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1.
BJOG ; 124(5): 796-803, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27307397

RESUMO

OBJECTIVE: To assess adverse event (AE) resolution, delivery mode and neonatal outcomes after misoprostol or dinoprostone vaginal insert (MVI or DVI) retrieval due to AE during induction of labour (IOL). DESIGN: Randomised, double-blind trial, EXPEDITE. SETTING: Thirty five obstetric departments, USA. POPULATION: Consisted of 1358 pregnant women with modified Bishop score ≤4 eligible for pharmacological IOL. METHODS: Post hoc analysis. MAIN OUTCOME MEASURES: AEs prompting insert retrieval, times to AE resolution, delivery, delivery mode and neonatal intensive care unit (NICU) admissions. RESULTS: 77/678 (11.4%) and 27/680 (4.0%) women had MVI and DVI retrieved due to AE, respectively (P < 0.001). The most common AEs prompting retrieval were uterine tachysystole with fetal heart rate (FHR) involvement and category II/III FHR pattern. Time to AE resolution varied for both treatments depending on the type of AE. For uterine tachysystole with FHR involvement, median resolution times were 1 hour 34.5 minutes (n = 36) and 8.5 minutes (n = 8) for MVI and DVI, respectively. Caesarean delivery occurred in a high proportion of women with insert retrieved due to AE (MVI: 44/77 (57.1%); DVI: 19/27 (70.4%)); the majority of caesareans were performed at least several hours after insert retrieval. Median times from retrieval to any delivery were not increased for women with insert retrieved due to AE. NICU admissions were 8/77 (10.4%) and 1/27 (3.7%) for MVI and DVI, respectively (P = 0.440). CONCLUSIONS: AEs leading to insert retrieval were primarily uterine tachysystole with FHR involvement and category II/III FHR patterns. Insert retrieval due to an AE did not prolong time to delivery for either prostaglandin insert. TWEETABLE ABSTRACT: Induction with prostaglandin vaginal inserts: outcomes following retrieval due to intrapartum adverse event.


Assuntos
Dinoprostona/efeitos adversos , Trabalho de Parto Induzido/efeitos adversos , Misoprostol/efeitos adversos , Ocitócicos/efeitos adversos , Prostaglandinas/efeitos adversos , Administração Intravaginal , Adulto , Cesárea/estatística & dados numéricos , Dinoprostona/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Misoprostol/administração & dosagem , Ocitócicos/administração & dosagem , Gravidez , Resultado da Gravidez/epidemiologia , Prostaglandinas/administração & dosagem , Estados Unidos , Suspensão de Tratamento , Adulto Jovem
2.
Vet Pathol ; 52(2): 260-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24829287

RESUMO

The prognostic significance of histologic and clinical features was evaluated in a retrospective study of 70 dogs treated with nephrectomy for renal cell carcinoma. Dogs presenting with hematuria and cachexia had significantly decreased overall and tumor-specific survival. Mitotic index (MI), nuclear size, nuclear pleomorphism, tumor differentiation, invasiveness, Fuhrman nuclear grade, and clear cell morphology were significantly associated with survival times (overall and tumor specific) in univariate analyses. A multivariate Cox proportional hazards model was constructed using stepwise selection to evaluate potential histologic predictor variables. This multivariate analysis revealed MI, defined as the number of mitotic figures in ten 400× fields, as the sole independent prognostic variable. Median survival for dogs with an MI >30 was 187 days compared with 1184 days for dogs with an MI of <10. Dogs with an intermediate MI of 10 to 30 had a median survival of 452 days. Canine renal carcinomas were categorized into the following subtypes based on histologic features and histochemical and immunohistochemical staining: (1) clear cell, (2) chromophobe, (3) papillary, and (4) multilocular cystic renal cell carcinomas. Clear cell carcinoma was diagnosed in 6 of 70 (9%) canine tumors and was associated with a significantly decreased median survival time. Papillary carcinomas were identified in 15 of 70 tumors (21%), chromophobe in 6 of 70 (9%), and the multilocular cystic variant of canine renal cell carcinoma in 3 of 70 tumors (4%). These findings facilitate uniform categorization of canine renal cell carcinoma and provide veterinary pathologists with criteria to determine prognostic information.


