Journal of Investigative Medicine

Increased autoantibody prevalence has been described in instances of high-dose exposure to polychlorinated biphenyls (PCBs). In 1996, an equipment malfunction at the Swan Hills Treatment Centre in Alberta, Canada, caused the release of gases containing PCBs into the ambient air. In view of the immune effects of PCBs and their potential as endocrine disruptors, we assessed autoantibody prevalence and looked for correlations with PCB levels.

Fifty-seven persons living within a 100 km radius of the waste treatment facility were assessed. Autoantibodies were measured by indirect immunofluorescence, double immunodiffusion, and immunoblotting. The levels of 26 congeners of PCBs were measured by gas chromatography and mass spectrometry. Provincial health records for physician visits and hospitalizations were reviewed for diagnoses of autoimmune disease.

The prevalence of autoantibodies was 11% in the study participants and 0% in healthy controls. There was no correlation of PCB levels with autoantibody results. There was no associated increase in autoimmune disease noted on physician visits or hospitalizations. PCB levels were comparable to background levels reported for other populations.

A correlation of titers of autoantibodies in the sera of individuals at risk and the blood levels of PCBs was not found, and the prevalence of autoantibodies in the at-risk group was not statistically different (p > .05) from that of an unexposed control group. The study group had higher titers of autoantibodies and some strong reactivity with intracellular antigens, but the significance of this observation may be understood only after long-term clinical assessments and follow-up.

Little is known about the effects of statins on the quality of circulating low-density lipoprotein (LDL) in relation to atherosclerosis progression.

In a double-blind, randomized trial of 325 patients with familial hypercholesterolemia (FH), we assessed the effects of high-dose atorvastatin (80 mg) and conventional-dose simvastatin (40 mg) on LDL subtraction profile (n = 289), LDL oxidizability (n = 121), and circulating autoantibodies to oxidized LDL (n = 220). Progression of atherosclerosis was measured by carotid intima media thickness (IMT) (n = 325).

At baseline, the patients showed an intermediate LDL subtraction profile composed of three LDL subtractions (LDL1, LDL2, LDL3), with LDL2 as the predominant subtraction. A strong negative correlation was found between plasma triglycerides and the LDL subtraction profile (r = - .64, p = .000). Both plasma levels of triglycerides and small dense LDL3 correlated weakly with baseline IMT (r = .11, p = .04 and r = .15, p = .01, respectively; n = 289). No association was found between baseline IMT and oxidation parameters or circulating antibodies to oxidized LDL. Atorvastatin reduced triglycerides, LDL cholesterol, and all LDL subtractions to a greater extent than did simvastatin and led to regression of carotid IMT. However, LDL subtraction pattern and plasma levels of autoantibodies to oxidized LDL remained unchanged in both treatment groups, and LDL oxidizability increased minimally to a similar extent in both groups. Significant treatment differences were found for the rate of in vitro oxidation of LDL and the amount of dienes formed during in vitro oxidation of LDL, which both decreased more following atorvastatin than after simvastatin.

Change of IMT after statin treatment was associated with baseline IMT (r = .41), LDL cholesterol (r = -.20), and the amount of dienes formed during in vitro oxidation of LDL (r = .28) but not with plasma levels of antibodies to oxidized LDL, in vitro LDL oxidizability, and LDL subtraction profile.

Angiotensin-converting enzyme (ACE) inhibitor use is presumed to be contraindicated in patients with aortic stenosis (AS). We determined the hemodynamic effects of ACE inhibitors in patients with mild to moderate aortic stenosis (AS) and preserved left ventricular function.

Thirteen elderly patients (mean [SD] age = 65 [17] years), with mild to moderate AS (aortic jet velocity 2.5–4.0 m/s), normal left ventricular and renal function, and no clinical coronary artery disease, were enrolled in a single-center, open-label trial comparing the hemodynamic effects at baseline and following titration of ramipril to a maximum dose of 7.5 mg twice daily. Patients were identified from echocardiography laboratory logs. Despite a presumed contraindication to ACE inhibitor use in AS patients, 30% (71 of 235) of patients otherwise meeting inclusion or exclusion criteria were excluded owing to current ACE inhibitor use. Patients were monitored with weekly clinic visits, biweekly laboratory tests, and monthly echocardiograms.

There were no significant changes from baseline to week 8 in echocardiographic parameters, including mean (SD) aortic jet velocity [2.9 (0.4) vs 2.9 (0.4) m/s], calculated aortic transvalvular gradient [18 (6) vs 18 (6) mm Hg], or cardiac output [5.5 (1.2) vs 6.0 (2.1) L/min], or significant changes in blood pressure or heart rate. Early discontinuations were for asymptomatic low blood pressure (one patient) or a reversible creatinine increase of 0.3 mg/dL (one patient).

Short-term treatment with up to 7.5 mg twice daily of ramipril was well tolerated in patients with mild to moderate AS and preserved left ventricular function. A surprisingly high proportion of patients with documented AS were already receiving ACE inhibitors.

Abuse of methylphenidate, a treatment of attention-deficit/hyperactivity disorder, is reported to be increasing among students for the purpose of improving cognition.

A single capsule, containing methylphenidate (20 mg) or placebo, was administered to healthy young adults orally following 24 hours of sleep deprivation. Measurements included percent change in score from sleep-deprived baseline on four standardized tests of cognitive function: Hopkins Verbal Learning, Digit Span, Modified Stroop, and Trail Making tests. Measurements also included percent changes in blood pressure and heart rate from sleep-deprived baseline and plasma methylphenidate concentration.

Differences in cognitive test performance were not observed between intervention groups. In subjects receiving methylphenidate, mean percent changes from baseline for systolic blood pressure and heart rate were increased relative to placebo between 90 and 210 minutes following capsule administration (maximum increases of 9.45% and 11.03%, respectively). The timing of peak differences in physiologic measures did not correlate with peak serum methylphenidate concentrations. Exit questionnaire ratings of “capsule effect” and perceived performance on the postcapsule administration of the most challenging cognitive test were both higher (p = .044 and p = .009, respectively) for the methylphenidate group than for the placebo group. Conclusions: Cognitive improvement among sleep-deprived young adults was not observed following methylphenidate administration. Benefits perceived by abusers may relate to increased confidence and sense of well-being, as well as to sympathetic nervous system stimulation. Moreover, methylphenidate administration results in physiologic effects that could be harmful to certain individuals.