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1.
Clin Radiol ; 78(12): e1057-e1064, 2023 12.
Article En | MEDLINE | ID: mdl-37833143

AIM: To investigate the hypothesis that lung cancer screening allows for earlier identification of ascending thoracic aortic aneurysms (aTAAs) and that growth rates for aTAAs are greatest at larger sizes. MATERIALS AND METHODS: This single referral centre retrospective study manually gathered computed tomography (CT) data from 732 patients presenting from July 2002 to August 2022. Five hundred and seventeen patients with aTAA >39 mm were identified to compare presenting diameter by year of presentation. Four hundred and thirty-two patients had CT examinations >3 months apart, allowing for growth analysis. Patients were separated by initial examination date (before or after 12/31/2013) for presenting size comparison. Patients were then divided into five groups based on aTAA diameter for growth rate analysis. RESULTS: At identification, patients had a median aTAA diameter of 44 mm (IQR 41-47 mm). Patients with aTAAs identified prior to December 2013 (n=129) had an average aTAA diameter 1.7 mm larger than those identified later (n=388; p=0.003). The growth analysis showed an average growth rate of 0.1 mm/year (p<0.001) across the entire cohort. Patients with an aTAA diameter of ≥55 mm (n=12) grew the fastest at 1.9 mm/year (p<0.001). In the <40 mm group (n=43), the aTAAs expanded at 0.2 mm/year, faster than the 0.1 mm/year of the slowest expanding 45-49 mm group (n=130; p=0.04). CONCLUSION: aTAA size at discovery was larger before lung cancer screening guidelines took effect in December 2013. The largest aTAAs expanded fastest, but growth rates were slowest in the medium-sized 45-49 mm diameter group.


Aortic Aneurysm, Thoracic , Lung Neoplasms , Humans , Retrospective Studies , Early Detection of Cancer , Lung Neoplasms/diagnostic imaging , Aortic Aneurysm, Thoracic/diagnostic imaging , Tomography, X-Ray Computed
2.
Community Dent Health ; 39(4): 260-266, 2022 Nov 30.
Article En | MEDLINE | ID: mdl-36264006

OBJECTIVES: To determine the effectiveness of training the early year's workforce on their knowledge, skills and/or behaviours in delivering oral health advice. METHODS: Four databases: PubMed, Web of Science, Embase and Scopus were searched to evaluate the effectiveness of oral health training on knowledge, skills and behaviour of the early year's workforce with a minimum of one-month follow-up. Randomised or quasi-randomised trials and before and after studies were included. RESULTS: All six included studies showed improved knowledge and one of the five studies showed significant changes in behaviours of participants post oral health training. None of the included studies addressed changes in skills as an outcome. CONCLUSION: This systematic review found evidence that oral health training of the early year's workforce is effective in improving their knowledge but not necessarily their behaviours delivering oral health advice. Although training of the wider workforce on oral health is recommended, high quality research is required with longitudinal follow-up to assess changes in behaviours and ultimately impacts on oral health.


Oral Health , Humans , Oral Health/education , Workforce , Health Knowledge, Attitudes, Practice , Clinical Competence
4.
J Intern Med ; 286(4): 438-448, 2019 10.
Article En | MEDLINE | ID: mdl-30861229

BACKGROUND: Patients with postural tachycardia syndrome (POTS) experience chronic symptoms of orthostatic intolerance. There are minimal data detailing the demographics, clinical features and clinical course of this condition. This online, community-based survey highlights patients' experience with POTS. It consists of the largest sample of POTS patients reported to date. OBJECTIVES: To describe the demographics, past medical history, medications, treatments and diagnostic journey for patients living with POTS. METHODS: Postural tachycardia syndrome patients completed an online, community-based, cross-sectional survey. Participants were excluded if they had not received a diagnosis of POTS from a physician. The questions focused on the patient experience and journey, rather than physiological responses. RESULTS: The final analysis included 4835 participants. POTS predominantly affects white (93%) females (94%) of childbearing age, with approximately half developing symptoms in adolescence (mode 14 years). POTS is a chronic multisystem disorder involving a broad array of symptoms, with many patients diagnosed with comorbidities in addition to POTS. POTS patients often experience lengthy delays [median (interquartile range) 24 (6-72) months] and misdiagnosis, but the diagnostic delay is improving. POTS patients can present with a myriad of symptoms most commonly including lightheadedness (99%), tachycardia (97%), presyncope (94%), headache (94%) and difficulty concentrating (94%). CONCLUSIONS: These data provide important insights into the background, clinical features and diagnostic journey of patients suffering from POTS. These data should serve as an essential step for moving forward with future studies aimed at early and accurate diagnoses of these patients leading to appropriate treatments for their symptoms.


