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1.
Group Decis Negot ; 32(1): 147-176, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36258887

RESUMO

In this paper, we apply the Analytic Hierarchy Process approach to conflict resolution in the context of the Russia-Ukraine conflict. We build models that illustrate the evaluation criteria, strategic and sub-criteria, and concessions for each party in this negotiation. Ratings are used to evaluate the degree to which concessions contribute or take away from successful resolution of the conflict. Afterwards, gain ratios are built to determine the benefit-cost scores so that concessions may be traded that result in equitable solutions. The approach presented here demonstrates for the first time why all concessions that parties to a conflict may offer might not trade all at once. A Max-Min optimization approach is used to maximize the gain to both parties of the conflict while minimizing the disparity in gain between the two.

3.
Medicine (Baltimore) ; 102(39): e34485, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37773818

RESUMO

BACKGROUND: Some previous studies have highlighted the high rate of mental health problems associated with type II diabetes (T2DM). The primary purpose of this study was to investigate the effect of a religious coping intervention of rational emotive behavior therapy (REBT) on the mental health of adult learners with T2DM. METHODS: This study utilized a randomized controlled trial to select 146 adult learners with T2DM and mental health-related problems. The treatment group was made up of 73 adult learners, while the control group was also made up of 73 adult learners. The experimental group received 8 sessions of a religious coping intervention of REBT, while the control group received usual care. Data were collected using the patient health questionnaire, Warwick-Edinburgh mental well-being scale, and Kessler psychological distress scale. Repeated ANOVA and univariate analysis of covariance were used for data analyses. RESULTS: The religious coping intervention of REBT substantially enhanced the mental health of adult learners with T2DM as measured by Warwick-Edinburgh mental well-being scale (P < .000) and patient health questionnaire (P < .000). The religious coping intervention of REBT significantly alleviated the psychological distress of adult learners with T2DM as measured by Kessler psychological distress scale (P < .000). CONCLUSION: In this study, it has been demonstrated that a religious coping intervention of REBT effectively improves the mental health of adult learners with T2DM. The study concludes that the religious coping intervention of REBT is a practical alternative medicine approach to enhancing the mental health of adult learners with T2DM.


Assuntos
Terapia Cognitivo-Comportamental , Diabetes Mellitus Tipo 2 , Humanos , Adulto , Saúde Mental , Diabetes Mellitus Tipo 2/terapia , Adaptação Psicológica , Psicoterapia , Terapia Comportamental
4.
J Clin Invest ; 59(4): 704-15, 1977 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-845257

RESUMO

The metabolism of the fifth component of complement (C5), and its relatonship to metabolism of the third component of complement (C3), has been studied in normal subjects and patients by simultaneous administration of radioiodine labeled C5 and C3. In seven normal subjects the fractional catabolic rate of C5 ranged from 1.5 to 2.1% of the plasma pool/h and extravascular/intravascular distribution ratio from 0.22 to 0.78, these values being similar to those obtained for C3, and synthesis rate from 71 to 134 mug/kg per h, In patients with complement activation the increase in fractional catabolic rate of C5 was nearly always less than that of C3. The data also showed that there was increased extravascular distribution of C3 and C5 in most patients and considerable extravascular catabolism of both proteins in some. However, there were differences in metabolic parameters between patients with different types of complement activation. In patients with systemic lupus erythematosus, fractional catabolism and extravascular distribution of C3 and C5 were both increased, and there was marked extravascular catabolism of both proteins. There was increased fractional catabolism and extravascular distribution of C3 in patients with mesangiocapillary nephritis and (or) partial lipodystrophy, and fractional catabolism of C5 was also increased in three of six studies although distribution of C5 was always within the normal range; however, in two patients with nephritic factor in their serum fractional catabolism of C5 was normal despite markedly increased C3 turnover, suggesting that in patients with alternative pathway activation by nephritic factor little or no C5 convertase is generated.


