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1.
Mar Pollut Bull ; 119(1): 102-109, 2017 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-28389076

RESUMO

The effects of oil spills on marine biological systems are of great concern, especially in regions with high biological production of harvested resources such as in the Northeastern Atlantic. The scientific studies of the impact of oil spills on fish stocks tend to ignore that spatial patterns of natural mortality may influence the magnitude of the impact over time. Here, we first illustrate how spatial variation in natural mortality may affect the population impact by considering a thought experiment. Second, we consider an empirically based example of Northeast Arctic cod to extend the concept to a realistic setting. Finally, we present a scenario-based investigation of how the degree of spatial variation in natural mortality affects the impact over a gradient of oil spill sizes. Including the effects of spatial variations in natural mortality tends to widen the impact distribution, hence increasing the probability of both high and low impact events.


Assuntos
Peixes , Poluição por Petróleo , Poluentes Químicos da Água/toxicidade , Animais , Dinâmica Populacional
2.
Ginecol. obstet. Méx ; 85(11): 719-726, mar. 2017. tab
Artigo em Espanhol | LILACS | ID: biblio-953691

RESUMO

Resumen OBJETIVO: reportar la experiencia con el balón de Bakri en el control de la hemorragia obstétrica, su relación con la cantidad y concentraciones de hemoglobina antes y después de su aplicación. MATERIALES Y MÉTODOS: estudio prospectivo y observacional efec- tuado en dos unidades hospitalarias del 1 de enero al 31 de diciembre de 2016. A todas las pacientes se les aplicó el balón de Bakri por falta de respuesta a los uterotónicos. Variables de estudio: datos clínicos, cantidad de pérdida sanguínea antes y después de la aplicación del balón, cantidad de sangrado en el posparto y transcesárea, tiempo trascurrido entre el diagnóstico y la colocación, tiempo de llenado y volumen administrado, concentraciones de hemoglobina y pruebas de coagulación al ingreso a la unidad de atención, postsangrado y posterior a la aplicación, indicación de hemocomponentes, cantidad y tiempo de permanencia del balón, éxito y complicaciones. Se realizó análisis estadístico de todas estas variables. RESULTADOS: se incluyeron 20 pacientes con hemorragia posparto y transcesárea. La cantidad de sangrado después de la aplicación, tanto en los casos de posparto como transcesárea, fue menor y se obtuvo una adecuada respuesta. El tiempo medio entre el diagnóstico de la hemorragia y la colocación del balón fue de 30 minutos, tiempo medio de llenado de 5 minutos y cantidad media de llenado de 400 mL. El tiempo medio de permanencia del balón fue de 29.5 horas. En 95% de los casos se consiguió una respuesta favorable para el control de la hemorragia, sin complicaciones. CONCLUSIONES: la aplicación del balón de Bakri resultó en una medida útil, rápida y sin complicaciones para controlar la hemorragia obstétrica.


Abstract OBJECTIVE: To present the results obtained by using the Bakri Balloon to control obstetric hemorrhage. MATERIALS AND METHOD: Prospective, observational study within two inpatient medical care units from January 1 to December 31 2016. All of them were applied the Bakri Balloon because of failure to respond to uterotonic drug therapy. The following were analized: clinical data, amount of bleeding before and after the balloon, amount of postpartum or transcesarean bleeding, time between diagnosis and insertion, insufflation time and supplied volumen, hemoglobin levels and coagulation tests results initially, post-hemorrhage and post insertion, use of and amount of haemocomponents ministered, and the balloons use time, success, and complications. RESULTS: 20 patients with postpartum and transesarean hemorrhage are included. The amount of bleeding after insertion, both in postpartum and trans cesarean was reduced and there was an adequate response in hemoglobin levels. The average time between hemorrhage diagnosis and balloon insertion was thirty minutes; average insufflation time, five minutes, and average volumen supplied 400 mL. Balloon's average use time, 29.5 hours. In 95% of the cases there was a positive response for hemorrhage control, with no complications derived from use. CONCLUSIONS: The Bakri Balloon proved to be a useful, quick and complication-free therapy for controlling obstetric hemorrhage.

