RESUMO
PURPOSE: To compare three different radiotherapy devices able to perform pulmonary stereotactic radiotherapy: CyberKnife® (CK), Helical Tomotherapy® (HT), and volumetric modulated arc therapy (VMAT). This study aims to define the patients' outcome in terms of SBRT efficacy and toxicities depending of the device choice. MATERIALS AND METHODS: We retrospectively analyzed the clinical, radiological, and dosimetric data of patients treated with lung SBRT between 2016 and 2020 at Lausanne University Hospital, using the Chi2 test for proportions, the t-test for means comparisons, the Kaplan-Meier method for survival, and the Log-rank test and Cox-regression for intergroups comparisons. RESULTS: We identified 111 patients treated by either CK (59.9%), VMAT (38.0%), or HT (2.1%). Compared to other techniques, CK treated comparable gross tumor volume (GTV; 2.1 vs. 1.4cm3, P=0.84) with smaller planning treatment volume (PTV; 12.3 vs. 21.9cm3, P=0.013) and lower V5 (13.5 vs. 19.9cm3, P=0.002). Local control rates at 2years were not different whatever the irradiation device, respectively of 96.2% (range, 90.8-100) and 98.1% (range, 94.4-100), P=0.68. Toxicity incidence significantly increased with V5 value>17.2% (56.0 vs. 77.4%, P=0.021). CONCLUSION: Compared to other SBRT techniques, CK treatments permitted to treat comparable GTV with reduced PTV and V5. Toxicity incidence was less frequent when reducing the V5. CK is particularly attractive in case of multiple courses of lung SBRT or lung reirradiation.
Assuntos
Neoplasias Pulmonares , Radiocirurgia , Radioterapia de Intensidade Modulada , Humanos , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Estudos Retrospectivos , Neoplasias Pulmonares/patologia , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Dosagem Radioterapêutica , PulmãoRESUMO
Thyrotropin releasing hormone (TRH) stimulation testing is often used to support a diagnosis of pituitary pars intermedia dysfunction (PPID) in horses although it is unclear whether or not repeat TRH stimulation testing post-treatment is a valid means of assessing response to medical therapy. Laboratory submissions from 64 suspected equine PPID cases were examined including the initial pre-treatment TRH stimulation test and a follow up test within 100 days of starting medical therapy with pergolide. In a subset of cases, further follow-up tests were examined beyond 100 days of starting treatment. Results from tests conducted between 1 July and 30 November were excluded. Significant improvements were seen in both the baseline and TRH-stimulated adrenocorticotrophic hormone (ACTH) concentrations within 100 days with no further improvements seen in the subset of cases examined thereafter. Although 88% (n = 56/64) of all cases showed a decreased response to TRH post-treatment, only 24% (n = 9/38) of horses with positive pre-treatment TRH stimulation tests normalised following treatment, with a further 34% (n = 13/38) improving into an equivocal test outcome category. Most commonly (42%; n = 16/38), horses with positive pre-treatment TRH stimulation tests remained positive following treatment, although 75% (n = 12/16) of these showed a numerically lower post-treatment response to TRH. These results will help inform practitioners of expected changes in TRH stimulation test results when assessing response of horses with PPID to medical therapy with pergolide.
Assuntos
Doenças dos Cavalos , Doenças da Hipófise , Hormônio Adrenocorticotrópico/farmacologia , Animais , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/tratamento farmacológico , Cavalos , Pergolida/farmacologia , Pergolida/uso terapêutico , Doenças da Hipófise/diagnóstico , Doenças da Hipófise/tratamento farmacológico , Doenças da Hipófise/veterinária , Hormônio Liberador de Tireotropina/farmacologia , Hormônio Liberador de Tireotropina/uso terapêuticoRESUMO
Spinal metastasis are a daily challenge in clinical practice. Stereotactic body radiotherapy (SBRT) allows delivery of definitive treatment with excellent long-term control rates. Its implementation needs dedicated devices and day-to-day image-guided radiotherapy (IGRT). The XSight™ spine tracking system, integrates with the CyberKnife® (Accuray™), provides a fiducial-free tracking system for spinal SBRT. We report a rare case of tracking failure during treatment due to the occurrence of a vertebral compression fracture (VCF).