Postural Orthostatic Tachycardia Syndrome/psychology , Postural Orthostatic Tachycardia Syndrome/therapy , Adult , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Postural Orthostatic Tachycardia Syndrome/diagnosis , Postural Orthostatic Tachycardia Syndrome/physiopathology , Surveys and Questionnaires
5.
Eur J Prosthodont Restor Dent ; 26(4): 203-211, 2018 Nov 29.
Article En | MEDLINE | ID: mdl-30398816

OBJECTIVE: To evaluate the clinical longevity of 58 adhesively bonded single unit yttria-stabilized tetragonal zirconia polycrystalline (Y-TZP) ceramic Resin Bonded Bridges (RBB). MATERIALS AND METHODS: Twenty six consecutive patients with at least one congenitally missing tooth in the maxilla or mandible were provided with 58 single unit Y-TZP RBBs. The cantilever RBBs were designed and milled using a CAD-CAM system to produce frameworks which were veneered using a glass-ceramic material and cemented with a self-etching dual-cure resin cement. RESULTS: Following a mean follow up period of 36.2 months (maximum 62.3 months, minimum 25.4 months), 48 restorations remain in service with a survival rate of 82.7%. One anterior retainer fracture was encountered and no fractures of the posterior framework or ceramic were noted within the time frame reported. CONCLUSIONS: All ceramic Y-TZP RBBs replacing maxillary and mandibular teeth in the anterior and posterior areas demonstrated an 82.7% Kaplan Meier survival rate over 3 years, which was comparable to previously published survival rates for the non-perforated metal framework RBBs. CLINICAL IMPLICATIONS: Replacement of anterior or posterior teeth using single unit cantilevered RBBs using Y-TZP ceramics should be considered a viable restorative option with a high survival rate.


Ceramics , Denture, Partial, Fixed, Resin-Bonded , Zirconium , Computer-Aided Design , Humans , Resin Cements
6.
Osteoporos Int ; 29(10): 2309-2314, 2018 Oct.
Article En | MEDLINE | ID: mdl-30076454

A poorer functional status at the time of fracture is a predictor of non-adherence to oral bisphosphonates initiated after a hip fracture, and suggests further opportunities for optimization of secondary fracture prevention in this high-risk population. INTRODUCTION: Low adherence to treatment is a problem in post-fracture secondary prevention. We aimed to analyze the prognostic factors (related and predictive) associated with non-adherence to oral bisphosphonate prescription for hip fracture due to bone fragility (HFBF) 12 months after discharge from an acute geriatric unit. METHODS: Prospective study of bivariate data analyzing related and multivariate factors predicting non-adherence of oral bisphosphonates at 12 months after treatment for HFBF. The statistical study was performed with SPSS 19.0.0. RESULTS: We attended 368 patients with HFBF. At discharge, oral bisphosphonates were prescribed to 226 (61.42%) patients. At 12 months, we followed up 160 (70.7%) patients, 104 (65%) of whom had non-adherence to oral bisphosphonates. Bivariate analysis (adherent vs. non-adherent): age (83.79 ± 5.82 vs. 85.78 ± 5.80, p = .029); Lawton and Brody Index (4.29 ± 3.40 vs. 2.67 ± 3.31, p = .004); baseline Barthel Index (BI) (85.89 ± 21.99 vs. 74.18 ± 26.70) (p = .004); BI at admission (18.84 ± 10.00 vs. 14.47 ± 11.71, p = .004); BI at discharge (34.20 ± 15.40 vs. 27.45 ± 16.71, p = .011); baseline Functional Ambulation Classification (5.66 ± 0.98 vs. 5.43 ± 0.99, p = .025). Multivariate analysis: BI 0.980 (0.965-0.995, p = .007). Discriminatory capacity of the AUC model (± 95% CI): 0.634 (0.545-0.722). CONCLUSIONS: At 12 months, there was low adherence to treatment with oral bisphosphonates in our model. A lower BI prior to treatment is a predictive factor for non-adherence treatment with oral bisphosphonate.


