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1.
Artigo em Inglês | MEDLINE | ID: mdl-31628482

RESUMO

OBJECTIVES: 3-hydroxy-3-methylglutaryl coenzyme-A (HMG Co-A) reductase inhibitors (statins) are standard treatment for hyperlipidaemia. In addition to lipid-lowering abilities, statins exhibit multiple anti-inflammatory effects. The objectives of this study were to determine whether treatment of patients with RA with lovastatin decreased CRP or reduced disease activity. METHODS: We conducted a randomized double-blind placebo-controlled 12 week trial of lovastatin vs placebo in 64 RA patients with mild clinical disease activity but an elevated CRP. The primary efficacy end point was the reduction in mean log CRP. Secondary end points included disease activity, RF and anti-CCP antibody titres. Mechanistic end points included levels of serum cytokines. Safety was assessed; hepatic and muscle toxicities were of particular interest. RESULTS: Baseline features were similar between groups. No significant difference in mean log CRP reduction between the two groups was observed, and disease activity did not change from baseline in either treatment group. Mechanistic analyses did not reveal significant changes in any biomarkers. A post hoc analysis of subjects not using biologic therapy demonstrated a significantly greater proportion achieving ⩾20% reduction in CRP from baseline in the lovastatin group compared with placebo (P-value = 0.007). No difference was observed in subjects receiving biologics. Lovastatin was well tolerated with no serious safety concerns. CONCLUSION: This study showed no anti-inflammatory or clinical effects on RA disease activity after 12 weeks of treatment with lovastatin. Lovastatin had a modest effect on CRP in subjects not using biologics, suggesting statins may be anti-inflammatory in selected patients. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT00302952.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31497844

RESUMO

OBJECTIVE: To address heterogeneity complicating primary SS (pSS) clinical trials, research and care by characterizing and clustering patients by their molecular phenotypes. METHODS: pSS patients met American-European Consensus Group classification criteria and had at least one systemic manifestation and stimulated salivary flow of ⩾0.1 ml/min. Correlated transcriptional modules were derived from gene expression microarray data from blood (n = 47 with appropriate samples). Patients were clustered based on this molecular information using an unbiased random forest modelling approach. In addition, multiplex, bead-based assays and ELISAs were used to assess 30 serum cytokines, chemokines and soluble receptors. Eleven autoantibodies, including anti-Ro/SSA and anti-La/SSB, were measured by Bio-Rad Bioplex 2200. RESULTS: Transcriptional modules distinguished three clusters of pSS patients. Cluster 1 showed no significant elevation of IFN or inflammation modules. Cluster 2 showed strong IFN and inflammation modular network signatures, as well as high plasma protein levels of IP-10/CXCL10, MIG/CXCL9, BLyS (BAFF) and LIGHT. Cluster 3 samples exhibited moderately elevated IFN modules, but with suppressed inflammatory modules, increased IP-10/CXCL10 and B cell-attracting chemokine 1/CXCL13 and trends toward increased MIG/CXCL9, IL-1α, and IL-21. Anti-Ro/SSA and anti-La/SSB were present in all three clusters. CONCLUSION: Molecular profiles encompassing IFN, inflammation and other signatures can be used to separate patients with pSS into distinct clusters. In the future, such profiles may inform patient selection for clinical trials and guide treatment decisions.

3.
Arthritis Rheumatol ; 70(9): 1470-1480, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29604186

RESUMO

OBJECTIVE: To evaluate the clinical efficacy and safety of baminercept, a lymphotoxin ß receptor IgG fusion protein (LTßR-Ig), for the treatment of primary Sjögren's syndrome (SS), and to explore the possible mechanisms of action of this treatment. METHODS: In this multicenter trial, 52 patients with primary SS were randomized in a 2:1 ratio to receive subcutaneous injections of 100 mg of baminercept every week for 24 weeks or matching placebo. The primary end point was the change between screening and week 24 in the stimulated whole salivary flow (SWSF) rate. Secondary end points included the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI), as well as measurements of select chemokines and cytokines and enumeration of peripheral blood B and T cell subsets. RESULTS: The change from baseline to week 24 in the SWSF rate was not significantly different between the baminercept and placebo treatment groups (baseline-adjusted mean change -0.01 versus 0.07 ml/minute; P = 0.332). The change in the ESSDAI during treatment was also not significantly different between the treatment groups (baseline-adjusted mean change -1.23 versus -0.15; P = 0.104). Although the incidence of adverse events was similar between the treatment groups, baminercept therapy was associated with a higher incidence of liver toxicity, including 2 serious adverse events. Baminercept also produced a significant decrease in plasma levels of CXCL13 and significant changes in the number of circulating B and T cells, consistent with its known inhibitory effects on LTßR signaling. CONCLUSION: In this trial, treatment with baminercept failed to significantly improve glandular and extraglandular disease in patients with primary SS, despite evidence from mechanistic studies showing that it blocks LTßR signaling.