Assuntos
Carcinoma de Células Renais/veterinária , Doenças do Cão/diagnóstico , Neoplasias Renais/veterinária , Animais , Carcinoma de Células Renais/diagnóstico , Cães , Feminino , Neoplasias Renais/diagnóstico , Masculino , Nefrectomia/veterinária , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
3.
Vet Pathol ; 51(3): 560-2, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-23794148

RESUMO

Mast cell tumors are uncommon in horses and typically have a benign clinical course, but there are occasional reports of more aggressive behavior. The objective of this study was to review histologic features and KIT expression patterns of 72 previously diagnosed equine cutaneous mast cell tumors to determine if either is associated with clinical outcomes. Biopsy specimens were reviewed using histologic criteria derived from grading schemes, and KIT antibody expression patterns used in canine tumors and surveys were sent to referring veterinarians for follow-up clinical data. Arabians were overrepresented relative to the reference population. Most tumors were well differentiated with low mitotic rates (96%), and aberrant KIT staining patterns, as described in dogs, were uncommonly identified (12%). Associated clinical disease was uncommon and no tumors exhibited malignant behavior. Overall, KIT staining pattern and histologic features were not associated with poor clinical outcome or abnormal tumor behavior.


Assuntos
Doenças dos Cavalos/metabolismo , Doenças dos Cavalos/patologia , Mastocitose Cutânea/veterinária , Animais , Cavalos , Masculino , Mastocitose Cutânea/metabolismo , Mastocitose Cutânea/patologia , Gradação de Tumores/veterinária , Proteínas Proto-Oncogênicas c-kit/metabolismo , Fatores Sexuais
4.
Vet Pathol ; 48(1): 73-84, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21139143

RESUMO

Soft tissue sarcomas (STSs) develop from mesenchymal cells of soft tissues, and they commonly occur in the skin and subcutis of the dog. Although phenotypically diverse with frequently controversial histogenesis, STSs are considered as a group because they have similar features microscopically and clinically. Following resection, local recurrence rates are low in general but vary according to histologic grade and completeness of surgical margins. Complete margins predict nonrecurrence. Even most grade I STSs with "close" margins will not recur, but propensity for recurrence increases with grade. The frequency of metastasis has not been accurately estimated, but it is believed to be rare for grade I STSs and most likely to occur with grade III STSs. However, metastasis does not necessarily equate with poor survival. High mitotic index is prognostic for reduced survival time. Further research is needed to determine more precise estimates for recurrence rates and survival as related to completeness of surgical margins and to delineate potential differences in metastatic rate and median survival time between grades. Other potential indicators of prognosis that presently require further investigation include histologic type, tumor dimension, location, invasiveness, stage, markers of cellular proliferation, and cytogenetic profiles. Common issues limiting prognostic factor evaluation include biases from retrospective studies, small sample sizes, poor verification of metastasis, inconsistent STS classification and use of nomenclature, difficulties in differentiating STS phenotype, and diversity of the study population (stage of disease and treatment status).


Assuntos
Doenças do Cão/patologia , Sarcoma/veterinária , Neoplasias de Tecidos Moles/veterinária , Animais , Cães , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia
5.
Vet Pathol ; 48(1): 19-31, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21123864

RESUMO

Neoplastic diseases are typically diagnosed by biopsy and histopathological evaluation. The pathology report is key in determining prognosis, therapeutic decisions, and overall case management and therefore requires diagnostic accuracy, completeness, and clarity. Successful management relies on collaboration between clinical veterinarians, oncologists, and pathologists. To date there has been no standardized approach or guideline for the submission, trimming, margin evaluation, or reporting of neoplastic biopsy specimens in veterinary medicine. To address this issue, a committee consisting of veterinary pathologists and oncologists was established under the auspices of the American College of Veterinary Pathologists Oncology Committee. These consensus guidelines were subsequently reviewed and endorsed by a large international group of veterinary pathologists. These recommended guidelines are not mandated but rather exist to help clinicians and veterinary pathologists optimally handle neoplastic biopsy samples. Many of these guidelines represent the collective experience of the committee members and consensus group when assessing neoplastic lesions from veterinary patients but have not met the rigors of definitive scientific study and investigation. These questions of technique, analysis, and evaluation should be put through formal scrutiny in rigorous clinical studies in the near future so that more definitive guidelines can be derived.


