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OBJECTIVES: The Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial compared hematopoietic stem cell transplant to CYC treatment in patients with early SSc with progressive skin and lung or kidney involvement. Here we describe lymphocyte phenotype abnormalities at study entry and the relation to prior DMARD therapy. METHODS: Lymphocyte subsets (n = 26) measured by flow cytometry were compared in 123 heathy controls and 71 SCOT participants, including those given (n = 57) or not given (n = 14) DMARDs within 12 months of randomization. RESULTS: Compared with healthy controls, individuals with SSc showed significant reductions in central memory CD8 T cells, activated total and CD4 T cells, γ/δ T cells, memory B cells, myeloid and plasmacytoid dendritic cells and FOXP3+CD25+ Treg cells and increases in naïve CD4 T cells, effector memory CD4 T cells and effector CD8 T cells. A greater bias towards a IL-4+ Th2/T cytotoxic 2 (Tc2) phenotype based on the Th2:Th1 CD4 ratio and Tc2:Tc1 CD8 T cells was also found. Notably, no difference in any lymphocyte subset was observed between those given or not given prior DMARDs. CONCLUSIONS: In patients with early, severe SSc, significant lymphocyte subset abnormalities were observed. Prior treatment with immunosuppressive therapy did not impact the immunophenotype, suggesting that lymphocyte disturbances in scleroderma appeared to be due to the disease itself. TRIAL REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov), NCT00114530.
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Antirreumáticos , Células TH1 , Linfocitos T CD8-positivos , Ciclofosfamida/uso terapéutico , Factores de Transcripción Forkhead , Terapia de Inmunosupresión , Inmunosupresores/uso terapéutico , Interleucina-4 , Subgrupos Linfocitarios , Fenotipo , Subgrupos de Linfocitos T , Células Th2RESUMEN
OBJECTIVES: We sought to examine the relationship between measures of ILD severity and PH in patients with SSc. METHODS: We identified 55 subjects from 12 PHAROS sites with RHC-proven PH and HRCT evidence of ILD. Subjects with PH due to left heart disease were excluded. Baseline HRCT scans were scored by a standardised system that graded severity of ILD. Summary statistics were generated for baseline characteristics. Spearman correlation and linear regression were used to examine relationships between ILD and PH severity variables. RESULTS: The majority of subjects were white women; nearly half had limited cutaneous SSc. Most subjects were New York Heart Association functional class II or III. Pulmonary function testing revealed moderate restriction (mean FVC 64.3 ± 17.2% predicted) with severe reduction in diffusing capacity (mean DLco 34.2 ± 13.3% predicted). RHC demonstrated mild to moderate PH (mean PAP 35 ± 9 mmHg, mean PVR 5.1 ± 3.7 WU). There was no correlation between severity of ILD (by either HRCT or PFT) and cardiac haemodynamic parameters of PH. CONCLUSIONS: No association between severity of ILD and cardiac haemodynamic profiles were identified in this cohort. We believe this underscores the complex nature of PH and ILD in individuals with SSc. We do suspect that some individuals with SSc-ILD will also have concomitant pulmonary vascular disease but simple assessments to grade severity of ILD - by PFT or HRCT estimates of ILD extent - are likely not enough to reliably distinguish between PAH versus PH-ILD. Further research into how to distinguish and manage these subsets is warranted.