Assuntos
Proteínas Recombinantes de Fusão/uso terapêutico , Síndrome de Sjogren/tratamento farmacológico , Adulto , Idoso , Linfócitos B/efeitos dos fármacos , Quimiocina CXCL13/sangue , Método Duplo-Cego , Feminino , Humanos , Receptor beta de Linfotoxina/imunologia , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes de Fusão/imunologia , Síndrome de Sjogren/sangue , Síndrome de Sjogren/imunologia , Linfócitos T/efeitos dos fármacos , Resultado do Tratamento
5.
Diabetes ; 62(11): 3766-74, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23835333

RESUMO

Trials of immune therapies in new-onset type 1 diabetes (T1D) have shown success, but not all subjects respond, and the duration of response is limited. Our aim was to determine whether two courses of teplizumab, an Fc receptor-nonbinding anti-CD3 monoclonal antibody, reduces the decline in C-peptide levels in patients with T1D 2 years after disease onset. We also set out to identify characteristics of responders. We treated 52 subjects with new-onset T1D with teplizumab for 2 weeks at diagnosis and after 1 year in an open-label, randomized, controlled trial. In the intent to treat analysis of the primary end point, patients treated with teplizumab had a reduced decline in C-peptide at 2 years (mean -0.28 nmol/L [95% CI -0.36 to -0.20]) versus control (mean -0.46 nmol/L [95% CI -0.57 to -0.35]; P = 0.002), a 75% improvement. The most common adverse events were rash, transient upper respiratory infections, headache, and nausea. In a post hoc analysis we characterized clinical responders and found that metabolic (HbA1c and insulin use) and immunologic features distinguished this group from those who did not respond to teplizumab. We conclude that teplizumab treatment preserves insulin production and reduces the use of exogenous insulin in some patients with new-onset T1D. Metabolic and immunologic features at baseline can identify a subgroup with robust responses to immune therapy.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Peptídeo C/metabolismo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Adolescente , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Criança , Feminino , Humanos , Masculino
6.
Violence Against Women ; 18(4): 506-11, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22865619

RESUMO

In this article, the editor of Everyday Pornography offers a response to Ronald Weitzer's 2011 review of that book, addressing questions about objectivity, the framing of pornography as violence against women, the role of women's testimony in debates about pornography, and research on porn's consumers.


Assuntos
Literatura Erótica , Sexualidade , Humanos
7.
Diabetes ; 61(9): 2340-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22721971

RESUMO

Rapamycin/interleukin-2 (IL-2) combination treatment of NOD mice effectively treats autoimmune diabetes. We performed a phase 1 clinical trial to test the safety and immunologic effects of rapamycin/IL-2 combination therapy in type 1 diabetic (T1D) patients. Nine T1D subjects were treated with 2-4 mg/day rapamycin orally for 3 months and 4.5 × 10(6) IU IL-2 s.c. three times per week for 1 month. ß-Cell function was monitored by measuring C-peptide. Immunologic changes were monitored using flow cytometry and serum analyses. Regulatory T cells (Tregs) increased within the first month of therapy, yet clinical and metabolic data demonstrated a transient worsening in all subjects. The increase in Tregs was transient, paralleling IL-2 treatment, whereas the response of Tregs to IL-2, as measured by STAT5 phosphorylation, increased and persisted after treatment. No differences were observed in effector T-cell subset frequencies, but an increase in natural killer cells and eosinophils occurred with IL-2 therapy. Rapamycin/IL-2 therapy, as given in this phase 1 study, resulted in transient ß-cell dysfunction despite an increase in Tregs. Such results highlight the difficulties in translating therapies to the clinic and emphasize the importance of broadly interrogating the immune system to evaluate the effects of therapy.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Células Secretoras de Insulina/fisiologia , Interleucina-2/administração & dosagem , Sirolimo/administração & dosagem , Linfócitos T Reguladores/imunologia , Animais , Diabetes Mellitus Tipo 1/imunologia , Quimioterapia Combinada , Humanos , Células Secretoras de Insulina/efeitos dos fármacos , Interleucina-2/uso terapêutico , Camundongos , Camundongos Endogâmicos NOD
8.
Public Health Nurs ; 27(6): 482-91, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21087301

RESUMO

OBJECTIVE: To assess the needs of clients in a home-based care (HBC) program aimed at improving the quality of lives of people living with HIV in Region 4 of Guyana (Demerara-Mahaica region) following their involvement with the HBC program, volunteers, and nurse providers. DESIGN AND SAMPLE: A cross-sectional analysis of a needs assessment conducted through a verbally administered questionnaire. We collected a cross-sectional sample of 84 HBC clients living with HIV from Region 4 in Guyana. MEASURES: Respondents were administered a questionnaire that asked questions regarding the demographics; services received; quality of service delivery; and mental health and substance abuse. RESULTS: The services most commonly received by respondents included nutritional assessment and counseling, HIV prevention education, emotional support, hygiene education, support for antiretroviral adherence, and support for HIV disclosure. Respondents reported further need of referrals to income-generation opportunities, food and nutritional supplement support, and support for children. Forty-two percent of the respondents screened positive for probable depression, and 37% of respondents screened positive for being at risk for a drinking problem. CONCLUSIONS: While a substantial portion of needs were addressed by the HBC program, outstanding needs included linking people living with HIV to income-generation opportunities, food support, mental health, and services for children. We suggest that mental health and substance use services be factored into HIV programming and that referral systems be strengthened to ensure access to support services for people living with HIV.