Assuntos
Biópsia , Neoplasias/veterinária , Patologia Cirúrgica/normas , Guias de Prática Clínica como Assunto , Manejo de Espécimes , Medicina Veterinária/normas , Animais , Biópsia/métodos , Biópsia/normas , Biópsia/veterinária , Neoplasias/diagnóstico
6.
J Gen Intern Med ; 25 Suppl 1: 68-71, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20077155

RESUMO

While many patient self-management (PSM) programs have been developed and evaluated for effectiveness, less effort has been devoted to translating and systematically delivering PSM in primary and specialty care. Therefore, the purpose of this paper is to review delivery system design considerations for implementing self-management programs in practice. As lessons are learned about implementing PSM programs in Veterans Health Administration (VHA), resource allocation by healthcare organization for formatting PSM programs, providing patient access, facilitating PSM, and incorporating support tools to foster PSM among its consumers can be refined and tailored. Redesigning the system to deliver and support PSM will be important as implementation researchers translate evidence based PSM practices into routine care and evaluate its impact on the health-related quality of life of veterans living with chronic disease.


Assuntos
Atenção à Saúde/métodos , Medicina Baseada em Evidências/métodos , Autocuidado/métodos , United States Department of Veterans Affairs , Veteranos , Atenção à Saúde/tendências , Humanos , Satisfação do Paciente , Autocuidado/tendências , Estados Unidos , United States Department of Veterans Affairs/tendências
7.
Science ; 175(4025): 1003-5, 1972 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-5061863

RESUMO

Lesions in the medial preoptic area of ovariectomized female rats reduced the quantity of estrogen needed to induce sexual receptivity in these animals. In addition, the number of days over which receptive behavior could be elicited after a single initial estrogen injection and with subsequent daily progesterone treatment was significantly increased by lesions in the medial preoptic area. These findings support the view that estrogen acts to reduce an inhibitory action that is tonically exerted by the medial preoptic area on pathways mediating estrous behavior.


Assuntos
Estradiol/farmacologia , Hipotálamo/fisiologia , Comportamento Sexual Animal/efeitos dos fármacos , Animais , Castração , Estradiol/administração & dosagem , Estro , Feminino , Gravidez , Progesterona/farmacologia , Ratos
8.
Acta Neurol Scand ; 119(3): 172-9, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18705678

RESUMO

BACKGROUND: To determine the effects of memantine on cognition in a normal population of postmenopausal women with putative risk factors for Alzheimer's disease (AD) using a built-in control for the genetic risk factor for AD (apoE-epsilon4 status). METHODS: A prospective, open-label, 6-month pilot medication trial with memantine and follow-up after discontinuance conducted at the Center for Neuroscience in Women's Health, Stanford University School of Medicine. Neuropsychological data were collected on 22 community-dwelling postmenopausal women (11 apoE-epsilon4 carriers and 11 apoE-epsilon4 non-carriers) with at least one putative risk factor for AD. RESULTS: ApoE-epsilon4 status was not a significant predictor of change in neuropsychological performance. Changes associated with memantine treatment for entire sample included significant declines in some variables associated with verbal learning and memory that improved upon medication withdrawal. A positive medication effect was noted with executive functions and possibly category fluency. Trend-level improvements were seen in motor dexterity of the non-dominant hand and maintained even after drug discontinuance. CONCLUSIONS: Treatment with memantine appeared to have differential effects on cognitive performance in a population of women with putative risk factors for AD. ApoE-epsilon4 carrier status did not account for observed changes in cognition.