Bone Density Conservation Agents/administration & dosage , Diphosphonates/administration & dosage , Hip Fractures/prevention & control , Medication Adherence/statistics & numerical data , Osteoporotic Fractures/prevention & control , Administration, Oral , Aged , Aged, 80 and over , Bone Density Conservation Agents/therapeutic use , Diphosphonates/therapeutic use , Drug Prescriptions , Female , Follow-Up Studies , Health Services for the Aged , Hip Fractures/etiology , Humans , Male , Osteoporosis/complications , Osteoporosis/drug therapy , Prospective Studies , Secondary Prevention/methods
7.
BMC Public Health ; 18(1): 125, 2018 01 11.
Article En | MEDLINE | ID: mdl-29325516

BACKGROUND: Brucellosis is an endemic zoonotic disease in most of the developing world that causes devastating losses to the livestock industry and small-scale livestock holders. Infected animals exhibit clinical signs that are of economic significance to stakeholders and include reduced fertility, abortion, poor weight gain, lost draught power, and a substantial decline in milk production. In humans, brucellosis typically manifests as a variety of non-specific clinical signs. Chronicity and recurring febrile conditions, as well as devastating complications in pregnant women are common sequelae. DISCUSSION: In regions where the disease is endemic, brucellosis has far-reaching and deleterious effects on humans and animals alike. Deeply entrenched social misconceptions and fear of government intervention contribute to this disease continuing to smolder unchecked in most of the developing world, thereby limiting economic growth and inhibiting access to international markets. The losses in livestock productivity compromise food security and lead to shifts in the cognitive competency of the working generation, influence the propagation of gender inequality, and cause profound emotional suffering in farmers whose herds are affected. The acute and chronic symptoms of the disease in humans can result in a significant loss of workdays and a decline in the socioeconomic status of infected persons and their families from the associated loss of income. The burden of the disease to society includes significant human healthcare costs for diagnosis and treatment, and non-healthcare costs such as public education efforts to reduce disease transmission. CONCLUSION: Brucellosis places significant burdens on the human healthcare system and limits the economic growth of individuals, communities, and nations where such development is especially important to diminish the prevalence of poverty. The implementation of public policy focused on mitigating the socioeconomic effects of brucellosis in human and animal populations is desperately needed. When developing a plan to mitigate the associated consequences, it is vital to consider both the abstract and quantifiable effects. This requires an interdisciplinary and collaborative, or One Health, approach that consists of public education, the development of an infrastructure for disease surveillance and reporting in both veterinary and medical fields, and campaigns for control in livestock and wildlife species.


Brucellosis/prevention & control , Developing Countries , Endemic Diseases/prevention & control , Neglected Diseases/prevention & control , One Health , Zoonoses/prevention & control , Animals , Brucellosis/epidemiology , Female , Humans , Livestock , Male , Neglected Diseases/epidemiology , Poverty , Pregnancy , Public Policy , Zoonoses/epidemiology
8.
Zoonoses Public Health ; 64(8): 647-654, 2017 12.
Article En | MEDLINE | ID: mdl-28391650

Various tissues, nasal swabs, urine and blood samples were collected from 376 feral swine at two federally inspected abattoirs in Texas during six separate sampling periods in 2015. Samples were tested for Brucella spp. by culture and serology. Brucella spp. were cultured from 13.0% of feral swine, and antibodies were detected in 9.8%. Only 32.7% of culture-positive feral swine were also antibody positive, and 43.2% of antibody-positive feral swine were culture positive. Approximately, the same number of males (14.0%) and females (12.1%) were culture positive, and slightly more males (10.5%) than females (8.7%) were antibody positive. Our results indicate that serology likely underestimates the prevalence of feral swine infected, and that those who come in contact with feral swine should be aware of the symptoms of infection with Brucella spp. to ensure prompt treatment.


