RESUMO
BACKGROUND: Fungal infections impact over 25% of the global population. For the opportunistic fungal pathogen, Cryptococcus neoformans, infection leads to cryptococcosis. In the presence of the host, disease is enabled by elaboration of sophisticated virulence determinants, including polysaccharide capsule, melanin, thermotolerance, and extracellular enzymes. Conversely, the host protects itself from fungal invasion by regulating and sequestering transition metals (e.g., iron, zinc, copper) important for microbial growth and survival. RESULTS: Here, we explore the intricate relationship between zinc availability and fungal virulence via mass spectrometry-based quantitative proteomics. We observe a core proteome along with a distinct zinc-regulated protein-level signature demonstrating a shift away from transport and ion binding under zinc-replete conditions towards transcription and metal acquisition under zinc-limited conditions. In addition, we revealed a novel connection among zinc availability, thermotolerance, as well as capsule and melanin production through the detection of a Wos2 ortholog in the secretome under replete conditions. CONCLUSIONS: Overall, we provide new biological insight into cellular remodeling at the protein level of C. neoformans under regulated zinc conditions and uncover a novel connection between zinc homeostasis and fungal virulence determinants.
Assuntos
Cryptococcus neoformans/patogenicidade , Chaperonas Moleculares/metabolismo , Proteoma/metabolismo , Secretoma/metabolismo , Zinco/metabolismo , Cryptococcus neoformans/metabolismo , Cápsulas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Melaninas/metabolismo , Chaperonas Moleculares/genética , Mutação , Proteômica , Termotolerância , Virulência/genéticaRESUMO
Olfactory ensheathing cells (OECs) are crucial for promoting the regeneration of the primary olfactory nervous system that occurs throughout life. Transplantation of OECs has emerged as a promising therapy for nervous system injuries, in particular for spinal cord injury repair. Functional outcomes in both animals and humans are, however, highly variable, primarily because it is difficult to rapidly obtain enough OECs for transplantation. Compounds which can stimulate OEC proliferation without changing the phenotype of the cells are therefore highly sought after. Additionally, compounds which can stimulate favourable cell behaviours such as migration and phagocytic activity are desirable. We conducted a medium-throughput screen testing the Davis open access natural product-based library (472 compounds) and subsequently identified the known plant natural product 2-methoxy-1,4-naphthoquinone as a stimulant of OEC viability. We showed that 2-methoxy-1,4-naphthoquinone: (i) strongly stimulates proliferation over several weeks in culture whilst maintaining the OEC phenotype; (ii) stimulates the phagocytic activity of OECs, and (iii) modulates the cell cycle. We also identified the transcription factor Nrf2 as the compound's potential molecular target. From these extensive investigations we conclude that 2-methoxy-1,4-naphthoquinone may enhance the therapeutic potential of OECs by stimulating proliferation prior to transplantation.
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Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Naftoquinonas/farmacologia , Bulbo Olfatório/citologia , Fagocitose/efeitos dos fármacos , Animais , Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Transplante de Células , Células Cultivadas , Eremophila (Planta)/química , Ensaios de Triagem em Larga Escala/métodos , Humanos , Camundongos , Fator 2 Relacionado a NF-E2 , Naftoquinonas/isolamento & purificação , Traumatismos da Medula Espinal , Regeneração da Medula EspinalRESUMO
Angiotensin I convertase activity has been found in human alveolar macrophages from normal volunteers and patients with pulmonary sarcoidosis. This activity is higher in the alveolar macrophages from smokers than from nonsmokers, and is even more elevated in sarcoid patients. The activity can be detected with both angiotensin I and bradykinin analogs and appears to require protein synthesis, but the enzyme is not secreted by alveolar macrophages in culture.