3.
Ann Oncol ; 25(9): 1807-1812, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24948692

RESUMO

BACKGROUND: Forodesine is a potent inhibitor of purine nucleoside phosphorylase (PNP) that leads to intracellular accumulation of deoxyguanosine triphosphate (dGTP) in T and B cells, resulting in apoptosis. Forodesine has demonstrated impressive antitumor activity in early phase clinical trials in cutaneous T-cell lymphoma (CTCL). PATIENTS AND METHODS: In this phase II study, patients with CTCL who had already failed three or more systemic therapies were recruited. We investigated the response rate, safety and tolerability of oral forodesine treatment in subjects with cutaneous manifestations of CTCL, stages IB, IIA, IIB, III and IVA. The safety population encompassing all stages was used for analysis of accountability, demographics and safety. The efficacy population differed from the safety population by exclusion of stage IB and IIA patients. RESULTS: All 144 patients had performance status 0-2. The median duration of CTCL from diagnosis was 53 months (5-516 months). The median number of pretreatments was 4 (range: 3-15). No complete remissions were observed. In the efficacy group of patients, 11% achieved partial remission and 50% had stable disease. The median time to response was 56 days and the median duration of response was 191 days. A total of 96% of all treated patients reported one or more adverse events (AEs) and 33% reported a serious AE. The majority of AEs were classified as mild or moderate in severity. The most commonly reported AEs (>10%) were peripheral edema, fatigue, insomnia, pruritus, diarrhea, headache and nausea. Overall eight patients died during the study: five due to sepsis and infections, one due to a second malignancy (esophageal cancer), one due to disease progression and one due to liver failure. CONCLUSION: Oral forodesine at a dose of 200 mg daily is feasible and shows partial efficacy in this highly selected CTCL population and some durable responses.


Assuntos
Antineoplásicos/uso terapêutico , Micose Fungoide/tratamento farmacológico , Nucleosídeos de Purina/uso terapêutico , Pirimidinonas/uso terapêutico , Síndrome de Sézary/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Apoptose/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nucleosídeos de Purina/efeitos adversos , Purina-Núcleosídeo Fosforilase/antagonistas & inibidores , Pirimidinonas/efeitos adversos , Falha de Tratamento
4.
J Vet Intern Med ; 28(2): 630-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24612411

RESUMO

BACKGROUND: Reproducible and accurate recognition of presence and severity of ataxia in horses with neurologic disease is important when establishing a diagnosis, assessing response to treatment, and making recommendations that might influence rider safety or a decision for euthanasia. OBJECTIVES: To determine the reproducibility and validity of the gait assessment component in the neurologic examination of horses. ANIMALS: Twenty-five horses referred to the Royal Veterinary College Equine Referral Hospital for neurological assessment (n = 15), purchased (without a history of gait abnormalities) for an unrelated study (n = 5), or donated because of perceived ataxia (n = 5). METHODS: Utilizing a prospective study design; a group of board-certified medicine (n = 2) and surgery (n = 2) clinicians and residents (n = 2) assessed components of the equine neurologic examination (live and video recorded) and assigned individual and overall neurologic gait deficit grades (0-4). Inter-rater agreement and assessment-reassessment reliability were quantified using intraclass correlation coefficients (ICC). RESULTS: The ICCs of the selected components of the neurologic examination ranged from 0 to 0.69. "Backing up" and "recognition of mistakes over obstacle" were the only components with an ICC > 0.6. Assessment-reassessment agreement was poor to fair. The agreement on gait grading was good overall (ICC = 0.74), but poor for grades ≤ 1 (ICC = 0.08) and fair for ataxia grades ≥ 2 (ICC = 0.43). Clinicians with prior knowledge of a possible gait abnormality were more likely to assign a grade higher than the median grade. CONCLUSION AND CLINICAL IMPORTANCE: Clinicians should be aware of poor agreement even between skilled observers of equine gait abnormalities, especially when the clinical signs are subtle.


Assuntos
Ataxia/veterinária , Marcha , Doenças dos Cavalos/diagnóstico , Doenças do Sistema Nervoso/veterinária , Animais , Ataxia/diagnóstico , Feminino , Cavalos , Masculino , Doenças do Sistema Nervoso/diagnóstico , Variações Dependentes do Observador , Exame Físico/métodos , Exame Físico/normas , Exame Físico/veterinária , Reprodutibilidade dos Testes , Gravação em Vídeo
5.
Clin Exp Immunol ; 177(1): 295-309, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24593816

RESUMO

The innate immune system has been recognized to play a role in the pathogenesis of HIV infection, both by stimulating protective activities and through a contribution to chronic immune activation, the development of immunodeficiency and progression to AIDS. A role for DNA sensors in HIV recognition has been suggested recently, and the aim of the present study was to describe the influence of HIV infection on expression and function of intracellular DNA sensing. Here we demonstrate impaired expression of interferon-stimulated genes in responses to DNA in peripheral blood monuclear cells from HIV-positive individuals, irrespective of whether patients receive anti-retroviral treatment. Furthermore, we show that expression levels of the DNA sensors interferon-inducible protein 16 (IFI16) and cyclic guanosine monophosphate-adenosine monophosphate synthase were increased in treatment-naive patients, and for IFI16 expression was correlated with high viral load and low CD4 cell count. Finally, our data demonstrate a correlation between IFI16 and CD38 expression, a marker of immune activation, in CD4(+) central and effector memory T cells, which may indicate that IFI16-mediated DNA sensing and signalling contributes to chronic immune activation. Altogether, the present study demonstrates abnormal expression and function of cytosolic DNA sensors in HIV patients, which may have implications for control of opportunistic infections, chronic immune activation and T cell death.