Abattoirs , Brucellosis/veterinary , Swine Diseases/microbiology , Animals , Antibodies, Bacterial/isolation & purification , Bacteriological Techniques , Brucellosis/epidemiology , Brucellosis/pathology , Female , Male , Serologic Tests , Swine , Swine Diseases/epidemiology , Texas/epidemiology
9.
J Chem Phys ; 146(11): 114102, 2017 Mar 21.
Article En | MEDLINE | ID: mdl-28330360

The non-exponential room temperature luminescence decay of colloidal quantum dots is often well described by a stretched exponential function. However, the physical meaning of the parameters of the function is not clear in the majority of cases reported in the literature. In this work, the room temperature stretched exponential luminescence decay of colloidal quantum dots is investigated theoretically in an attempt to identify the underlying physical mechanisms associated with the parameters of the function. Three classes of non-radiative transition processes between the excited and ground states of colloidal quantum dots are discussed: long-range resonance energy transfer, multiphonon relaxation, and contact quenching without diffusion. It is shown that multiphonon relaxation cannot explain a stretched exponential functional form of the luminescence decay while such dynamics of relaxation can be understood in terms of long-range resonance energy transfer to acceptors (molecules, quantum dots, or anharmonic molecular vibrations) in the environment of the quantum dots acting as energy-donors or by contact quenching by acceptors (surface traps or molecules) distributed statistically on the surface of the quantum dots. These non-radiative transition processes are assigned to different ranges of the stretching parameter ß.

10.
New Microbes New Infect ; 16: 1-2, 2017 Mar.
Article En | MEDLINE | ID: mdl-28116103

We report a case of Nocardia amamiensis pulmonary infection in a 43-year-old immunocompromised woman. The patient was treated with imipenem/cilastatin and trimethoprim/sulfamethoxazole and had a favourable outcome. It is important that laboratories perform species identification to understand the epidemiology and susceptibility patterns of the different Nocardia spp.

11.
Rev. Soc. Esp. Dolor ; 23(6): 287-291, nov.-dic. 2016. tab, ilus, graf
Article Es | IBECS | ID: ibc-158423

Introducción: La neuroestimulación de las raíces sacras bajo técnica retrógrada (NERSR) es eficaz para el tratamiento del dolor perineal crónico (DPC) refractario a tratamiento farmacológico. Este reporte busca demostrar la utilidad de la NERSR para el control del dolor y su impacto en la calidad de vida del paciente. Material y métodos: Se presentan tres casos con DPC por coxigodinia (caso 1 y 2) y neuralgia del nervio pudendo (caso 3) sin respuesta a tratamientos convencionales e intervencionistas, previamente seleccionados en el Servicio de Clínica del Dolor, Centro Médico Nacional '20 de Noviembre'- Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE), México D.F., desde junio 2006 a septiembre 2014. La neuroestimulación sacra se realizó en dos etapas: primero con la colocación de un electrodo de neuroestimulación de prueba positiva (CENPP) y posteriormente implantación del NERSR. Se evaluó al paciente a la primera y segunda semana, después una vez al mes durante seis meses y, posteriormente, cada cuatro meses hasta el momento actual. Resultados: Se exponen tres casos clínicos, con edad promedio de 55,6 años, dos de sexo femenino y uno de sexo masculino con DPC. Caso 1 y 2 con diagnóstico de coxigodinia y caso 3 con neuralgia del nervio pudendo. Previo a la implantación presentaban dolor severo (valorada con la Escala Verbal Análoga del dolor (EVA 8-10/10), un Oswestry con limitación funcional discapacitante (32 puntos equivalente a un 64 % de discapacidad) y una entrevista psicológica con presencia de depresión moderada y ansiedad alta en promedio (Cuestionario Depresión de Beck y Salud de Goldberg). En la actualidad presentan un dolor leve (EVA 1-3/10), un Oswestry con limitación funcional moderada (18 puntos equivalente a 35 % de discapacidad), depresión y ansiedad leve en promedio. Se reportó una complicación menor, posterior a la implantación, por fístula de líquido cefalorraquídeo (LCR). Conclusión: En esta pequeña serie de casos se demostró que una alternativa para el tratamiento del DPC es la estimulación medular. Al controlar el dolor, mejora la calidad de vida del paciente y el estado psico-emocional que presentaba previo a la implantación (AU)