Assuntos
Fraturas por Compressão/diagnóstico por imagem , Radiocirurgia/instrumentação , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/secundário , Idoso , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Fracionamento da Dose de Radiação , Evolução Fatal , Fraturas por Compressão/complicações , Fraturas por Compressão/cirurgia , Humanos , Cifoplastia , Neoplasias Pulmonares/patologia , Masculino , Cervicalgia/etiologia , Radiocirurgia/métodos , Radioterapia Guiada por Imagem/instrumentação , Medula Espinal/efeitos da radiação , Fraturas da Coluna Vertebral , Neoplasias da Coluna Vertebral/diagnóstico por imagemRESUMO
BACKGROUND: Heart surgery with cardio-pulmonary bypass (CPB) is associated with lung ischemia leading to injury and inflammation. It has been suggested this is a result of the lungs being kept deflated throughout the duration of CPB. Low frequency ventilation (LFV) during CPB has been proposed to reduce lung dysfunction. METHODS: We used a semi-biased multi-omic approach to analyse lung biopsies taken before and after CPB from 37 patients undergoing coronary artery bypass surgery randomised to both lungs left collapsed or using LFV for the duration of CPB. We also examined inflammatory and oxidative stress markers from blood samples from the same patients. RESULTS: 30 genes were induced when the lungs were left collapsed and 80 by LFV. Post-surgery 26 genes were significantly higher in the LFV vs. lungs left collapsed, including genes associated with inflammation (e.g. IL6 and IL8) and hypoxia/ischemia (e.g. HIF1A, IER3 and FOS). Relatively few changes in protein levels were detected, perhaps reflecting the early time point or the importance of post-translational modifications. However, pathway analysis of proteomic data indicated that LFV was associated with increased "cellular component morphogenesis" and a decrease in "blood circulation". Lipidomic analysis did not identify any lipids significantly altered by either intervention. DISCUSSION: Taken together these data indicate the keeping both lungs collapsed during CPB significantly induces lung damage, oxidative stress and inflammation. LFV during CPB increases these deleterious effects, potentially through prolonged surgery time, further decreasing blood flow to the lungs and enhancing hypoxia/ischemia.
Assuntos
Ponte Cardiopulmonar , Proteômica , Ponte Cardiopulmonar/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Humanos , Pulmão/cirurgia , RespiraçãoAssuntos
Doenças do Sistema Endócrino/veterinária , Doenças dos Cavalos/fisiopatologia , Animais , Doenças do Sistema Endócrino/diagnóstico , Doenças do Sistema Endócrino/fisiopatologia , Doenças dos Cavalos/diagnóstico , Cavalos , Ilhotas Pancreáticas/fisiopatologia , Síndrome Metabólica/fisiopatologia , Síndrome Metabólica/veterinária , Doenças da Hipófise/fisiopatologia , Doenças da Hipófise/veterinária , Adeno-Hipófise Parte Intermédia/fisiopatologiaRESUMO
Both COPD and lung cancer are major worldwide health concerns owing to cigarette smoking, and represent a huge, worldwide, preventable disease burden. Whilst the majority of smokers will not develop either COPD or lung cancer, they are closely related diseases, occurring as co-morbidities at a higher rate than if they were independently triggered by smoking. Lung cancer and COPD may be different aspects of the same disease, with the same underlying predispositions, whether this is an underlying genetic predisposition, telomere shortening, mitochondrial dysfunction or premature aging. In the majority of smokers, the burden of smoking may be dealt with by the body's defense mechanisms: anti-oxidants such as superoxide dismutases, anti-proteases and DNA repair mechanisms. However, in the case of both diseases these fail, leading to cancer if mutations occur or COPD if damage to the cell and proteins becomes too great. Alternatively COPD could be a driving factor in lung cancer, by increasing oxidative stress and the resulting DNA damage, chronic exposure to pro-inflammatory cytokines, repression of the DNA repair mechanisms and increased cellular proliferation. Understanding the mechanisms that drive these processes in primary cells from patients with these diseases along with better disease models is essential for the development of new treatments.