Assuntos
Macrófagos/enzimologia , Peptidil Dipeptidase A/metabolismo , Alvéolos Pulmonares/enzimologia , Sarcoidose/enzimologia , Fumar/fisiopatologia , Granuloma/enzimologia , Humanos , Prostaglandinas/metabolismo , Teprotida/farmacologiaRESUMO
The 25 April 1992 magnitude 7.1 Cape Mendocino thrust earthquake demonstrated that the North America-Gorda plate boundary is seismogenic and illustrated hazards that could result from much larger earthquakes forecast for the Cascadia region. The shock occurred just north of the Mendocino Triple Junction and caused strong ground motion and moderate damage in the immediate area. Rupture initiated onshore at a depth of 10.5 kilometers and propagated up-dip and seaward. Slip on steep faults in the Gorda plate generated two magnitude 6.6 aftershocks on 26 April. The main shock did not produce surface rupture on land but caused coastal uplift and a tsunami. The emerging picture of seismicity and faulting at the triple junction suggests that the region is likely to continue experiencing significant seismicity.
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OBJECTIVES: We sought to test the hypothesis that C-reactive protein, a marker of inflammation, would correlate positively with coronary calcium, a marker of atherosclerosis, in postmenopausal women. BACKGROUND: High sensitivity testing for C-reactive protein (hsCRP) has recently been shown in large population studies to predict cardiac events in asymptomatic postmenopausal women. Coronary calcification determined by electron beam computerized tomography (EBCT) has also been suggested to be predictive of cardiac events in women. METHODS: We performed hsCRP testing and determined calcium scores by EBCT in 172 asymptomatic postmenopausal women (mean age: 64.5 +/- 7.9 years) at risk for cardiac disease. Risk factors were determined by history, physical, electrocardiogram, exercise testing, and lipoprotein profiles. RESULTS: Calcium scores ranged from 0 to 2,618. For analysis, calcium scores were divided into three groups; none (0 to 10), minimal (>10 to 50), and significant (>50). Overall, there was no significant positive relationship between hsCRP level and calcium score. Specifically, the hsCRP levels (mg/dl) were 0.24 +/- 0.43, 0.33 +/- 0.47 and 0.17 +/- 0.32 (medians 0.11, 0.15, and 0.06) for women with none, minimal, and significant coronary calcification, respectively. In subgroup analysis, a similar lack of positive association was observed after stratification by smoking status and by hormone replacement therapy use, two factors known to increase hsCRP. CONCLUSIONS: In contrast to our a priori hypothesis, we found no evidence of a positive association between hsCRP and calcium score by EBCT. These data thus raise the possibility that hsCRP and EBCT calcium score reflect different pathologic processes, an issue with implications for coronary artery disease screening.
Assuntos
Proteína C-Reativa/metabolismo , Calcinose/diagnóstico por imagem , Doença das Coronárias/diagnóstico por imagem , Pós-Menopausa , Tomografia Computadorizada por Raios X , Idoso , Biomarcadores , Calcinose/sangue , Angiografia Coronária , Doença das Coronárias/sangue , Estudos Transversais , Feminino , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Lipoproteínas/sangue , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Fumar/efeitos adversosRESUMO
OBJECTIVE: To determine whether syringe exchange program use is associated with cessation of syringe sharing among high-risk injection drug users. DESIGN AND METHODS: Between 1992 and 1996, street-recruited injection drug users were interviewed and received HIV testing and counseling semi-annually, as part of a dynamic cohort study. We examined a cohort of 340 high-risk injection drug users for whom two observations, 6-months apart, were available and who reported syringe sharing at the first interview. Multivariate logistic regression analysis was performed to determine the relationship between syringe exchange program use and cessation of syringe sharing, while controlling for confounding factors. RESULTS: At follow-up interview, 60% (204 of 340) reported quitting syringe sharing. High-risk injection drug users who began using the syringe exchange program were more likely to quit sharing syringes [adjusted odds ratio (AOR), 2.68; 95% confidence interval (CI), 1.35-5.33], as were those who continued using the syringe exchange program (AOR,1.98; 95% CI, 1.05-3.75) in comparison with non-syringe exchange program users, while controlling for confounding factors. CONCLUSIONS: The initiation and continuation of syringe exchange program use among high-risk injection drug users is independently associated with cessation of syringe sharing. Syringe exchange program use can be an important component in reducing the spread of blood-borne infectious diseases among high-risk injection drug users.