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Hipertensión Pulmonar/fisiopatología , Enfermedades Pulmonares Intersticiales/fisiopatología , Pulmón/fisiopatología , Esclerodermia Difusa/fisiopatología , Esclerodermia Limitada/fisiopatología , Anciano , Prueba de Esfuerzo , Femenino , Humanos , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/etiología , Pulmón/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/etiología , Masculino , Persona de Mediana Edad , Capacidad de Difusión Pulmonar , Esclerodermia Difusa/complicaciones , Esclerodermia Difusa/diagnóstico por imagen , Esclerodermia Limitada/complicaciones , Esclerodermia Limitada/diagnóstico por imagen , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnóstico por imagen , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X , Capacidad VitalRESUMEN
OBJECTIVE: Among individuals with systemic sclerosis (SSc) randomized to cyclophosphamide (CYC) (n = 34) or hematopoietic stem cell transplantation (HSCT) (n = 33), we examined longitudinal trends of clinical, pulmonary function, and quality of life measures while accounting for the influence of early failures on treatment comparisons. METHODS: Assuming that data were missing at random, mixed-effects regression models were used to estimate longitudinal trends for clinical measures when comparing treatment groups. Results were compared to observed means and to longitudinal trends estimated from shared parameter models, assuming that data were missing not at random. Longitudinal trends for SSc intrinsic molecular subsets defined by baseline gene expression signatures (normal-like, inflammatory, and fibroproliferative signatures) were also studied. RESULTS: Available observed means for pulmonary function tests appeared to improve over time in both arms. However, after accounting for participant loss, forced vital capacity in HSCT recipients increased by 0.77 percentage points/year but worsened by -3.70/year for CYC (P = 0.004). Similar results were found for diffusing capacity for carbon monoxide and quality of life indicators. Results for both analytic models were consistent. HSCT recipients in the inflammatory (n = 20) and fibroproliferative (n = 20) subsets had superior long-term trends compared to CYC for pulmonary and quality of life measures. HSCT was also superior for modified Rodnan skin thickness scores in the fibroproliferative subset. For the normal-like subset (n = 22), superiority of HSCT was less apparent. CONCLUSION: Longitudinal trends estimated from 2 statistical models affirm the efficacy of HSCT over CYC in severe SSc. Failure to account for early loss of participants may distort estimated clinical trends over the long term.
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Trasplante de Células Madre Hematopoyéticas , Esclerodermia Localizada , Esclerodermia Sistémica , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Inmunosupresores/uso terapéutico , Calidad de Vida , Trasplante Autólogo , Ciclofosfamida/uso terapéutico , Esclerodermia Sistémica/diagnóstico , Esclerodermia Sistémica/tratamiento farmacológico , Esclerodermia Localizada/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: People with multiple sclerosis (PwMS) have reduced bone mineral density (BMD), but the causes are unclear. Some factors that may cause reduced BMD in PwMS have been understudied, including physical activity, inflammation, cortisol, symptomatic fatigue, and depression. The aim of this study was to investigate factors that may uniquely contribute to reduced BMD in PwMS as compared to people without MS. We hypothesized that physical activity would be the primary determinant of low BMD in PwMS, with additional contributions from inflammation and sympathetic nervous system activation. METHODS: We tested 23 PwMS (16 women; median EDSS: 2) and 22 control participants (16 women). BMD was measured from the femoral neck and lumbar spine with dual x-ray absorptiometry. Disability was measured with the Expanded Disability Status Scale, and functional capacity was measured with the Multiple Sclerosis Functional Composite. Questionnaires measured symptomatic fatigue and depression. A blood draw was used to measure calcium, phosphate, vitamin D, N-terminal telopeptide, osteopontin, and cytokine markers of inflammation. Physical activity was measured with accelerometry. Salivary cortisol and cardiac heart rate variability also were obtained. All outcome variables were compared between groups with independent samples t-tests. Variables that were different between groups and significantly correlated (Pearson product-moment) with femoral neck BMD, were included in a theoretical model to explain femoral neck BMD. The expected direction of relations in the theoretical model were developed based upon the results of previous research. A Bayesian path analysis was used to test the relations of predictive variables with femoral neck BMD and interrelations among predictive variables, as detailed in the theoretical model. RESULTS: PwMS had lower BMD at the femoral neck than controls (p = =0.04; mean difference: -0.09; 95% CI: -0.2, -0.004; Cohen's d = =0.65), and there was a smaller, statistically non-significant difference in BMD at the lumbar spine (p = =0.07; mean difference: -0.08; 95% CI: -0.17, 0.007; Cohen's d = =0.59). PwMS also had lower functional capacity (p ≤ 0.001; Cohen's d = =1.50), greater fatigue (p<0.001; Cohen's d = =1.88), greater depression (p<0.001; d = =1.31), and decreased physical activity (p = =0.03; Cohen's d = =0.62). Using path analysis to test our theoretical model, we found that disability (standardized estimate= -0.17), physical activity (standardized estimate=0.39), symptomatic fatigue (standardized estimate= -0.36), depression (standardized estimate= -0.30), and inflammatory markers (standardized estimate=0.27) explained 51% of the variance in femoral neck BMD. Inflammatory markers were also predictive of disability (standardized estimate=0.44) and physical activity (standardized estimate= -0.40). Symptomatic fatigue and depression were correlated (r = =0.64). CONCLUSION: Physical activity, symptomatic fatigue, depression, disability, and inflammation all contributed independently to decreased femoral neck BMD in PWMS. Bone metabolism in PwMS is complex. Efforts to increase physical activity and address symptomatic fatigue and depression may improve bone mineral density in PwMS. Future research should investigate the mechanisms through which symptomatic fatigue and depression contribute to reduced BMD in PwMS.
