Familial clustering of autoimmune diseases in patients with dilated cardiomyopathy

In this study, we examined the hypothesis that dilated cardiomyopathy (DCM) shares genetic risk factors with other diseases of presumed autoimmune etiology, and, therefore, the same multiple genes in combination with environmental factors lead to numerous different autoimmune diseases. In accordance with this hypothesis, we showed an increased prevalence of autoimmune diseases in first-degree relatives of patients with DCM. Also, T-cell activation, as reflected in high levels of the soluble interleukin-2 receptor, appears to identify patients with DCM with a clustering of autoimmune diseases.     

Outcomes in patients with normal serum creatinine and with artificial renal support for acute renal failure developing after coronary artery bypass grafting

This retrospective study of cardiac surgical patients with normal serum creatinine who developed acute renal failure requiring artificial renal support was undertaken to (1) determine the prevalence of acute renal failure and hospital mortality in this subgroup, (2) identify the independent predictors of early mortality, and (3) determine long-term survival and prognosis.     

Neuroendocrine aspects of chronic fatigue syndrome

Chronic fatigue syndrome (CFS) is a serious health concern affecting over 800000 Americans of all ages, races, socioeconomic groups and genders. The etiology and pathophysiology of CFS are unknown, yet studies have suggested an involvement of the neuroendocrine system. A symposium was organized in March 2001 to explore the possibility of an association between neuroendocrine dysfunction and CFS, with special emphasis on the interactions between neuroendocrine dysfunction and other abnormalities noted in the immune and autonomic nervous systems of individuals with CFS. This paper represents the consensus of the panel of experts who participated in this meeting.     

From cannabis to cannabinergics: new therapeutic opportunities

The molecular basis of cannabinoid activity is better understood since the discovery of the CB(1) receptor in the mammalian brain and the CB(2) receptor in peripheral tissues. Subsequently, an endogenous CB(1) receptor ligand, arachidonylethanolamide (anandamide), was isolated from porcine brain and shown to be metabolized by the enzyme arachidonylethanolamide amidohydrolase or fatty acid amide hydrolase. Recently, we have characterized a reuptake system for the transport of anandamide across the cell membrane, and have shown that selective inhibition of this transporter is associated with analgesia and peripheral vasodilation. The four cannabinoid system proteins, including the CB(1) and CB(2) receptors, fatty acid amide hydrolase, and the anandamide transporter, are excellent targets for the development of novel medications for various conditions, including pain, immunosuppression, peripheral vascular disease, appetite enhancement or suppression, and motor disorders. During the last decade, numerous selective ligands for each of these proteins were designed and synthesized. Many of these agents serve as important molecular probes, providing structural information about their binding sites, as well as pharmacological tools imparting information about the roles of their targets in physiological and disease states. All of the above compounds that modulate the functions of the endocannabinoid system can be collectively described under the term cannabinergics, regardless of chemical classification or type of resultant pharmacological action.     

Management of mild aortic stenosis during coronary artery bypass surgery: an update, 1992-2001

BACKGROUND: "Prophylactic" aortic valve replacement (AVR) in patients with asymptomatic, mild-to-moderate aortic stenosis (AS) at the time of CABG is controversial. In 1994, we reported our initial experience involving 44 patients and have now updated our series in an attempt to further evaluate outcomes. METHODS: Between January 1992 and July 2001, 100 consecutive patients underwent reoperative AVR following previous CABG. Forty patients had their initial surgery at the Brigham & Women's Hospital (BWH) and 60 patients had their coronary surgery elsewhere. None of the 40 BWH patients had a mean valve gradient greater than 25 mmHg at the time of CABG. RESULTS: The mean time interval from CABG to AVR for the entire group was 9.0 years (range: 1.4-21 years). Overall operative mortality (OM) was 7% including 5 deaths (10.2%) among 49 patients requiring additional CABG at the time of AVR and 2 deaths (3.9%) among 51 patients without additional coronary artery intervention. This OM rate was a notable decrease from our earlier report of 18.2% (P = 0.07). Furthermore, operative mortality decreased progressively from 15.4% in 1992-1993 to 0% in 2000-2001 (P = NS). CONCLUSION: The OM of reoperative AVR following CABG has fallen in recent years. Given the relevance of newer techniques and approaches, it may be reasonable to adopt an expectant management approach in patients with asymptomatic mild-to-moderate AS (i.e., mean systolic gradient less than 25 mmHg) at the time of CABG.     

Methotrexate intolerance in elderly patients with rheumatoid arthritis: what are the alternatives?

Rheumatoid arthritis (RA) in the elderly may be mild or severe, with features that are similar to those seen in younger patients. As such, the treatment regimen in the elderly is almost the same as in younger patients. Methotrexate is the most popular disease-modifying antirheumatic drug (DMARD) for the treatment of RA in the US and Europe. It has excellent efficacy and an acceptable toxicity profile. However, a number of patients do not tolerate methotrexate and an alternative DMARD should be chosen.In the elderly, choice of an alternative DMARD should be made after careful consideration of several age-related factors including concomitant diseases, existing medication, drug compliance, and altered age-related physiology and pharmacokinetics.In elderly patients with RA who are unable to tolerate methotrexate, the alternatives are hydroxychloroquine or sulfasalazine for mild-to-moderate disease and cyclosporin or leflunomide for severe disease, given in combination with low-dose oral corticosteroids. This is primarily due to their efficacy combined with a relatively low toxicity profile compared with other DMARDs, such as gold compounds, penicillamine, azathioprine and alkylating agents. Where the above DMARDs are contraindicated, anticytokine therapy should be considered.The therapy of RA is a dynamic process and requires a delicate balance of benefits and risks. Experience and familiarity with the currently available agents, and knowledge of the nature of the disease are necessary in order to make better therapeutic decisions.