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Neoplasias Pulmonares/genética , Doença Pulmonar Obstrutiva Crônica/genética , Fumar/genética , Animais , Dano ao DNA/genética , Humanos , Estresse Oxidativo/genéticaRESUMO
BACKGROUND: Extraparenchymal spinal cord hematoma has been described in veterinary medicine in association with neoplasia, intervertebral disk disease, and snake envenomation. There are rare reports of spontaneous extraparenchymal spinal cord hematoma formation with no known cause in human medicine. Multiple cases of spontaneous extraparenchymal spinal cord hematoma have not been described previously in veterinary medicine. OBJECTIVES: To describe the signalment, clinical findings, magnetic resonance imaging (MRI) features, and surgical outcomes in histopathologically confirmed extraparenchymal spinal cord hematomas in dogs with no identified underlying etiology. ANIMALS: Six dogs had MRI of the spinal cord, decompressive spinal surgery, and histopathologic confirmation of extraparenchymal spinal cord hematoma not associated with an underlying cause. METHODS: Multi-institutional retrospective study. RESULTS: Six patients had spontaneous extraparenchymal spinal cord hematoma formation. MRI showed normal signal within the spinal cord parenchyma in all patients. All hematomas had T2-weighted hyperintensity and the majority (5/6) had no contrast enhancement. All dogs underwent surgical decompression and most patients (5/6) returned to normal or near normal neurologic function postoperatively. Follow-up of the patients (ranging between 921 and 1,446 days) showed no progression of neurologic clinical signs or any conditions associated with increased bleeding tendency. CONCLUSIONS AND CLINICAL IMPORTANCE: Before surgery and histopathology confirming extraparenchymal hematoma, the primary differential in most cases was neoplasia, based on the MRI findings. This retrospective study reminds clinicians of the importance of the combination of advanced imaging combined with histopathologic diagnosis. The prognosis for spontaneous spinal cord extraparenchymal hematoma with surgical decompression appears to be favorable in most cases.
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Doenças do Cão/patologia , Hematoma/veterinária , Imageamento por Ressonância Magnética , Traumatismos da Medula Espinal/veterinária , Animais , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/cirurgia , Cães , Feminino , Hematoma/diagnóstico por imagem , Hematoma/patologia , Hematoma/cirurgia , Masculino , Radiografia , Estudos Retrospectivos , Traumatismos da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/cirurgiaRESUMO
BACKGROUND: Paired measurement of ACTH concentration may be more reliable than a single measurement. HYPOTHESIS/OBJECTIVES: To determine whether the mean of 2 measurements of ACTH concentration is more reliable in assessing pituitary pars intermedia dysfunction (PPID) than a single measurement. ANIMALS: Paired ACTH measurements were performed on (1) 148 occasions from 124 horses being investigated for PPID, (2) 90 occasions from 76 horses with PPID that were receiving treatment with pergolide, and (3) 63 occasions from 50 horses in which there was no clinical suspicion of PPID. Histologic examination of the pars intermedia was performed in 67 of the untreated horses. METHODS: Outcome of testing using single and the mean of paired samples was compared directly and both methods were compared against histology, which was considered the gold standard. RESULTS: Paired ACTH measurement altered binary classification as healthy or diseased in 6 of 211 cases, all off which had equivocal initial ACTH concentrations between 20 and 39 pg/mL. Using histology as the gold standard, optimal sensitivity and specificity for diagnosing PPID were 69.4 and 80.9%, respectively, for a single measurement and 72.2 and 76.2%, respectively, for paired measurements. The area under the receiver operating characteristic curve was 0.72 and 0.73 for single and paired measurements compared with histopathologic diagnosis, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Paired measurement of ACTH concentration offers no advantage over a single measurement.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Doenças dos Cavalos/diagnóstico , Doenças da Hipófise/veterinária , Adeno-Hipófise Parte Intermédia/patologia , Animais , Agonistas de Dopamina/uso terapêutico , Feminino , Doenças dos Cavalos/sangue , Doenças dos Cavalos/tratamento farmacológico , Cavalos , Masculino , Pergolida/uso terapêutico , Doenças da Hipófise/sangue , Doenças da Hipófise/diagnóstico , Doenças da Hipófise/tratamento farmacológicoRESUMO
