ISSN:0002-9629    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The cause of rheumatoid arthritis (RA) is unknown; however, extensive research has yielded great insight into its pathogenesis. Lymphocytes play a significant role, but a lesser role in the perpetuation of late disease. The rheumatoid synovium is composed primarily of fibroblasts and monocytes that produce inflammatory cytokines, of which interleukin-1 and tumor necrosis factor are of key importance. Potential regulatory mechanisms balancing the effects of these cytokines are inadequate to prevent joint damage and subsequent disability. These cytokines seem responsible for stimulating destructive processes in the joint via induction of prostaglandins, angiogenesis, chemokines, adhesion molecules, osteoclastogenesis, and matrix metalloproteinases. This review discusses recent research findings in the immunopathogenesis of RA with respect to potential targets for therapy.

ISSN:0002-9629    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The elucidation of inducible cyclooxygenase (Cox-2) dependent inflammatory pathways led to the development of specific Cox-2 inhibitors, the coxibs. These agents include the currently available celecoxib and rofecoxib and such second-generation agents as parecoxib, valdecoxib, and etoricoxib. The therapeutic advantage of coxibs is founded primarily in their lack of significant gastrointestinal (GI) side effects. Clinical trials have demonstrated the efficacy of coxibs to be completely comparable with traditional nonsteroidal anti-inflammatory drugs (NSAIDs), and pharmacoeconomics suggest favorable cost/benefit ratios with these agents compared with traditional NSAIDs, related to their reduced GI complication profiles and lower indirect costs associated with disability. Although several clinical questions remain (eg, use with low-dose aspirin, risk of thrombosis, myocardial infarction, edema, and hypertension), the emergence and clinical utility of coxibs is likely to continue on the basis of their efficacy and relative GI safety advantage. Although newer, more specific Cox-2 inhibitors may alter the choice, it is likely that this class of anti-inflammatories will become (if they have not already) the drugs of first choice in the treatment of acute pain, chronic pain, and most rheumatic conditions in the 21st century. In addition to the treatment of rheumatic conditions, it is possible that coxibs will also be of clinical utility in protection against malignant transformation and Alzheimer disease.

ISSN:0002-9629    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Leflunomide, a new oral immunomodulatory agent, is effective for the treatment of rheumatoid arthritis. Its mechanism of action in suppressing inflammation is based in its inhibition of dihydroorotate dehydrogenase, an enzyme responsible for de novo synthesis of pyrimidine containing ribonucleotides. It is the first disease-modifying antirheumatic drug approved for treatment of rheumatoid arthritis with an indication for retardation of joint damage by radiography. Side effects are generally mild and include diarrhea, rashes, reversible alopecia, and elevation of hepatic transaminases. Despite the concern about hepatotoxicity, combination use with methotrexate in treating patients with rheumatoid arthritis has been shown to be safe. Other autoimmune diseases in which leflunomide has been used successfully include Felty syndrome, vasculitis, Sjogren syndrome, Wegener granulomatosis, and bullous pemphigoid.

ISSN:0002-9629    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Mycphenolate mofetil is a suppressor of T cell proliferation and adhesion. Its primary mode of action is inhibition of inosine monophosphate dehydrogenase, a purine salvage pathway required by T lymphocytes. Although the role of T cells in rheumatoid arthritis (RA) has been controversial, a preliminary report of mycophenolate mofetil’s successful use in RA patients clearly suggests that its efficacious properties need further investigation. Its favorable risk/benefit ratio, a broad clinical experience in kidney transplantation, and its recent extension to other rheumatic diseases suggests that this new antirheumatic agent has significant therapeutic potential for suppression of synovial inflammation.

ISSN:0002-9629    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The recent elucidation of pathogenic processes involving tumor necrosis factor &agr; and interleukin-1&bgr; in the pathogenesis and persistence of rheumatoid arthritis led to the development of biological modifier agents that have had significant impact on disease severity and progression. These agents—etanercept, infliximab, and anakinra—produce a dramatic reduction in RA disease activity with relatively low toxicity compared with currently available disease-modifying antirheumatic drugs. The main prohibition to their broader utilization is cost. The success of these agents underscores the investigative approaches to the pathogenesis of RA and the appropriate design of pharmaceutical agents to target specific proinflammatory molecules.