Assuntos
Cognição/efeitos dos fármacos , Demência/prevenção & controle , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Memantina/uso terapêutico , Nootrópicos/uso terapêutico , Pós-Menopausa , Idoso , Doença de Alzheimer/genética , Doença de Alzheimer/prevenção & controle , Apolipoproteína E4/genética , Demência/genética , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Predisposição Genética para Doença , Humanos , Hipotireoidismo/epidemiologia , Memantina/farmacologia , Transtornos da Memória/prevenção & controle , Pessoa de Meia-Idade , Transtornos do Humor/epidemiologia , Transtornos do Humor/genética , Testes Neuropsicológicos , Nootrópicos/farmacologia , Projetos Piloto , Estudos Prospectivos , Risco , Resultado do Tratamento
9.
J Frailty Aging ; 8(4): 205-209, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31637407

RESUMO

BACKGROUND: Sedentary lifestyle leads to worse health outcomes with aging, including frailty. Older adults can benefit from regular physical activity, but exercise promotion in the clinical setting is challenging. OBJECTIVES: The objective of this clinical demonstration project was to implement a Geriatric Walking Clinic for older adults and determine whether this clinical program can lead to improvements in characteristics of frailty. DESIGN: This was a clinical demonstration project/quality improvement project. SETTING: Outpatient geriatrics clinic at the South Texas Veterans Health Care System (STVHCS). PARTICIPANTS: Older Veterans, aged ≥60 years. INTERVENTION: A 6-week structured walking program, delivered by a registered nurse and geriatrician. Patients received a pedometer and a comprehensive safety evaluation at an initial face-to-face visit. They were subsequently followed with weekly phone calls and participated in a final face-to-face follow-up visit at 6 weeks. MEASUREMENTS: Grip strength (handheld dynamometer), gait speed (10-ft walk), Timed Up and Go (TUG), and body mass index (BMI) were assessed at baseline and follow-up. Frailty status for gait speed was assessed using Fried criteria. RESULTS: One hundred eighty five patients completed the program (mean age: 68.4 ±7 years, 88% male). Improvements from baseline to follow-up were observed in average steps/day, gait speed, TUG, and BMI. Improvement in gait speed (1.13 ±0.20 vs. 1.24 ± 0.23 meter/second, p<0.0001) resulted in reduced odds of meeting frailty criteria for slow gait at follow-up compared to the baseline examination (odds ratio = 0.31, 95% confidence interval: 0.13-0.72, p = 0.01). CONCLUSIONS: Our findings demonstrate that a short duration, low-intensity walking intervention improves gait speed and TUG. This new clinical model may be useful for the promotion of physical activity, and for the prevention or amelioration of frailty characteristics in older adults.


Assuntos
Terapia por Exercício/métodos , Fragilidade/prevenção & controle , Veteranos/estatística & dados numéricos , Caminhada/fisiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Velocidade de Caminhada/fisiologia
10.
J Vet Intern Med ; 22(6): 1301-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18823406

RESUMO

BACKGROUND: Activation of the KIT receptor tyrosine kinase is associated with the development of canine mast cell tumors (MCT). HYPOTHESIS/OBJECTIVE: To evaluate the efficacy of masitinib, a potent and selective inhibitor of KIT, in the treatment of canine MCT. ANIMALS: Two hundred and two client-owned dogs with nonmetastatic recurrent or nonresectable grade II or III MCT. METHODS: Double-blind, randomized, placebo-controlled phase III clinical trial. Dogs were administered masitinib (12.5 mg/kg/d PO) or a placebo. Time-to-tumor progression (TTP), overall survival, objective response at 6 months, and toxicity were assessed. RESULTS: Masitinib increased overall TTP compared with placebo from 75 to 118 days (P = .038). This effect was more pronounced when masitinib was used as first-line therapy, with an increase in the median TTP from 75 to 253 days (P = .001) and regardless of whether the tumors expressed mutant (83 versus not reached [P = .009]) or wild-type KIT (66 versus 253 [P = .008]). Masitinib was generally well tolerated, with mild (grade I) or moderate (grade II) diarrhea or vomiting as the most common adverse events. CONCLUSIONS AND CLINICAL IMPORTANCE: Masitinib is safe and effective at delaying tumor progression in dogs presenting with recurrent or nonresectable grade II or III nonmetastatic MCT.