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Enfermedades Óseas Metabólicas , Depresión , Ejercicio Físico , Fatiga , Inflamación , Esclerosis Múltiple , Absorciometría de Fotón , Adulto , Densidad Ósea/fisiología , Enfermedades Óseas Metabólicas/diagnóstico por imagen , Enfermedades Óseas Metabólicas/epidemiología , Enfermedades Óseas Metabólicas/etiología , Comorbilidad , Depresión/epidemiología , Ejercicio Físico/fisiología , Fatiga/epidemiología , Femenino , Cuello Femoral/diagnóstico por imagen , Humanos , Inflamación/epidemiología , Inflamación/inmunología , Inflamación/metabolismo , Vértebras Lumbares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/fisiopatología , Esclerosis Múltiple/psicología , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To review current literature on the gastrointestinal tract (GIT) manifestations of systemic sclerosis (SSc) and to report on 5 patients with severe gastrointestinal SSc. MATERIALS AND METHODS: The clinical course and histopathology of 5 patients are described. A review of the medical literature registered in MedLine and PreMedLine databases from 1996 through mid-2004 was performed using the keywords systemic sclerosis and scleroderma and combining them with text words such as gastric, gastrointestinal, anorectal, colonic, and hepatic. RESULTS: All 5 patients had severe GIT involvement: 4 with diffuse cutaneous SSc (dcSSc) and 1 with limited cutaneous SSc (lcSSc). Autopsy results of 2 patients who died from severe malnutrition and aspiration pneumonia are presented. Literature review includes involvement from oral cavity to anus with varying degrees of severity. Most GIT manifestations result from dysmotility secondary to infiltration of the gastrointestinal wall with fibrous tissue and can cause life-threatening malabsorption and malnutrition. Diagnostic tests, pathology, and treatments of GIT SSc are reviewed. CONCLUSIONS: GIT involvement in SSc can be severely debilitating and even life-threatening. Although morbidity is inevitable, appropriate supportive treatment can prolong survival. RELEVANCE: GI complications of SSc cause significant morbidity and mortality.
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Enfermedades Gastrointestinales/etiología , Esclerodermia Localizada/complicaciones , Esclerodermia Sistémica/complicaciones , Adulto , Femenino , Enfermedades Gastrointestinales/mortalidad , Enfermedades Gastrointestinales/patología , Humanos , Persona de Mediana EdadRESUMEN
An 85-year-old woman with rheumatoid arthritis that was treated with azathioprine presented with a posterior thoracic soft-tissue mass. A computed tomographic scan demonstrated a large mass in the chest wall that extended into the pleural space and several pulmonary nodules that were consistent with metastatic disease. A fine-needle biopsy was performed, and a morphologic diagnosis of sarcoma was made. As the patient was relatively asymptomatic and the lesion was inaccessible to a surgical procedure, no therapy was recommended. Therapy with azathioprine was discontinued. One year later, the mass had resolved. To our knowledge, this is the first reported case of a soft-tissue sarcoma complicating azathioprine treatment of rheumatoid arthritis.