BACKGROUND: Clinical standards of reporting microwave ablation outcomes have not been defined with regard to ablation success, 90-day morbidity, local recurrence after ablation, and nonablation hepatic recurrence. We propose recommendations for microwave ablation reporting and quality standards. METHODS: Literature review of clinical studies focusing on microwave ablation of primary and metastatic hepatic tumors was reported. RESULTS: Ablation success remains the highest quality reporting standard with variations in nomenclature, but with a universal agreement of complete destruction of the target lesion within 1 month after initial microwave ablation. Local recurrence after ablation remains highly variable, with reports as low as 2.2% to as high as 22%; standards lack a common, clearly defined distance from the initial target ablated lesion and the requirement that the target lesion be defined as an ablation success before it can be called a recurrence. Nonablation hepatic recurrence, nonhepatic recurrence, and 90-day morbidity and mortality remain limited in the current literature. CONCLUSIONS: Standardization of hepatic microwave ablation reporting standards are proposed. Current reporting standards in microwave ablation of hepatic malignancies are suboptimal and lack standardization for comparison across institutions.
Assuntos
Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Micro-Ondas/uso terapêutico , Avaliação de Resultados em Cuidados de Saúde/normas , Carcinoma Hepatocelular/mortalidade , Ablação por Cateter , Humanos , Neoplasias Hepáticas/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: Lipogranulomatous lymphangitis is inflammation of the intestinal lymphatic vessels and surrounding tissues caused by chronic leakage of lipid-laden chyle. Grossly, lipogranulomas are typically disseminated small masses on the serosa and surrounding lymphatic vessels and consist of epithelioid macrophages, multinucleated giant cells, and cholesterol. Lipogranulomatous lymphangitis is occasionally seen in patients with lymphangiectasia and protein-losing enteropathy (PLE). OBJECTIVES: To characterize the historical features, clinical signs, treatment, histopathology, and outcome of dogs with focal lipogranulomatous lymphangitis. ANIMALS: Six dogs with ultrasonographic evidence of focal, regional small intestinal masses, often with involvement of the adjacent mesentery, and a diagnosis of focal lipogranulomatous lymphangitis based on histopathology of biopsied masses. RESULTS: The median age of dogs was 6.9 years (range 3-10 years). All dogs had total protein, globulin, and albumin concentrations within the reference range at initial presentation and had intestinal masses identified on abdominal ultrasound examination. Histopathologic evaluation of lesions identified severe mural and mesenteric lipogranulomatous lymphangitis. Lymphangiectasia was noted in 5 cases and only in sections within the mass-like lesion; tissue without lipogranulomas had minimal lymphangiectasia, suggesting a localized phenomenon. Postoperative outcomes ranged from remission of clinical signs with no subsequent treatment for 10-12 months in 2 dogs, postoperative management with medical and nutritional management in 3 dogs, and no outcome for 1 case. CONCLUSIONS AND CLINICAL IMPORTANCE: This case series describes a unique mass-like manifestation of intestinal lipogranulomatous lymphangitis and should be considered as a possible differential diagnosis in dogs with an intestinal mass.
