Antiarrhythmic Effects of Combining Dofetilide and Ranolazine in a Model of Acutely Induced Atrial Fibrillation in Horses.

BACKGROUND: Antiarrhythmic compounds against atrial fibrillation (AF) often have reduced efficacy and may display cardiac and/or noncardiac toxicity. Efficacy can be improved by combining 2 compounds with distinct mechanisms, and it may be possible to use lower doses of each compound, thereby reducing the likelihood of adverse side effects. The purpose of this study was to investigate whether the effective doses of dofetilide and ranolazine can be reduced if the drugs are combined. METHODS: Dofetilide, ranolazine, and a combination of these were administered in 4 incremental dosing regimens to horses with acutely pacing-induced AF. Time to cardioversion, atrial effective refractory period, and AF vulnerability and duration were assessed. RESULTS: Of 8 horses, 6 cardioverted to sinus rhythm after infusion with a combination of 0.889 µg/kg dofetilide and 0.104 mg/kg ranolazine. Two horses cardioverted with 0.104 mg/kg ranolazine alone, and 3 cardioverted with 0.889 µg/kg dofetilide alone. The combination therapy decreased AF vulnerability (P < 0.05) and AF duration (P < 0.05). No change in atrial effective refractory period was detected with any of the drugs. CONCLUSIONS: The combination of dofetilide and ranolazine showed increased antiarrhythmic effects on acutely induced AF in horses, affecting time to cardioversion, AF vulnerability, and AF duration.

Hereditary angioedema in childhood: a challenging diagnosis you cannot afford to miss.

Hereditary angioedema (HAE) is a rare inherited disease that is often difficult to diagnose. We report a case of a 9-year-old boy with a spontaneous mutation causing HAE, diagnosed after a life-threatening episode of angioedema of the head and upper respiratory tract after a 5-year history of recurrent skin swellings and abdominal pain leading to several hospital admissions. The aim of this report is to direct focus on this rare disease, which can be treated effectively, to diminish morbidity and mortality of children suffering from undiagnosed HAE.

Adjustable continence balloons: clinical results of a new minimally invasive treatment for male urinary incontinence.

OBJECTIVE: This study aimed to evaluate the results of the Danish experience with the ProACT urinary continence device inserted in men with stress urinary incontinence. MATERIAL AND METHODS: The ProACT was inserted in 114 patients. Data were registered prospectively. The main endpoints were complications, pad use per day and 24 h urinary leakage. A questionnaire evaluating symptoms and satisfaction was sent to the patients. RESULTS: Data including preoperative and postoperative pad use and urinary leakage were available for 92 and 90 patients, respectively. A decrease in the median 24 h urinary leakage (352.5 vs 11 ml, p < 0.001) and in the median number of pads used per day (4.75 vs 2.25, p = 0.001) was demonstrated. Forty-six patients had a pad use of 0-1 pads per day and/or a daily urinary leakage less than 8 g, corresponding to an overall dry rate of 50%. A decrease in urinary leakage > 50% was seen in 72 patients (80%). Complications were seen in 23 patients. All of these were treated successfully by removal of the device in the outpatient setting followed by replacement of the device. Another eight patients had a third balloon inserted to improve continence further. Fourteen patients (12%) ended up with an artificial sphincter or a urethral sling. Sixty patients (63%) experienced no discomfort and 58 (61%) reported being dry or markedly improved. Overall, 50 patients (53%) reported being very or predominantly satisfied. CONCLUSIONS: Adjustable continence balloons seem to be a good alternative in the treatment of male urinary incontinence. Complications are mild and easily treated.