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1.
Vet Surg ; 52(3): 370-378, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36647241

RESUMO

OBJECTIVE: The objective of this study was to describe the clinical features, prognostic factors, and outcomes in dogs with surgically treated salivary gland carcinoma. STUDY DESIGN: Multi-institutional retrospective case series. ANIMALS: Seventy-two client-owned dogs from 16 institutions with surgically excised salivary gland carcinoma. METHODS: Medical records of dogs undergoing sialoadenectomy from January 1, 2000 to January 1, 2020 were reviewed for signalment, clinical signs, preoperative staging results, preoperative mass evaluation, complications, histopathologic diagnosis, local recurrence, metastatic disease, and survival times. Survival functions were estimated using the Kaplan-Meier estimator. Factors related to survival were individually tested using the log-rank test. RESULTS: The overall median survival time (MST) associated with salivary carcinoma was 1886 days. Local recurrence occurred in 29/69 (42%) dogs with an overall disease-free interval (DFI) of 191 days. Metastatic disease occurred in 22/69 (31.9%) dogs, with an overall DFI of 299 days. Lymph node metastasis was present at the time of surgery in 11/38 (28.9%) dogs in which lymphadenectomy was performed at the time of surgery; these dogs had a shorter DFI at 98 days (P = .03) and MST at 248 days (P < .001). CONCLUSION: The prognosis for dogs with salivary gland carcinoma treated surgically was more favorable than previously reported. Nodal metastasis was a negative prognostic factor for canine salivary gland carcinoma. CLINICAL SIGNIFICANCE: Surgical intervention should be considered for dogs with salivary carcinoma.


Assuntos
Carcinoma , Doenças do Cão , Oncologia Cirúrgica , Cães , Animais , Estudos Retrospectivos , Resultado do Tratamento , Sociedades Veterinárias , Prognóstico , Carcinoma/cirurgia , Carcinoma/veterinária , Doenças do Cão/diagnóstico
2.
Psychosom Med ; 76(5): 379-88, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25076512

RESUMO

CONTEXT: Unexplained fatigue states are prevalent, with uncertain diagnostic boundaries. OBJECTIVE: Patients with fatigue-related illnesses were investigated by questionnaire and a novel semistructured interview to identify discriminatory features. METHODS: Cross-sectional samples of women from specialist practices with chronic fatigue syndrome (n = 20), postcancer fatigue (PCF; n = 20), or major depression (n = 16) were recruited. Additionally, two longitudinal samples were studied: women with fatigue associated with acute infection who subsequently developed postinfective fatigue syndrome (n = 20) or recovered uneventfully (n = 21), and women undergoing adjuvant therapy for breast cancer experiencing treatment-related fatigue who subsequently developed PCF (n = 16) or recovered uneventfully (n = 16). Patients completed self-report questionnaires, and trained interviewers applied the Semi-structured Clinical Interview for Neurasthenia. The receiver operating characteristics curves of the interview were measured against clinician-designated diagnoses. Cluster analyses were performed to empirically partition participants by symptom characteristics. RESULTS: The interview had good internal consistency (Cronbach alpha "fatigue" = .83), and diagnostic sensitivity and specificity for chronic fatigue syndrome (100% and 83%) and major depression (100% and 72%), with reasonable parameters for PCF (72% and 58%). Empirical clustering by "fatigue" or "neurocognitive difficulties" items allocated most patients to one group, whereas "mood disturbance" items correctly classified patients with depression only. CONCLUSIONS: The Semi-structured Clinical Interview for Neurasthenia offers reliable diagnostic use in assessing fatigue-related conditions. The symptom domains of fatigue and neurocognitive difficulties are shared across medical and psychiatric boundaries, whereas symptoms of depression such as anhedonia are distinguishing.