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Antirreumáticos/administración & dosificación , Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Azatioprina/administración & dosificación , Azatioprina/efectos adversos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Sarcoma/inducido químicamente , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Sarcoma/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
The hypothesis, that cytochrome P4502D6, cytochrome P4502CMP, cytochrome P4503A4 or N-acetyl-transferase may form active intermediary metabolites that could be etiologically related to vinyl chloride-induced disease was investigated in 21 drug-free workers with previous development of vinyl chloride-induced disease and in 23 drug-free workers from the same plant who did not develop the syndrome. Each subject received simultaneous oral administration of debrisoquin (10 mg), mephenytoin (100 mg), and dapsone (100 mg). Measurement of the debrisoquin recovery ratio, the 8-hour recovery of 4-hydroxymephenytoin, and the dapsone recovery ratio in the subsequent 8-hour urine sample provided in vivo phenotypic indexes of cytochromes P4502D6, P4502CMP, and P4503A4 activity, respectively. An 8-hour blood sample was used to measure the acetylation ratio, a measure of N-acetyltransferase activity. The frequency distributions of each drug metabolizing activity were similar between groups. Within this small sample, there was no evidence to implicate cytochromes P4502D6, P4502CMP, and P4503A4 and N-acetyltransferase in the pathogenesis of vinyl chloride-induced disease.
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Dapsona/metabolismo , Debrisoquina/metabolismo , Mefenitoína/metabolismo , Enfermedades Profesionales/metabolismo , Cloruro de Vinilo/efectos adversos , Arilamina N-Acetiltransferasa/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/enzimología , Oxidación-Reducción , Fenotipo , Análisis de RegresiónRESUMEN
Exposure to certain environmental agents may induce a scleroderma-like syndrome in a small proportion of individuals. Differences in susceptibility could involve metabolic activation of a protoxin, with affected patients having a greater converting ability. This possibility was investigated in 84 patients with scleroderma and 108 control subjects with in vivo probes of specific pathways of metabolism. Scleroderma was associated with reduced hydroxylating activity for dapsone and S-mephenytoin, whereas the ability to hydroxylate debrisoquin and N-acetyl dapsone was similar in both groups. Logistic regression confirmed these associations based on the shift in frequency distribution. Individuals who were poor metabolizers for mephenytoin and only modest N-hydroxylators of dapsone had a tenfold increased risk of scleroderma (p = 0.008). Thus this combined metabolic impairment may be causally involved in the development of scleroderma or, alternatively, the disease may produce inhibition of selected metabolizing enzymes in a subset of patients.
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Dapsona/metabolismo , Debrisoquina/metabolismo , Hidantoínas/metabolismo , Isoquinolinas/metabolismo , Mefenitoína/metabolismo , Esclerodermia Sistémica/metabolismo , Acetilación , Adulto , Biotransformación , Dapsona/efectos adversos , Debrisoquina/efectos adversos , Susceptibilidad a Enfermedades , Femenino , Humanos , Hidroxilación , Modelos Logísticos , Londres , Masculino , Mefenitoína/efectos adversos , Persona de Mediana Edad , Oxidación-Reducción , Esclerodermia Sistémica/epidemiología , Esclerodermia Sistémica/etiología , TennesseeRESUMEN
The recent development of other nonsteroidal anti-inflammatory agents (NSAIDs) has challenged the role of aspirin in the initial treatment of rheumatoid arthritis. The ready availability of aspirin as "an over-the-counter" preparation has contributed to its low esteem among both patients and physicians as a truly potent anti-inflammatory agent. But whether these newer, more expensive NSAIDs are more efficacious in the treatment of rheumatoid arthritis than aspirin remains to be proven. Most clinical trials of the newer agents have compared their efficacy against fixed doses of aspirin which were almost always too small to produce optimal anti-inflammatory serum salicylate levels. In our experience, individually tailored doses of aspirin remains the most predictable and consistently effective NSAID available for the initial treatment of rheumatoid arthritis. We also want to make it clear that we almost never rely on aspirin or other NSAIDs to control seropositive rheumatoid arthritis. Their chief advantage is rapidity of action. We do rely on the use of remittive agents to control rheumatoid joint inflammation, in conjunction with aspirin or other NSAID.
