Continuous in-home monitoring of essential tremor.

BACKGROUND: Essential tremor (ET) is typically measured in the clinic with subjective tremor rating scales which require the presence of a clinician for scoring and are not appropriate for measuring severity throughout the day. Motion sensors can accurately rate tremor severity during a set of predefined tasks in a laboratory. METHODS: We evaluated the ability of motion sensors to quantify tremor during unconstrained activities at home. 20 ET subjects wore a wireless sensor continuously for up to 10 h daily on two days and completed hourly standardized tremor assessments involving pre-defined tasks. Mathematical models were used to predict tremor rating scores from the sensor data. RESULTS: At home tremor scores from hourly standardized assessments correlated with at home tremor scores estimated during unconstrained activities immediately following the standardized assessments. The hourly standardized assessments did not significantly fluctuate throughout the day, while fluctuations in the continuous assessments tended to follow changes in voluntary activity level. Both types of tremor ratings (standardized and continuous) showed high day-to-day test-retest reliability with intraclass correlation coefficients ranging from 0.67 to 0.90 for continuous ratings and 0.77 to 0.95 for standardized ratings. CONCLUSIONS: Results demonstrate the feasibility of continuous monitoring of tremor severity at home, which should provide clinicians with a measure of the temporal pattern of tremor in the context of daily life and serve as a useful tool for the evaluation of novel anti-tremor medications in clinical trials.

Safety of esmolol in patients with acute myocardial infarction treated with thrombolytic therapy who had relative contraindications to beta-blocker therapy.

OBJECTIVE: This study was conducted to evaluate the safety of esmolol in 114 patients treated with thrombolytic therapy for acute myocardial infarction who also had relative contraindications to beta-blockade, and the predictive value of patient tolerance to esmolol and subsequent patient tolerance of oral beta-blocker therapy. PATIENTS: One hundred and fourteen patients with myocardial infarction documented by enzyme concentrations and electrocardiographic changes who also had relative contraindications to beta-blockade. METHODS: Esmolol was initiated during acute myocardial infarction for myocardial ischemia (n = 88), hypertension (n = 13), or supraventricular tachycardia (n = 13). Relative contraindications to beta-blocker therapy included either active signs/symptoms of left ventricular dysfunction or a history of congestive heart failure (n = 40), a history of chronic obstructive pulmonary disease or asthma (n = 31), bradycardia (HR < 60 beats/min; n = 18), peripheral vascular disease (n = 15), or hypotension (systolic BP < 100 mm Hg; n = 14). RESULTS: During initial esmolol dose titration, 69 patients tolerated 300 micrograms/kg/min, 12 patients tolerated 200 micrograms/kg/min, 17 patients tolerated 100 micrograms/kg/min, and 16 patients tolerated 50 micrograms/kg/min. Twenty-eight patients (25 percent) developed dose-limiting adverse effects during esmolol maintenance infusions. Sixteen patients required esmolol dose reduction and 12 required esmolol discontinuation. Adverse effects reversed within 30-45 minutes following dose reduction or discontinuation. The 86 patients who tolerated esmolol infusions without dose reduction or drug discontinuation were subsequently treated with oral beta-blockers. Eleven of these patients (13 percent) developed adverse effects requiring oral beta-blocker discontinuation. Nine of these patients had tolerated only 50 micrograms/kg/min of esmolol, and the other 2 patients had tolerated only 100 micrograms/kg/min. CONCLUSIONS: Esmolol can be used safely in most patients treated with thrombolytic therapy for acute myocardial infarction who have relative contraindications to beta-blockers. Tolerance to higher maintenance doses of esmolol is a good predictor of subsequent outcome with oral beta-blocker therapy.

Loss of efficacy during long-term cifenline therapy: development of antiarrhythmic resistance?

OBJECTIVE: To describe the possible development of antiarrhythmic resistance to cifenline, an investigational Class I agent. METHODS: Forty patients with chronic ventricular premature depolarizations (VPDs) underwent dose-ranging studies with cifenline, an investigational Class I antiarrhythmic agent. Patients had a minimum of 30 VPDs/h detected by ambulatory electrocardiographic (ECG) monitoring over a 48-hour baseline placebo lead-in period. Twenty-two patients (55 percent) who initially responded received long-term cifenline therapy. Ambulatory ECG monitoring over 24 hours was repeated during active cifenline therapy at three-month intervals and during placebo reintroduction at six-month intervals. RESULTS: After an average follow-up of 28 months, VPD frequency during cifenline therapy was similar to that during initial baseline placebo therapy in 8 of the 22 patients (36 percent) who initially responded. Placebo reintroduction following cifenline failure showed a VPD frequency similar to that with active therapy. All patients had further cifenline dosage increases without success. Plasma cifenline concentrations increased in all patients and were in the high therapeutic range. All 8 patients were switched to other Class I antiarrhythmic agents with successful VPD suppression during treatment with the first alternative drug. CONCLUSIONS: We conclude that antiarrhythmic resistance occurred with cifenline in these patients as (1) initial efficacy was established for a minimum of two years, (2) VPD frequency was similar during cifenline therapy and placebo reintroduction, (3) cifenline therapy failure continued despite further dosage titration, and (4) alternative Class I antiarrhythmic therapy was successful in all patients. Repeat intermittent ambulatory ECG monitoring is necessary not only to assess the continued need for antiarrhythmic drug therapy, but also to establish continued long-term efficacy.