Assuntos
Infecções por HIV/prevenção & controle , Uso Comum de Agulhas e Seringas/efeitos adversos , Programas de Troca de Agulhas , Avaliação de Programas e Projetos de Saúde/estatística & dados numéricos , Abuso de Substâncias por Via Intravenosa/virologia , Adulto , Estudos de Coortes , Feminino , Infecções por HIV/epidemiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Abuso de Substâncias por Via Intravenosa/epidemiologia , Inquéritos e QuestionáriosRESUMO
The TNM classification (tumor-node-metastasis) was adopted by the American Joint Committee on Cancer and the International Union against Cancer a decade ago to avoid heterogeneity of prognostic classification schemes used for differentiated thyroid cancers. To date, however, clinical data based on this classification are lacking. We retrospectively evaluate the prognosis of 700 patients (208 men and 492 women) with papillary (89%) and follicular (11%) thyroid cancers according to the pathological TNM (pTNM) staging system, treated over a 25-yr period (1970-1995). Patients who received primary treatment at our center constituted 87.4% of the cases; the majority underwent total thyroidectomy, followed by 131I ablative therapy in high risk groups, as standard treatment. Clinical and follow-up data were obtained from the medical records and our cancer registry. Disease-free and cancer-specific survival data were analyzed by Kaplan-Meier product limit estimates and Cox proportional hazard models. Patient distribution by the pTNM system were: stage I, 516 patients; stage II, 57 patients; stage III, 104 patients; and stage IV, 23 patients. Over a mean +/- SE follow-up of 11.3 +/- 0.3 yr, the overall cancer recurrence and mortality rates were 20.5% and 8.4%, respectively. However, the respective cancer recurrence and mortality rates were distinctly different in the various pTNM stages: 15.4% and 1.7% in stage I, 22% and 15.8% in stage II, 46.4% and 30% in stage III, and 66.7% and 60.9% in stage IV tumors. Using actuarial survival plots, a clear separation in both disease-free survival and cancer-specific survival was noted among all the stages (P < 0.0001). Risk factors analyses showed a significant association between all the prognostic variables used in TNM staging (age, tumor size, extent of primary tumor, and presence of nodal or distant metastases) and the observed end points of recurrence or death from thyroid cancer. After correcting for TNM stages, the risk of cancer recurrence was halved in female compared to male patients, whereas this was 1.7-fold higher in multifocal than unifocal tumors. Conversely, cancer mortality was 3.4-fold higher in follicular than papillary thyroid cancer. In the analysis of effect of primary treatment among 492 patients with tumor more advanced than the T1N0M0 category, patients who underwent less extensive surgery (lobectomy or subtotal thyroidectomy) had a 2.5-fold risk of cancer recurrence (P < 0.0001) and a 2.2-fold risk of death (P < 0.01) compared to those who underwent total or near-total thyroidectomy. Patients not treated with 131I ablation had a 2.1-fold greater risk of cancer recurrence (P < 0.0001) than those given 131I ablation, although no difference was noted in deaths from thyroid cancer. Based on our data, the pTNM classification is useful in distinguishing patients with different prognostic outcomes. However, the small patient numbers in pTNM stages other than stages I precludes us from evaluating its usefulness as a guide for therapy. Until prospective data could be accrued from controlled treatment trials, we support the standard practice of total thyroidectomy followed by 131I ablative therapy (if focal iodide uptake was noted) in patients with papillary thyroid cancer more advanced than the T1N0M0 category or of multicentric nature and in the majority of patients with follicular thyroid cancer.