Assuntos
Complemento C3/metabolismo , Complemento C5/metabolismo , Proteínas do Sistema Complemento/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Nefrite/metabolismo , Adolescente , Adulto , Complemento C3/análise , Complemento C5/análise , Feminino , Hepatite/metabolismo , Humanos , Falência Renal Crônica/metabolismo , Lipodistrofia/metabolismo , Masculino , Pessoa de Meia-Idade
6.
Transplantation ; 72(11): 1795-802, 2001 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-11740391

RESUMO

BACKGROUND: The systematic application of living-related and cadaveric, in situ split-liver transplantation has helped to alleviate the critical shortage of suitable-sized, pediatric donors. Undoubtedly, both techniques are beneficial and advantageous; however, the superiority of either graft source has not been demonstrated directly. Because of the potential living-donor risks, we reserve the living donor as the last graft option for pediatric recipients awaiting liver transplantation. Inasmuch as no direct comparison between these two graft types has been performed, we sought to perform a comparative analysis of the functional outcomes of left lateral segmental grafts procured from these donor sources to determine whether differences do exist. METHODS: A retrospective analysis of all liver transplants performed at a single institution between February 1984 and January 1999 was undertaken. Only pediatric (<18 years) recipients of left lateral segmental grafts procured from either living-related (LRD) or cadaveric, in situ split-liver (SLD) donors were included. A detailed analysis of preoperative, intraoperative, and postoperative variables was undertaken. Survival was estimated using the Kaplan-Meier method, and comparison of variables between groups was undertaken using the t test of Wilcoxon rank sum test. RESULTS: There were no significant differences in the preoperative variables between the 39 recipients of SLD grafts and 34 recipients of LRD grafts. The donors did differ significantly in mean age, ABO blood group matching, and preoperative liver function testing. Postoperative liver function testing revealed significant early differences in aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, prothrombin time, and alkaline phosphatase, with grafts from LRD performing better than those from SLD. SLD grafts also had significantly longer ischemia times and a higher incidence of graft loss owing to primary nonfunction and technical complications (9 vs. 2, P<0.05). However, six of these graft losses in the SLD group were because of technical or immunologic causes, which, theoretically, should not differ between the two groups. Furthermore, these graft losses did not negatively impact early patient survival as most patients were successfully rescued with retransplantation (30-day actuarial survival, 97.1% SLD vs. 94.1% LRD, P=0.745). In the surviving grafts, the early differences in liver function variables normalized. CONCLUSIONS: Inherent differences in both donor sources exist and account for differences seen in preoperative and intraoperative variables. Segmental grafts from LRD clearly performed better in the first week after transplantation as demonstrated by lower liver function variables and less graft loss to primary nonfunction. However, the intermediate function (7-30 days) of both grafts did not differ, and the early graft losses did not translate into patient death. Although minimal living-donor morbidity was seen in this series, the use of this donor type still carries a finite risk. We therefore will continue to use SLD as the primary graft source for pediatric patients awaiting liver transplantation.


Assuntos
Transplante de Fígado/métodos , Fígado/fisiopatologia , Adulto , Criança , Feminino , Humanos , Transplante de Fígado/efeitos adversos , Doadores Vivos , Masculino , Estudos Retrospectivos , Fatores de Tempo , Doadores de Tecidos , Resultado do Tratamento
7.
Br J Pharmacol ; 128(1): 234-40, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10498857

RESUMO

1. Liposomes with conventional and long-circulation times were employed as carriers for the methotrexate derivative MTX-gamma-DMPE (MTX-EPC and MTX-PEG respectively), their mechanism of action was investigated in vitro and in vivo and their therapeutic efficacy assessed using the rat collagen-induced arthritis (CIA) model. 2. At non-toxic dose, both MTX-EPC and MTX-PEG inhibited the lipopolysaccharide (LPS) induced release of IL-1beta from activated rat peritoneal macrophages (rPMPhi) in a dose and time dependent manner. Free methotrexate (MTX) was not active in this respect. After a single intravenous injection (i.v.), and at equivalent doses, both free MTX (500 microg) and MTX-EPC inhibited the LPS induced rise in plasma IL-1beta levels observed in MTX-PEG and saline treated rats. 3. When used to treat established CIA, MTX-EPC resulted in significantly lower clinical score (CS) (1.0+/-0.42 (P<0.001)) and hind paw diameter (HPD) (6.5+/-0.34 mm (P<0.001)) measurements than controls (3.0+/-0.26; 7.33+/-0.41 mm), after only two i.v. doses, and remained significantly lower for the entire experimental period. By day 24 both CS (2+/-0.61 (P<0.001)) and HPD (6.97+/-0.25 mm (P<0.002)) measurements had also become significantly lower in MTX-PEG treated rats than in saline treated controls (3.62+/-0.17, 7. 92+/-0.38 mm) and remained lower until day 30. Joint inflammation in MTX treated rats was completely ameliorated by day 20 but the health and well being of the animals was compromised and the experiment terminated at this time-point. 4. Our results clearly demonstrate that both MTX-EPC and MTX-PEG liposomes have potential for development into therapeutic modalities for the treatment of inflammatory joint disease in man.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Artrite/tratamento farmacológico , Interleucina-1/biossíntese , Metotrexato/análogos & derivados , Fosfatidiletanolaminas/farmacologia , Animais , Anti-Inflamatórios não Esteroides/metabolismo , Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite/sangue , Artrite/induzido quimicamente , Artrite/patologia , Bovinos , Colágeno/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Portadores de Fármacos , Membro Posterior/efeitos dos fármacos , Membro Posterior/patologia , Interleucina-1/sangue , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Lipossomos , Macrófagos Peritoneais/metabolismo , Metotrexato/metabolismo , Metotrexato/farmacocinética , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Fosfatidiletanolaminas/metabolismo , Fosfatidiletanolaminas/farmacocinética , Fosfatidiletanolaminas/uso terapêutico , Ratos , Ratos Endogâmicos Lew , Fatores de Tempo
8.
Autoimmunity ; 13(4): 333-6, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1472644