Assuntos
Antineoplásicos/uso terapêutico , Doenças do Cão/tratamento farmacológico , Mastocitoma/veterinária , Animais , Antineoplásicos/efeitos adversos , Benzamidas , Progressão da Doença , Cães , Método Duplo-Cego , Feminino , Masculino , Mastocitoma/tratamento farmacológico , Piperidinas , Piridinas , Tiazóis/efeitos adversos , Tiazóis/uso terapêutico
11.
Vet Comp Oncol ; 15(1): 46-54, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25643914

RESUMO

Extraskeletal osteosarcoma (EOS) is a rare, highly malignant mesenchymal neoplasm arising from viscera or soft tissues characterised by the formation of osteoid in the absence of bone involvement. Owing to the rarity of these neoplasms very little information exists on treatment outcomes. The purpose of this study was to describe the outcome following surgical treatment of non-mammary and non-thyroidal soft tissue and visceral EOS in dogs. Thirty-three dogs were identified; the most common primary tumour site was the spleen. Dogs that had wide or radical tumour excision had longer survival times compared with dogs that had only marginal tumour excision performed [median survival time of 90 days (range: 0-458 days) versus median survival time of 13 days (range: 0-20 days)]. The use of surgery should be considered in the management of dogs with non-mammary and non-thyroidal soft tissue and visceral EOS.


Assuntos
Doenças do Cão/cirurgia , Osteossarcoma/veterinária , Neoplasias de Tecidos Moles/veterinária , Animais , Colorado , Doenças do Cão/patologia , Cães , Feminino , Estimativa de Kaplan-Meier , Masculino , Metástase Neoplásica , Osteossarcoma/patologia , Osteossarcoma/cirurgia , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia , Resultado do Tratamento
12.
J Perinatol ; 37(5): 488-491, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28125096

RESUMO

OBJECTIVE: The objective of this study is to analyze the association of diabetes mellitus with progress and outcomes of prostaglandin (PG) labor induction using a retrievable vaginal insert. STUDY DESIGN: This is a secondary analysis of data collected during the Misoprostol Vaginal Insert Trial (Miso-Obs-004), a multicenter, double-blind, randomized controlled trial of women undergoing induction of labor with PGs. The duration, characteristics and outcomes of labor were compared in women with and without diabetes. Multivariable regression analysis was performed on all outcomes of interest, adjusting for differences in baseline characteristics. RESULTS: There were 122 women with diabetes within the sample of 1275 women who delivered during their first admission. The time to reach active labor was significantly prolonged among women with diabetes compared with those without (22.0±13.0 vs 18.5±11.1, P=0.008) as was the time to delivery (30.2±15.0 vs 26.0±12.6, P=0.004). Fewer women with diabetes delivered within 36 h (adjusted odds ratio: 0.41, 95% confidence interval: 0.26 to 0.66, P=0.0003) and 48 h (adjusted odds ratio: 0.36, 95% confidence interval: 0.19 to 0.71, P=0.004). These relationships were significant after a multivariate regression analysis of baseline characteristics that adjusted for age, race, parity, body mass index, baseline modified Bishop Score, gestational age at induction and treatment group allocation. CONCLUSION: After PG labor induction, women with diabetes took longer to reach active labor and to deliver. We emphasize that this result comes from a secondary analysis and needs confirmation with additional studies.


Assuntos
Trabalho de Parto Induzido/métodos , Misoprostol/administração & dosagem , Ocitócicos/administração & dosagem , Gravidez em Diabéticas , Fatores de Tempo , Administração Intravaginal , Adulto , Método Duplo-Cego , Feminino , Idade Gestacional , Humanos , Análise Multivariada , Parto Normal , Paridade , Gravidez , Análise de Regressão , Estados Unidos , Adulto Jovem
13.
Cancer Res ; 50(1): 54-7, 1990 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-2403417

RESUMO

This report describes radiation-induced osteosarcomas in two groups of dogs. One group was given radiation therapy for spontaneous tumors and the second group of normal adult beagle dogs was given experimental intraoperative radiation therapy. Secondary tumors developed between 1.7 to 5 years after irradiation. Three of 87 spontaneous tumor-bearing dogs or 3.4% of dogs treated for soft tissue sarcomas developed osteosarcoma within the field of irradiation. Twenty-two dogs or 25% of dogs treated for soft tissue sarcomas survived 20 months. This high incidence may be due to the use of fractions in excess of 3.5 Gy. These dogs received 10 fractions in 3 weeks with fractions ranging from 3.5 to 5.0 Gy. Tumor induction may be included in the late effects of irradiation which are worsened by the use of coarse fractionation. There appeared to be a dose relationship for tumors induced after single intraoperative radiation doses combined with fractionated external beam irradiation. Seven of 27 dogs given this treatment and surviving at least 4 years developed osteosarcomas in the field of irradiation. One of 26 dogs given intraoperative radiation alone developed a tumor between 4 and 5 years. The lower incidence after intraoperative radiation alone may have been due to the lower total dose. However, the sequence of a course of fractionated irradiation followed by a large single dose seemed to enhance carcinogenicity.