Assuntos
Transtorno Depressivo/diagnóstico , Fadiga/diagnóstico , Entrevista Psicológica , Neurastenia/diagnóstico , Adulto , Neoplasias da Mama/complicações , Análise por Conglomerados , Estudos Transversais , Transtorno Depressivo/complicações , Diagnóstico Diferencial , Fadiga/etiologia , Fadiga/psicologia , Síndrome de Fadiga Crônica/psicologia , Feminino , Humanos , Infecções/complicações , Pessoa de Meia-Idade , Neurastenia/etiologia , Dor/complicações , Psiquiatria/métodos , Curva ROC , Autorrelato , Sensibilidade e Especificidade , Fatores Socioeconômicos
3.
Support Care Cancer ; 20(11): 2959-67, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22426503

RESUMO

INTRODUCTION: Dose-limiting neurotoxicity is a major side effect of oxaliplatin treatment, producing initial acute neurotoxicity and chronic neuropathy with increasing exposure. The improvement in survival for patients with early-stage colorectal cancer treated with oxaliplatin has highlighted the need for valid and reliable assessment of peripheral neuropathy. OBJECTIVES: The objective of this paper was to explore neuropathic symptoms in oxaliplatin-treated patients as assessed using different methods. METHODS: Consecutive symptomatic patients reporting peripheral neuropathy after oxaliplatin chemotherapy for colorectal cancer were interviewed using a semi-structured clinical interview. Neurotoxicity was also assessed using the National Cancer Institute Common Toxicity Criteria scale (clinician-rated), patient 'self-report' questionnaires (PNQ), nerve conduction and clinical assessment. RESULTS: Twenty patients were assessed, 12.6 ± 2.8 months after treatment cessation (mean cumulative oxaliplatin dose, 789 mg/m(2)). In 40% of patients, neurotoxicity necessitated early cessation of treatment. Only 10% of patients were designated by clinicians with severe neurotoxicity, whilst, in contrast, patient interviews and self-report questionnaires described significant physical limitations due to neuropathic symptoms in 60% of patients. The majority (85%) of patients had objective evidence of sensory neuropathy with nerve conduction studies. Reports from clinical interviews were strongly correlated with patient self-assessment (Pearson coefficient = 0.790, p < 0.0005). CONCLUSION: Given the discrepancies in symptom prevalence highlighted by these findings, the monitoring of oxaliplatin-induced neurotoxicity would benefit from more informative clinical assessment, with inclusion of patient-reported outcome measures. Such an approach would be beneficial in a clinical trial setting to monitor the efficacy of interventions and in prospective studies of survivorship to determine the true burden of peripheral neuropathy in oxaliplatin-treated patients.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Síndromes Neurotóxicas/etiologia , Compostos Organoplatínicos/efeitos adversos , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Neurotóxicas/diagnóstico , Síndromes Neurotóxicas/fisiopatologia , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/uso terapêutico , Avaliação de Resultados em Cuidados de Saúde , Oxaliplatina , Índice de Gravidade de Doença , Inquéritos e Questionários
4.
J Am Vet Med Assoc ; 260(7): 758-764, 2022 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-35201999

RESUMO

OBJECTIVE: To determine the outcome in dogs diagnosed with congenital extrahepatic portosystemic shunts (EHPSS) at ≥ 5 years of age treated with medical management only (M) or with surgical attenuation (S). The hypothesis was that dogs undergoing surgical attenuation would have a longer survival time than dogs undergoing medical management only. ANIMALS: 351 dogs definitively diagnosed with EHPSS at ≥ 5 years of age. PROCEDURES: Medical records from 2009 to 2019 at 16 veterinary teaching hospitals were evaluated. Data collected included signalment, clinical signs at diagnosis, clinicopathologic data, surgical and medical treatments, shunt morphology, clinical signs and medical treatments at 6 to 12 months after diagnosis, and survival time. RESULTS: 351 dogs (M, 119 [33.9%]; S, 232 [66.1%]) were included in the study. Survival time was longer with surgery than medical management (hazard ratio, 4.2; M, 3.4 years; S, 10.9 years). Continued clinical signs at 6 to 12 months after diagnosis were more common with medical management (M, 40% [33/88]; S, 14% [21/155]). Continued medical treatments at 6 to 12 months after diagnosis were more common in the medical management group (M, 78% [69/88]; S, 34% [53/155]). Perioperative mortality rate was 7.3%. CLINICAL RELEVANCE: Dogs diagnosed at ≥ 5 years of age with EHPSS have significantly better survival times and fewer clinical signs with surgical attenuation, compared with medical management. Older dogs have similar surgical mortality rates to dogs of all ages after surgical EHPSS attenuation.