RESUMO

Recent reports have detailed the presence of autoantibodies characteristic of non-organ specific autoimmune diseases in the serum of patients with autoimmune postpartum thyroiditis (PPT). These observations suggest that PPT could be part of a polyclonal B-cell activation postpartum. We have measured 4 non-organ specific autoantibodies (anti-DNA, anti-cardiolipin, anti-nuclear factor (ANF) and antibodies against extractable nuclear antigens (ENA)) together with autoantibodies against thyroglobulin and thyroid peroxidase in a group of PPT women at 4 time points during the first year postpartum (early, time of hyperthyroidism, time of hypothyroidism, late). Whilst 18/18 patients showed thyroid specific autoantibody changes there was only a low frequency of occurrence of the non-organ specific autoantibodies (ENA 2/18; ANF 1/18; anti-DNA 2/18; anti-dsDNA 0/18; anti-cardiolipin 0/18) and, when positive, the response was poor. We conclude that PPT is not associated with a polyclonal b-cell activation but is a postpartum rebound of a thyroid specific autoimmune phenomenon.


Assuntos
Autoanticorpos/análise , Transtornos Puerperais/imunologia , Tireoidite Autoimune/imunologia , Anticorpos Antinucleares/análise , Cardiolipinas/imunologia , Feminino , Humanos , Iodeto Peroxidase/imunologia , Tireoglobulina/imunologia
9.
Bone Marrow Transplant ; 4(5): 529-31, 1989 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2790331

RESUMO

Chronic graft-versus-host disease (cGVHD) bears clinical similarities to connective tissue diseases which are characterized by a spectrum of autoantibody formation. A wide range of autoantibody analyses in 19 allogeneic and 16 autologous bone marrow transplant (BMT) patients has determined that the most commonly detected antibody is IgM anti-cytoplasmic factor (ACF) occurring in 37% and 20% of allogeneic and autologous group respectively and of a type not normally seen in connective tissue disease. The antigen is as yet unidentified. These results suggest that autoantibody formation post-BMT is unrelated to the graft-versus-host process. Ophthalmic examination revealed evidence of a Sjögren-like syndrome in 20% autologous and 47% allogeneic patients, suggesting that the development of dry eyes post-BMT is not uniquely a feature of cGVHD.


Assuntos
Autoanticorpos/biossíntese , Transplante de Medula Óssea/imunologia , Doença Enxerto-Hospedeiro/imunologia , Adulto , Transplante de Medula Óssea/efeitos adversos , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Ceratoconjuntivite Seca/etiologia , Masculino , Pessoa de Meia-Idade , Síndrome de Sjogren/etiologia , Transplante Autólogo , Transplante Homólogo
10.
QJM ; 89(11): 821-9, 1996 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8977961