Assuntos
Doenças do Cão/radioterapia , Neoplasias Induzidas por Radiação/veterinária , Osteossarcoma/veterinária , Radioterapia/veterinária , Sarcoma/veterinária , Neoplasias de Tecidos Moles/veterinária , Animais , Ensaios Clínicos como Assunto , Doenças do Cão/etiologia , Doenças do Cão/cirurgia , Cães , Feminino , Masculino , Neoplasias Induzidas por Radiação/etiologia , Osteossarcoma/etiologia , Radioterapia/efeitos adversos , Radioterapia/métodos , Dosagem Radioterapêutica , Distribuição Aleatória , Sarcoma/radioterapia , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/radioterapia , Neoplasias de Tecidos Moles/cirurgia , Fatores de Tempo
14.
Cancer Res ; 50(19): 6176-8, 1990 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-2400984

RESUMO

Spontaneous canine osteosarcomas were analyzed for DNA aneuploidy and percentage of S phase cells using flow cytometry. Forty-eight dogs were studied in which both a primary tumor and subsequent metastases were available. The DNA index distributions for the primary tumors and the metastases were quite similar. However, when individual primary tumors and metastases derived from them were compared, many of the cases had different ploidy values. The tumor cells were also analyzed for percentage of S phase. The diploid metastases had less than 17% S phase cells, whereas the aneuploid metastases had up to 40% S phase cells. There was a direct correlation between the DNA index and the percentage of S phase in the metastases.


Assuntos
Aneuploidia , DNA de Neoplasias/análise , Doenças do Cão/genética , Osteossarcoma/genética , Osteossarcoma/veterinária , Animais , Ciclo Celular , Cães , Osteossarcoma/secundário
15.
Cancer Res ; 54(14): 3916-21, 1994 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-8033116

RESUMO

Intratumoral heterogeneity has been identified as a potential problem in the efficacy of predictive assays. Canine osteosarcoma is an extremely heterogeneous solid tumor that has been shown to be an excellent model for the human disease. Intratumoral heterogeneity of kinetic parameters and the effect of heterogeneity on predicting outcome of treatment (time until metastasis) were studied in dogs with naturally occurring osteosarcoma. Dogs were treated with amputation or tumor excision and limb-sparing followed by chemotherapy with cisplatin. Kinetic parameters evaluated included v, duration of DNA synthesis (Ts), and potential doubling time (Tpot), determined using in vivo labeling with bromodeoxyuridine and flow cytometry. In 30 tumors, multiple samples were obtained and evaluated. There was significantly more variation between tumors from different dogs than intratumoral variation of v, Ts, and Tpo. Variations in v, Ts, and Tpot within a tumor were associated with both sample location and tumor subpopulation. Time to metastasis was determined in 51 dogs with tumors sampled for kinetics. Multiple samples were available from 25 of these tumors. Cox proportional hazard analysis was performed using either the fastest or slowest Tpot from each sample. The fastest available Tpots were highly significant (P < 0.001) for prediction of outcome. The slowest available Tpots were also significant predictors, although the statistical strength was compromised (P = 0.024). Obtaining at least two samples in large tumors known to be heterogeneous is recommended to improve the predictive ability of Tpot. v is a more limited predictor but can useful when Tpot is not available. In canine osteosarcoma, an extremely heterogeneous tumor, kinetic parameters were shown to be predictors of outcome.


