Cholinergic augmentation with donepezil enhances recovery in short-term memory and sustained attention after traumatic brain injury

OBJECTIVE: To examine effects of donepezil on short-term memory and sustained attention in postacute patients with traumatic brain injury (TBI). DESIGN: A 24-week, randomized, placebo-controlled, double-blind crossover trial. SETTING: Outpatient clinics in 2 teaching hospitals. PARTICIPANTS: Eighteen postacute TBI patients with cognitive impairment. INTERVENTION: Patients were randomly assigned to group A or group B. Patients in group A received donepezil for the first 10 weeks and then a placebo for another 10 weeks. The 2 treatment phases were separated by a washout period of 4 weeks. Patients in group B received the preparations in the opposite order. MAIN OUTCOME MEASURES: Short-term memory and sustained attention were assessed by 2 indexes (Auditory Immediate Index [AII], Visual Immediate Index [VII]) of the Wechsler Memory Scale-III and the Paced Auditory Serial Addition Test (PASAT), at baseline, week 10, and week 24 of the trial. RESULTS: Intragroup comparison of different phases of the trial in both groups showed that donepezil significantly increased the testing scores of the AII and VII, as well as PASAT scores, compared with baseline. There was no significant change in the testing scores between assessment at baseline and the end of the placebo phase in group B. Intergroup comparison at the 10-week assessment showed significantly improved testing scores in group A with donepezil over group B with the placebo. The improved testing scores with donepezil in group A were sustained after the washout period and placebo phase, suggesting a carry-over effect of the medication. CONCLUSIONS: Donepezil increased neuropsychologic testing scores in short-term memory and sustained attention in postacute TBI patients. Cholinergic augmentation may be a viable approach to restore memory and attention after TBI.     

Electrophysiologic Evaluation of Asymptomatic Patients with the Wolff-Parkinson-White Pattern

In the past 4 years, 34 asymptomatic patients with the Wolff-Parkinson-White (WPW) pattern underwent electrophysiologic study. The effective refractory period (ERP) of antegrade conduction over the accessory pathway was 288 +/- 29 msec. In three asymptomatic patients (9%), the antegrade ERP of the accessory pathway was shorter than 250 msec. The antegrade ERP of the accessory pathway became shorter than 250 msec in an additional 12 of 22 (55%) patients after isoproterenol administration. Nineteen (56%) of the asymptomatic patients showed the absence of retrograde conduction over the accessory pathway even after isoproterenol administration. The rate of induction of orthodromic reciprocating tachycardia in the asymptomatic WPW patients was 15% (5/34), which was significantly lower than that in the symptomatic patients. These data suggest that in the asymptomatic patients, the absence of retrograde conduction over the accessory pathway is the reason they remained asymptomatic, free of reciprocating tachycardia. However, even in the asymptomatic patients, some had the accessory pathway in which antegrade ERP was shorter than 250 msec. They may result in rapid ventricular conduction over the accessory pathway when atrial fibrillation develops.     

Serum amyloid β protein in young and elderly depression: a pilot study

Background: Depression may increase the risk of developing Alzheimer's disease (AD). Recent large cohort studies have also shown that a low plasma amyloid β (Aβ)‐42 level combined with a high Aβ40 level increases the risk of developing AD, suggesting plasma Aβ42/40 ratio as useful for identifying risk of developing mild cognitive impairment and AD. Although several studies have examined Aβ levels in the peripheral blood of elderly individuals with depression, results have been inconsistent. Furthermore, no results have been described for younger depression. Methods: Serum Aβ40, Aβ42 level and Aβ40/42 ratio were evaluated using enzyme‐linked immunosorbent assay in 60 patients with major depressive disorder (MDD) and 60 healthy controls. The results were analyzed in two age groups (young, <60 years; elderly, ≥60 years). Results: Serum Aβ40 level was significantly higher in young MDD patients compared to young controls (P < 0.001), but it was not significantly deferent in the elderly group. Serum Aβ42 level did not differ significantly in both young and elderly groups. Aβ40/42 ratio was significantly higher in both young (P < 0.001) and elderly (P < 0.001) patients with MDD compared to controls. Conclusions: Serum Aβ40/42 ratio was significantly higher in MDD patients than in controls, and this difference was seen for both elderly and young subjects. This may suggest that even young subjects with MDD undergo pathological changes in the very early stage of amyloid deposition.     

Pharmacological effects of saw palmetto extract in the lower urinary tract

Saw palmetto extract （SPE）, an extract from the ripe berries of the American dwarf palm, has been widely used as a therapeutic remedy for urinary dysfunction due to benign prostatic hyperplasia （BPH） in Europe. Numerous mechanisms of action have been proposed for SPE, including the inhibition of 5a-reductase. Today, al-adrenoceptor antagonists and muscarinic cholinoceptor antagonists are commonly used in the treatment of men with voiding symptoms secondary to BPH. The improvement of voiding symptoms in patients taking SPE may arise from its binding to pharmacologically relevant receptors in the lower urinary tract, such as al-adrenoceptors, muscarinic cholinoceptors, 1,4-dihyropyridine receptors and vanilloid receptors. Furthermore, oral administration of SPE has been shown to attenuate the up-regulation of α1-adrenoceptors in the rat prostate induced by testosterone. Thus, SPE at clinically relevant doses may exert a direct effect on the pharmacological receptors in the lower urinary tract, thereby improving urinary dysfunction in patients with BPH and an overactive bladder. SPE does not have interactions with co-administered drugs or serious adverse events in blood biochemical parameters, suggestive of its relative safety, even with long-term intake. Clinical trials （placebo-controlled and active-controlled trials） of SPE conducted in men with BPH were also reviewed. This review should contribute to the understanding of the pharmacological effects of SPE in the treatment of patients with BPH and associated lower urinary tract symptoms （LUTS）.     

