Cardiovascular reactivity score for the assessment of dysautonomia in familial Mediterranean fever

Objective The aim of this study was to assess the presence of dysautonomia, as manifested in abnormal cardiovascular reactivity, in patients with familial Mediterranean fever (FMF).Methods Fifty-five consecutive patients with FMF and 23 age- and sex-matched healthy controls were evaluated. Cardiovascular reactivity was studied: (1) using recordings of blood pressure (BP) and heart rate (HR) during 10 min of recumbence and 30 min of head-up tilt test to identify clinical endpoints and (2) during tilt-test, identifying parameters acting as independent predictors of FMF reactivity and enabling computation of a cardiovascular reactivity score (CVRS).Results Clinically, vasovagal reaction, postural tachycardia syndrome, and/or orthostatic hypotension were observed in ten patients (18.1%). Utilizing a derived equation, the group average CVRS in FMF was 5.83±1.78 (healthy group –7.60±5.41) (P=<0.0001). A CVRS of >3.25 was associated with FMF, with 98% sensitivity and 100% specificity.Conclusion A very high percentage of FMF patients exhibit abnormal cardiovascular reactivity which is clinically occult but can be detected on autonomic challenge and application of the CVRS.     

Clinical evidence for utilization of the A3 adenosine receptor as a target to treat rheumatoid arthritis: data from a phase II clinical trial

OBJECTIVE: Adenosine exerts antiinflammatory effects via activation of the A3 adenosine receptor (A3AR), a Gi protein-associated cell-surface receptor, overexpressed in synovial tissue and peripheral blood mononuclear cells (PBMC) in patients with active rheumatoid arthritis (RA). CF101 is a highly specific orally bioavailable A3AR agonist. METHODS: This was a multicenter study, blinded to dose, designed to assess the clinical activity and safety of CF101 in active RA. Seventy-four patients were randomized to receive 0.1, 1.0, or 4.0 mg CF101 bid for 12 weeks. The primary efficacy endpoint was American College of Rheumatology 20% response (ACR20) at Week 12. A3AR expression levels were analyzed in PBMC from 18 patients. RESULTS:. Maximal responses were observed with 1.0 mg bid, lower at 0.1 and 4.0 mg bid. At 12 weeks, 55.6%, 33.3%, and 11.5% of the patients receiving 1.0 mg CF101 achieved ACR20%, 50%, and 70% responses, respectively. CF101 was generally well tolerated, with mild headache (4.1%), nausea (2.7%), and rash (2.7%) being the most common treatment-related adverse events. Statistically significant correlations between A3AR overexpression at baseline and ACR50 and ACR70 responses were observed. CONCLUSION: CF101 administered bid for 12 weeks resulted in improvement in signs and symptoms of RA that did not achieve statistical significance, and was safe and well tolerated. The expression level of A3AR was directly correlated with patient responses to CF101, suggesting its utilization as a biomarker for the pharmacodynamic and therapeutic effects of this novel agent. These findings require confirmation in a double-blind randomized placebo-controlled trial, currently under way.     

Biological warfare: Implications for antimicrobial use

Biological warfare is intended to incapacitate a large number of individuals at a single exposure, creating epidemictype disease, death, and social chaos. The organisms with potential for immediate use as bacteriologic weapons are Bacillus anthracis, Brucella melitensis, Yersinia pestis, and Vibrio cholera, all necessitating antibiotic therapy for a cure. It is reasonable, therefore, to assume that a biological attack, or even a hoax, would requiure thousands of individuals over a large area to begin antibiotic therapy. Issues such as antibiotic availability, logistical problems in antibiotic distribution, development of drug resistance, side effects influencing the individual, and adverse effects on the community due to the impact of mass therapy on the ecology, make biological warfare the most apocalyptic scenario for the creation of a "postantibiotic era."     