Assuntos
Doenças do Cão , Derivação Portossistêmica Transjugular Intra-Hepática , Animais , Doenças do Cão/diagnóstico , Doenças do Cão/tratamento farmacológico , Doenças do Cão/cirurgia , Cães , Sistema Porta/anormalidades , Sistema Porta/cirurgia , Derivação Portossistêmica Transjugular Intra-Hepática/veterinária , Estudos Retrospectivos
5.
Oncologist ; 16(9): 1333-44, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21835897

RESUMO

BACKGROUND: We recently reported that cancer-related fatigue (CRF) after adjuvant breast cancer therapy was prevalent and disabling, but largely self-limiting within 12 months. The current paper describes sexual functioning (SF) and its relationship to CRF, mood disorder, and quality of life (QOL) over the first year after completion of adjuvant therapy. METHODS: Women were recruited after surgery, but prior to commencing adjuvant treatment, for early-stage breast cancer. Self-reported validated questionnaires assessed SF, CRF, mood, menopausal symptoms, disability, and QOL at baseline, completion of therapy, and at 6 months and 12 months after treatment. RESULTS: Of the 218 participants, 92 (42%) completed the SF measure (mean age, 50 years). They were significantly younger, more likely to be partnered, and less likely to be postmenopausal than nonresponders. At baseline, 40% reported problems with sexual interest and 60% reported problems with physical sexual function. SF scores declined across all domains at the end of treatment, then improved but remained below baseline at 12 months, with a significant temporal effect in the physical SF subscale and a trend for overall satisfaction. There were significant correlations between the SF and QOL domains (physical and emotional health, social functioning, and general health) as well as overall QOL. The presence of mood disorder, but not fatigue, demographic, or treatment variables, independently predicted worse overall sexual satisfaction. CONCLUSIONS: Sexual dysfunction is common after breast cancer therapy and impacts QOL. Interventions should include identification and treatment of concomitant mood disorder.


Assuntos
Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/psicologia , Fadiga/etiologia , Comportamento Sexual/fisiologia , Comportamento Sexual/psicologia , Neoplasias da Mama/terapia , Fadiga/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários
6.
J Pain Symptom Manage ; 34(2): 126-35, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17544246

RESUMO

Cancer-related fatigue (CRF) is a common and disabling symptom complex reported by survivors. This study aimed to better understand the manifestations of CRF in women treated for breast cancer, and to compare them with those of women diagnosed with chronic fatigue syndrome (CFS). Women with CRF persisting 6 months after treatment for early stage breast cancer, and women with CFS participated in separate, audiotaped focus groups. Transcripts of the sessions were analyzed using the NUD*IST software, and interpreted using grounded theory. Twenty-eight women participated, 16 with CRF and 12 with CFS. Analysis of transcripts from both groups revealed a similar core set of symptoms, featuring fatigue, neurocognitive difficulties, and mood disturbances. Women with CFS reported additional symptoms including musculoskeletal pain and influenza-like manifestations. Both groups suffered disabling behavioral consequences of the symptom complex. Qualitatively, CRF appears closely related to CFS. These findings raise the emergent hypothesis of a conserved neurobehavioral symptom complex, which results from diverse triggering insults.


Assuntos
Neoplasias da Mama/complicações , Síndrome de Fadiga Crônica/complicações , Síndrome de Fadiga Crônica/psicologia , Fadiga/etiologia , Fadiga/psicologia , Adulto , Idoso , Neoplasias da Mama/psicologia , Neoplasias da Mama/terapia , Feminino , Grupos Focais , Humanos , Pessoa de Meia-Idade
7.
Sci Rep ; 7(1): 8218, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28811623

RESUMO

Peripheral immunity plays a key role in maintaining homeostasis and conferring crucial neuroprotective effects on the injured nervous system, while at the same time may contribute to increased vulnerability to neuropathic pain. Little is known about the reciprocal relationship between entrapment neuropathy and peripheral immunity. This study investigated immune profile in patients with carpal tunnel syndrome (CTS), the most prevalent entrapment neuropathy. All patients exhibited neurophysiological abnormalities in the median nerve, with the majority reporting neuropathic pain symptoms. We found a significant increase in serum CCL5, CXCL8, CXCL10 and VEGF, and in CD4+ central and effector memory T cells in CTS patients, as compared to healthy controls. CCL5 and VEGF were identified as having the highest power to discriminate between patients and controls. Interestingly, and contrary to the prevailing view of CCL5 as a pro-nociceptive factor, the level of circulating CCL5 was inversely correlated with neuropathic pain intensity and median nerve motor latency. In contrast, the level of central memory T cells was positively associated with abnormal neurophysiological findings. These results suggest that entrapment neuropathy is associated with adaptive changes in the homeostasis of memory T cells and an increase in systemic inflammatory modulating cytokines/chemokines, which potentially regulate neuropathic symptoms.


