico , Duodenopatias/veterinária , Endoscopia/veterinária , Gastropatias/veterinária , Animais , Biópsia/métodos , Gatos , Cães , Duodenopatias/diagnóstico , Endoscopia/métodos , Sensibilidade e Especificidade , Gastropatias/diagnósticoRESUMO
Heightened intraocular pressure (IOP) is not always indicative of glaucoma, but is an important risk factor for the progression of certain types of eye damage not obviously felt by the sufferer. A number of measurement systems have been devised in the past to measure the IOP by applying force or pressure to the cornea, but past studies have shown that the cornea thickness and its curvature have a significant effect on measurements which may ultimately lead to clinical misdiagnosis. A cyclic strain controlled dynamic probing measurement system has been developed using an indenter of diameter 3.06 mm operating at actuation frequencies of between 0.1 Hz and 4 Hz and displacements up to 1 mm. The cyclic strain is actuated by a linear stage with a load cell and indenter coupled in series. The load cell records the resultant cyclic force where the dynamic modulus is expressed as amplitude ratio and phase lag. The mechanical eye model consists of a silicone membrane that can be varied in thickness and it is distended hydraulically to simulate a range of IOP. A pressure sensor measures the dynamic IOP within the system which will be compared against the dynamic modulus. The relationship between the mechanical properties and the physical properties of the membrane will be established in order to develop a probe which can be used clinically taking into account the effects of corneal stiffness and hydraulic behaviour of the eye. The preliminary study reported here a significant increase in amplitude ratio and mean ratio with increasing the frequency similar to the behaviour found in biological materials and gelatin.
Assuntos
Córnea/fisiologia , Pressão Intraocular/fisiologia , Estresse Mecânico , Córnea/anatomia & histologia , Análise de Fourier , Humanos , Modelos Teóricos , TransdutoresRESUMO
The overall aim of this work is to determine the quality of biological tissues based on the relationship between the dynamic mechanical properties and their histology. Two sets of rigs have been developed for dynamic mechanical measurement, one for micro-scale testing and the other for macro-scale testing. Preliminary results using the macro-scale measurement system only are reported here. This system uses strain-controlled cyclic probing actuated by a linear stepper motor operating at actuation frequencies between 0.5Hz and 20Hz. A 1mm diameter indenter probes the specimen up to a displacement of 0.2mm and a load cell measures the resultant cyclic force. A series of tissue mimics were prepared using various formulations of gelatin and safflower oil and preliminary tests carried out to determine a suitable range of experimental variables and to establish the repeatability of the tests. The dynamic mechanical properties are expressed as amplitude ratio, phase difference and mean ratios of stress and strain, and the behaviour of these measurands with actuation frequency, mean strain and strain amplitude was observed. Results consistent with the literature were found which form a foundation for measurements on collagen-lipid biological tissues.
Assuntos
Força Compressiva/fisiologia , Gelatina , Imagens de Fantasmas , Estresse Mecânico , Resistência à Tração/fisiologia , Fenômenos Biomecânicos , Colágeno/fisiologia , Tecido Conjuntivo , Elasticidade , Humanos , Projetos de Pesquisa , Engenharia TecidualRESUMO
This paper concerns the operation of the actuator for a prototype micro-engineered mechanical palpation device for deployment via a cystoscope to measure the dynamic mechanical properties of the prostate gland in vivo. The subassembly consists of a 400x200 microm silicon (Si) piston manufactured using deep reactive ion etching (DRIE) housed within an anodically bonded glass-Si-glass sandwiched housing. The micro-channel on the Si layer was formed by powder blasting and contains the micro-piston with one end pointing to the side of the housing and the other facing a via hole leading to a capillary tube. The opening on the side of the housing was sealed by a 5 microm thick silicone membrane which acts to retain the micro-piston and act as a return spring. A 320 microm diameter capillary forms the connection between the micro-channel and a micro-syringe which is operated by a programmable syringe pump to produce a reciprocating action. A pressure sensor is connected along the capillary tube to measure the dynamic pressure within the system. The micro-piston has already been used, separately actuated to measure the dynamic mechanical properties of known viscoelastic materials and prostate tissue. The purpose of the present work is to assess the functionality of the actuator assembly.