Assuntos
Doenças do Cão/patologia , Osteossarcoma/veterinária , Animais , Divisão Celular , Cães , Osteossarcoma/patologia , Osteossarcoma/secundário
16.
Genes Brain Behav ; 4(1): 51-9, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15660668

RESUMO

Perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to alter spatial learning in rats tested on a radial arm maze (RAM). TCDD is believed to exert most of its effects through binding to the aryl hydrocarbon receptor (AhR). To determine whether the AhR mediates TCDD-induced alterations in spatial learning, we tested male and female AhR-knockout (AhR-/-), heterozygous (AhR+/-) and wild-type (AhR+/+) mice on the RAM. AhR+/- male and female mice were time mated, and treated dams were dosed with 5 microg TCDD/kg body weight on day 13 of gestation. When offspring reached adulthood, male and female AhR+/+, AhR+/- and AhR-/- mice from TCDD-exposed and unexposed litters were tested on the eight-arm RAM. After testing, we examined hippocampal morphology as visualized by the Timm's silver sulfide stain. TCDD-exposed female AhR+/- mice made more errors than their respective controls on the RAM and exhibited a decrease in the size of the intra- and infrapyramidal mossy fiber (IIP-MF) field of the hippocampus. None of the other TCDD-exposed groups differed from their respective control groups with regard to maze performance or hippocampal morphology. The reduction of IIP-MF field indicates a possible morphological basis for the learning deficit that was observed in the female AhR+/- mice. It is hypothesized that the effect of TCDD exposure is AhR dependent and that TCDD may alter GABAergic activity in the hippocampus of female mice during development.


Assuntos
Hipocampo/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Dibenzodioxinas Policloradas/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Receptores de Hidrocarboneto Arílico/efeitos dos fármacos , Teratogênicos/toxicidade , Animais , Feminino , Hipocampo/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fibras Musgosas Hipocampais/efeitos dos fármacos , Fibras Musgosas Hipocampais/patologia , Gravidez , Receptores de Hidrocarboneto Arílico/deficiência , Percepção Espacial/efeitos dos fármacos
17.
Arch Intern Med ; 146(6): 1183-6, 1986 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-3521519

RESUMO

A drug rechallenge proved chlorzoxazone to be hepatotoxic in a patient who had been treated with a combination of it and acetaminophen (Parafon Forte) for several months. Failure to demonstrate a toxic response to acetaminophen coupled with a dramatic response to a single dose of chlorzoxazone implicated chlorzoxazone as the hepatotoxic agent. A review of US Food and Drug Administration records and cases reported in the medical literature disclosed 23 cases of chlorzoxazone-associated hepatotoxic reactions occurring since 1970. These cases were examined in terms of age, duration of therapy, other confounding etiologic factors, and ultimate outcome. There were two deaths involving hepatic failure. Reports of adverse reactions among six commonly used analgesic-muscle relaxants in Sweden have indicated a low, but comparatively greater, incidence of hepatotoxic reactions associated with a chlorzoxazone-containing compound.


Assuntos
Benzoxazóis/efeitos adversos , Clorzoxazona/efeitos adversos , Fígado/efeitos dos fármacos , Acetaminofen/efeitos adversos , Adulto , Idoso , Biópsia , Combinação de Medicamentos , Avaliação de Medicamentos , Feminino , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Necrose , Fatores de Tempo
18.
J Vet Diagn Invest ; 27(3): 268-77, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25862711

RESUMO

Gastrointestinal stromal tumors (GISTs) and leiomyosarcomas are histologically similar primary neoplasms commonly occurring in the gastrointestinal tract of dogs and humans. Immunohistochemical staining (IHC) is needed to differentiate between these 2 entities and positive reactivity for KIT (cluster of differentiation [CD]117) is regarded as the gold standard for diagnosis of canine GIST. Studies estimate 5-10% of human GISTs stain negative or only weakly positive for KIT and have identified DOG1 (discovered on gastrointestinal stromal tumors protein 1) as a highly sensitive and specific marker for human GISTs. The purpose of this study was to evaluate immunoreactivity of a commercially available DOG1 antibody for use in diagnosis of canine GISTs. Fifty-five primary mesenchymal gastrointestinal tumors with histologic features consistent with GIST or leiomyosarcoma were evaluated via IHC for KIT, DOG1, and desmin. A subset of tumors was additionally evaluated for reactivity for smooth muscle actin (SMA). Thirty-three tumors (60%) were diagnosed as GIST based on positive immunoreactivity for KIT or DOG1 regardless of reactivity for desmin or SMA. Most GISTs (32/33, 97.0%) had similar staining for both KIT and DOG1. DOG1 expression was identified in 2 tumors (1 study tumor and 1 additional tumor) negative for KIT and desmin that had histologic features consistent with KIT-negative, platelet-derived growth factor receptor-alpha (PDGFRA)-mutant human GISTs. Our results suggest that DOG1 has improved specificity and sensitivity to that of KIT for differentiating between canine GISTs and leiomyosarcomas. Inclusion of both DOG1 and KIT IHC in diagnostic panels will improve the accuracy of canine GIST diagnosis.