Comparative pharmacodynamics of intravenous lidocaine in patients with acute and chronic ventricular arrhythmias.

OBJECTIVE: To evaluate the pharmacodynamics of intravenous lidocaine in patients with acute-onset and chronic ventricular arrhythmias. DESIGN: Open-label, pharmacodynamic evaluation. SETTING: Private, university-affiliated, hospital coronary-care unit. PATIENTS: Twenty cardiac patients with acute-onset ventricular ectopy and 20 with chronic ventricular ectopy. INTERVENTIONS: Intravenous lidocaine was administered to all patients as a 1-mg/kg bolus, a 0.5-mg/kg bolus, and a 2.8-mg/min constant infusion for 48 hours. MAIN OUTCOME MEASURES: Changes in ventricular premature beat (VPB) frequency against total treatment period frequency and by an hour-to-hour assessment of changes in VPB frequency compared with total baseline frequencies. Response was defined as greater than or equal to 80 percent total VPB reduction, greater than or equal to 90 percent paired VPB reduction, and total abolition of nonsustained ventricular tachycardia events. RESULTS: A statistically significant difference in the pharmacodynamic effects of lidocaine were observed during the first eight hours of treatment in patients with acute-onset and chronic VPBs. The number of patients with acute-onset VPBs who responded to lidocaine in the first hour of treatment did not change significantly over the remaining hours of treatment. Response to lidocaine was less in patients with chronic VPBs than in patients with acute-onset VPBs. The response rate to lidocaine was significantly less during the first eight hours in patients with chronic VPBs than in patients with acute-onset VPBs. Following eight hours of treatment, the response rates between acute-onset and chronic VPB patients were not significantly different. Mean lidocaine plasma concentrations were not different between the groups. In addition, there were no significant differences in the incidence of adverse effects between the two groups. CONCLUSIONS: The onset of antiarrhythmic effect as measured by suppression of ventricular ectopy is delayed in patients with chronic VPBs compared with patients with acute-onset VPBs. Decisions about lidocaine response in patients with chronic VPBs cannot be made accurately in the first eight hours of therapy.

Pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG) and various acute phase reactants in rheumatoid arthritis and osteoarthritis.

Pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG) concentrations have been measured in matched sera and synovial fluid samples obtained from 36 patients with rheumatoid arthritis and 10 patients with osteoarthritis. Levels of alpha 2-PAG in serum and synovial fluid were significantly higher in rheumatoid arthritis than in osteoarthritis. Calculation of the synovial fluid/serum ratios for alpha 2-PAG gave results which are explicable only if this protein were being synthesised locally. In a longitudinal study of 15 patients with rheumatoid arthritis, concentrations of alpha 2-PAG did not reflect disease activity, unlike those of the classical acute phase reactants, C-reactive protein and caeruloplasmin.

Association between pregnancy-associated alpha2-glycoprotein (alpha2-PAG) and mixed leucocyte reaction determinants on the leucocyte surface.

alpha2-PAG is present on the surface on mononuclear blood leucocytes and can be demonstrated predominantly on B-lymphocytes and monocytes. Pretreatment of cells with antibody to alpha2-PAG leads to a marked reduction in Fc-rosette formation. Competitive blocking experiments with specific antisera reveal a particularly close association between alpha2-PAG and MLR (mixed leucocyte reaction) determinants on the cell surface. These findings suggest one mechanism whereby alpha2-PAG may modify cell-mediated immune responses.

Study of pregnancy-associated alpha2-glycoprotein in relation to populations of human blood leucocytes.

Pregnancy-associated alpha2-glycoprotein (alpha2-PAG) was identified by immunofluorescence on the surface membrane of mononuclear cells from normal individuals with an extensive range of plasma concentrations of the glycoprotein. The incidence of positive cells did not correlate with plasma levels but was significantly raised in chronic lymphocytic leukaemia. Anti-alpha2-PAG antibody interfered with E and Fc rosette formation but not with production of C3 rosettes. A large proportion of C3 receptor-bearing cells (B lymphocytes) but only a tiny fraction of E-rosette-forming cells (T lymphocytes) were positive for the protein. Antibody directed against human Ia antigen markedly reduced staining for alpha2-PAG.