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Artritis Reumatoide/tratamiento farmacológico , Aspirina/farmacología , Animales , Aspirina/farmacocinética , Tiempo de Sangría , Química Farmacéutica , Sistema Digestivo/efectos de los fármacos , Hipersensibilidad a las Drogas/etiología , Humanos , Riñón/efectos de los fármacosRESUMEN
An understanding of the normal aging process and its effects on common laboratory values is essential when evaluating the elderly patient. Although results of research to determine precise changes in values for this age-group in hemoglobin, hematocrit, white cell count, ESR, serum bilirubin and alkaline phosphatase, SGOT, and glomerular filtration have not been conclusive in most instances, some of the findings described here warrant consideration. We believe that the established normal ranges for these values do not need to be significantly modified for the elderly and that slight deviations from them are normal for the healthy patient. However, all abnormal test results should not be attributed to aging alone; the clinician might overlook the need for further diagnostic workup for possible serious disorders.
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Anciano , Pruebas Hematológicas , Pruebas de Función Renal , Pruebas de Función Hepática , Adulto , Factores de Edad , Sedimentación Sanguínea , Estudios de Evaluación como Asunto , Femenino , Tasa de Filtración Glomerular , Hematócrito , Humanos , Masculino , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
OBJECTIVE: To assess cumulative survival rates and identify independent predictors of mortality in patients with incident systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH) who had undergone routine screening for PAH at SSc centers in the US. METHODS: The Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma registry is a prospective registry of SSc patients at high risk for PAH or with definite pulmonary hypertension diagnosed by right-sided heart catheterization within 6 months of enrollment. Only patients with World Health Organization group I PAH (mean pulmonary artery pressure >25 mm Hg and pulmonary capillary wedge pressure <15 mm Hg without significant interstitial lung disease) were included in these analyses. RESULTS: In total, 131 SSc patients with incident PAH were followed for a mean ± SD of 2.0 ± 1.4 years. The 1-, 2-, and 3-year cumulative survival rates were 93%, 88%, and 75%, respectively. On multivariate analysis, age >60 years (hazard ratio [HR] 3.0, 95% confidence interval [95% CI] 1.1- 8.4), male sex (HR 3.9, 95% CI 1.1-13.9), functional class (FC) IV status (HR 6.5, 95% CI 1.8 -22.8), and diffusing capacity for carbon monoxide (DLCO) <39% predicted (HR 4.2, 95% CI 1.3-13.8) were significant predictors of mortality. CONCLUSION: This is the largest study describing survival in patients with incident SSc-associated PAH followed up at multiple SSc centers in the US who had undergone routine screening for PAH. The survival rates were better than those reported in other recently described SSc-associated PAH cohorts. Severely reduced DLCO and FC IV status at the time of PAH diagnosis portended a poor prognosis in these patients.
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Hipertensión Pulmonar/mortalidad , Sistema de Registros , Esclerodermia Sistémica/complicaciones , Anciano , Hipertensión Pulmonar Primaria Familiar , Femenino , Humanos , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/etiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estados Unidos/epidemiologíaRESUMEN
We present a case of a 69-year-old woman who received external beam radiation for the treatment of breast cancer. Seven months later, she developed generalized morphea involving the area of irradiated skin of the breast as well as distant sites of the groin and distal lower extremity. Postirradiation morphea is an uncommon yet well-documented phenomenon, usually confined to the radiated site and the immediate surrounding tissue. To our knowledge, this is only the fourth reported case of morphea occurring distant from the radiation field. While most cases of postirradiation morphea have been shown to either resolve spontaneously or respond to topical corticosteroids, our patient required systemic therapy with methotrexate, which resulted in clinical improvement. With this paper, we hope to bring further awareness to this phenomenon and demonstrate a successful treatment response with the use of methotrexate in postirradiation generalized morphea.