RESUMO

We examined HLA-DR genotype risk in 288 patients with rheumatoid arthritis who were carefully categorized for disease severity. Five hundred ethnically-matched bone-marrow donors were controls. A hierarchy of positive allelic associations was noted with DRB1*0401 (p < 10(-38), *0404,8 (p < 10(-43), *0405 (p < 10(-8), *10 (p < 10(-3) and *0101,2 (p < 10(-2), while DRB1*0403 was negatively associated (p = 0.02). The DRB1 genotype relative risks (and 95% CIs) for RA were: *0404,5,8/*0404,5,8 = 36.2 (15-87), *0401/*0404,5,8 = 31.3 (18-55), *401/*0401 = 18.8 (11-35), *0101,2/*0404,5,8 = 6.0 (2-14), *0101,2/*0401 = 6.4 (3-12), *0101,2/*0101,2 = 1.3 (0.3-6), *10/*0404,5,8 = 27.8 (5-148), *10/*0401 = 20.8 (5-89), *10/*0101,2 = 22.3 (5-96), *0404,5,8/DRX = 5.0 (3-8), *0401/DRX = 4.7 (3-7), *0101,2/DRX = 2.3 (1.4-4), *10/DRX = 3.4 (0.8-14). No significant correlation of DRB1 genotypes was found with severity of RA as judged by nodules or articular erosions.


Assuntos
Artrite Reumatoide/genética , Antígeno HLA-DR1/genética , Artrite Reumatoide/patologia , Mapeamento Cromossômico , Suscetibilidade a Doenças , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Conformacional de Fita Simples , Estudos Prospectivos , Risco
11.
J Infect ; 10(1): 51-6, 1985 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-3981025

RESUMO

A patient is described who presented with chronic endocarditis, due to Neisseria meningitidis, affecting a previously normal mitral valve. The illness was associated with glomerulonephritis that caused renal impairment and the nephrotic syndrome. Despite antibiotic treatment and replacement of the mitral valve, serum complement values remained very low, only returning to normal when immune complexes and a type III cryoglobulin disappeared from the circulation three months after resection of the valve vegetation. Such acquired hypocomplementaemia may have contributed to the chronicity of the disease process in this patient.


Assuntos
Proteínas do Sistema Complemento/deficiência , Endocardite Bacteriana/imunologia , Infecções Meningocócicas/imunologia , Valva Mitral , Adulto , Complexo Antígeno-Anticorpo/análise , Doença Crônica , Feminino , Doenças das Valvas Cardíacas/imunologia , Humanos
12.
J Pharm Pharmacol ; 46(4): 291-5, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8051613

RESUMO

The ability of methotrexate and three lipophilic derivatives (methotrexate-gamma-dimyristoylphosphatidylethanolamine (M gamma D), methotrexate-alpha-dimyristoylphosphatidylethanolamine (M alpha D) and methotrexate-alpha-gamma-di-dimyristoylphosphatidylethanolamine (M alpha gamma D) to modulate mediator release by lipopolysaccharide-stimulated rat peritoneal macrophages was investigated. At nontoxic concentrations, approximately 10 nmol/10(5) cells, M alpha D and M gamma D produced 11.06 +/- 1.0 and 75.6 +/- 5.2%, respectively, inhibition of tumour necrosis factor (TNF) release (mean +/- s.e.m., n = 4). At this same dose M alpha gamma D resulted in 68.8 +/- 2.1% inhibition of TNF but cellular ATP levels were reduced by 80%. The inhibitory activity of all three derivatives was dose-dependent. Non-derivatized methotrexate at a concentration of 25 nmol/10(5) cells had no inhibitory effect upon TNF release (14.7 +/- 0.8%, n = 3). Determination of prostaglandin E2 (PGE2) levels in the same samples demonstrated that all three conjugates were powerful inhibitors of prostaglandin release. At a quarter of the conjugate concentrations described above the monoamides M alpha (3.1 nmol/10(5) cells) and M gamma D (2.5 nmol/10(5) cells) maintained their effects on PGE2 production with 73 +/- 2.3 and 71 +/- 2.0% (n = 4) inhibition, respectively. At this lower concentration, however, the diamide M alpha gamma D (3.1 nmol/10(5) cells) was less effective in reducing the amount of PGE2 released from the macrophages (29 +/- 18%, n = 4). Maximal PGE2 inhibition by each of the conjugates was attained at approximately 5 nmol/10(5) cells. Unconjugated methotrexate (range of 2.5-20 nmol/10(5) cells) did not inhibit the release of PGE2 from lipopolysaccharide-stimulated macrophages.