Assuntos
Síndrome do Túnel Carpal/imunologia , Imunidade , Adulto , Idoso , Biomarcadores , Síndrome do Túnel Carpal/sangue , Síndrome do Túnel Carpal/diagnóstico , Citocinas/sangue , Feminino , Humanos , Memória Imunológica , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Avaliação de Sintomas , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
8.
J Pain Symptom Manage ; 54(1): 74-84, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28502786

RESUMO

CONTEXT: Cancer-related fatigue is prevalent and disabling. When persistent and unexplained, it is termed post-cancer fatigue (PCF). Cognitive behavioral therapy (CBT) and graded exercise therapy (GET) may improve symptoms and functional outcomes. OBJECTIVES: To evaluate the outcomes of a randomized controlled trial, which assigned patients with post-cancer fatigue to education, or 12 weeks of integrated cognitive-behavioral therapy (CBT) and graded exercise therapy (GET). METHODS: Three months after treatment for breast or colon cancer, eligible patients had clinically significant fatigue, no comorbid medical or psychiatric conditions that explained the fatigue, and no evidence of recurrence. The CBT/GET arm included individually tailored consultations at approximately two weekly intervals. The education arm included a single visit with clinicians describing the principles of CBT/GET and a booklet. The primary outcome was clinically significant improvement in self-reported fatigue (Somatic and Psychological HEalth REport 0-12), designated a priori as greater than one SD of improvement in fatigue score. The secondary outcome was associated improvement in function (role limitation due to physical health problems-36-Item Short Form Health Survey 0-100) comparing baseline, end treatment (12 weeks), and follow-up (24 weeks). RESULTS: There were 46 patients enrolled, including 43 women (94%), with a mean age of 51 years. Fatigue severity improved in all subjects from a mean of 5.2 (±3.1) at baseline to 3.9 (±2.8) at 12 weeks, suggesting a natural history of improvement. Clinically significant improvement was observed in 7 of 22 subjects in the intervention group compared with 2 of 24 in the education group (P < 0.05, χ2). These subjects also had improvement in functional status compared with nonresponders (P < 0.01, t-test). CONCLUSION: Combined CBT/GET improves fatigue and functional outcomes for a subset of patients with post-cancer fatigue. Further studies to improve the response rate and the magnitude of the benefit are warranted.


Assuntos
Neoplasias da Mama/complicações , Terapia Cognitivo-Comportamental , Neoplasias do Colo/complicações , Terapia por Exercício , Fadiga/etiologia , Fadiga/terapia , Neoplasias da Mama/psicologia , Neoplasias da Mama/terapia , Neoplasias do Colo/psicologia , Neoplasias do Colo/terapia , Comorbidade , Fadiga/psicologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Índice de Gravidade de Doença , Resultado do Tratamento
9.
BMC Cancer ; 6: 240, 2006 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-17026776