Assuntos
Doenças do Cão/patologia , Granuloma/veterinária , Linfangite/veterinária , Enteropatias Perdedoras de Proteínas/veterinária , Animais , Biópsia/veterinária , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/cirurgia , Cães , Feminino , Granuloma/diagnóstico por imagem , Granuloma/patologia , Granuloma/cirurgia , Histocitoquímica/veterinária , Linfangite/diagnóstico por imagem , Linfangite/patologia , Linfangite/cirurgia , Masculino , Enteropatias Perdedoras de Proteínas/diagnóstico por imagem , Enteropatias Perdedoras de Proteínas/patologia , Enteropatias Perdedoras de Proteínas/cirurgia , UltrassonografiaRESUMO
The development of malignant neoplasia following solid organ transplantation and immunosuppression is well recognized in man. Post-transplantation malignant tumours include non-melanoma skin cancers, non-Hodgkin's lymphoma and Kaposi's sarcoma and many of these cancers have a known or suspected viral cause. A similar increased incidence of cancer is seen in cats that have received a renal transplant and lymphoma is the predominant neoplasm in this population. This study examines a population of cats that received renal transplants at the University of Pennsylvania School of Veterinary Medicine and subsequently developed neoplasia. From 1998 to 2010, 111 cats were transplanted and 25 cats developed cancer (22.5%). Fourteen of the 25 cats were diagnosed with lymphoma (56%), making it the most common tumour in this patient population. The median interval between transplantation and diagnosis of lymphoma was 617 days and the median survival time (MST) following the diagnosis of lymphoma was 2 days. Tissues from seven of these cats were available for histopathological review as either samples collected at necropsy examination (n = 5) or biopsy submissions (n = 2). Five of these cats had multiorgan involvement with sites including the liver, spleen, peripheral and mesenteric lymph nodes, small intestine, urinary bladder, heart, mesenteric fat and body wall. Four of the cats with multiorgan disease had involvement of the renal allograft two of which also had lymphoma of the native kidney. All lymphomas were classified as mid to high grade, diffuse large B-cell lymphoma, which is also the most common lymphoma subtype in human cases of post-transplantation lymphoproliferative disorders.
Assuntos
Doenças do Gato/patologia , Transplante de Rim/efeitos adversos , Rim/patologia , Linfoma/veterinária , Animais , Doenças do Gato/etiologia , Gatos , Feminino , Linfoma/etiologia , Linfoma/patologia , MasculinoRESUMO
Utilizing a clinically relevant haploidentical (HI) murine transplant model, lethally irradiated B6D2F1 (H2K(b/d)) mice were transplanted with T cell-depleted (TCD) BM from B6CBAF1 (H2K(b/k)) mice. We found that administration of IL-15 significantly increases the numbers of CD8+ T and natural killer (NK) cells in spleen and BM after transplantion without GVHD. Graft-versus-tumor (GVT) potency of the graft was evaluated upon tumor challenge using P815 tumor cells (H2(d)). IL-15 administration without T-cell infusion did not result in any survival improvement. However, IL-15 in combination with very low-dose T-cell infusion (1 × 10(4)) significantly increased GVT activity and improved survival in recipients of HI hematopoietic SCT (HSCT). This effect was observed when IL-15 was given at a later time point, rather than immediately following transplantation. IL-15 administration also specifically increased slow-proliferative CD8+ T-cell proliferation and IFN-γ secretion in CD8+ T cells in recipients of CFSE (carboxyfluorescein succinimidyl ester)-labeled HI T-cell infusion, whereas there was no effect on CD4+ T-cell proliferation, suggesting the critical effect of IL-15 on CD8+ T-cell homeostasis in HI host. We conclude that IL-15 can be used for enhancing antileukemia effect of HI-HSCT, which requires presence of donor-derived T cells.
Assuntos
Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Interleucina-15/administração & dosagem , Interleucina-15/imunologia , Condicionamento Pré-Transplante/métodos , Animais , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Feminino , Efeito Enxerto vs Leucemia/efeitos dos fármacos , Efeito Enxerto vs Leucemia/imunologia , Humanos , Imunoterapia Adotiva , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Ativação Linfocitária/efeitos dos fármacos , Mastocitoma/imunologia , Mastocitoma/cirurgia , Mastocitoma/terapia , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Transplante HomólogoRESUMO
Lymphoma is the most common malignant neoplasm in the horse. Single case reports and small retrospective studies of equine lymphomas are reported infrequently in the literature. A wide range of clinical presentations, tumor subtypes, and outcomes have been described, and the diversity of the results demonstrates the need to better define lymphomas in horses. As part of an initiative of the Veterinary Cooperative Oncology Group, 203 cases of equine lymphoma have been gathered from 8 institutions. Hematoxylin and eosin slides from each case were reviewed and 187 cases were immunophenotyped and categorized according to the World Health Organization classification system. Data regarding signalment, clinical presentation, and tumor topography were also examined. Ages ranged from 2 months to 31 years (mean, 10.7 years). Twenty-four breeds were represented; Quarterhorses were the most common breed (n = 55), followed by Thoroughbreds (n = 33) and Standardbreds (n = 30). Lymphomas were categorized into 13 anatomic sites. Multicentric lymphomas were common (n = 83), as were skin (n = 38) and gastrointestinal tract (n = 24). A total of 14 lymphoma subtypes were identified. T-cell-rich large B-cell lymphomas were the most common subtype, diagnosed in 87 horses. Peripheral T-cell lymphomas (n = 45) and diffuse large B-cell lymphomas (n = 26) were also frequently diagnosed.