Assuntos
Adenocarcinoma Folicular/patologia , Carcinoma Papilar/patologia , Metástase Linfática , Estadiamento de Neoplasias , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/mortalidade , Adenocarcinoma Folicular/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/mortalidade , Carcinoma Papilar/terapia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia , Resultado do TratamentoRESUMO
Serum levels of matrix metalloprotease-9 (MMP-9) and tissue inhibitor of MMP-1 (TIMP-1) were measured monthly in 7 patients with relapsing-remitting multiple sclerosis (MS) 6 months before and 6 months during treatment with weekly intramuscular (i.m.) injections of interferon-beta1a (IFN-beta1a) 30 microg. Within-patient median MMP-9 levels were unchanged on treatment. Within-patient median TIMP-1 levels were higher during months 1-6 (771.5 ng/ml) and during months 4, 5, and 6 of treatment (793 ng/ml) compared with 6 months pretreatment (414 ng/ml) (respectively, p = 0.10, p = 0.047; Wilcoxon signed-rank test). These preliminary data suggest that IFN-beta1a therapy may increase TIMP-1 levels.
Assuntos
Interferon beta/farmacologia , Esclerose Múltipla Recidivante-Remitente/sangue , Inibidor Tecidual de Metaloproteinase-1/sangue , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Injeções Intramusculares , Interferon beta-1a , Interferon beta/administração & dosagem , Interferon beta/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Metaloproteinase 9 da Matriz/sangue , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/enzimologia , Esclerose Múltipla Recidivante-Remitente/metabolismo , Fatores de TempoRESUMO
OBJECTIVE: To use the new consensus definitions of primary progressive multiple sclerosis (PPMS) and progressive relapsing multiple sclerosis (PRMS) to report the demographic, clinical, and natural history characteristics of multiple sclerosis (MS) that is progressive from the time of onset. DESIGN: Retrospective study by database/chart review and telephone interview. SETTING: Multiple sclerosis clinic at a university teaching hospital. PATIENTS: Eighty-three patients (prevalence, 6.9%) with PPMS and 12 patients (prevalence, 1.0%) with PRMS were studied. RESULTS: Fifty-nine percent of the patients with PPMS (n=49) and 67% of the patients with PRMS (n=8) were women. Mean +/- SD ages at the time of onset were 41.2 +/- 10.5 and 38.0 +/- 7.3 years, respectively; mean disease duration was 14.2 +/- 8.8 and 12.2 +/- 6.5 years, respectively. The initial symptoms involved leg weakness in 94% of the patients with PPMS (n = 78) and 100% of the patients with PRMS (n= 12). For the PPMS cohort, a syndrome consistent with isolated myelopathy was found in 36% of patients (n = 30) and arm weakness without leg weakness did not occur. Mean +/- SEM time of progression to a score of 6.0 on the Expanded Disability Status Scale was 10.2 +/- 1.0 years for patients with PPMS and 10.9 +/- 2.6 years for patients with PRMS. CONCLUSIONS: The clinical characteristics and disability progression of these MS subtypes were indistinguishable, with the exception of 1 or 2 relapses in patients with PRMS that occurred 8 months to 9 years after the onset of symptoms. We see little reason to consider PPMS and PRMS separate clinical entities; however, whether they can be better distinguished by radiological, histopathological, or immunological markers of disease activity remains unknown.
Assuntos
Avaliação da Deficiência , Esclerose Múltipla/diagnóstico , Adulto , Idade de Início , Idoso , Encéfalo/patologia , Progressão da Doença , Potenciais Evocados , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Recidiva , Estudos Retrospectivos , Fatores de Risco , Medula Espinal/patologia , Fatores de TempoRESUMO
OBJECTIVE: To compare MS normal-appearing white matter (NAWM) where new gadolinium-enhancing (Gd+) lesions do and do not arise. METHODS: A total of 22 relapsing-remitting MS patients and 11 healthy control subjects completed as many as 12 monthly brain MRI sessions. Quantitative measures of gadolinium enhancement (GDR), water proton density (PDN), water proton T2 relaxation time constants (T2), magnetization transfer ratio (MTR), and T1-weighted signal intensity (T1N) were followed serially in healthy control and MS NAWM. RESULTS: A total of 129 new Gd+ lesions were identified in 11 patients. PDN, T2, MTR, and T1N were diffusely abnormal in MS NAWM. NAWM regions in which new Gd+ lesions arose have increased GDR, PDN, and T2, and reduced MTR and T1N compared with contralateral homologous NAWM regions in which no new Gd+ lesions arose. Differences between these NAWM regions preceded lesion appearance for at least several months. After lesions became visible, GDR returned to baseline within 2 months, and PDN and MTR had larger residual abnormalities than T2 or T1N. CONCLUSIONS: Quantitative MRI measures are diffusely abnormal in MS NAWM. These measures are, on average, more abnormal in NAWM regions in which new Gd+ lesions arise. After the appearance of Gd+ lesions, measures of PDN and MTR may provide more appealing markers of relatively irreversible tissue damage than measures of T2 and T1N.