Assuntos
Nanomedicina/instrumentação , Palpação/métodos , Próstata/fisiologia , Engenharia Tecidual/métodos , Estudos de Viabilidade , Fricção , Humanos , Masculino , SiliconesRESUMO
A 10-year-old male cairn terrier cross was presented with a history of myxomatous mitral valve disease diagnosed six months previously and with a four-week history of intermittent collapse. On 24 hour electrocardiograph (Holter) analysis, periods of no discernable electrical cardiac activity, which coincided with three collapsing episodes, were identified. Unfortunately, on re-presentation for removal of the Holter monitor, the dog collapsed and died. A post-mortem examination was conducted, and histology of the right and left atrium showed evidence of myocarditis. This is the first reported case, to our knowledge, of collapse because of electrical asystole in a dog with atrial myocarditis.
Assuntos
Doenças do Cão/diagnóstico , Átrios do Coração/patologia , Insuficiência da Valva Mitral/veterinária , Miocardite/veterinária , Animais , Morte Súbita/veterinária , Diagnóstico Diferencial , Doenças do Cão/patologia , Cães , Eletrocardiografia Ambulatorial/veterinária , Masculino , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/diagnóstico , Miocardite/complicações , Miocardite/diagnósticoRESUMO
OBJECTIVES: To evaluate the clinical utility of serum tumour necrosis factor-alpha, C-reactive protein and microalbuminuria as disease activity markers in canine idiopathic inflammatory bowel disease. METHODS: Dogs with chronic gastrointestinal disease for which no underlying cause could be identified were considered to have idiopathic inflammatory bowel disease and were included in the study. Serum tumour necrosis factor-alpha was assessed using a canine-specific ELISA, C-reactive protein by immunoturbidometric assay and quantitative microalbuminuria was analysed using a monoclonal antibody directed against canine albumin. The canine inflammatory bowel disease activity index and histopathologic grade were used to assess disease severity; biologic markers were then compared with the canine inflammatory bowel disease activity index and histopathologic grade. RESULTS: Sixteen dogs were included in the study. C-reactive protein level was mildly elevated in 15 dogs. Microalbuminuria was elevated in two of 15 dogs, and tumour necrosis factor-alpha was not detected in any dog tested. No correlation was found between the canine inflammatory bowel disease activity index and C-reactive protein or microalbuminuria or between histopathologic grade and C-reactive protein or microalbuminuria. There was no correlation between histopathologic grade and the canine inflammatory bowel disease activity index. CLINICAL SIGNIFICANCE: Although only a small number of dogs were evaluated, this study does not support the use of serum tumour necrosis factor-alpha measured by canine-specific ELISA or microalbuminuria in the evaluation of disease activity in dogs with idiopathic inflammatory bowel disease. Although mildly elevated in most dogs, C-reactive protein did not reflect disease severity as assessed by the canine inflammatory bowel disease activity index or histopathologic grade.
Assuntos
Albuminúria/veterinária , Doenças do Cão/sangue , Doenças Inflamatórias Intestinais/veterinária , Animais , Biomarcadores/sangue , Biomarcadores/urina , Proteína C-Reativa/metabolismo , Doenças do Cão/patologia , Doenças do Cão/urina , Cães , Feminino , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/urina , Masculino , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/sangueRESUMO
Novel ruthenium(II) organo-metallic compounds are active in ovarian cancer models [Aird RE, Cummings J, Ritchie AA, Muir M, Morris RE, Chen H, et al. In vitro and in vivo activity and cross resistance profiles of novel ruthenium(II) organometallic arene complexes in human ovarian cancer. Br J Cancer 2002;86(10):1652-7]. [(eta6-C6H5C6H5)Ru(en)Cl]+ (as a PF6 salt, where en=ethylenediamine (RM175)) has been evaluated in a 13-cell line panel. Particular sensitivity (approximately 10-fold lower than mean IC50) was noted in breast cancer and non-small cell lung cancer cell lines. In addition, IC50 in the A549 was 2 microM and RM175 (25 mg kg-1, days 1 and 5, i.p.) caused a significant (p=0.004) growth delay in a xenograft model. HC11 [(eta6-tetrahydroanthracene)Ru(en)Cl]PF6 was more potent in the A549 cell line (IC50 0.5 microM). HC11 (25 mg kg-1, days 1, 8 and 15, i.p.) was also active in vivo. Following RM175 25 mg kg-1, days 1 and 5, and 15 mg kg-1, days 1-5, HC11 25 and 40 mg kg-1, day 1, elevated alanine transaminase levels were detected, suggesting hepatotoxicity. No changes were observed in kidney or haematological parameters. In liver sections, multi-focal hepatic necrosis was seen, becoming confluent at high doses of HC11. In vitro studies confirmed that HC11 was more toxic than RM175 to fresh human hepatocytes and equitoxic to mithramycin. Liver toxicity may be related to the arene ligand and modification may reduce the potential for hepatic toxicity, while maintaining the anti-tumour activity seen.