Edward Dwyer

Association of Chronic Lyme Arthritis with HLA-DR4 and HLA-DR2 Alleles

BACKGROUND AND METHODS A small percentage of patients infected with Borrelia burgdorferi have chronic Lyme arthritis that does not respond to antibiotic therapy. To learn whether genetically determined variations in the host immune response might account for such outcomes, we determined the immunogenetic profiles of 130 patients with various manifestations of Lyme disease. RESULTS Of the 80 patients with arthritis, 57 percent of those with chronic arthritis (12 to 48 months in duration) had the HLA-DR4 specificity; only 23 percent of those with arthritis of moderate duration (6 to 11 months) and only 9 percent of those with arthritis of short duration (1 to 5 months) had this specificity (P = 0.003). After the HLA-DR4-positive patients were excluded from each group, a secondary association was noted with HLA-DR2, which was found in 75 percent of the remaining patients with chronic arthritis and in 50 percent of those with arthritis of moderate duration, but in only 20 percent of those with arthritis of short duration (P = 0.023). Altogether, 25 of the 28 patients with chronic arthritis (89 percent) had HLA-DR2 or HLA-DR4, or both, as compared with 27 percent of those with arthritis of short duration (relative risk, 22; P = 0.00006). These HLA specificities appeared to act as independent, dominant markers of susceptibility. Nucleotide-sequence typing, performed in five patients with chronic arthritis, identified the HLA-DR2 allele as Dw2 (DR beta 1*1501), and the HLA-DR4 alleles as Dw4, Dw14, and Dw13 (DR beta 1*0401, DR beta 1*0404, and DR beta 1*0403, respectively). The presence of HLA-DR4 in patients with arthritis was associated with a lack of response to antibiotic therapy (P = 0.01). CONCLUSIONS Particular Class II major histocompatibility genes determine a host immune response to B. burgdorferi that results in chronic arthritis and lack of response to antibiotic therapy.

Effects of nitroglycerin on the major determinants of myocardial oxygen consumption: An angiographic and hemodynamic assessment

A direct and quantitative study of the effects of sublingually administered nitroglycerin on the major determinants of myocardial oxygen consumption was carried out in 10 patients, 7 with coronary artery disease. Left ventricular wall tension, estimates of the contractile state and heart rate were studied directly using simultaneous pressure measurements and angiographically obtained volume determinations. The peak systolic left ventricular wall tension decreased 15 percent after administration of nitroglycerin, suggesting a diminished myocardial oxygen requirement. Increased myocardial oxygen requirements were suggested by the occurrence of both positive chronotropic and inotropic effects. Heart rate increased 15 percent. The mean circumferential fiber shortening velocity increased 26 percent and the ejection fraction 30 percent; these findings, in association with a 23 percent reduction in left ventricular end-diastolic volume, were considered consistent with an increase in the contractile state. The mechanism of action of nitroglycerin seems to relate best to the decrease in systolic wall tension. The end-diastolic tension decreased 57 percent, suggesting the possibility that diastolic coronary blood flow may be augmented by diminished extravascular resistance to flow.

Oral disopyramide therapy for obstructive hypertrophic cardiomyopathy

Seven patients with obstructive hypertrophic cardiomyopathy (HC) were treated with oral disopyramide. Left ventricular outflow tract gradients were estimated using either Doppler or M-mode echocardiography. Gradients were measured before treatment, after acute and chronic dosing, after washout and after rechallenge. Disopyramide serum levels were measured at the time of echocardiography. With the first dose, mean outflow gradient decreased from 64 to 14 mm Hg (p less than 0.0001). This decrease in gradient was still present after long-term oral treatment 23 days later, with a mean gradient of 13 mm Hg (p less than 0.001). After withdrawal from the drug, gradient returned to the pretreatment value, 79 mm Hg. After rechallenge, the gradient once again declined to 30 mm Hg (p less than 0.001). High disopyramide serum levels correlated with lower outflow tract gradients, r = -0.77 (p less than 0.0001). Even at low therapeutic drug levels, there was a 49% reduction in outflow tract gradient. Four patients were symptomatically improved and have been maintained on disopyramide for greater than 1 year. In symptomatic patients, disopyramide acutely decreases obstruction and also provides sustained pharmacologic control of obstruction. Disopyramide should be considered as a good alternative to treatment with adrenergic blockers, calcium antagonists or surgery.

Long-term prognostic significance of ST segment depression during acute myocardial infraction☆

Objectives. The purpose of this study was to evaluate the long-term prognostic value of ST segment depression on the electrocardiogram (ECG) in patients with acute myocardial infarction. Background. The prognostic importance of ST depression on the ECG has been studied in small groups of patients with infarction, but larger numbers are needed. Methods. Coronary care unit ECGs of 1,234 patients who survived the coronary care unit with acute Q wave (n = 896) or non-Q wave (n = 338) myocardial infarction were analyzed for the presence of ST segment depression. Patients were followed up for up to 4 years. Results. ST segment depression was present in 607 patients. Those with ST segment depression had a 1-year mortality rate of 10.3% compared with a rate of 5.6% for those without ST segment depression (p = 0.002). This effect was seen in both the Q wave and non-Q wave subgroups, of the 437 patients with anterior ST segment elevation, those with ST segment depression in other regions had a 13,6% 1-year mortality rate compared with a rate of 6.9% for those with no ST segment depression (p = 0.0005). Of the 514 patients with inferior ST segment elevation, those with ST segment depression in other leads had an 11.0% 1-year mortality rate compared with a 1.8% rate for those with no ST segment depression (p = 0.0001). The Cox proportional hazards model showed that ST segment depression was an independent predictor of mortality over the follow-up period. Conclusions. ST segment depression on the admitting ECG in patients with acute myocardial infarction is a predictor of increased mortality in the year after infarction.