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OBJECTIVE: Raynaud's phenomenon (RP) affects 3-9% of the general population and >90% of patients with systemic sclerosis. Nitrates are often prescribed for the treatment of RP, but currently available formulations are limited by side effects, particularly headaches, dizziness, and skin irritation. The purpose of this study was to evaluate the tolerability and efficacy of a novel formulation of topical nitroglycerin, MQX-503, in the treatment of RP in an ambulatory setting. METHODS: We conducted a multicenter, randomized, placebo-controlled study with a 2-week single-blind run-in period to determine baseline severity, followed by a 4-week double-blind treatment phase. Two hundred nineteen adult patients with a clinical diagnosis of primary or secondary RP received 0.9% MQX-503 gel or matching placebo during the treatment period. Gel was applied immediately before or within 5 minutes of the beginning of an episode of RP (maximum of 4 applications daily). End points included the change in the mean Raynaud's Condition Score (RCS; scale 0-10), the frequency and duration of episodes, and subjective assessments at the target week (the week during the treatment phase that most closely matched the run-in period in terms of ambient temperature) compared with baseline. RESULTS: The mean (%) change in the RCS at the target week compared with baseline was significantly greater in the MQX-503 group (0.48 [14.3%]) than that in the placebo group (0.04 [1.3%]; P = 0.04). Changes in the frequency and duration of RP episodes and subjective assessments were not statistically different between the groups. MQX-503 had a side effect profile similar to that of placebo. CONCLUSION: MQX-503 is well tolerated and more effective than placebo for the treatment of RP.
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Nitroglicerina/uso terapéutico , Enfermedad de Raynaud/tratamiento farmacológico , Vasodilatadores/uso terapéutico , Administración Tópica , Adulto , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nitroglicerina/administración & dosificación , Nitroglicerina/efectos adversos , Enfermedad de Raynaud/patología , Índice de Severidad de la Enfermedad , Método Simple Ciego , Vasodilatadores/administración & dosificación , Vasodilatadores/efectos adversosRESUMEN
OBJECTIVE: To determine the prevalence of sexual abuse in women diagnosed as having fibromyalgia (FM) compared with controls. METHODS: A self-administered questionnaire designed to obtain information regarding demographics, health care utilization, and history of sexual and physical abuse was completed by 40 women with FM and by 42 women who had no evidence of connective tissue disease or other major medical condition. RESULTS: Women with FM reported more physical symptoms and were significantly different on multiple indices of health compared with controls. Twenty-six FM subjects (65%) reported sexual abuse, in comparison with 22 controls (52%). The prevalence and type of abuse were not significantly different between groups. Sexually abused FM subjects reported significantly more symptoms than did non-sexually abused FM women, but did not differ in the number of symptoms for which they sought medical treatment. CONCLUSION: Sexual abuse does not appear to be a specific factor in the etiology of FM, but is correlated with the number and severity of associated symptoms.
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Abuso Sexual Infantil/estadística & datos numéricos , Fibromialgia/complicaciones , Fibromialgia/psicología , Adolescente , Adulto , Preescolar , Femenino , Humanos , Persona de Mediana Edad , PrevalenciaRESUMEN
A 47-year-old woman with rheumatoid arthritis (RA) had been treated with greater than 7 g of gold sodium thiomalate over a 5 year period when aplastic anemia developed. Treatment with corticosteroids, plasmapheresis and infusion of N-acetylcysteine (NAC) resulted in complete hematologic remission. Infusion of NAC increased daily urinary excretion of gold and use of an ambulatory infusion pump with a Hickman catheter allowed protracted outpatient infusion for more than 4 months' duration. It is now 20 months since the onset of aplastic anemia and she remains in complete hematologic remission.