Assuntos
ADP-Ribosil Ciclase 1/metabolismo , Linfócitos T CD4-Positivos/imunologia , DNA/metabolismo , Infecções por HIV/imunologia , HIV/fisiologia , Espaço Intracelular/metabolismo , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Subpopulações de Linfócitos T/imunologia , ADP-Ribosil Ciclase 1/genética , Adulto , Linfócitos T CD4-Positivos/virologia , Células Cultivadas , Doença Crônica , DNA/imunologia , Feminino , Humanos , Imunidade Inata , Memória Imunológica , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Fosfoproteínas/genética , Receptores de Reconhecimento de Padrão/imunologia , Subpopulações de Linfócitos T/virologia , Carga Viral
6.
Eur J Dent Educ ; 16(4): 246-53, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23050507

RESUMO

In Scandinavia, as in many European countries, most patients consult their general dentist once a year or more. This gives the dentist a unique opportunity and an obligation to make an early diagnosis of oral diseases, which is beneficial for both the patient and the society. Thus, the dentist must have knowledge of clinical symptoms, local and systemic signs and clinical differential diagnoses to make an accurate diagnosis. The dentist must be competent in selecting appropriate diagnostic tests, for example, tissue biopsy and microbiological samples, and conducting them correctly, as well as in interpreting test results and taking appropriate action accordingly. Furthermore, the dentist must be aware of diseases demanding multidisciplinary cooperation and be able to recognise his/her professional limitation, and to refer to other specialists when required. The dental curriculum changes over time as new approaches, treatments and diagnostic possibilities develop. Likewise, the role of the dentist in the community changes and may vary in different countries. As members of the Scandinavian Fellowship for Oral Pathology and Oral Medicine and subject representatives of oral pathology and oral medicine, we feel obliged to contribute to the discussion of how the guidelines of the dental curriculum support the highest possible standards of dental education. This article is meant to delineate a reasonable standard of oral pathology and oral medicine in the European dental curriculum and to guide subject representatives in curriculum development and planning. We have created an advisory topic list in oral pathology and oral medicine.


Assuntos
Educação em Odontologia/métodos , Medicina Bucal/educação , Patologia Bucal/educação , Competência Clínica , Currículo , Europa (Continente) , Humanos , Países Escandinavos e Nórdicos
7.
Scand J Immunol ; 71(6): 431-9, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20500695

RESUMO

Human herpesvirus 6B (HHV-6B) is the causative agent of the common childhood febrile illness, exanthema subitum. The virus is predominantly regarded as a T-cell tropic virus, although in reality it has the ability to infect a wide variety of cell types including monocytes, macrophages and dendritic cells (DC). Although DC are important immune regulators, the modulating effects of HHV-6B on DC are controversial. Here, we examine the phenotypic and functional consequences of HHV-6B infection of DC. The addition of HHV-6B to immature DC led to expression of the nuclear viral p41 protein and cell surface expression of the viral glycoprotein gp60/110 consistent with HHV-6B infection. Nevertheless, HHV-6B did not induce noticeable cytopathogenic effects or cell death in infected DC. Importantly, HHV-6B infection induced a partial phenotypic maturation of immature DC as demonstrated by a substantial increase in the expression of HLA-DR, CD86 and CD40, whereas only a minor increase in CD80 and CD83 was observed. This phenotypic maturation was, however, not followed by functional maturation, because HHV-6B infection did not induce IL-10 and IL-12p70 production in immature DC. However, infected DC were still able to react to bacteria-derived stimuli such as lipopolysaccaharide by an even more pronounced production of IL-10 and IL-12p70 when compared to that of uninfected DC.


Assuntos
Células Dendríticas/imunologia , Células Dendríticas/virologia , Herpesvirus Humano 6/imunologia , Interleucina-10/biossíntese , Interleucina-12/biossíntese , Infecções por Roseolovirus/imunologia , Antígenos CD/imunologia , Antígeno B7-1/imunologia , Antígeno B7-2/imunologia , Antígenos CD40/imunologia , Células Dendríticas/ultraestrutura , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Antígenos HLA-DR/imunologia , Humanos , Imunoglobulinas/imunologia , Imunofenotipagem , Interleucina-10/imunologia , Interleucina-12/imunologia , Glicoproteínas de Membrana/imunologia , Microscopia Confocal , Infecções por Roseolovirus/sangue , Infecções por Roseolovirus/virologia , Antígeno CD83
8.
Dent Today ; 26(5): 120, 122-3; quiz 123, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17555196

RESUMO

The integration of ultrasonic tips in conventional and surgical endodontic treatment can be useful for the clinician. An ultrasonic tip is used in conventional endodontic treatment to remove or bypass a separated instrument or a post within a canal, and can replace a slow-speed handpiece and round bur to detect or provide better access to a canal. In endodontic surgery, the replacement of the slow-speed or miniature handpiece with an ultrasonic tip will allow for better instrument ergonomics and depth of a root-end preparation. When used in conjunction with magnification and illumination, visualization for the clinician is markedly improved. In addition, advancements in polymer science have allowed for the development of plastic ultrasonic tips.