Assuntos
Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/patologia , Fibras Nervosas/patologia , Adulto , Atrofia/diagnóstico , Feminino , Gadolínio , Humanos , Masculino , RecidivaRESUMO
OBJECTIVE: To 1) compare monthly serum levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-type 1 (TIMP-1) in patients with relapsing-remitting MS (RRMS) versus healthy controls and 2) determine the relationship among monthly serum levels of MMP-9 and TIMP-1 and MRI activity. BACKGROUND: Activated T-cells and macrophages secrete MMPs that may facilitate their migration across vascular subendothelial basement membranes into the CNS. The serum concentration of MMP-9 is reported to be higher in patients with RRMS than healthy controls. METHODS: Monthly evaluations including gadolinium-enhanced (Gd+) brain MRI and measures of serum MMP-9 and TIMP-1 were performed for up to 15 months in 24 patients with RRMS and for up to 4 months in 10 controls. RESULTS: Serum MMP-9 but not TIMP-1 levels are elevated in RRMS patients compared to healthy controls (p = 0.025, p = 0.61). In a univariate analysis, high MMP-9 and low TIMP-1 levels precede appearance of new Gd+ lesions (respectively; odds ratio = 3.3, p = 0.008; odds ratio = 2.2, p = 0.086). In a multivariate analysis, in comparison to months when MMP-9 is low and TIMP-1 high, MRI scans obtained the month following high MMP-9 and low TIMP-1 serum concentrations are more likely to report new Gd+ lesions (p = 0.0006, odds ratio = 21.5). CONCLUSION: An increase in the activity of matrix metalloproteinase-9 (MMP-9) relative to tissue inhibitor of MMP-type 1 (TIMP-1) may be related to formation of new MS lesions, suggesting that serum levels of MMP-9 and TIMP-1 may be surrogate markers of disease activity in relapsing-remitting MS.
Assuntos
Imageamento por Ressonância Magnética , Metaloproteinase 9 da Matriz/sangue , Esclerose Múltipla/sangue , Esclerose Múltipla/diagnóstico , Inibidor Tecidual de Metaloproteinase-1/sangue , Adolescente , Adulto , Encéfalo/patologia , Criança , Feminino , Gadolínio , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva , Valores de Referência , Análise de RegressãoRESUMO
BACKGROUND: The purposes of this study were to: (1) compare monthly serum IL-10 in patients with relapsing remitting (RR) multiple sclerosis (MS) and healthy controls, (2) determine the relationship between IL-10 and MRI activity and (3) determine the effect of interferon beta-1a (IFNB-1a) treatment on IL-10 levels. RESULTS: Median serum IL-10 levels were lower in untreated RRMS (185.5 pg/ml) compared to controls (438.5 pg/ml) (P=0.19). Serum levels of IL-10 did not appear to predict the appearance of new gadolinium-enhancing (Gd+) lesions concurrently or 1 month thereafter. However, IL-10 levels were more likely to be elevated the month during which Gd+ lesions resolved (OR=3.14, P=0.01). Median IL-10 levels were lower during IFNB-1a treatment (P=0.01). CONCLUSIONS: These observations suggest a relationship between serum IL-10 levels and resolution of abnormal vascular permeability in new lesions.