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Acetilcisteína/uso terapéutico , Anemia Aplásica/inducido químicamente , Oro/efectos adversos , Plasmaféresis , Prednisona/uso terapéutico , Anemia Aplásica/tratamiento farmacológico , Anemia Aplásica/patología , Anemia Aplásica/terapia , Artritis Reumatoide/tratamiento farmacológico , Médula Ósea/patología , Femenino , Oro/sangre , Oro/orina , Humanos , Persona de Mediana EdadRESUMEN
OBJECTIVE: To determine if minocycline therapy improved skin thickness in early, diffuse systemic sclerosis (SSc) by > or =30%, a level of improvement unlikely to occur in the natural history of the disease as determined by recent controlled trials. METHODS: Subjects with diffuse SSc of < or =5 years' duration were treated with oral minocycline for 1 year. The primary outcome measure was the modified Rodnan skin thickness score (MRSS). RESULTS: Of 36 subjects initially enrolled, 31 returned for at least 1 followup visit and were included in the analysis (modified intent-to-treat analysis). The group consisted of 23 women and 8 men, with a mean age of 51.7 years (range 26-82 years) and a mean disease duration of 23.5 months (range 6-60 months). The mean MRSS at entry was 22.7 (range 12-43), and at the final visit it was 18.6 (range 2-48). There was no statistically significant difference in the change in skin scores between the minocycline-treated subjects and subjects previously reported in the D-penicillamine (D-Pen) trial. In addition, when adjusted for disease duration, a comparison of MRSS in the minocycline trial subjects (including all subjects active at each time point) and the previously reported D-Pen trial subjects showed no difference and no treatment effect. Fourteen subjects did not complete all 12 months of treatment; 10 of them withdrew due to disease progression. Disease duration was significantly shorter for the noncompleters than for the completers (P < 0.03). CONCLUSION: The degree of change in the MRSS was similar to that expected in the natural course of this disease. Based on these data, minocycline is not an effective therapy for SSc.
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Antibacterianos/uso terapéutico , Minociclina/uso terapéutico , Esclerodermia Sistémica/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Minociclina/administración & dosificación , Penicilamina/uso terapéutico , Esclerodermia Sistémica/patología , Índice de Severidad de la Enfermedad , Piel/efectos de los fármacos , Piel/patología , Resultado del TratamientoRESUMEN
We describe a patient with viral induced aplastic anemia who developed severe bone pain after treatment with multiple courses of antithymocyte globulin, cyclosporine A, recombinant human granulocyte macrophage colony stimulating factor and deferoxamine. Radiographs and bone biopsy revealed extensive new trabecular bone formation in long bone diaphyses and adjacent periosteal reaction. The effects of hematopoietic growth factors, cyclosporine A and deferoxamine on bone metabolism are reviewed.
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Anemia Aplásica/tratamiento farmacológico , Huesos/efectos de los fármacos , Ciclosporinas/uso terapéutico , Sustancias de Crecimiento/uso terapéutico , Adolescente , Anemia Aplásica/diagnóstico por imagen , Anemia Aplásica/patología , Suero Antilinfocítico/uso terapéutico , Huesos/diagnóstico por imagen , Huesos/patología , Deferoxamina/uso terapéutico , Femenino , Peroné/diagnóstico por imagen , Peroné/efectos de los fármacos , Peroné/patología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Humanos , Radiografía , Proteínas Recombinantes/uso terapéutico , Tibia/diagnóstico por imagen , Tibia/efectos de los fármacos , Tibia/patologíaRESUMEN
Concurrent joint infection with Mycobacterium tuberculosis (TB) and demonstration of intraarticular monosodium urate (MSU) crystals has not previously been reported. We describe a patient with chronic tophaceous gout from whose joints both TB and MSU crystals were isolated. We propose a mechanism to explain this condition.