Assuntos
Tratamento do Canal Radicular/instrumentação , Terapia por Ultrassom/instrumentação , Apicectomia/instrumentação , Cimentos Dentários/química , Calcificações da Polpa Dentária/terapia , Cavidade Pulpar/patologia , Desenho de Equipamento , Falha de Equipamento , Corpos Estranhos/terapia , Humanos , Iluminação/instrumentação , Microscopia/instrumentação , Polímeros/química , Técnica para Retentor Intrarradicular , Preparo de Canal Radicular/instrumentação , Propriedades de Superfície , Ápice Dentário/patologia , Vibração/uso terapêutico
9.
Clin Radiol ; 59(2): 117-23, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14746780

RESUMO

The radiological findings in paediatric Gaucher disease (GD) are reviewed and future challenges for radiology are discussed. This overview is based on a literature review and our experience of children with GD in one of two national institutions for paediatric GD in the UK. GD is known to progress more rapidly in childhood. Current imaging is mainly suitable for ascertaining the complications of GD. The UK recommendations for routine radiological surveillance are discussed. With enzyme replacement therapy (ERT), which dramatically modifies the course of the disorder, the challenge for radiology in the future is likely to be assessing treatment efficacy rather than the detection of disease complications. Disease manifestations are likely to change in those on ERT and the most notable recent alteration in the disease profile in childhood is the virtual disappearance of the acute bone crisis in this population.


Assuntos
Doença de Gaucher/diagnóstico , Densidade Óssea , Doenças Ósseas/diagnóstico , Doenças Ósseas/diagnóstico por imagem , Doenças da Medula Óssea/diagnóstico , Criança , Doença de Gaucher/diagnóstico por imagem , Humanos , Hepatopatias/diagnóstico , Pneumopatias/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Esplenopatias/diagnóstico , Tomografia Computadorizada por Raios X/métodos
10.
Pediatr Radiol ; 33(11): 782-5, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12961047

RESUMO

BACKGROUND: Routine magnetic resonance imaging (MRI) surveillance of bone marrow change in patients with Gaucher disease (GD) is recommended, but interpretation of imaging findings in the developing skeleton may be difficult. OBJECTIVES: To assess the agreement between routine spinal MRI findings and clinical course in paediatric GD patients receiving enzyme replacement therapy (ERT). MATERIALS AND METHODS: A retrospective institutional review of all GD patients on ERT who had had repeated routine spinal MRI in accordance with national recommendations ( n=14) was carried out. Vertebral body bone marrow MRI T1 signal was assessed relative to intervertebral discs. MRI findings were then compared with recorded date(s) of ERT initiation and possible therapy changes. RESULTS: Nine patients had spinal MRI both before and after the start of ERT. MRI T1 marrow signal was normal in two and abnormal in three of the nine patients both before and after the start of ERT. Two of the nine patients had normalization and one had conversion from normal to abnormal T1 signal. Interpretation was uncertain in one. Seven episodes of treatment intensification occurred. MRI T1 marrow signal was normal before five and uncertain before two of the seven episodes. CONCLUSION: Routine spinal MRI had low accuracy for predicting clinically indicated therapy intensification.


Assuntos
Doença de Gaucher/patologia , Imageamento por Ressonância Magnética , Coluna Vertebral/patologia , Medula Óssea/patologia , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos
11.
Biochem Biophys Res Commun ; 296(3): 671-6, 2002 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-12176034

RESUMO

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is produced by immune cells and by mediating apoptosis, TRAIL plays an important role in tumor surveillance. TRAIL binds four different membrane-bound receptors: DR4, DR5, DcR1, and DcR2. The DR4- and DR5-receptors mediate apoptosis, whereas the others do not. We demonstrated by reverse transcriptase-polymerase chain reaction and flow cytometry that, in vitro, normal human articular chondrocytes express the receptors mediating apoptosis (DR4 and DR5) and one of the decoy receptors (DcR2). Also, we demonstrated that chondrocytes were subjected to cell death within few hours after challenge with TRAIL and that cytotoxicity was dose-dependent. Treated cells had apoptotic morphology accompanied by active caspase-3 immunoreactivity. These data indicate that normal human articular chondrocytes are susceptible to TRAIL-mediated apoptosis, which otherwise is typical for transformed cells, and also that death receptors and their respective ligands may have a crucial role in cartilage generation and destruction.