The changing pattern of humoral rejection in cardiac transplant recipients.

Background. Most humoral rejection (HR) episodes occur early after cardiac transplantation and are associated with hemodynamic compromise and poor prognosis. Late cases of HR (>6 months after transplant) have been reported. We examined the differences in clinical characteristics and outcomes in patients presenting with HR in the early (<6 months) and late transplant periods. Methods. A retrospective chart review was performed of all cases of HR at a single large transplant center from January 1, 1995 to March 1, 2006. Results. A total of 37 adult transplants had biopsy-proven HR; 13 patients had early HR and 24 patients had HR a mean of 5 yr after transplantation (range, 7 months to 17 yrs). Treatment for HR included plasmapheresis, cyclophosphamide, and rituximab. The age of the early and late humoral rejecters was similar (58±14 vs. 50±14 yrs; P=0.12). There was a trend toward more women in the early HR group (54% vs. 33%). Use of left ventricular assist devices was similar (38% vs. 33%). Early rejecters were more likely to have positive cross-matches (46% vs. 8%; P<0.01). Patients with late HR had a coexistent diagnosis of malignancy, or significant recent infection in 50% vs. 8% for early HR, suggesting an activation of a nonhuman leukocyte antigen antibody-mediated immune response to an acute illness. One-year survival after the diagnosis of HR was 78% for the both groups (P=NS). Conclusions. Humoral rejection occurs now more frequently in patients with remote transplants and is commonly associated with the presence of malignancy or infection.

Dynamic optical imaging of vascular and metabolic reactivity in rheumatoid joints

Dynamic optical imaging is increasingly applied to clinically relevant areas such as brain and cancer imaging. In this approach, some external stimulus is applied and changes in relevant physiological parameters (e.g., oxy- or deoxyhemoglobin concentrations) are determined. The advantage of this approach is that the prestimulus state can be used as a reference or baseline against which the changes can be calibrated. Here we present the first application of this method to the problem of characterizing joint diseases, especially effects of rheumatoid arthritis (RA) in the proximal interphalangeal finger joints. Using a dual-wavelength tomographic imaging system together with previously implemented model-based iterative image reconstruction schemes, we have performed initial dynamic imaging case studies on a limited number of healthy volunteers and patients diagnosed with RA. Focusing on three cases studies, we illustrated our major finds. These studies support our hypothesis that differences in the vascular reactivity exist between affected and unaffected joints.

Clinical characteristics and natural history of survivors of pulmonary congestion during acute myocardial infarction

Abstract Although pulmonary congestion during acute myocardial infarction (AMI) is recognized as an important adverse event, the detailed clinical features, natural history and predictive value of standard diagnostic tests in such patients have not been well characterized. As part of a multicenter prospective postinfarction trial, 123 patients with pulmonary congestion during AMI, who survived and were discharged from the coronary care unit, were studied. These patients were compared with similar patients who did not develop pulmonary congestion. Patients with pulmonary congestion had a significantly higher 1-year mortality rate compared with 744 patients without pulmonary congestion during AMI (28 vs 5.5%). Patients with pulmonary congestion were characterized by a lower ejection fraction, more frequent anterior infarction, diminished ability to perform exercise testing and higher incidence of subsequent cardiac events. Even without these variables, pulmonary congestion was associated with increased mortality. In patients with pulmonary congestion, ejection fraction (dichotomized at 30%) and exercise testing were the most discriminating tests in risk stratification. An ejection fraction >30% and completion of the exercise test was associated with a 7% mortality while an ejection fraction

Association between transient pulmonary congestion during acute myocardial infarction and high incidence of death in six months

In a prospective multicenter study of 866 patients after acute myocardial infarction (AMI), an increased or excessive mortality rate (13%) was confined to the first 6 months after AMI. In the subsequent 18 months of follow-up, the mortality rate (4%) was similar to that in coronary patients in chronic stable condition. Analysis of patients who died in the first 6 months revealed that 55% had had pulmonary congestion at the time of the index AMI. Neither these patients nor the others who died in the early period were found to have more severe ventricular dysfunction, more malignant arrhythmias or more severe ischemia than patients who died after 6 months. The reason for the high and early mortality in patients with pulmonary congestion is not clear, particularly because 30% had reasonable ventricular function, with an ejection fraction of more than 40%. However, given the poor prognosis of these patients, early and aggressive diagnostic efforts should be undertaken to exclude jeopardized regions remote from the initial AMI.

Successful medical therapy of mitral anular abscess complicating infective endocarditis.

A case of staphylococcal endocarditis with the echocardiographic findings of mitral anular abscess is described. The anular mass resolved after 9 weeks of antibiotic therapy. This case illustrates that perivalvular abscess complicating infective endocarditis may respond to medical therapy.

Protracted tolbutamide hypoglycemia

Abstract Three cases of prolonged tolbutamide-induced hypoglycemia are reported. Four additional cases, with hypoglycemia greater than twenty-four hours duration, are collected from the literature. The high mortality rate may result, in part, from clinical unfamiliarity with this complication of tolbutamide administration. Vigorous and sustained glucose therapy is recommended. The possible mechanisms of protracted tolbutamide hypoglycemia are discussed.