Assuntos
Dinoprostona/biossíntese , Lipopolissacarídeos/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Metotrexato/toxicidade , Fator de Necrose Tumoral alfa/biossíntese , Animais , Sobrevivência Celular/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Masculino , Metotrexato/análogos & derivados , Camundongos , Radioimunoensaio , Ratos , Ratos Wistar , Células Tumorais Cultivadas
13.
J Pharm Pharmacol ; 44(1): 10-4, 1992 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1350620

RESUMO

125I-Labelled polyvinylpyrrolidone ([125I]PVP) of a range of molecular weights (mol. wt 10, 40 and 360 kDa) was injected i.v. into adjuvant-induced arthritic and normal rats and the blood clearance and tissue distribution of the polymers determined. The half-life of PVP in the circulation increased with increasing mol. wt; 10, 40 and 360 kDa polymers had mean terminal half-lives of 2.2, 6.9 and 16.4 h, respectively. Tissue uptake was also found to be mol. wt dependent, the largest PVP molecule accumulating to a greater extent in the spleen, liver, lungs and paws in both normal and arthritic rats (P less than 0.01) than the two lower mol. wt polymers. Accumulation of the polymer in inflamed paws (g tissue)-1 greatly exceeded that of normal paws (P less than 0.01). This difference was particularly noticeable with 360 kDa PVP, where arthritic paws amassed 7 times more PVP than normal paws.


Assuntos
Artrite Experimental/metabolismo , Pé/fisiologia , Povidona/farmacocinética , Animais , Cromatografia em Gel , Feminino , Meia-Vida , Radioisótopos do Iodo , Povidona/química , Ratos , Ratos Endogâmicos , Distribuição Tecidual
14.
Clin Rheumatol ; 8(3): 381-5, 1989 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2805613

RESUMO

We describe a 63-year-old female who developed the CREST syndrome within two years. Even though she was anticentromere antibody positive, her illness followed a very aggressive course and was associated with severe polyarthritis, renal impairment, hypocomplementaemia and mixed cryoglobulinaemia.


Assuntos
Anticorpos Antinucleares/análise , Artrite/complicações , Calcinose/imunologia , Centrômero/imunologia , Cromossomos/imunologia , Crioglobulinemia/complicações , Transtornos da Motilidade Esofágica/imunologia , Deformidades Adquiridas da Mão/imunologia , Doença de Raynaud/imunologia , Telangiectasia/imunologia , Doença Aguda , Artrite/imunologia , Crioglobulinemia/imunologia , Feminino , Humanos , Pessoa de Meia-Idade , Síndrome
15.
J Speech Lang Hear Res ; 41(4): 834-45, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9712130

RESUMO

The SCAN is a popular screening test that was developed to provide a rapidly administered, standardized method for determining the potential of central auditory processing disorder (CAPD) in children between the ages of 3 and 11 years. It can be administered in 20 minutes with a portable stereo cassette player and contains three subtests: filtered words (FW), auditory figure ground (AFG), and competing words (CW). Published SCAN test-retest reliability data (Keith, 1986) used a 6-month retest interval and indicated that SCAN scores may be unreliable. No additional reliability data are available, and studies indicate that SCAN has been used by both researchers and clinicians despite reliability concerns. This investigation examined the stability of SCAN outcomes for 25 first-grade and 22 third-grade children (ages 6 to 9 years) using a 6- to 7-week retest interval. Time of day and examiner were held constant, and participants were normal-hearing, were Caucasian, and spoke English as their primary language. ANOVA outcomes indicated that both raw and standard scores improved significantly from Test 1 to Test 2 for two of the three SCAN subtests (FW and CW) and for the composite (COMP) score. Additionally, COMP-percentile-rank and age-equivalent outcomes demonstrated significant improvement from test to retest for both grades. The AFG subtest was the only SCAN measure for which a significant test-retest difference did not emerge. The highest test-retest correlation values (r) were moderately strong (0.70 < or = r < or = 0.78) and occurred for the CW and COMP scores. Implications of correlations and factor analyses are discussed. It is suggested that examiners base recommendations for additional testing, follow up, and remediation on the COMP score only. Further, it appears that second administration of the SCAN can provide a better estimate of an individual child's best performance, but lack of second-score norms confounds simple interpretation of such scores.