Assuntos
Apoptose , Cartilagem Articular/citologia , Condrócitos/metabolismo , Glicoproteínas de Membrana/toxicidade , Fator de Necrose Tumoral alfa/toxicidade , Adulto , Proteínas Reguladoras de Apoptose , Caspase 3 , Caspases/metabolismo , Células Cultivadas , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Humanos , RNA Mensageiro/biossíntese , Receptores do Fator de Necrose Tumoral/genética , Receptores do Fator de Necrose Tumoral/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF
12.
Ann N Y Acad Sci ; 941: 177-84, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11594571

RESUMO

Recent phase I and phase II trials using recombinant human interleukin-12 (rhIL-12) for cutaneous T cell lymphoma (CTCL) have been completed. Observations on 32 evaluable patients revealed an overall response rate approaching 50 percent. Biopsy of regressing lesions revealed an increase in numbers of CD8+ and/or TIA-1+ T cells. These results suggest that rhIL-12 may induce lesion regression by augmenting antitumor cytotoxic T cell responses. Future trials will be focused on strategies for further immune enhancement by the concomitant use of additional immune augmenting cytokines with rhIL-12.


Assuntos
Antineoplásicos/uso terapêutico , Interleucina-12/uso terapêutico , Linfoma Cutâneo de Células T/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Antígenos de Diferenciação de Linfócitos T/análise , Antígenos de Diferenciação de Linfócitos T/imunologia , Antineoplásicos/efeitos adversos , Humanos , Imuno-Histoquímica , Interleucina-12/efeitos adversos , Linfócitos do Interstício Tumoral/imunologia , Linfoma Cutâneo de Células T/imunologia , Proteínas Recombinantes/uso terapêutico , Neoplasias Cutâneas/imunologia , Subpopulações de Linfócitos T/classificação , Linfócitos T Citotóxicos/imunologia , Resultado do Tratamento
13.
Arch Dermatol ; 137(5): 581-93, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11346336

RESUMO

OBJECTIVES: To determine the safety and efficacy of oral bexarotene (Targretin capsules; Ligand Pharmaceuticals Incorporated, San Diego, Calif). DESIGN: The effects of 2 randomized doses of 6.5 mg/m(2) per day (with crossover for progression) vs 650 mg/m(2) per day (later modified to 300 mg/m(2) per day) were evaluated in an open-label, multicenter, phase 2 and 3 study conducted between February 1997 and November 1998. SETTING: Eighteen international cutaneous T-cell lymphoma clinics at academic referral centers. PATIENTS: Fifty-eight patients with biopsy-proven stage IA through IIA cutaneous T-cell lymphoma that was refractory to (or patients were intolerant of) treatment or had reached at least a 6-month response plateau under at least 2 forms of prior therapy (median of 3.5 prior therapies). INTERVENTION: Bexarotene (Targretin capsules) administered once daily with meal for 16 weeks or longer. MAIN OUTCOME MEASURES: Primary end point classification of overall response rate of complete and partial remissions determined by either the Physician's Global Assessment of Clinical Condition or the objective Composite Assessment of Index Lesion Severity. Body surface area, time to response, duration of disease control, time to disease progression, individual index lesion signs and symptoms, and quality of life parameters were secondary outcomes. RESULTS: Responses (> or = 50% improvement) were seen in 3 (20%) of 15 patients with an initial dose at 6.5 mg/m(2) per day (95% confidence interval [CI], 0%-40%), 15 (54%) of 28 patients at 300 mg/m(2) per day (95% CI, 35%-72%), and 10 (67%) of 15 patients at above 300 mg/m(2) per day (95% CI, 43%-91%). The rate of progressive disease was 47%, 21%, and 13% at the same dose levels, respectively. Eight (73%) of 11 patients crossing over from 6.5 mg/m(2) per day to higher doses subsequently responded. The median duration of response from start of therapy could not be estimated for the 15 patients at 300 mg/m(2) per day owing to low relapse rates in 2 patients (13%); at higher doses it was 516 days. The following drug-related adverse effects were reversible and treatable: hypertriglyceridemia (46 patients [79%]), hypercholesterolemia (28 patients [48%]), headache (27 patients [47%]), central hypothyroidism (23 patients [40%]), asthenia (21 patients [36%]), and leukopenia (16 patients [28%]). No cases of drug-related neutropenic fever, sepsis, or death occurred. Pancreatitis occurred in 3 patients with triglyceride levels higher than 14.69 mmol/L (1300 mg/dL), all of whom were taking 300 mg/m(2) or more of oral bexarotene per day. CONCLUSIONS: Bexarotene (Targretin capsules) (the first retinoid X receptor-selective rexinoid) was well tolerated and effective as an oral treatment for 15 (54%) of 28 patients with refractory or persistent early-stage cutaneous T-cell lymphoma at doses of 300 mg/m(2) per day. Hypertriglyceridemia and hypothyroidism require monitoring but are reversible and manageable with concomitant medication.