RESUMO

BACKGROUND: Persistent fatigue is recognised as one of the most common, ongoing symptoms reported by patients following cancer treatment and may have profound effects on the quality of life. However, recent cross-sectional studies also highlight the close relationship between cancer related fatigue (CRF) and diagnoses of depression or anxiety disorder. There is currently limited information about the relationships between these conditions over time. We sought to examine the longitudinal relationships between fatigue and mood disorder in women treated with adjuvant therapy for early stage breast cancer. METHODS: Women who had recently completed adjuvant therapy for Stage I or II breast cancer (n = 212) were sent a questionnaire with established case thresholds for clinically-significant fatigue and psychological disorder, as well as a questionnaire assessing disability. Potentially relevant variables linked to fatigue states, including age, treatment modality, menopausal status, and hematological indices were recorded. The illness outcomes were assessed over 48 months of follow-up. RESULTS: The 176 women who responded to the questionnaire (84%) had a mean age of 55 (range 24-83) years and had completed adjuvant treatment on average 10 (range 4.7-16.3) months previously. Radiotherapy had been administered, either alone (50% of women) or in combination with chemotherapy (36%). Responses from 87 women (48%) indicated a significant fatigue state (termed here post-cancer fatigue; PCF), and from 59 women (33%) responses indicated significant psychological distress. Thirty-four women (19%) were cases of fatigue alone (i.e. unaccompanied by psychological disorder), whereas 52 (30%) were cases of both disorders. Multivariate analysis did not reveal any association between demographic, clinical or laboratory variables, and caseness for PCF. Self-reported functional disability was significantly associated with fatigue. Follow-up at 24, 36 and 48 months revealed high rates of ongoing PCF in conjunction with psychological distress, despite falling rates of psychological distress alone and fatigue alone. CONCLUSION: Post-cancer fatigue was prevalent and sustained on follow-up. Concurrent psychological disorder was evident in the majority, but not all, cases of PCF and tended to be sustained over time. Further prospective cohort studies to define the longitudinal co-morbid relationships between fatigue, mood disorder, and ongoing disability after cancer treatment are indicated.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Fadiga/etiologia , Transtornos do Humor/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Comorbidade , Fadiga/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Mastectomia Segmentar/efeitos adversos , Pessoa de Meia-Idade , Transtornos do Humor/epidemiologia , Prevalência , Inquéritos e Questionários , Fatores de Tempo
11.
Psychosom Med ; 66(4): 614-9, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15272111

RESUMO

OBJECTIVE: This paper reports the effects of naturally occurring levels of distress on the development of delayed-type hypersensitivity (DTH) skin test responses. These in vivo measures provide a biologically relevant assessment of cellular immune competence. METHODS: Subjects (N = 166) were immunized (baseline) with the novel antigen, keyhole limpet hemocyanin (KLH), and DTH skin test responses against KLH were assessed 3 weeks later (follow-up). The CMI Multitest (Merieux, France), which evaluates DTH responses to a panel of seven antigens, was also administered at follow-up. Emotional distress was assessed at baseline and follow-up by the Profile of Mood States. RESULTS: Distress levels at baseline were associated with a reduced likelihood of developing DTH responses against KLH at follow-up (r = -0.22, p =.01). There was no relationship between distress at follow-up and cutaneous DTH in response to KLH (r = 0.09, p =.24) or in the Multitest (r = -0.03, p =.70). In addition, higher levels of alcohol consumption at baseline (r = -0.19, p =.02) and at follow-up (r = -0.20, p =.01) were associated with a decreased likelihood of developing cutaneous DTH against KLH. CONCLUSIONS: Everyday levels of distress predicted the capacity of the cellular arm of the immune system to exhibit recall responses to an antigen, when the experimental paradigm allowed the assessment of distress at the time of antigen sensitization. Moderate alcohol consumption independently affected cutaneous DTH.


Assuntos
Consumo de Bebidas Alcoólicas/imunologia , Hipersensibilidade Tardia/imunologia , Estresse Psicológico/imunologia , Adolescente , Adulto , Etanol/farmacologia , Feminino , Nível de Saúde , Hemocianinas/administração & dosagem , Hemocianinas/imunologia , Humanos , Hipersensibilidade Tardia/psicologia , Imunização/métodos , Imunização/psicologia , Modelos Logísticos , Masculino , Modelos Imunológicos , Inventário de Personalidade , Psiconeuroimunologia , Testes Cutâneos , Estresse Psicológico/psicologia
12.
J AOAC Int ; 85(3): 676-81, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12083260

RESUMO

A procedural modification of the AOAC Official Method for extracting light filth from ground oregano and ground marjoram was tested in an intralaboratory study. The modified method specifies isopropanol defatting, 975.49A(a), rather than chloroform-isopropanol defatting, 975.49A(b), followed by direct flotation as directed in AOAC Official Method, 975.49B(b). The modified method provided comparable results in less time while also providing safety, health, and financial benefits.