Introduction: Neurostimulation of the sacral nerves by Retrograde Technique (NESRT) is effective for the treatment of drug refractory Chronic Perineal Pain (CPP). This paper seeks to understand the usefulness of NERSR for pain control and its impact on the patients’ quality of life. Materials and methods: Three cases are presented, previously selected from the Service of Pain Clinic, '20 de Noviembre' National Medical Center - Institute for Social Security and Services for State Workers (ISSSTE), Mexico D.F. from June 2006 to September 2014, with PPC: cases one and two caused by coccygodynia, and case three with pudendal nerve neuralgia, all unresponsive to conventional and interventional treatments. Sacral neuromodulation was performed in two stages: first with the placement of a Neurostimulation Positive Test Electrode (NPTP) and then by implementing NESRT. The patient was evaluated during the first and second week, then once a month for six months and finally every four months up to current time. Results: Three clinical cases with DPC, mean age 55.6 years, two female and one male, are exposed. Case one and two diagnosed with coccydynia and Case three with neuralgia of the pudendal nerve. Prior to implantation they showed severe pain (assessed with the Pain Verbal Analogue Scale (VAS 8-10 / 10), an Oswestry with disabling functional limitations (32 points equivalent to a 64 % disability) and a psychological interview with presence of average moderate depression and high anxiety (Beck Depression Questionnaire and Goldberg Health). Currently, they show mild pain (VAS 1-3/10), an Oswestry with moderate functional limitation (18 points equivalent to 35 % of disability) and average mild depression and anxiety. There was only one mild complication after implantation, due to fistula of cerebrospinal fluid (CSF). Conclusion: Spinal cord stimulation has proven to be and effective alternative treatment in dealing with DPC. By controlling pain, it improves the patients’ quality of life and the psycho- emotional state shown prior to implantation (AU)


Humans , Male , Female , Middle Aged , Aged , Electric Stimulation/methods , Perineum/injuries , Perineum/pathology , Pain Management/methods , Chronic Pain/therapy , Chronic Pain , Quality of Life , Pudendal Nerve , Electrodes , Electrodes, Implanted , Sacrum , Sacrum
12.
Phys Chem Chem Phys ; 16(40): 22062-72, 2014 Oct 28.
Article En | MEDLINE | ID: mdl-25208925

Gas phase absorption far-infrared (FIR) spectra of six flexible hydrocarbon molecules containing two phenyl groups -biphenyl, diphenylmethane, bibenzyl and 2-, 3-, 4-phenyltoluene- are reported for the first time, allowing an accurate determination of most of their active low-frequency vibrational modes. DFT calculations have been carried out at the harmonic and perturbative anharmonic levels to predict the vibrational spectra of these molecules and unambiguously assign observed vibrational modes.

13.
J Comp Pathol ; 150(4): 361-5, 2014 May.
Article En | MEDLINE | ID: mdl-24456749

The peripheral neuroblastic tumours (PNTs) include neuroblastoma, ganglioneuroblastoma and ganglioneuromas. These subtypes reflect a spectrum of differentiation of progenitor cells of the sympathetic nervous system from tumours with predominant undifferentiated neuroblasts to those consisting of neuronal cell bodies that are well differentiated. Peripheral neuroblastoma is a tumour composed of neuroblastic cells with no or limited neuronal differentiation. In dogs, peripheral neuroblastoma is rare. The present report documents nine cases of canine peripheral neuroblastoma, the majority occurring as large masses in the craniodorsal abdominal cavity of young dogs (mean age of 3 years at diagnosis). Microscopically, all of the masses consisted of round to oval cells with a scant cytoplasm and hyperchromatic nuclei. Homer-Wright rosettes and pseudorosettes were evident in three of the nine cases. Neoplastic cells were immunoreactive in varying degrees to S100, neuron-specific enolase, synaptophysin, chromogranin A, tyrosine hydroxylase (one case) and were negative for vimentin, cytokeratin, CD3 and CD79a, indicating a neurogenic nature. Four of the nine cases occurred in Labrador retrievers (44%) and two (22%) in boxers, suggesting a possible breed predisposition.