Assuntos
Anticarcinógenos/administração & dosagem , Linfoma de Células T/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Tetra-Hidronaftalenos/administração & dosagem , Administração Oral , Adulto , Idoso , Anticarcinógenos/efeitos adversos , Anticarcinógenos/farmacocinética , Anticarcinógenos/uso terapêutico , Bexaroteno , Cápsulas , Estudos Cross-Over , Relação Dose-Resposta a Droga , Feminino , Humanos , Linfoma de Células T/patologia , Linfoma de Células T/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Qualidade de Vida , Retratamento , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/fisiopatologia , Análise de Sobrevida , Tetra-Hidronaftalenos/efeitos adversos , Tetra-Hidronaftalenos/farmacocinética , Tetra-Hidronaftalenos/uso terapêutico , Resultado do Tratamento
14.
J Am Acad Dermatol ; 44(6): 940-7, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11369904

RESUMO

BACKGROUND: The purine nucleoside phosphorylase inhibitor peldesine is a new agent being evaluated as a T-cell inhibitor. OBJECTIVE: We attempted to determine the efficacy of peldesine (BCX-34) in a 1% dermal cream formulation as a treatment for cutaneous T-cell lymphoma (CTCL). METHODS: Ninety patients with patch and plaque phase CTCL, histologically confirmed by a referee dermatopathologist, were enrolled in a randomized, double-blind, placebo-controlled study. BCX-34 dermal cream 1% or the vehicle cream (as a placebo control) was applied twice daily to the entire skin surface for up to 24 weeks. Efficacy of the topical therapy was assessed in terms of complete or partial (> or = 50%) clearing of patches and plaques. RESULTS: Of the 89 patients able to be examined, 43 received BCX-34 and 46 received the placebo vehicle cream. One patient withdrew early and was not analyzed. The two groups were well balanced for potential prognostic factors. A total of 28% (12/43) of the patients treated with BCX-34 showed a response, but 24% (11/46) of patients who received vehicle also responded (P =.677). CONCLUSION: Although BCX-34 dermal cream 1% was not significantly better than the control as therapy for patch and plaque-phase CTCL, this appears to be the first published placebo-controlled trial evaluating treatment for CTCL. Whether the vehicle cream has more than a placebo therapeutic effect is unclear. The relatively high (24%) placebo response rate should be kept in mind in assessing other treatments for early-stage CTCL.


Assuntos
Inibidores Enzimáticos/farmacologia , Guanina/análogos & derivados , Guanina/farmacologia , Linfoma Cutâneo de Células T/tratamento farmacológico , Administração Cutânea , Adulto , Idoso , Método Duplo-Cego , Inibidores Enzimáticos/administração & dosagem , Feminino , Guanina/administração & dosagem , Humanos , Linfoma Cutâneo de Células T/patologia , Masculino , Pessoa de Meia-Idade , Placebos , Resultado do Tratamento
15.
Med Care ; 39(5): 500-12, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11317098

RESUMO

BACKGROUND: The Unified Psychogeriatric Biopsychosocial Evaluation and Treatment (UPBEAT) program provides individualized interdisciplinary mental health treatment and care coordination to elderly veterans whose comorbid depression, anxiety, or alcohol abuse may result in overuse of inpatient services and underuse of outpatient services. OBJECTIVES: To determine whether proactive screening of hospitalized patients can identify unrecognized comorbid psychiatric conditions and whether comprehensive assessment and psychogeriatric intervention can improve care while reducing inpatient use. DESIGN: Randomized trial. SUBJECTS: Veterans aged 60 and older hospitalized for nonpsychiatric medical or surgical treatment in 9 VA sites (UPBEAT, 814; usual care, 873). MEASURES: The Mental Health Inventory (MHI) anxiety and depression subscales, the Alcohol Use Disorder Identification Test (AUDIT) scores, RAND 36-Item Health Survey Short Form (SF-36), inpatient days and costs, ambulatory care clinic stops and costs, and mortality and readmission rates. RESULTS: Mental health and general health status scores improved equally from baseline to 12-month follow-up in both groups. UPBEAT increased outpatient costs by $1,171 (P <0.001) per patient, but lowered inpatient costs by $3,027 (P = 0.017), for an overall savings of $1,856 (P = 0.156). Inpatient savings were attributable to fewer bed days of care (3.30 days; P = 0.016) rather than fewer admissions. Patients with 1 or more pre-enrollment and postenrollment hospitalizations had the greatest overall savings ($6,015; P = 0.069). CONCLUSIONS: UPBEAT appears to accelerate the transition from inpatient to outpatient care for acute nonpsychiatric admissions. Care coordination and increased access to ambulatory psychiatric services produces similar improvement in mental health and general health status as usual care.