Assuntos
Adaptação Psicológica , Infecções por HIV/terapia , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Assistência Domiciliar/estatística & dados numéricos , Estresse Psicológico , Adulto , Estudos Transversais , Feminino , Guiana , Infecções por HIV/enfermagem , Infecções por HIV/psicologia , Indicadores Básicos de Saúde , Humanos , Entrevista Psicológica , Modelos Logísticos , Masculino , Saúde Mental , Satisfação do Paciente , Psicometria , Inquéritos e Questionários , Resultado do Tratamento
9.
Urology ; 71(1): 110-2, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18242376

RESUMO

OBJECTIVES: The purpose of this study was to determine the prevalence of sperm within post-ejaculatory urine in both fertile and infertile men. METHODS: Fifteen men of proven fertility and 66 non-azoospermic men being evaluated for infertility were recruited in two academic centers. Laboratory studies included a semen analysis and the examination of post-ejaculate urine for the presence and concentration of sperm. RESULTS: The median total urine sperm count for the fertile group (26.6 million) was not significantly greater than the infertile group (8.3 million, P = 0.63). The median percentage of total sperm (urine plus semen) present in urine for the fertile group (14.8%) was not different from that in the infertile group (15.3%, P = 0.36). Sperm were found in the urine of 73% of fertile and 65% of infertile patients (P = 0.54). CONCLUSIONS: The prevalence of sperm in the post-ejaculatory urine in the fertile population is similar to that in infertile patients, which suggests that a great deal more information is needed to interpret this test in the management of these patients.


Assuntos
Ejaculação/fisiologia , Infertilidade Masculina/urina , Contagem de Espermatozoides , Urinálise/normas , Urina/citologia , Adulto , Idoso , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sêmen
10.
Fertil Steril ; 85(4): 961-4, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16580381

RESUMO

OBJECTIVE: To determine whether sperm harvesting and cryopreservation at the time of vasectomy reversal is cost-effective. DESIGN: Model of actual costs and results at five institutions. SETTING: Multicenter study comprising five centers, including university hospitals and private practices. PATIENT(S): Men undergoing vasectomy reversal. INTERVENTION(S): We established two models for vasectomy reversal. The first model was sperm harvesting and cryopreservation at the time of vasectomy reversal. The second model was sperm harvesting at the time of IVF only if the patient remained azoospermic after vasectomy reversal. Vasectomy reversal procedures modeled included bilateral vasovasostomy and bilateral epididymovasostomy. The costs for each procedure at the five institutions were collated and median costs determined. MAIN OUTCOME MEASURE(S): Median cost of procedure and calculated financial comparisons. RESULT(S): The median cost of testicular sperm extraction/cryopreservation performed at the time of bilateral vasovasostomy was $1,765 (range, $1,025-$2,800). The median cost of microsurgical epididymal sperm aspiration or testicular sperm extraction with cryopreservation performed at the time of epididymovasostomy was $1,209 (range, $905-$2,488). The average of the median costs for percutaneous sperm aspiration or testicular sperm aspiration for those patients with a failed vasectomy reversal was $725 (range, $400-$1,455). CONCLUSION(S): Sperm retrieval with cryopreservation at the time of vasectomy reversal is not a cost-effective management strategy.


Assuntos
Criopreservação/economia , Preservação do Sêmen/economia , Coleta de Tecidos e Órgãos/economia , Vasovasostomia/economia , Análise Custo-Benefício , Criopreservação/métodos , Criopreservação/tendências , Humanos , Masculino , Preservação do Sêmen/métodos , Preservação do Sêmen/tendências , Coleta de Tecidos e Órgãos/métodos , Coleta de Tecidos e Órgãos/tendências , Vasovasostomia/métodos , Vasovasostomia/tendências
13.
Eur J Pediatr ; 161(7): 377-9, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12111189

RESUMO

UNLABELLED: Methylmalonic acidemia unresponsive to cobalamin is often fatal in infancy. Patients have been considered candidates for hepatic transplantation and experience has been that the procedure eliminates the life-threatening episodes of ketoacidosis that characterize this disease. CONCLUSION: experience with a 24-year-old patient treated with hepatic transplantation indicates that this procedure does not prevent progressive renal failure and neurologic dysfunction.


Assuntos
Lesão Renal Aguda/etiologia , Transplante de Fígado , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/cirurgia , Ácido Metilmalônico/sangue , Metilmalonil-CoA Mutase/deficiência , Doenças do Sistema Nervoso/etiologia , Qualidade de Vida , Lesão Renal Aguda/fisiopatologia , Lesão Renal Aguda/terapia , Adulto , Progressão da Doença , Feminino , Humanos , Erros Inatos do Metabolismo/complicações , Metilmalonil-CoA Mutase/metabolismo , Doenças do Sistema Nervoso/fisiopatologia , Doenças do Sistema Nervoso/terapia , Prognóstico , Diálise Renal/métodos , Medição de Risco , Resultado do Tratamento
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