Assuntos
Doenças dos Cavalos/classificação , Linfoma/veterinária , Animais , Feminino , Doenças dos Cavalos/patologia , Cavalos , Imunofenotipagem/veterinária , Linfoma/classificação , Linfoma/patologia , Masculino , Mitose , Estudos Retrospectivos , Pele/patologia , Organização Mundial da SaúdeRESUMO
Indolent lymphoma comprises up to 29% of all canine lymphoma; however, limited information exists regarding the subtypes and biological behaviour. This retrospective study describes the clinical characteristics, histopathological and immunohistochemical features, treatment, outcome and prognostic factors for 75 dogs with indolent lymphoma. WHO histopathological classification and immunohistochemistry (IHC) for CD79a, CD3, Ki67 and P-glycoprotein (P-gp) was performed. The most common histopathological subtype was T-zone, 61.7%, (MST 33.5 months), followed by marginal zone, 25%, (MST 21.2 months), P = 0.542. The addition of IHC to preliminary histopathological classification resulted in a revised diagnosis in 20.4% of cases. The use of systemic treatment did not influence survival, P = 0.065. Dogs treated with chlorambucil and prednisone did not reach a MST, compared with a MST of 21.6 months with CHOP-based chemotherapy, P = 0.057. The overall MST of 4.4 years confirms that this is indeed an indolent disease. However, the effect of systemic treatment must be determined through prospective trials.
Assuntos
Doenças do Cão/patologia , Imuno-Histoquímica/veterinária , Linfoma/veterinária , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais , Complexo CD3/genética , Complexo CD3/metabolismo , Antígenos CD79/genética , Antígenos CD79/metabolismo , Estudos de Coortes , Cães , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Linfoma/tratamento farmacológico , Linfoma/patologia , Masculino , Estudos Retrospectivos , Análise de SobrevidaRESUMO
REASONS FOR PERFORMING STUDY: Pituitary pars intermedia dysfunction (PPID) is a common endocrinopathy, frequently diagnosed via plasma adrenocorticotropic hormone (ACTH) concentrations. Seasonal variation in plasma ACTH concentrations has been described in normal horses prompting caution in diagnosing PPID at certain times of the year. The aims of this study were to determine appropriate reference intervals for equine plasma ACTH throughout the year; and to examine the circannual variation of plasma ACTH concentrations in PPID cases. HYPOTHESIS: Plasma ACTH can be used as a test for PPID throughout the year with the use of appropriate reference intervals. METHODS: Data for reference interval calculations were obtained from samples collected from inpatients of Liphook Equine Hospital (non-PPID group, n=156). Data from PPID cases (n=941) were obtained from samples submitted to the Liphook Equine Hospital Laboratory from horses with a clinical suspicion of PPID found to have plasma ACTH concentrations greater than our upper reference interval for that time of year. RESULTS: Upper limits for reference interval of plasma ACTH were 29 pg/ml between November and July and 47 pg/ml between August and October. Circannual variation in plasma ACTH occurred in both non-PPID and PPID horses with the highest ACTH concentrations found between August and October in both groups (P<0.0001). The greatest difference between the 2 populations also occurred between August and October. CONCLUSIONS: Plasma ACTH can be used for the diagnosis and monitoring of PPID throughout the year with the use of appropriate reference intervals. These findings demonstrate an increase in pituitary gland secretory activity during the late summer and autumn in both normal and PPID cases.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Doenças dos Cavalos/sangue , Doenças da Hipófise/veterinária , Adeno-Hipófise Parte Intermédia/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Animais , Feminino , Cavalos , Masculino , Doenças da Hipófise/sangue , Doenças da Hipófise/metabolismo , Estações do Ano , Fatores de TempoRESUMO