Assuntos
Alcoolismo/complicações , Alcoolismo/diagnóstico , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/diagnóstico , Continuidade da Assistência ao Paciente/organização & administração , Transtorno Depressivo/complicações , Transtorno Depressivo/diagnóstico , Avaliação Geriátrica , Psiquiatria Geriátrica/organização & administração , Hospitais de Veteranos/estatística & dados numéricos , Programas de Rastreamento/organização & administração , Serviços de Saúde Mental/organização & administração , Equipe de Assistência ao Paciente/organização & administração , United States Department of Veterans Affairs/estatística & dados numéricos , Idoso , Alcoolismo/terapia , Análise de Variância , Transtornos de Ansiedade/terapia , Comorbidade , Análise Custo-Benefício , Transtorno Depressivo/terapia , Feminino , Seguimentos , Nível de Saúde , Hospitais de Veteranos/economia , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Avaliação de Programas e Projetos de Saúde , Escalas de Graduação Psiquiátrica , Estados Unidos , United States Department of Veterans Affairs/economia , Veteranos
16.
Appl Radiat Isot ; 54(5): 839-44, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11258534

RESUMO

The cyclotron alpha beam production of 211At and of the contaminant 210At related to beam energy were studied. Radiochemical purification of 211At from the other main contaminant, 210Po, by an extraction procedure was also evaluated. To avoid impurities 28MeV has previously been considered as a maximum beam energy, but by using instead 29.1 MeV as a limit a large increase in EOB yield and sufficient radiochemical purity of extracted 211At were obtained. More cyclotrons could thereby deliver quantities useful for clinical cancer trials.


Assuntos
Astato , Bismuto , Radioisótopos , Compostos Radiofarmacêuticos/síntese química , Ciclotrons , Polônio
17.
J Clin Oncol ; 19(2): 376-88, 2001 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-11208829

RESUMO

PURPOSE: The objective of this phase III study was to determine the efficacy, safety, and pharmacokinetics of denileukin diftitox (DAB389IL-2, Ontak [Ligand Pharmaceuticals Inc, San Diego, CA]) in patients with stage Ib to IVa cutaneous T-cell lymphoma (CTCL) who have previously received other therapeutic interventions. PATIENTS AND METHODS: Patients with biopsy-proven CTCL that expressed CD25 on > or = 20% of lymphocytes were assigned to one of two dose levels (9 or 18 microg/kg/d) of denileukin diftitox administered 5 consecutive days every 3 weeks for up to 8 cycles. Patients were monitored for toxicity and clinical efficacy, the latter assessed by changes in disease burden and quality of life measurements. Antibody levels of antidenileukin diftitox and anti-interleukin-2 and serum concentrations of denileukin diftitox were also measured. RESULTS: Overall, 30% of the 71 patients with CTCL treated with denileukin diftitox had an objective response (20% partial response; 10% complete response). The response rate and duration of response based on the time of the first dose of study drug for all responders (median of 6.9 months with a range of 2.7 to more than 46.1 months) were not statistically different between the two doses. Adverse events consisted of flu-like symptoms (fever/chills, nausea/vomiting, and myalgias/arthralgias), acute infusion-related events (hypotension, dyspnea, chest pain, and back pain), and a vascular leak syndrome (hypotension, hypoalbuminemia, edema). In addition, 61% of the patients experienced transient elevations of hepatic transaminase levels with 17% grade 3 or 4. Hypoalbuminemia occurred in 79%, including 15% with grade 3 or 4 changes. Tolerability at 9 and 18 microg/kg/d was similar, and there was no evidence of cumulative toxicity. CONCLUSION: Denileukin diftitox has been shown to be a useful and important agent in the treatment of patients whose CTCL is persistent or recurrent despite other therapeutic interventions.


Assuntos
Antineoplásicos/uso terapêutico , Toxina Diftérica , Interleucina-2 , Linfoma Cutâneo de Células T/tratamento farmacológico , Proteínas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Esquema de Medicação , Feminino , Humanos , Imuno-Histoquímica , Linfoma Cutâneo de Células T/metabolismo , Linfoma Cutâneo de Células T/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas/administração & dosagem , Proteínas/farmacocinética , Receptores de Interleucina-2/metabolismo , Proteínas Recombinantes de Fusão , Indução de Remissão
18.
Meat Sci ; 59(2): 127-31, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22062670

RESUMO

The effect on meat quality of a low stress handling system (LSS) compared with a traditional handling system (TS) was investigated in Duroc×(Landrace×Yorkshire; n=117) and (Hampshire×Duroc)×(Landrace×Yorkshire) pigs (n=110) under commercial conditions. In the low-stress handling system the pigs were kept in groups of 15 during lairage and movement up to the stunner. Before the stunner the groups were divided into three groups of five pigs for the CO(2)-stunning in a specially designed set-up. The pH and temperature were determined in m. longissimus dorsi (LD) and m. biceps femoris (BF) at various times post mortem. Immediately after exsanguination a biopsy was taken from the LD and analysed for the concentration of glycogen, lactate and creatine phosphate. The day after slaughter the pH was determined in the LD, BF, m. semimembranosus (SM) and m. semispinalis capitis (SC). The temperature was determined in the LD and BF, the internal reflectance was determined in the LD, SM and BF, the colour was determined in LD, the drip loss was determined in LD and BF, and the amount of blood splashing/bruising was evaluated in LD. There was a tendency for a higher concentration of creatine phosphate in the LSS-group (P=0.06). The pH in both the LD and BF on the day of slaughter decreased more slowly from 5 min post mortem to 40 min post mortem in the LSS-group than in the TS-group (P<0.001). From 40 min to 6 h post mortem the rate of the pH decline was similar in the two groups producing the lowest pH-level in the TS group. The day after slaughter the pH was similar in the two groups in the LD and SC, whereas in the BF and SM it was lower in the LSS-group than in the TS-group. The drip loss was lower in the LSS-group in both LD (P<0.01) and BF (P<0.05) whereas the internal reflectance was only different in LD with the lowest value in the LSS-group (P<0.001). The lightness (L*) was higher in the LSS-group (P<0.05). There was no effect of stunning system on the amount of blood splashing/bruishing in the LD. The study showed that by using a low stress stunning system it is possible to decrease drip loss, possibly by increasing the concentration of creatine phosphate and thereby delaying the acceleration of pH fall in muscles after death.