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Compostos Organometálicos/farmacologia , Compostos de Rutênio/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Alanina Transaminase/sangue , Animais , Antineoplásicos/química , Antineoplásicos/toxicidade , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Injeções Intraperitoneais , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/ultraestrutura , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Camundongos Nus , Compostos Organometálicos/química , Compostos Organometálicos/toxicidade , Compostos de Rutênio/química , Compostos de Rutênio/toxicidade , Redução de Peso/efeitos dos fármacosRESUMO
The overall aim of this study is to establish relationships between the histology of biological tissues and their mechanical properties, especially their dynamic modulus. The emphasis is on the physical scale of the probe used in relation to the size of the histological features in the material of interest. The selection of a model system (connective tissue) is described along with a corresponding gelatin-based system in which the make-up of the material can be "engineered" reproducibly. Next three experimental rigs are described with regard to their suitability for making measurements at a variety of scales; the micro-scale, the meso-scale and the macro-scale. Finally, some preliminary measurements on the micro-scale rig are presented and preliminary conclusions drawn on the methodology.
Assuntos
Tecido Conjuntivo/fisiologia , Gelatina/análise , Engenharia Tecidual , Fenômenos Biomecânicos , Força Compressiva , Simulação por Computador , Tecido Conjuntivo/química , Elasticidade , Humanos , Modelos Biológicos , Estimulação Física , Projetos Piloto , Reprodutibilidade dos Testes , Projetos de Pesquisa , Estresse Mecânico , ViscosidadeRESUMO
Bronchoalveolar lavage fluid was collected postmortem from the lungs of 113 sheep, and total and differential cell counts were analysed in relation to the presence of gross and microscopic lung pathology. The diffuse lung diseases, maedi and adenomatosis, were both characterised by an increase in overall cellularity and by increases in the percentages of lymphocytes and neutrophils, respectively. Focal parasitic lung disease was characterised by an increase in the percentage of eosinophils and mast cells. Consolidated lung lesions were characterised by a slight increase in cellularity but no change in the differential cell profile. In regions of parasitised and consolidated lungs without lesions the differential cell profile was consistent with focal lung pathology, although the slight increase in cellularity observed in the consolidated regions was not observed in the regions without lesions. A decision tree was developed to facilitate the interpretation and indicate the likely predictive capacity of the differential cytology of the fluid.
Assuntos
Líquido da Lavagem Broncoalveolar/citologia , Pneumopatias/veterinária , Pulmão/patologia , Doenças dos Ovinos/diagnóstico , Animais , Contagem de Células/veterinária , Eosinófilos , Feminino , Pulmão/citologia , Pulmão/imunologia , Pneumopatias/diagnóstico , Pneumopatias/imunologia , Pneumopatias/patologia , Contagem de Linfócitos/veterinária , Macrófagos , Masculino , Mastócitos , Neutrófilos , Ovinos , Doenças dos Ovinos/imunologia , Doenças dos Ovinos/patologiaRESUMO
Posterior reversible encephalopathy syndrome (PRES) may cause irreversible brain damage. The diagnosis is confirmed by magnetic resonance imaging (MRI), where vasogenic edema may be seen especially in the posterior parts of the brain. MR spectroscopy (MRS) may be included to help predict the outcome by measuring selected metabolites for instance lactate. Usually lactate is immeasurable in brain tissue, but elevates in cases of hypoxia, and it has been associated with poor outcome. We report a case of a patient with eclampsia and PRES, who had elevated lactate initially, but complete remission clinically and on MRI.