The disproportionate cost of treating asthmatic patients who do not respond to conventional anti-inflammatory therapies makes delineation of the mechanism for glucocorticoid resistance an important field of asthma research. Unbiased cluster analysis indicates that asthma is a syndrome with a number of distinct phenotypes and 5-10% of asthmatics fall into this category of relative glucocorticoid insensitivity. This sub-population is itself divided into smaller subsets which have different underlying mechanisms for this relative glucocorticoid resistance ranging from an inherited genetic basis to specific kinase signalling pathways triggered by exposure to environmental stressors such as cigarette smoking or infection. Whilst the underlying mechanisms are becoming better understood there remains a lack of effective novel therapies. However it is clear that relative glucocorticoid insensitive patients who are smokers should be encouraged to quit, thereby reducing their oxidant load. Novel treatments will consist of either developing new anti-inflammatory treatments targeting pathways aberrantly activated in these patients or of suppressing signalling pathways that attenuate glucocorticoid receptor function and thereby restoring glucocorticoid sensitivity. It will be important to uncover non-invasive biomarkers for aberrant pathway activation and for discerning which components of glucocorticoid receptor activation are abnormal if future treatments are to be tailored to address these specific issues. Conventional combination therapies will continue to be used in the near future but additional add-on treatments using drugs directed against aberrantly expressed inflammatory pathways or mediators along with an inhaled glucocorticoid are likely to prove the most effective new therapies in the future.
Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Índice de Gravidade de Doença , Esteroides/uso terapêutico , Animais , Antiasmáticos/farmacologia , Asma/imunologia , Resistência a Medicamentos/efeitos dos fármacos , Resistência a Medicamentos/imunologia , Previsões , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Receptores de Glucocorticoides/imunologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Esteroides/farmacologiaRESUMO
A study was carried out to test the accuracy and consistency of veterinary pathologists, not specialists in hematopathology, in applying the World Health Organization (WHO) system of classification of canine lymphomas. This study represents an initiative of the ACVP Oncology Committee, and the classification has been endorsed by the World Small Animal Veterinary Association (WASVA). Tissue biopsies from cases of canine lymphoma were received from veterinary oncologists, and a study by pathologists given only signalment was carried out on 300 cases. Twenty pathologists reviewed these 300 cases with each required to choose a diagnosis from a list of 43 B and T cell lymphomas. Three of the 20 were hematopathologists who determined the consensus diagnosis for each case. The 17 who formed the test group were experienced but not specialists in hematopathology, and most were diplomates of the American or European Colleges of Veterinary Pathology. The overall accuracy of the 17 pathologists on the 300 cases was 83%. When the analysis was limited to the 6 most common diagnoses, containing 80% of all cases, accuracy rose to 87%. In a test of reproducibility enabled by reintroducing 5% of cases entered under a different identity, the overall agreement between the first and second diagnosis ranged from 40 to 87%. The statistical review included 43,000 data points for each of the 20 pathologists.