Embolism from the aorta: Atheroemboli and thromboemboli

Opinion statement  |

Case finding and referral model for emergency department elders: a randomized clinical trial

STUDY OBJECTIVE: Elderly emergency department patients have complex medical needs and limited social support. A transitional model of care adapted from hospitals was tested for its effectiveness in the ED in reducing subsequent service use. METHODS: A randomized clinical trial was conducted at 2 urban, academically affiliated hospitals. Participants were 650 community-residing individuals 65 years or older who were discharged home after an ED visit. Main outcomes were service use rates, defined as repeat ED visits, hospitalizations, or nursing home admissions, and health care costs at 30 and 120 days. Intervention consisted of comprehensive geriatric assessment in the ED by an advanced practice nurse and subsequent referral to a community or social agency, primary care provider, and/or geriatric clinic for unmet health, social, and medical needs. Control group participants received usual and customary ED care. RESULTS: The intervention had no effect on overall service use rates at 30 or 120 days. However, the intervention was effective in lowering nursing home admissions at 30 days (0.7% versus 3%; odds ratio 0.21; 95% confidence interval [CI] 0.05 to 0.99) and in increasing patient satisfaction with ED discharge care (3.41 versus 3.03; mean difference 0.37; 95% CI 0.13 to 0.62). The intervention was more effective for high-risk than low-risk elders. CONCLUSION: An ED-based transitional model of care reduced subsequent nursing home admissions but did not decrease overall service use for older ED patients. Further studies are needed to determine the best models of care for this setting and for at-risk patients.     

Arthropathy,hypouricemia and normal serum iron studies in hereditary hemochromatosis

A patient manifesting the arthropathy of hemochromatosis without abnormal serum iron studies is described. Hemochromatosis was confirmed by liver biopsy. This case serves to emphasize the diagnostic value of the characteristic arthropathy of hemochromatosis. Our observations in this patient support the hypothesis that the pathogenesis of hereditary hemochromatosis differs from that of acquired iron overload states. The concurrent presence of hypouricemia is explored in this patient and in 18 other patients with hereditary hemochromatosis. Men with hereditary hemochromatosis were found to have lower serum uric acid levels than expected. In our patient, a renal defect in tubular reabsorption of uric acid appears responsible for hypouricemia.The apparent association of hemochromatosis and hypouricemia deserves further investigation.     

The importance of timing in melatonin administration in a blind man

An 18-year-old blind man suffered from chronic sleep disturbances associated with daytime fatigue and excessive daytime somnolence. After two unsuccessful treatment regimens with 5 mg and 10 mg melatonin administered at bedtime (2200-2230), a third regimen of 5 mg melatonin administered at 2000 for 3 weeks resulted in a successful resolution of his sleep disturbances. We suggest that the efficacy of melatonin in ameliorating sleep disturbances because of alterations in circadian rhythmicity may be dependent on the time of administration.     

Subclinical atherosclerosis in psoriatic arthritis: a case-control study

OBJECTIVE: To investigate the prevalence of subclinical atherosclerosis among patients with psoriatic arthritis (PsA). METHODS: Forty patients with PsA were enrolled. Controls were matched by age, sex, and atherosclerotic risk factors. All patients and controls underwent duplex scan of the carotid arteries. Carotid intima-media thickness (IMT) was evaluated and the presence of atherosclerotic plaques was recorded. The plaques were graded and carotid plaque index was calculated. RESULTS: Patients with PsA had a higher IMT (mean +/- standard deviation, 1.04 +/- 0.35 mm vs 0.88 +/- 0.29 mm in controls; p = 0.03), and had a higher carotid plaque index than did matched controls (2.3 +/- 2.6, compared to 1.12 +/- 2.09; p = 0.03). Multivariate analysis demonstrated that PsA status as well as age and triglyceride levels were associated with the presence of carotid plaque. Other traditional risk factors were more prevalent among patients with PsA; however, they were not statistically significant. CONCLUSION: Our study demonstrates that patients with PsA may have an increased prevalence of subclinical atherosclerosis. These findings may not be solely attributable to traditional risk factors alone. Special attention and strict control of atherosclerotic risk factors in patients with PsA is warranted.