Assuntos
Condimentos/análise , Contaminação de Alimentos/análise , Origanum , Cabelo
13.
J Health Law ; 37(2): 225-65, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15357281

RESUMO

The application of the federal privacy regulations promulgated pursuantto the Health Insurance Portability and Accountability Act of 1996 (HIPAA) to employer benefit plans is arguably the most conceptually difficult area of a complex law. A purely textual reading of the Rule, when applied to employer plans, results in varying interpretations on some significant issues and puzzling results on others. This Article offers a practical approach for interpreting the rule when clear-cut answers are not provided by the text and DHHS guidance is nonexistent or unclear. In addition, this approach can be applied to the interpretation of other statutes and regulations.


Assuntos
Confidencialidade/legislação & jurisprudência , Fidelidade a Diretrizes/legislação & jurisprudência , Planos de Assistência de Saúde para Empregados/legislação & jurisprudência , Health Insurance Portability and Accountability Act , Planos de Assistência de Saúde para Empregados/classificação , Serviços de Saúde do Trabalhador/economia , Serviços de Saúde do Trabalhador/legislação & jurisprudência , Estados Unidos
14.
PLoS One ; 8(3): e58438, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23472197

RESUMO

BACKGROUND: Lymphocyte inhibition by antagonism of α4 integrins is a validated therapeutic approach for relapsing multiple sclerosis (RMS). OBJECTIVE: Investigate the effect of CDP323, an oral α4-integrin inhibitor, on lymphocyte biomarkers in RMS. METHODS: Seventy-one RMS subjects aged 18-65 years with Expanded Disability Status Scale scores ≤6.5 were randomized to 28-day treatment with CDP323 100 mg twice daily (bid), 500 mg bid, 1000 mg once daily (qd), 1000 mg bid, or placebo. RESULTS: Relative to placebo, all dosages of CDP323 significantly decreased the capacity of lymphocytes to bind vascular adhesion molecule-1 (VCAM-1) and the expression of α4-integrin on VCAM-1-binding cells. All but the 100-mg bid dosage significantly increased total lymphocytes and naive B cells, memory B cells, and T cells in peripheral blood compared with placebo, and the dose-response relationship was shown to be linear. Marked increases were also observed in natural killer cells and hematopoietic progenitor cells, but only with the 500-mg bid and 1000-mg bid dosages. There were no significant changes in monocytes. The number of samples for regulator and inflammatory T cells was too small to draw any definitive conclusions. CONCLUSIONS: CDP323 at daily doses of 1000 or 2000 mg induced significant increases in total lymphocyte count and suppressed VCAM-1 binding by reducing unbound very late antigen-4 expression on lymphocytes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00726648.


Assuntos
Integrina alfa4/metabolismo , Integrina alfa4beta1/antagonistas & inibidores , Esclerose Múltipla/tratamento farmacológico , Fenilalanina/análogos & derivados , Adulto , Método Duplo-Cego , Esquema de Medicação , Feminino , Citometria de Fluxo , Humanos , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Naftiridinas , Fenilalanina/administração & dosagem , Fenilalanina/farmacologia , Recidiva , Resultado do Tratamento , Molécula 1 de Adesão de Célula Vascular/metabolismo
15.
PLoS One ; 7(11): e49518, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23166694

RESUMO

BACKGROUND: Cognitive difficulties and autonomic dysfunction have been reported separately in patients with chronic fatigue syndrome (CFS). A role for heart rate variability (HRV) in cognitive flexibility has been demonstrated in healthy individuals, but this relationship has not as yet been examined in CFS. The objective of this study was to examine the relationship between HRV and cognitive performance in patients with CFS. METHODS: Participants were 30 patients with CFS and 40 healthy controls; the groups were matched for age, sex, education, body mass index, and hours of moderate exercise/week. Questionnaires were used to obtain relevant medical and demographic information, and assess current symptoms and functional impairment. Electrocardiograms, perceived fatigue/effort and performance data were recorded during cognitive tasks. Between-group differences in autonomic reactivity and associations with cognitive performance were analysed. RESULTS: Patients with CFS showed no deficits in performance accuracy, but were significantly slower than healthy controls. CFS was further characterized by low and unresponsive HRV; greater heart rate (HR) reactivity and prolonged HR-recovery after cognitive challenge. Fatigue levels, perceived effort and distress did not affect cognitive performance. HRV was consistently associated with performance indices and significantly predicted variance in cognitive outcomes. CONCLUSIONS: These findings reveal for the first time an association between reduced cardiac vagal tone and cognitive impairment in CFS and confirm previous reports of diminished vagal activity.