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Doenças do Cão/classificação , Linfoma/veterinária , Animais , Cães , Linfonodos/patologia , Linfoma/classificação , Variações Dependentes do Observador , Patologia Veterinária/normas , Médicos Veterinários/normas , Organização Mundial da SaúdeRESUMO
BACKGROUND: About 5-10% of patients with asthma suffer from poorly-controlled disease despite corticosteroid (CS) therapy. OBJECTIVE: We determined whether there were any differences in inflammatory biomarkers between severe and non-severe asthma patients. METHODS: Nineteen severe and 20 non-severe asthma patients were recruited and underwent collection of induced sputum, bronchoalveolar lavage (BAL) fluid and bronchial biopsies. RESULTS: Biopsy results showed no differences in eosinophils (major basic protein positive), neutrophils, macrophages, T cells and mast cells in the bronchial submucosa. However, subbasement membrane (SBM) thickness and smooth muscle area were increased in the biopsies. No significant differences were observed in the induced sputum inflammatory cells. In BAL fluid, there was a significant increase in neutrophils but a significant decrease in macrophages. Eosinophil counts were non-significantly increased threefold in both sputum and BAL in severe asthma. Levels of IL-8 and IL-13 in sputum supernatants were similar in both groups of asthma patients. There was a significant inverse correlation between post-bronchodilator forced expiratory volume in 1 s and provocative concentration of methacholine causing a 20% fall in FEV(1) with SBM thickness. CONCLUSION: Differences in inflammatory cells were observed mainly in terms of increased neutrophils and reduction in macrophage numbers in BAL fluid with a trend towards increased eosinophils in severe asthma compared with non-severe asthma. However, the most notable features are the increase in features of airway wall remodelling of SBM thickness and smooth muscle area.
Assuntos
Asma/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-13/metabolismo , Interleucina-8/metabolismo , Leucócitos/metabolismo , Mucosa Respiratória/metabolismo , Adulto , Asma/patologia , Asma/fisiopatologia , Biomarcadores/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/fisiopatologia , Leucócitos/patologia , Masculino , Mucosa Respiratória/patologia , Mucosa Respiratória/fisiopatologia , Índice de Gravidade de Doença , Escarro/metabolismoRESUMO
BACKGROUND: Feline mammary carcinomas (FMC) are locally invasive and highly metastatic tumors. Because of the high metastatic potential, patients often are treated with adjuvant doxorubicin-based chemotherapy, but little data exist to evaluate the effect of this strategy. HYPOTHESIS: Adjuvant doxorubicin-based chemotherapy improves outcome for FMC compared with surgery alone. ANIMALS: Cats with naturally occurring, biopsy-confirmed FMC treated with either surgery alone (Sx) or with surgery plus adjuvant doxorubicin-based chemotherapy (Sx + Chemo). METHODS: Retrospective cohort study. Clinical data were collected and compared to identify differences between groups. Outcome results were determined and compared. Prognostic factors for disease-free survival (DFS) and overall survival were evaluated. RESULTS: Seventy-three cats were evaluated, of which 37 were in the Sx group and 36 in the Sx + Chemo group. No differences in clinical data were found between Sx and Sx + Chemo groups. Median DFS times for the Sx and Sx + Chemo groups were 372 and 676 days, respectively (P= .15) and median survival times (ST) were 1,406 and 848 days, respectively (P= .78). For cats that underwent a unilateral radical mastectomy, ST was significantly longer for the Sx + Chemo compared with the Sx group (1,998 versus 414 days, respectively; P= .03). CONCLUSIONS AND CLINICAL IMPORTANCE: This study did not find a benefit to adjuvant doxorubicin-based chemotherapy in cats with FMC. Additional studies are required to determine whether patient subgroups with negative prognostic factors may benefit from adjuvant chemotherapy.
Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Doenças do Gato/tratamento farmacológico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Neoplasias Mamárias Animais/tratamento farmacológico , Animais , Doenças do Gato/cirurgia , Gatos , Quimioterapia Adjuvante , Estudos de Coortes , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Feminino , Masculino , Neoplasias Mamárias Animais/cirurgia , Estudos RetrospectivosRESUMO
Five horses with sabulous cystitis were managed for up to three years. They were treated by emptying the bladder through a urinary catheter and saline lavage with cytoscopic guidance to remove residual sabulous material. The cystitis was treated with antimicrobial and anti-inflammatory medications, and bethanechol chloride was also administered. Frequent catheterisation and emptying of the bladder was an alternative to regular cystoscopic examination with saline lavage but it resulted in the development of a urethral stricture in one case. Four of the horses returned to work and one was retired owing to persistent incontinence.