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Interferon beta/uso terapêutico , Interleucina-10/sangue , Esclerose Múltipla/tratamento farmacológico , Adolescente , Adulto , Criança , Feminino , Humanos , Interferon beta-1a , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologiaRESUMO
BACKGROUND: Disease progression in cystic fibrosis (CF) is marked by deterioration across a number of physiological systems. In addition, there is evidence that females have a worse prognosis than males. The current work assesses the impact of both these factors on health related quality of life (HRQoL). METHODS: Two hundred and twenty-three adolescents and adults completed the cystic fibrosis quality of life (CFQoL) questionnaire with a further 185 approached and not responding by non-completion of the questionnaire. The CFQoL is divided into nine domains: physical, social, treatment, chest symptoms, emotional functioning, concerns for the future, relationships, body image, and career. Measurement of objective clinical status included, body mass index (BMI), and percentage of predicted forced expiratory volume in one second (FEV1). General health perceptions (GHP) were also measured. RESULTS: Patients were sub-divided by gender and disease severity (mild > 70% FEV1, moderate 40-69% and severe < 40%). Factorial analysis of variance indicated significant main effects for FEV1 (F = 587.98, P < or = 0.001) and BMI (F = 17.29, P < or = 0.001) as a function of disease severity. Post hoc tests revealed significant two-group differences for FEV1 and BMI between disease severity groups. No differences were observed for gender across FEV1 or BMI. Differences emerged across most CFQoL domains for disease severity, with the exception of concerns for the future, which was consistently low throughout. Gender differences emerged for chest symptoms, emotional functioning, concerns for the future, body image and career. With the exception of body image, females exhibited poorer HRQoL. Pearson correlations indicated that females' perception of health was more closely related to clinical status than males. CONCLUSIONS: Disease severity has an impact on HRQoL in adolescents and adults with CF. Some differences emerged between males and females, with females generally reporting poorer HRQoL. Evidence indicated that males and females perceived their health status differently, with females having a more accurate perception of objective clinical health status.
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Atitude Frente a Saúde , Fibrose Cística/psicologia , Qualidade de Vida , Adaptação Psicológica , Adolescente , Adulto , Fatores Etários , Estudos Transversais , Fibrose Cística/diagnóstico , Fibrose Cística/terapia , Feminino , Seguimentos , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Percepção , Probabilidade , Testes de Função Respiratória , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Perfil de Impacto da Doença , Inquéritos e Questionários , Reino UnidoRESUMO
BACKGROUND: Generic health-related quality of life measures are often applied to disease groups without assessment of their psychometric properties. The current work assesses the properties of the Short Form 36-item (SF-36) questionnaire in a British sample of adolescents and adults with cystic fibrosis (CF). METHODS: Two hundred and twenty-three adolescents and adults with CF completed the SF-36 with a further 185 approached and not responding by non-completion of the questionnaire. The structure and internal reliability of the instrument was assessed by principal components analysis, Cronbach alpha coefficients and item to domain correlations. Differences between disease severity groups were assessed by analysis of variance. RESULTS: Factor analysis of the SF-36 scores broadly confirmed domain structures for the SF-36. Cronbach alpha coefficients were high (range 0.82-0.91) and item-to-same domain correlations were stronger than item-to-unrelated domain correlations. Examination of differences between mild, moderate and severe disease states revealed four significant main effects for: physical functioning, role limitation due to physical functioning, general health perceptions and energy and vitality. The analysis also revealed the presence of numerous ceiling effects across domains. CONCLUSIONS: The domain structure of the SF-36 was demonstrated to be robust. However, the discriminatory ability of the measure was disappointing. The presence of ceiling effects and the low frequency of differences between intermediate disease severity groups indicated that the SF-36 was not discriminatory with respect to mild disease states or progression of illness.