Assuntos
Cognição/fisiologia , Síndrome de Fadiga Crônica/fisiopatologia , Coração/fisiopatologia , Nervo Vago/fisiopatologia , Adulto , Estudos de Casos e Controles , Feminino , Frequência Cardíaca , Humanos , Masculino , Memória de Curto Prazo , Pessoa de Meia-Idade , Adulto Jovem
16.
J Clin Oncol ; 30(15): 1805-12, 2012 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-22508807

RESUMO

PURPOSE: Prolonged and disabling fatigue is prevalent after cancer treatment, but the early natural history of cancer-related fatigue (CRF) has not been systematically examined to document consistent presence of symptoms. Hence, relationships to cancer, surgery, and adjuvant therapy are unclear. PATIENTS AND METHODS: A prospective cohort study of women receiving adjuvant treatment for early-stage breast cancer was conducted. Women (n = 218) were enrolled after surgery and observed at end treatment and at 1, 3, 6, 9, and 12 months as well as 5 years. Structured interviews and self-report questionnaires were used to record physical and psychologic health as well as disability and health care utilization. Patients with CRF persisting for 6 months were assessed to exclude alternative medical and psychiatric causes of fatigue. Predictors of persistent fatigue, mood disturbance, and health care utilization were sought by logistic regression. RESULTS: The case rate for CRF was 24% (n = 51) postsurgery and 31% (n = 69) at end of treatment; it became persistent in 11% (n = 24) at 6 months and 6% (n = 12) at 12 months. At each time point, approximately one third of the patients had comorbid mood disturbance. Persistent CRF was predicted by tumor size but not demographic, psychologic, surgical, or hematologic parameters. CRF was associated with significant disability and health care utilization. CONCLUSION: CRF is common but generally runs a self-limiting course. Much of the previously reported high rates of persistent CRF may be attributable to factors unrelated to the cancer or its treatment.


Assuntos
Neoplasias da Mama/terapia , Fadiga/epidemiologia , Mastectomia/efeitos adversos , Adulto , Afeto , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Quimiorradioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Distribuição de Qui-Quadrado , Comorbidade , Avaliação da Deficiência , Fadiga/diagnóstico , Fadiga/psicologia , Feminino , Humanos , Entrevistas como Assunto , Modelos Lineares , Modelos Logísticos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , New South Wales , Razão de Chances , Estudos Prospectivos , Radioterapia Adjuvante/efeitos adversos , Medição de Risco , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral
17.
Neurotherapeutics ; 4(1): 117-22, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17199025

RESUMO

Better pharmacotherapies for epilepsy are needed for patients who are refractory to or have tolerability difficulties with current treatments. Seletracetam, a new drug in epilepsy development, is a pyrrolidone derivative structurally related to levetiracetam (trade name Keppra). It was discovered because of its high binding affinity to the synaptic vesicle 2A (SV2A) protein, which is now known to be the binding site for this family of compounds. Seletracetam shows very potent seizure suppression in models of acquired or genetic epilepsy, as well as high CNS tolerability in various animal models. Pharmacokinetic studies in animals suggest that seletracetam is rapidly and highly absorbed, with linear and time-independent pharmacokinetics. Seletracetam appears neither to inhibit nor to induce the major human drug metabolizing enzymes, and it demonstrates low plasma protein binding (<10%), which suggests a low potential for drug-drug interactions. Initial studies in humans demonstrated first-order monocompartmental kinetics with a half-life of 8 h and an oral bioavailability of >90%. Studies in healthy volunteers showed that the treatment emergent adverse events were of mild to moderate severity, were mostly of CNS origin and were resolved within 24 h. Altogether, these results suggest that seletracetam represents a promising new antiepileptic drug candidate, one that demonstrates a potent, broad spectrum of seizure protection and a high CNS tolerability in animal models, with initial clinical findings suggestive of straightforward pharmacokinetics and good tolerability.