Dog Diseases/pathology , Neuroblastoma/veterinary , Peripheral Nervous System Neoplasms/veterinary , Animals , Dogs , Neuroblastoma/pathology , Peripheral Nervous System Neoplasms/pathology
14.
Int J Dent Hyg ; 11(4): 280-6, 2013 Nov.
Article En | MEDLINE | ID: mdl-23802751

UNLABELLED: To describe the perceptions of senior dental officers (SDOs) on the roles of dental therapists (DTs) and their education needs in Malaysia. METHODS: A cross-sectional survey was conducted using a self-administered postal questionnaire targeting all 112 SDOs in the Malaysian Ministry of Health. The SDOs were asked about their perceptions of DT's roles in relation to clinical tasks, oral health promotion, administration and the dental team and their perceptions of DT's future education needs. Data were analysed using spss software, version 17 (SPSS Inc., Chicago, IL, USA). RESULTS: The response rate was 60%. A majority of SDOs were women (68%) with a mean age of 44.9 (SD: 8.04). Generally, the majority of SDOs perceived the current roles of DT in non-complex clinical tasks such as examination and diagnosis, preventive treatment, extraction of deciduous teeth and oral health promotion as very important. Fewer than half of SDOs perceived DT's role in the extraction of permanent teeth as important. Most SDOs perceived the need to train DT in 'scaling and polishing for adults' (80.5%), 'delivering inferior alveolar nerve block' (57.3%) and 'pulp therapy' (59.2%). They also had positive perceptions of providing education for DT up to degree level (70.8%). CONCLUSION: This study suggests that Malaysian SDOs have positive perceptions of the current roles of DT and of the expansion of some of their clinical tasks to include broader client groups through further training and education. These findings indicate a need to revise the current curriculum and legislation pertaining to DT's education and scope of practice in Malaysia.


Attitude of Health Personnel , Dental Auxiliaries/education , Dentists/psychology , Health Services Needs and Demand , Adult , Child , Child, Preschool , Clinical Competence , Cross-Sectional Studies , Delegation, Professional , Dental Auxiliaries/organization & administration , Dental Care/organization & administration , Dental Prophylaxis , Dental Restoration, Permanent , Dental Scaling , Female , Health Promotion , Humans , Malaysia , Male , Mandibular Nerve , Nerve Block , Oral Health , Patient Care Team/organization & administration , Physical Examination , Preventive Dentistry , Root Canal Therapy , Tooth Extraction
15.
Br Dent J ; 213(9): E16, 2012 Nov.
Article En | MEDLINE | ID: mdl-23138831

OBJECTIVES: To describe the prevalence of oral diseases and their impact on oral-health-related quality of life in people with severe mental illness undertaking community-based psychiatric care. METHODS: A survey was conducted at eight outpatient psychiatric care clinics in Tower Hamlets, London, UK. One hundred and twelve consecutive patients with mental illness were invited to participate in this study. They were clinically examined and asked to complete the oral health impact profile (OHIP) questionnaire. RESULTS: The response rate was 79% (n = 89); 57 (64%) males and 58 persons over 45 years of age (65%) participated in this survey. Overall OHIP score was 25.4 (95% CI 23.3, 27.4), 70 (78%) were smokers and 45 (51%) had been to the dentist in the last two years. Forty-seven (53%) respondents had caries in at least one tooth, 60 (67%) had 21 teeth and more, and 14 (16%) used dentures. Advanced periodontal treatment was indicated in 42 (55%) of patients and 52.8% (n = 47) patients reported current pain. CONCLUSION: Overall, this survey found that oral health has a great impact on patients with severe mental illness being treated in the community setting and their oral health is poorer than the national adult general population. Future research should consider the causes that relate to the poorer oral health in this population and potential health promotion mechanisms in this population to encourage an upstream approach to health.


Mental Disorders/complications , Mouth Diseases/epidemiology , Oral Health/statistics & numerical data , Quality of Life , Adult , Community Mental Health Services , Female , Health Services Needs and Demand , Humans , London/epidemiology , Male , Mental Disorders/therapy , Middle Aged , Mouth Diseases/complications , Prevalence , Surveys and Questionnaires
16.
Vet Pathol ; 49(3): 524-7, 2012 May.
Article En | MEDLINE | ID: mdl-21934101