Assuntos
Fibrose Cística , Indicadores Básicos de Saúde , Qualidade de Vida , Inquéritos e Questionários , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fatores SexuaisRESUMO
AIMS: Possible risk factors were evaluated for herpes simplex virus (HSV) epithelial keratitis in patients with stromal keratouveitis. METHODS: The study population included 260 patients who had active stromal keratitis and/or iridocyclitis without epithelial disease and who were enrolled in one of three clinical trials of the Herpetic Eye Disease Study. Study treatment involved a 10 week course of topical placebo, topical prednisolone phosphate, or topical prednisolone phosphate with oral acyclovir. All groups received topical trifluridine four times daily for 3 weeks then twice daily for another 7 weeks. Patients were examined for HSV epithelial keratitis for 16 weeks. RESULTS: Dendritic or geographic epithelial keratitis occurred in 12 (4.6%) study patients. Adverse effects attributable to trifluridine prophylaxis were acute allergic blepharoconjunctivitis in 10 (3.8%) study patients and corneal epithelial erosions in 11 (4.2%) study patients. No significant difference in the occurrence of HSV epithelial keratitis was found among the study treatment groups: one (2.0%) of 49 topical placebo treated patients, nine (6.5%) of 138 patients treated with topical corticosteroids without acyclovir, and two (2.7%) of 73 patients treated with topical corticosteroids and oral acyclovir. Univariate exponential models suggested that patients with a history of previous HSV epithelial keratitis and non-white patients were more likely to develop HSV epithelial keratitis during treatment of stromal keratouveitis. CONCLUSION: Individuals with prior HSV epithelial keratitis and certain ethnic groups may have a higher rate of recurrent epithelial keratitis during the acute treatment of HSV stromal keratouveitis.
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Endotélio Corneano/virologia , Iridociclite/tratamento farmacológico , Ceratite Herpética/tratamento farmacológico , Aciclovir/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Iridociclite/virologia , Ceratite Dendrítica/etiologia , Ceratite Herpética/patologia , Masculino , Prednisolona/uso terapêutico , Recidiva , Fatores de Risco , Trifluridina/efeitos adversos , Trifluridina/uso terapêuticoRESUMO
When presterilized, closed canister, membrane filter units for sterility testing are validated for process, large volumes of therapeutic products for injection can be tested for sterility, recovered, and added to a subsequent bulk prior to sterile filtration. Intermittent positive pressure, applied to the canisters through the vent filters, makes possible the relatively rapid filtration, with minimal foaming, of viscous solutions such as 25% (w/v) normal serum albumin (human). Canister systems appear to be at least as effective as the standard membrane filter method, and the canisters are particularly suited to the sterility testing of bulks.
Assuntos
Contaminação de Medicamentos/prevenção & controle , Esterilização , Bactérias/crescimento & desenvolvimento , Tamanho da Partícula , UltrafiltraçãoRESUMO
Dentine specimens were prepared from freshly extracted third molars and initial permeability measured. Each specimen was subjected to Nd:yttrium-aluminium-garnet (YAG) (1.06 or 1.32 microns wavelength) or Ho:YAG (2.10 microns wavelength) laser energy while temperatures in the pulp chambers were recorded. Permeability was again measured and the surfaces examined by scanning electron microscopy. Six crown segments were used for each laser variable and eight permeability measurements were taken before and eight after laser exposure, while temperature was recorded during treatment. All wavelengths reduced permeability but temperature rises were high enough to have caused pulpal damage, indicating that shorter treatment times and lower power settings may be necessary if used in vivo.