Assuntos
Doenças do Cão/diagnóstico , Neoplasias Gastrointestinais/veterinária , Tumores do Estroma Gastrointestinal/veterinária , Leiomiossarcoma/veterinária , Animais , Biomarcadores Tumorais/metabolismo , Doenças do Cão/imunologia , Cães , Feminino , Neoplasias Gastrointestinais/diagnóstico , Tumores do Estroma Gastrointestinal/diagnóstico , Imuno-Histoquímica/veterinária , Leiomiossarcoma/diagnóstico , Masculino , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Sensibilidade e Especificidade
19.
Bone ; 8(4): 231-40, 1987.
Artigo em Inglês | MEDLINE | ID: mdl-3446259

RESUMO

The pathogenesis of avian osteopetrosis caused by rapid and slow-onset isolates of myeloblastosis associated virus, MAV-2(0), was studied by inoculation of 10-day-old chick embryos with virus. Femur and calvarium were examined at 15, 17 and 19 days in ovo and 7 and 25 days after hatching by histologic and immunoperoxidase techniques. Femur and calvarium were also examined by electron microscopy at 17 and 19 days in ovo and at 7 days after hatching. Avian osteopetrotic bone lesions were characterized by exuberant periosteal proliferation; the time of onset varied with different virus isolates. In the femur virus was first associated with osteoprogenitor cells, then with osteoblasts and finally with osteocytes as the cells progressed through normal sequences of differentiation. The amount of virus produced by these cells did not correlate with onset of periosteal proliferation. Slow onset isolates provoked early virus production, but proliferative lesions did not develop until later. Conversely, the rapid onset isolate induced little early virus production, although lesions were present. Periosteal proliferation was associated with and preceded by perivascular edema and perivascular cell necrosis within the bone cortex following infection by all isolates. However, the rapid onset isolate caused more severe lesions than other isolates. These lesions included vascular thrombosis, capillary necrosis and focal bone necrosis. The relationship between early vascular lesions and late periosteal proliferation seen with the slow onset isolates is not as clear as with the rapid onset isolate. Calvarial bone, a representative flat bone, was found to have virus present, but at a level less than the femur. Vascular lesions were rarely seen in the calvarium and bone proliferation did not occur at this site.


Assuntos
Leucose Aviária/patologia , Doenças Ósseas/veterinária , Galinhas/microbiologia , Osteopetrose/veterinária , Doenças das Aves Domésticas/microbiologia , Animais , Vírus da Mieloblastose Aviária , Doenças Ósseas/microbiologia , Doenças Ósseas/patologia , Fêmur/patologia , Osteopetrose/microbiologia , Osteopetrose/patologia , Doenças das Aves Domésticas/patologia , Crânio/patologia
20.
Am J Med ; 67(4): 715-8, 1979 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-573969

RESUMO

Campylobacter fetus ss. jejuni has recently been recognized as a human enteric pathogen. Laboratory isolation has been hindered by its fastidious nature. Methods for recovery of this organism from stool culture and a specific serologic test are described. An outbreak is reported in which three members of the same family became simultaneously ill with fever, severe abdominal cramps and diarrhea. C. fetus ss. jejuni was recovered from stool specimens from all three. A fourfold increase in serum immunoglobulin G (IgG) titer to this organism was demonstrated in each patient. All three patients had been consuming unpasteurized milk from a cow whose feces were infected with C. fetus ss. jejuni.


Assuntos
Infecções por Campylobacter/etiologia , Enterite/etiologia , Leite/efeitos adversos , Adulto , Animais , Infecções por Campylobacter/epidemiologia , Campylobacter fetus , Bovinos , Colorado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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