Primary sclerosing cholangitis is a chronic and progressive cholestatic liver disease that has been extensively documented in the human literature. Although it shares many features in common with chronic lymphocytic cholangitis in cats, primary sclerosing cholangitis has never been reported in a nonhuman primate. Primary sclerosing cholangitis is characterized by the presence of intrahepatic and/or extrahepatic inflammation and concentric fibrosis of bile ducts, eventually leading to cirrhosis and hepatic failure. The pathogenesis and cause remain unknown, but the disease likely involves a multifactorial mechanism with genetic- and immune-mediated components. The authors report 2 cases that histologically resemble the condition in humans; they consist of 2 adult male baboons with a clinical history of chronic elevated liver enzymes. In both cases, the liver was histologically characterized by thick bands of fibrosis and mild lymphoplasmacytic periportal cholangiohepatitis with concentric periductal fibrosis, resulting in atrophy and loss of bile ducts. Immunohistochemical analysis revealed positivity of hepatocytes to cytokeratin 7. Masson stain demonstrated marked biliary fibrosis. This is the first report that resembles sclerosing cholangitis in a nonhuman primate, and it suggests that the baboon may provide a useful animal model for this condition in humans.


Cholangitis, Sclerosing/veterinary , Liver/pathology , Papio , Primate Diseases/pathology , Animals , Cholangitis, Sclerosing/pathology , Humans , Immunohistochemistry/veterinary , Keratin-7/metabolism , Male , Species Specificity
17.
Clin Vaccine Immunol ; 19(2): 249-60, 2012 Feb.
Article En | MEDLINE | ID: mdl-22169089

The global distribution of brucellosis and high incidence in certain areas of the world warrant the development of a safer and efficacious vaccine. For the past 10 years, we have focused our attention on the development of a safer, but still highly protective, live attenuated vaccine for human and animal use. We have demonstrated the safety and protective efficacy of the vaccine candidates 16 MΔvjbR and S19ΔvjbR against homologous and heterologous challenge in multiple immunocompetent animal models, including mice and deer. In the present study, we conducted a series of experiments to determine the safety of the vaccine candidates in interferon regulatory factor-1-knockout (IRF-1(-/-)) mice. IRF-1(-/-) mice infected with either wild-type Brucella melitensis 16 M or the vaccine strain Brucella abortus S19 succumb to the disease within the first 3 weeks of infection, which is characterized by a marked granulomatous and neutrophilic inflammatory response that principally targets the spleen and liver. In contrast, IRF-1(-/-) mice inoculated with either the 16 MΔvjbR or S19ΔvjbR vaccine do not show any clinical or major pathological changes associated with vaccination. Additionally, when 16 MΔvjbR- or S19ΔvjbR-vaccinated mice are challenged with wild-type Brucella melitensis 16M, the degree of colonization in multiple organs, along with associated pathological changes, is significantly reduced. These findings not only demonstrate the safety and protective efficacy of the vjbR mutant in an immunocompromised mouse model but also suggest the participation of lesser-known mechanisms in protective immunity against brucellosis.


Brucella Vaccine/adverse effects , Brucella Vaccine/immunology , Brucella/immunology , Brucellosis/prevention & control , Animals , Brucellosis/immunology , Disease Models, Animal , Female , Interferon Regulatory Factor-1/genetics , Mice , Mice, Knockout , Vaccination , Vaccines, Attenuated/genetics , Vaccines, Attenuated/immunology
18.
Infect Immun ; 79(9): 3653-8, 2011 Sep.
Article En | MEDLINE | ID: mdl-21708998

Brucellosis is a zoonosis of nearly worldwide distribution. Vaccination against this pathogen is an important control strategy to prevent the disease. Currently licensed vaccine strains used in animals are unacceptable for human use due to undesirable side effects and modest protection. Substantial progress has been made during the past 10 years toward the development of improved vaccines for brucellosis. In part, this has been achieved by the identification and characterization of live attenuated mutants that are safer in the host but still can stimulate an adequate immune response. In the present study, the identification and characterization of the mucR mutant (BMEI 1364) as a vaccine candidate for brucellosis was conducted. BALB/c mice were vaccinated intraperitoneally at a dose of 10(5) CFU with the mutant to evaluate safety and protective efficacy against intraperitoneal and aerosol challenge. All animals vaccinated with the vaccine candidate demonstrated a statistically significant degree of protection against both intraperitoneal and aerosol challenge. Safety was revealed by the absence of Brucella associated pathological changes, including splenomegaly, hepatomegaly, or granulomatous disease. These results suggest that the 16MΔmucR vaccine is safe, elicits a strong protective immunity, and should be considered as a promising vaccine candidate for human use.


