Randomized, placebo-controlled trials of dichlorphenamide in periodic paralysis.

OBJECTIVE: To determine the short-term and long-term effects of dichlorphenamide (DCP) on attack frequency and quality of life in hyperkalemic (HYP) and hypokalemic (HOP) periodic paralysis. METHODS: Two multicenter randomized, double-blind, placebo-controlled trials lasted 9 weeks (Class I evidence), followed by a 1-year extension phase in which all participants received DCP. Forty-four HOP and 21 HYP participants participated. The primary outcome variable was the average number of attacks per week over the final 8 weeks of the double-blind phase. RESULTS: The median attack rate was lower in HOP participants on DCP than in participants on placebo (0.3 vs 2.4, p = 0.02). The 9-week mean change in the Physical Component Summary score of the Short Form-36 was also better in HOP participants receiving DCP (treatment effect = 7.29 points, 95% confidence interval 2.26 to 12.32, p = 0.006). The median attack rate was also lower in HYP participants on DCP (0.9 vs 4.8) than in participants on placebo, but the difference in median attack rate was not significant (p = 0.10). There were no significant effects of DCP on muscle strength or muscle mass in either trial. The most common adverse events in both trials were paresthesia (47% DCP vs 14% placebo, both trials combined) and confusion (19% DCP vs 7% placebo, both trials combined). CONCLUSIONS: DCP is effective in reducing the attack frequency, is safe, and improves quality of life in HOP periodic paralysis. CLASSIFICATION OF EVIDENCE: These studies provide Class I evidence that DCP significantly reduces attack frequency in HOP but lacked the precision to support either efficacy or lack of efficacy of DCP in HYP.

A randomized controlled phase IIb trial of beta(1)-receptor blockade for chronic degenerative mitral regurgitation.

OBJECTIVES: The purpose of the study was to evaluate the effect of long-term ß(1)-aderergic receptor (AR) blockade on left ventricular (LV) remodeling and function in patients with chronic, isolated, degenerative mitral regurgitation (MR). BACKGROUND: Isolated MR currently has no proven therapy that attenuates LV remodeling or preserves systolic function. METHODS: Thirty-eight asymptomatic subjects with moderate to severe, isolated MR were randomized either to placebo or ß(1)-AR blockade (Toprol-XL, AstraZeneca, London, United Kingdom) for 2 years. Magnetic resonance imaging with tissue tagging and 3-dimensional analysis was performed at baseline and at 6-month intervals for 2 years. Rate of progression analysis was performed for endpoint variables for primary outcomes: LV end-diastolic volume/body surface area, LV ejection fraction, LV end-diastolic (ED) mass/ED volume ratio, LV ED 3-dimensional radius/wall thickness; LV end-systolic volume/body surface area, LV longitudinal strain rate, and LV early diastolic filling rate. RESULTS: Baseline LV magnetic resonance imaging or demographic variables did not differ between the 2 groups. Significant treatment effects were found on LV ejection fraction (p = 0.006) and LV early diastolic filling rate (p = 0.001), which decreased over time in untreated patients on an intention-to-treat analysis and remained significant after sensitivity analysis. There were no significant treatment effects found on LV ED or LV end-systolic volumes, LV ED mass/LV ED volume or LV ED 3-dimensional radius/wall thickness, or LV longitudinal strain rate. Over 2 years, 6 patients treated in the placebo group and 2 patients in the ß(1)-AR blockade group required mitral valve surgery (p = 0.23). CONCLUSIONS: ß(1)-AR blockade improves LV function over a 2-year follow-up in isolated MR and provides the impetus for a large-scale clinical trial with clinical outcomes. (Molecular Mechanisms of Volume Overload-Aim 1 [SCCOR in Cardiac Dysfunction and Disease]; NCT01052428).

Impact of differing protein sources and a creatine containing nutritional formula after 12 weeks of resistance training.

OBJECTIVE: We evaluated whether colostrum (Col) or an isocaloric and isonitrogenous blend of whey and casein in addition to creatine (Cr) affects body composition, muscular strength and endurance, and anaerobic performance during resistance training. METHODS: Forty-nine resistance-trained subjects participated in a standardized 12-wk total body resistance training program. In a double-blind and randomized manner, subjects supplemented their diet with a protein control (Pro), Pro/Col, Pro/Cr, or Col/Cr. Supplements were isocaloric and isonitrogenous and provided 60 g/d of casein/whey (Pro) or Col as the protein source. At 0, 8, and 12 wk of supplementation, subjects were weighed, had body composition determined using dual-energy X-ray absorptiometry (DXA), performed one-repetition maximum (1RM) and 80% of 1RM tests on the bench press and leg press, and 30-s anaerobic sprint capacity tests. Data (mean +/- SD) were analyzed by repeated measures analysis of variance and reported as raw data in all tables and as changes from baseline for all figures for the Pro, Pro/Col, Pro/Cr, and Col/Cr groups, respectively. RESULTS: Resistance training increased 1RM strength, muscular endurance, and anaerobic sprint capacity equally in all groups. Significant main and interaction effects (P < 0.05) were found for body mass, DXA total scanned mass, and fat-free mass (FFM; lean plus bone), whereas no changes (P > 0.05) were noted for fat mass, percent fat, or bone content. Post hoc analysis showed that, compared with Pro, subjects ingesting Pro/Col, Pro/Cr, and Col/Cr showed greater gains in body mass and DXA total scanned mass. Subjects ingesting Pro/Cr and Col/Cr had greater increases in FFM during training in comparison with Pro/Col. CONCLUSION: In conjunction with 12 wk of resistance training, ingestion of Col or a blend of whey and casein protein with a vitamin/mineral supplement containing Cr resulted in greater improvements in FFM in comparison with Pro and Pro/Col.

Exploding vs. imploding headache in migraine prophylaxis with Botulinum Toxin A.

Migraine headache is routinely managed using medications that abort attacks as they occur. An alternative approach to migraine management is based on prophylactic medications that reduce attack frequency. One approach has been based on local intramuscular injections of Botulinum Toxin Type A (BTX-A). Here, we explored for neurological markers that might distinguish migraine patients who benefit from BTX-A treatment (100 units divided into 21 injections sites across pericranial and neck muscles). Responders and non-responders to BTX-A treatment were compared prospectively (n=27) and retrospectively (n=36) for a host of neurological symptoms associated with their migraine. Data pooled from all 63 patients are summarized below. The number of migraine days per month dropped from 16.0+/-1.7 before BTX-A to 0.8+/-0.3 after BTX-A (down 95.3+/-1.0%) in 39 responders, and remained unchanged (11.3+/-1.9 vs. 11.7+/-1.8) in 24 non-responders. The prevalence of aura, photophobia, phonophobia, osmophobia, nausea, and throbbing was similar between responders and non-responders. However, the two groups offered different accounts of their pain. Among non-responders, 92% described a buildup of pressure inside their head (exploding headache). Among responders, 74% perceived their head to be crushed, clamped or stubbed by external forces (imploding headache), and 13% attested to an eye-popping pain (ocular headache). The finding that exploding headache was impervious to extracranial BTX-A injections is consistent with the prevailing view that migraine pain is mediated by intracranial innervation. The amenability of imploding and ocular headaches to BTX-A treatment suggests that these types of migraine pain involve extracranial innervation as well.