Assuntos
Transtornos da Percepção/diagnóstico , Testes de Discriminação da Fala/métodos , Percepção da Fala/fisiologia , Fatores Etários , Análise de Variância , Criança , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes
16.
J Am Acad Audiol ; 6(6): 407-13, 1995 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8580500

RESUMO

Draft American National Standard "Evaluating the Effectiveness of Hearing Conservation Programs" identifies potentially important links between audiometric threshold variability outcomes and occupational hearing conservation program (HCP) practices. Unacceptable threshold variability in annual audiograms may identify poor testing practices and temporary threshold shifts. This preliminary investigation reveals pre-existing hearing loss to be a potentially important confounding viable to interpreting ANSI S12.13 outcomes. Poor hearing groups in this study consistently yielded greater threshold variability (i.e., "poorer" HCP performance) than better hearing groups. Gender may also be a confounding variable, however, to a far lesser degree. HCP managers should exercise caution when interpreting relative ANSI S12.13 outcomes among HCPs differing in baseline hearing sensitivity. Potential causes for these findings are discussed, and implications for future research are identified.


Assuntos
Transtornos da Audição/diagnóstico , Programas Nacionais de Saúde , Adulto , Audiometria , Feminino , Humanos , Masculino , Fatores Sexuais
17.
J Am Acad Audiol ; 9(2): 112-20, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9564673

RESUMO

Draft ANSI S12.13 1991 Standard Evaluating the Effectiveness of Hearing Conservation Programs presents statistical protocols purportedly sensitive to temporary threshold shift (TTS) in occupational hearing conservation program (HCP) audiometric databases. Because it is well established that less TTS is found in humans with hearing loss than in those with essentially normal hearing, one might predict baseline hearing level to be a confounding variable in interpreting ANSI S12.13 outcomes, with better-hearing industrial populations tending to demonstrate greater year-to-year audiometric variability than poorer-hearing groups. However, in a large industrial sample from the public domain audiometric database, poorer-hearing groups systematically demonstrated greater audiometric threshold variability than better-hearing groups, and ANSI S12.13 outcome magnitudes were highly positively correlated to baseline hearing levels. These findings generally do not support notions that ANSI S12.13 outcomes clearly provide indirect measures of TTS. HCP managers should exercise extreme caution in interpreting ANSI S12.13 outcomes to rate overall program performance. In particular, HCP managers should not rely upon these outcomes for decisions regarding hearing protection policies without careful consideration of pre-existing hearing loss in the populations involved.


Assuntos
Transtornos da Audição/diagnóstico , Adulto , Audiometria , Limiar Auditivo , Seguimentos , Humanos , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Fatores de Tempo
19.
Br J Pharmacol ; 167(3): 505-14, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22506619

RESUMO

BACKGROUND AND PURPOSE: Excess morbidity/mortality in rheumatoid arthritis (RA) is associated with increased incidence of cardiovascular disease. In this 'proof-of-concept' study, vascular function was characterized in the murine collagen-induced arthritis (mCIA) model, the benchmark choice for evaluation of the pathological processes and assessment of new therapies. EXPERIMENTAL APPROACH: Mice in the very early stages of arthritis development [and appropriate naïve (non-immunized) age-matched controls] were used in the study. Blood pressure was measured using tail cuff plethysmography. Vascular function in rings of isolated aorta was studied with isometric tension myography. Levels of NO metabolites (NO(x)), MMP-9 protein and IL-1ß in plasma and MMP-9 protein in aortic homogenates were quantified. KEY RESULTS: Impaired vascular contractile responses in arthritis were unaffected by ex vivo inhibition of NOS (endothelial/neuronal and inducible) or COX activities. Endothelium-dependent and -independent relaxation, plasma NO(x) and blood pressure were unaffected by arthritis. Plasma and aortic homogenate MMP-9 protein levels were increased significantly in arthritis. Incubation of aortic tissues from naïve control animals with exogenous MMP-9 impaired subsequent contractile responses, mirroring that observed in arthritis. A role for IL-1ß in perpetuating contractile dysfunction and increasing aortic MMP-9 was excluded. CONCLUSIONS AND IMPLICATIONS: These data identify for the first time a relationship between early arthritis and contractile dysfunction and a possible role for MMP-9 therein, in the absence of overt endothelial dysfunction or increased NO production. As such, MMP-9 may constitute a significant target for early intervention in RA patients with a view to decreasing risk of cardiovascular disease.


Assuntos
Aorta Torácica/metabolismo , Artrite Experimental/fisiopatologia , Metaloproteinase 9 da Matriz/metabolismo , Músculo Liso Vascular/metabolismo , Animais , Aorta Torácica/enzimologia , Artrite Experimental/complicações , Pressão Sanguínea , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Interleucina-1beta/sangue , Masculino , Camundongos , Camundongos Endogâmicos DBA , Contração Muscular , Miografia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo
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