Bacterial Proteins/immunology , Brucella Vaccine/immunology , Brucella melitensis/immunology , Brucellosis/prevention & control , Aerosols , Animals , Bacterial Proteins/genetics , Brucella Vaccine/administration & dosage , Brucella melitensis/genetics , Brucellosis/immunology , Female , Mice , Mice, Inbred BALB C , Mutation , Sequence Deletion , Vaccination , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/immunology
19.
J Comp Pathol ; 144(4): 328-33, 2011 May.
Article En | MEDLINE | ID: mdl-21251669

Haemangiosarcomas (HSAs) are malignant tumours of endothelial cell origin. Epithelioid HSA is a variant of the histologically conventional HSA that has little or no morphological evidence of a vascular origin and has been reported rarely in domestic animals. The following report documents six cases of equine epithelioid HSA occurring in the ocular tissues of horses with a mean age of 19.8 years at the time of diagnosis. Microscopically, all of the lesions consisted of solid sheets or cords of epithelioid cells with rare narrow clefts or small spaces containing erythrocytes that were often the only feature indicating a vascular origin. On immunohistochemistry, the neoplastic cells expressed vimentin, CD31 and factor VIII-related antigen, but not cytokeratin, indicating an endothelial nature.


Epithelioid Cells/pathology , Eye Neoplasms/veterinary , Hemangiosarcoma/veterinary , Horse Diseases/pathology , Animals , Biomarkers, Tumor/metabolism , Epithelioid Cells/metabolism , Eye Neoplasms/metabolism , Eye Neoplasms/pathology , Hemangiosarcoma/metabolism , Hemangiosarcoma/pathology , Horse Diseases/metabolism , Horses , Male , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Vimentin/metabolism , von Willebrand Factor/metabolism
20.
Int J Clin Pharmacol Ther ; 48(5): 342-8, 2010 May.
Article En | MEDLINE | ID: mdl-20420791

Changes in bioavailability of anticonvulsant drugs such as topiramate may cause loss of or worsened seizure control. Thus, the purpose of this study was to evaluate, in a double-blind crossover design, the bioavailability between two oral formulations of topiramate in healthy volunteers after a single dose. The protocol, approved by the Institutional Committee of Ethics, consisted of administration of 1 tablet of 100 mg of topiramate of each formulation (Toprel and Topamax), to 20 healthy volunteers after a 12 h overnight fast, using an open, two-period, randomized, crossover and double-blind design. Thus, the plasma concentrations (Cp) of topiramate were measured at predetermined intervals of time, from 0 to 24 h, using a validated UPLC-MS/MS method. Based on plasma concentration-time profiles we obtained the following pharmacokinetic parameters: AUC(0-inf) 63,418.31 +/- 22,141.69 and 67,094.70 +/- 22,487.2 ngh/ml; AUC0-24: 30,421.02 +/- 9,964.0 and 30,489.35 +/- 9,407.17, ng x h/ml; tmax: 2.77 +/- 1.76 and 1.95 +/- 1.89 h; C(max): 2,143.33 +/- 724.26 and 2,262.51 +/- 751.12 ng/ml, for A (Toprel) and B (Topamax), respectively. All these differences were not statically significant with 90% confidence interval. The test of bioequivalence showed that Cmax, AUC(0-24) and AUC(0-inf) parameters are found within the range of 0.8 - 1.25 recommended by the FDA with a probability of bioequivalence of 100%. In accordance with these results, we can conclude that Toprel 100 mg, A (Test), is a bioequivalent generic and interchangeable with Topamax 100 mg, B (Reference).


Anticonvulsants/pharmacokinetics , Chromatography, Liquid/methods , Fructose/analogs & derivatives , Tandem Mass Spectrometry/methods , Adult , Anticonvulsants/administration & dosage , Area Under Curve , Biological Availability , Cross-Over Studies , Double-Blind Method , Drugs, Generic/administration & dosage , Drugs, Generic/pharmacokinetics , Female , Fructose/administration & dosage , Fructose/pharmacokinetics , Humans , Male , Tablets , Therapeutic Equivalency , Topiramate , Young Adult
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