Asunto(s)
Artritis Gotosa/complicaciones , Artritis Infecciosa/complicaciones , Articulación de la Rodilla/microbiología , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis , Adulto , Humanos , Articulación de la Rodilla/química , Masculino , Ácido Úrico/aislamiento & purificaciónRESUMEN
BACKGROUND: Relaxin is a pregnancy-related hormone that has tissue remodeling and antifibrotic effects. Systemic sclerosis (scleroderma) is characterized by fibrosis of the skin, vasculature, and internal organs. OBJECTIVE: To assess the efficacy, safety, and dose-response effect of recombinant human relaxin in patients with scleroderma. DESIGN: Multicenter, parallel-group, randomized, double-blind, placebo-controlled trial. SETTING: Academic referral centers. PATIENTS: 68 patients who had had stable, diffuse scleroderma (moderate to severe) for less than 5 years. INTERVENTION: Recombinant human relaxin, 25 or 100 microg/kg of body weight per day, or placebo administered by continuous subcutaneous infusion over 24 weeks. MEASUREMENTS: Modified Rodnan skin score was the primary efficacy measure. Secondary measurements were pulmonary function, the Health Assessment Questionnaire, and other measures of scleroderma that reflected fibrosis. RESULTS: Patients who received 25 microg/kg of recombinant human relaxin per day had significantly lower skin scores than those who received placebo (mean change, -3.6 at 4 weeks [P = 0.021], -7.5 at 12 weeks [P < 0.001], and -8.7 at 24 weeks [P = 0.040]). Similar trends were noted in other outcome measures, including forced vital capacity, measures of oral aperture and hand extension, functional status, and global assessment. Patients who received 100 microg/kg of relaxin per day did not differ from those who received placebo. Drug-related adverse events included menometrorrhagia, reversible anemia, and complications of the subcutaneous drug administration system (site irritation and local infection). CONCLUSIONS: Twenty-four weeks of recombinant human relaxin, 25 microg/kg per day, is associated with reduced skin thickening, improved mobility, and improved function in patients with moderate to severe diffuse scleroderma.
Asunto(s)
Relaxina/administración & dosificación , Esclerodermia Sistémica/tratamiento farmacológico , Adolescente , Adulto , Anciano , Análisis de Varianza , Anemia/inducido químicamente , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Erupciones por Medicamentos/etiología , Exantema/inducido químicamente , Femenino , Humanos , Masculino , Menorragia/inducido químicamente , Persona de Mediana Edad , Placebos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Relaxina/efectos adversos , Esclerodermia Sistémica/patologíaRESUMEN
OBJECTIVE: To evaluate the efficacy and tolerability of an oral preparation of iloprost, a prostacyclin analog, in patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis (scleroderma). METHODS: A multicenter, randomized, parallel-group, placebo-controlled double-blind study was performed at university and community-based medical centers. Patients were randomly assigned to receive either 50 microg of iloprost orally twice daily or an identical gelatin-coated capsule containing placebo for 6 weeks. Outcome measures included average total daily duration of RP attacks, average number of RP attacks, and RP condition scored via a standardized daily diary. RESULTS: Three hundred eight patients with scleroderma (272 women, 36 men, mean age 49 years [range 18-80]) were enrolled. One hundred fifty seven were assigned to receive iloprost and 151 to receive placebo. One hundred forty-three patients in the iloprost group (91.1%) and 144 in the placebo group (95.4%) completed the 6-week treatment phase. Fifteen of these treated patients (8 iloprost, 7 placebo) failed to complete all of the followup visits. The mean reduction in the average duration of attacks from baseline to week 5-6 was 24.32 minutes in the iloprost group and 34.34 minutes in the placebo group (P = 0.569). Likewise, the mean reduction from baseline to week 5-6 in the daily frequency of attacks was 1.02 in the iloprost group and 0.83 in the placebo group (P = 0.459). The Raynaud's condition score, a patient-completed assessment of the severity of RP attacks, was reduced by 1.32 in the iloprost group and 1.00 in the placebo group (P = 0.323). The lack of significant difference between treatment groups did not change when a variety of factors, including use of other vasodilators, duration of disease, classification of scleroderma (limited versus diffuse), or number of baseline digital ulcers were taken into account. Premature withdrawal from the study due to adverse events occurred in 10 patients (6.4%) in the iloprost group and 3 (2.0%) in the placebo group (P = 0.058). CONCLUSION: Oral iloprost at a dosage of 50 microg twice daily is no better than placebo for management of RP secondary to scleroderma, either during 6 weeks of treatment or during 6 weeks of posttreatment followup.