Assuntos
Temperatura Corporal/efeitos da radiação , Cavidade Pulpar/efeitos da radiação , Líquido Dentinal/efeitos da radiação , Lasers , Silicatos de Alumínio , Análise de Variância , Polpa Dentária/lesões , Polpa Dentária/efeitos da radiação , Cavidade Pulpar/fisiologia , Cavidade Pulpar/ultraestrutura , Dentina/fisiologia , Dentina/efeitos da radiação , Dentina/ultraestrutura , Permeabilidade da Dentina/efeitos da radiação , Líquido Dentinal/metabolismo , Hólmio , Humanos , Microscopia Eletrônica de Varredura , Dente Serotino , Neodímio , Lesões por Radiação/etiologia , Coroa do Dente/efeitos da radiação , ÍtrioRESUMO
The effects of duration of storage and selection of storage solution upon dentin permeability and bond strength were studied over a period of 8 days to 6 mon. Teeth were stored immediately after extraction in one of five commonly used solutions: 70% ethanol (E); 10% formalin (F); distilled water (W); distilled water with thymol (WT); or phosphate-buffered saline with thymol (ST). Permeability and lap shear bond strength measurements were evaluated in a repeated measures design (n = 20) after 8 days, 15 days and 6 mon. Dentin permeability varied with solution type and duration of storage as demonstrated by ANOVA, increasing F, E and the water-based solutions, respectively. Saline storage resulted in large significant decreases in permeability after prolonged storage, suggesting changes in dentin. Bond strengths were unaffected by duration of storage or by solution type, except for saline. Thus, permeability and bond strength values may be affected by storage conditions. The results of this study indicate that saline, the most commonly used solution in dental materials research, may be unsuitable for use as a result of its effect on dentin permeability and bond strength.
Assuntos
Colagem Dentária , Permeabilidade da Dentina , Cimentos de Resina , Preservação de Tecido/métodos , Análise de Variância , Resinas Compostas , Permeabilidade da Dentina/efeitos dos fármacos , Etanol/farmacologia , Formaldeído/farmacologia , Humanos , Teste de Materiais , Cloreto de Sódio/farmacologia , Timol/farmacologia , Fatores de Tempo , ÁguaRESUMO
OBJECTIVES: Tooth storage conditions in studies of dentine have not been standardized. The objective of this investigation was to determine the effects of storage solution and time on dentine, using spectroscopic methods. METHODS: Twenty-seven dentine disks (0.75 mm thick) were prepared from freshly extracted third molars with documented histories. The teeth were sectioned parallel to the occlusal plane using a diamond saw. Specimens were analysed non-destructively for surface chemical changes using specular reflectance infra-red Fourier transform spectroscopy (SRIFTS), and changes in optical properties were measured in the ultraviolet, visible and near-infra-red spectral ranges with an integrating sphere spectrophotometer (UV/VIS/NIR) before and after storage. A minimum of five specimens were stored in distilled water with 0.02% thymol, purified and filtered water, phosphate buffered saline with 0.02% thymol, 70% ethanol or 10% buffered formalin and evaluated at 0, 1, 2, 7, 14, 21 and 28 days. After each measurement, specimens were stored in fresh solutions. IR spectra were obtained from 4400 to 400 wave-numbers (cm-1). Optical properties of reflectance and transmittance were determined from 200 to 2500 nm, and absorbance was calculated. RESULTS: Analysis of the IR spectra indicated no significant differences in collagen or mineral peak positions for any solution at any time period. There were significant differences in peak intensities of dentine stored in distilled water, purified and filtered water and phosphate-buffered saline over time in the IR spectra. Furthermore, differences in optical properties of dentine disks were detected by UV/VIS/NIR. CONCLUSION: It was concluded that changes in surface chemistry and optical properties of dentine occur as a function of storage solution and time, which must be considered when studying dentine.
Assuntos
Dentina/química , Manejo de Espécimes , Anti-Infecciosos , Soluções Tampão , Colágeno/análise , Etanol , Formaldeído , Humanos , Óptica e Fotônica , Fosfatos , Cloreto de Sódio , Soluções/química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Espectroscopia de Luz Próxima ao Infravermelho , Timol , Fatores de Tempo , ÁguaRESUMO
This review focuses on the two major psychosocial areas currently topical in cystic fibrosis research: treatment adherence and quality of life. First, the paper discusses the importance of evaluating adherence to treatments and medical advice, its measurement, predictors of adherence and non-adherence and whether the data should be used to inform clinical practice and policy decisions. Second, the purpose of evaluating quality of life in cystic fibrosis and an overview of the data are discussed. Both areas have suffered from problems with terminology and definition, inappropriate methodologies and hence difficulties with data interpretation. Future directions for research are advocated.