Assuntos
Anticonvulsivantes , Encéfalo/efeitos dos fármacos , Epilepsia/tratamento farmacológico , Pirrolidinonas/farmacologia , Animais , Ensaios Clínicos como Assunto , Humanos
18.
Psychooncology ; 14(3): 196-203, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15386776

RESUMO

There has been an ongoing debate in the literature on the extent to which women with a family history of breast cancer are at risk of psychological morbidity. This study compares psychological morbidity in 557 women participating in a large Australian registry of high-risk breast cancer families (kConFab) with 2 age and education matched samples, 1494 general practitioner attendees and 158 members of a twin registry. Participants completed the Somatic and Psychological Health Report (SPHERE). There were no significant differences between the three groups on psychological distress (F(2, 670) = 1.77, p = 0.17). Unsurprisingly, GP attendees reported more symptoms of somatic distress than the kConFab group (t411 = 2.89, p = 0.004); there were no differences between the twins and the kConFab group on somatic distress (t174 = 0.40, p = 0.687). Clinically significant anxiety/depression, a combination of psychological and somatic distress, therefore was significantly higher in GP attendees (28%) than the kConFab and twin samples (both 20%). These results refute the hypothesis that women with a family history of breast cancer are at greater psychological risk.


Assuntos
Transtornos de Ansiedade/epidemiologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/psicologia , Transtorno Depressivo Maior/epidemiologia , Transtornos Psicofisiológicos/epidemiologia , Adulto , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Austrália/epidemiologia , Demografia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Pessoa de Meia-Idade , Morbidade , Vigilância da População/métodos , Estudos Prospectivos , Transtornos Psicofisiológicos/diagnóstico , Transtornos Psicofisiológicos/psicologia , Sistema de Registros , Fatores de Risco , Inquéritos e Questionários , Estudos em Gêmeos como Assunto
19.
Brain Behav Immun ; 19(2): 147-52, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15664787

RESUMO

This paper examined the interaction between genetic influences of the polymorphic human leukocyte antigens (DRB1 and DQB1) and psychological distress on the development of cellular immunity to the novel antigen, keyhole limpet hemocyanin (KLH). Participants (n = 227) were immunized with KLH and the development of cutaneous delayed-type hypersensitivity (DTH) against KLH was examined 3 weeks later. Distress was assessed using the Profile of Mood States. DNA was typed for the serologically defined DRB1 and DQB1 antigens. There was a significant correlation between distress at immunization and the development of DTH skin test responses to KLH (n = 214, r = .24, p = .003). HLA DQ2 was weakly associated with a decreased likelihood of developing a cutaneous delayed-type hypersensitivity response against KLH (odds ratio [OR] = 1.6; confidence interval [CI] 0.9-2.7). HLA DQ5 was weakly associated with an increased likelihood of responding to the antigen (OR=0.6; CI=0.3-1.0). The correlation between distress and immune function in HLA DQ2 negative individuals was .34 (n = 136, p = .00) and in HLA DQ2 positive individuals it was .06 (n = 74, p =. 64). For HLA DQ5 negative individuals the correlation was .26 (n = 140, p = .00) and for HLA DQ5 positive individuals it was .22 (n = 70, p = .07). These results suggest that the distress/immune relationship in genetically susceptible or protected individuals may be underestimated in psychoneuroimmunology research.


Assuntos
Sintomas Afetivos/genética , Sintomas Afetivos/imunologia , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Hipersensibilidade Tardia/genética , Hipersensibilidade Tardia/imunologia , Adjuvantes Imunológicos/administração & dosagem , Adolescente , Adulto , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Antígenos HLA-DQ/imunologia , Cadeias beta de HLA-DQ , Antígenos HLA-DR/imunologia , Cadeias HLA-DRB1 , Hemocianinas/administração & dosagem , Humanos , Imunização , Masculino , Psiconeuroimunologia
20.
J Food Prot ; 54(2): 127-130, 1991 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31051657

RESUMO

A commercially available colorimetric DNA hybridization test was compared with the USDA/FSIS conventional culture method for detection of salmonellae in naturally contaminated meat and poultry products and inoculated ground beef samples. All samples which were Salmonella -positive by the culture method were also positive by the DNA probe assay. There were no false-negative or false-positive results by the colorimetric DNA hybridization test, which was slightly more sensitive than the culture method.

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