19.
J Am Acad Dermatol ; 43(5 Pt 1): 768-76, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11050579

RESUMO

BACKGROUND: Finasteride, an inhibitor of type 2 5alpha-reductase, decreases serum and scalp dihydrotestosterone (DHT) by inhibiting conversion of testosterone to DHT and has been shown to be effective in men with androgenetic alopecia (AGA). The effects of finasteride in women with AGA have not been evaluated. OBJECTIVE: The purpose of this study was to evaluate the efficacy of finasteride in postmenopausal women with AGA. METHODS: In this 1-year, double-blind, placebo-controlled, randomized, multicenter trial, 137 postmenopausal women (41-60 years of age) with AGA received finasteride 1 mg/day or placebo. Efficacy was evaluated by scalp hair counts, patient and investigator assessments, assessment of global photographs by a blinded expert panel, and histologic analysis of scalp biopsy specimens. RESULTS: After 1 year of therapy, there was no significant difference in the change in hair count between the finasteride and placebo groups. Both treatment groups had significant decreases in hair count in the frontal/parietal (anterior/mid) scalp during the 1-year study period. Similarly, patient, investigator, and photographic assessments as well as scalp biopsy analysis did not demonstrate any improvement in slowing hair thinning, increasing hair growth, or improving the appearance of the hair in finasteride-treated subjects compared with the placebo group. Finasteride was generally well tolerated. CONCLUSION: In postmenopausal women with AGA, finasteride 1 mg/day taken for 12 months did not not increase hair growth or slow the progression of hair thinning.


Assuntos
Alopecia/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Finasterida/farmacologia , Administração Oral , Adulto , Alopecia/patologia , Biópsia , Progressão da Doença , Método Duplo-Cego , Inibidores Enzimáticos/administração & dosagem , Feminino , Finasterida/administração & dosagem , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Couro Cabeludo/patologia , Resultado do Tratamento
20.
Ophthalmology ; 107(2): 231-40, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10690817

RESUMO

OBJECTIVE: To determine clinical outcomes of primary intracapsular cataract surgery with and without implantation of anterior chamber lenses. DESIGN: A multicenter randomized clinical trial. PARTICIPANTS: One thousand two hundred twenty-nine male and female patients 40-75 years of age with senile cataract. METHODS: Study patients were recruited from screening eye camps and outpatient clinics. Randomization to the two treatment groups was performed after screening for predetermined inclusion and exclusion criteria. Demographics, visual acuity, intraocular pressures, and corneal endothelial cell data were recorded before surgery and at 6 weeks, 12 months, and 24 months after surgery. Monitoring of the study was secured by a standardized image documentation procedure on all patients using the IMAGEnet digital imaging system. Analysis of corneal endothelial cell images was performed with the Cell Soft software (Topcon Corporation, Japan). MAIN OUTCOME MEASURES: Visual acuity and central corneal endothelial cell loss. RESULTS: The patients were randomized to intraocular lens (IOL; n = 616) and no IOL (n = 613) implantation. Surgical complications were reported in 177 (14.4%) patients (IOL = 14.8%; no IOL = 14.0%). The most frequent complication observed was vitreous loss which occurred in 10.3% of eyes (IOL = 11.2%; no IOL = 9.5%). At the final examination (2 years after surgery), 88% of the operated eyes had a best corrected vision of 6/18 or better (IOL = 88.8%; no IOL = 86.6%). Analysis of corneal endothelial cell data showed a small but significantly greater cell loss 6 weeks after surgery in eyes with IOL compared with those without IOL, but no overall difference was found between the treatment groups in the long term follow-up. CONCLUSIONS: The findings indicate that there is a rationale for the use of anterior chamber intraocular lenses in primary intracapsular cataract surgery.


Assuntos
Câmara Anterior/cirurgia , Extração de Catarata/efeitos adversos , Endotélio Corneano/patologia , Complicações Intraoperatórias , Implante de Lente Intraocular , Acuidade Visual , Adulto , Idoso , Ásia Ocidental , Extração de Catarata/métodos , Contagem de Células , Sobrevivência Celular , Feminino , Humanos , Pressão Intraocular , Lentes Intraoculares , Masculino , Pessoa de Meia-Idade
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