ISSN:0002-9629    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Leptin is the protein product of theobese(ob) gene, a lipostatic hormone that contributes to body weight regulation through suppressing appetite and/or stimulating energy expenditure in humans and/or rodents. In humans, serum leptin concentrations are increased in relation to increased body fat content. Studies have shown a higher leptin level in women compared with men. However, the gender influence on serum leptin concentrations has never been evaluated in patients with type 1 diabetes. In this study, serum leptin levels and percentage body fat mass were measured in men and women with type 1 diabetes. Fasting serum leptin levels were higher in women (16.7 ± 11.6 ng/mL) than in men (3.0 ± 1.5 ng/mL;P< 0.05) and were independent of exogenous insulin intake and of glucose control. Percentage body fat and fat mass were significant determinants of leptin concentration, whereas age and duration of diabetes were not related to leptin concentration. Subgroups of men (n = 12) and women (n = 11) with total body fat between 20 and 30% were compared. Leptin levels were also higher in women compared with men (13.5 ± 8.3 ng/mL versus 3.2 ± 1.7 ng/mL;P< 0.05, respectively). In conclusion, our findings indicate that gender is an important determinant of serum leptin concentration in type 1 diabetics, this gender difference is partly explained by body fat distribution and that type 1 diabetic women may be more resistant than type 1 diabetic men to leptin’s alleged lipostatic actions.

ISSN:0002-9629    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundParathyroid hormone (PTH) suppression in patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis is achieved largely by the use of intravenous calcitriol. Aspects of the utility and efficacy of this therapy remain controversial. It is debated whether oral versus intravenous therapy is more effective. Most existing studies examine the effect of calcitriol in isolation, without adjusting for other factors that might influence PTH levels. Thus, the simultaneous role of factors such as dosing, control of serum calcium and phosphorus, and demographic variables such as age, sex, race, and duration of ESRD is not well understood.MethodsWe examined the relationship between the administration of calcitriol and PTH suppression in a cohort of hemodialysis patients at a large urban dialysis facility over a period of 30 months. Hemodialysis patients (n = 155) who received at least 3 months of treatment in this facility were included.ResultsUsing a time sensitive multiple linear regression modeling technique, we found that second and subsequent PTH levels were positively correlated with black race (P< 0.0001) and serum phosphate (P< 0.03) and strongly negatively correlated with serum calcium (P< 0.0001) and diabetes (P< 0.0039). Drug dose (in micrograms per kilogram per month) was weakly negatively correlated (P< 0.04). Unlike previous studies, we adjusted for the simultaneous confounding influence of demographic and laboratory variables, as well as for drug dose normalized for body weight.ConclusionsThis analysis suggests that calcitriol therapy in hemodialysis patients is adversely affected by higher phosphate levels and needs to account for such patient characteristics as race and diabetes and such laboratory variables as calcium and phosphate control. Finally, as has been recently suggested by others, the patient’s race may require us to aim for different PTH target levels with therapy.

ISSN:0002-9629    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

With the arrival of Europeans in the Western Hemisphere, Native American populations were exposed to new infectious diseases, diseases for which they lacked immunity. These communicable diseases, including smallpox and measles, devastated entire native populations. In this article, we focus on the effect of smallpox on the Native Americans from the 15th through the 19th centuries. Among the “new” infectious diseases brought by the Europeans, smallpox was one of the most feared because of the high mortality rates in infected Native Americans. This fear may have been well-founded, because the Native Americans were victims of what was probably one of the earliest episodes of biological warfare. Fortunately, they were also major beneficiaries of early vaccination programs. Thus, the arrival of smallpox and the decline of the Native American populations are inexorably linked, as the history summarized here illustrates.

ISSN:0002-9629    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

A 54-year-old man developed unstable angina pectoris and was found to have both an anomalous left coronary artery, which arose from the right sinus of Valsalva and followed an intramyocardial (septal) course, and severe atherosclerotic stenosis of the mid-right coronary artery. Stress perfusion imaging showed ischemia in the distribution of the right coronary artery, leading to successful percutaneous transluminal balloon angioplasty of the right coronary artery rather than surgical correction of the congenital anomaly.

ISSN:0002-9629    

出版商:OVID    

年代:2002

数据来源: OVID