Current Density Distribution by Ring and Diagonally Arranged Half‐Ring Electrodes in Bipolar and Overlapping Biphasic Impulse Stimulation

Background: We have studied the acute and long‐term efficacy of overlapping biphasic impulse (OLBI) stimulation for atrial pacing with VDD pacemakers and demonstrated the feasibility of DDD pacing in OLBI with diagonally arranged half‐ring (Half‐Ring) electrodes. We made two three‐dimensional computational analysis models to verify our clinical studies. Methods and Results: Model I was composed of a heart, a pacemaker, and a human body. Model II was a cube with dimensions of 20 by 20 by 20 mm quarried from Model I for the detailed study of current density distributions. Laplace's equation was solved using the finite element method and the current density J was calculated. For Model I, the distal and proximal voltages were ?10 V, 0 V in bipolar and ?5 V, +5 V in OLBI, using Ring electrodes. In Model II, the actual measurements of electrode impedances obtained from the clinical study (1,180 Ω for Ring and 630 Ω for Half‐Ring) were added to the analysis conditions. Model I showed that OLBI produced more concentrated current density distributions than those by bipolar. According to Model II, at the atrial myocardium position current density produced by Half‐Ring was larger than that by Ring electrodes, 70 μA/mm² versus 30 μA/mm² in OLBI configuration. It also indicated that even if electrode impedances were equal between Half‐Ring and Ring electrodes, the maximum current density produced by Half‐Ring would be greater than that by Ring electrodes. Conclusions: It was considered that OLBI configuration with Half‐Ring electrodes provides more effective current density distributions. (PACE 2010; 33:1063–1073)     

Use of inhaled fluticasone propionate to control respiratory manifestations of relapsing polychondritis

Effective management of respiratory tract involvement is very important in improving the prognosis of relapsing polychondritis (RPC). This case report describes a 19-year-old patient with RPC, who required frequent hospitalization due to recurrent exacerbations of airway obstruction. Use of high-dose fluticasone propionate effectively reduced the amount of oral corticosteroid necessary to control inflammation of the airway mucosa and dramatically decreased the patient's obstructive airway impairment. This report is the first illustrating the effectiveness and safety of inhaled corticosteroids in the control of the respiratory manifestations of RPC.     

Housing density does not influence the longevity effect of calorie restriction

This study examined the effect of housing density on the longevity-extending and disease-delaying actions of calorie restriction (CR). Singly or multiply housed (four per cage) mice were either fed ad libitum (AL) or were on CR beginning at 2 months. All CR mice were fed 40% less food than were multiply housed AL mice. CR increased median longevity by 19%, and housing density had no effect on this increase. CR also reduced neoplastic lesions in both housing groups, but lymphoma, the most common neoplasm, was reduced more in singly than in multiply housed mice. Singly housed AL mice ate 40% more food than did multiply housed AL mice, but weighed the same and lived as long as multiply housed AL mice. These results indicate that CR can extend life span as effectively in multiply as in singly housed mice, even though housing density can differentially affect the cancer-reducing effect of CR.     

Bone loss following hypogonadism in men with prostate cancer treated with GnRH analogs

It is known that bone mineral density (BMD) is low in men who are hypogonadal. However, the rate and sites of bone loss following testosterone deficiency are not known. The resulting hypogonadism after GnRH analog therapy for the treatment of prostate cancer allows us to examine bone loss and bone resorption immediately after testosterone withdrawal. Therefore, we examined the effects of GnRH analog treatment on bone loss and bone resorption in men with prostate cancer. BMD and serum and urine concentrations of markers of bone turnover were determined in men with prostate cancer and in age-matched controls. Measurements were taken before GnRH therapy and 6 and 12 months after instituting therapy. After 12 months of GnRH therapy, the BMD of the total hip and ultra distal radius decreased significantly (P < 0.001) in men with prostate cancer compared with the controls. The mean bone loss was 3.3% and 5.3%, respectively. The observed reduction in BMD in the spine (2.8%) and the femoral neck (2.3%) did not reach statistical significance. No significant bone loss was observed in the control subjects. The concentration of the urine marker of bone resorption, N-telopeptide, was significantly increased from baseline and from controls at both 6 and 12 months in patients treated with GnRH analog therapy compared with control subjects (P < 0.05). The concentration of a serum marker of bone formation, bone-specific alkaline phosphatase, was not significantly different from baseline or from controls at 6 and 12 months. Thus, the decreased total hip and ultra distal radius BMD and increased urinary N-telopeptide concentration after testosterone withdrawal demonstrate an increase in trabecular bone loss and enhanced bone resorption. These findings demonstrate a significant loss of bone in men with prostate cancer after receiving GnRH therapy and suggest that the total hip and radius are the preferred sites for monitoring bone loss in older men. In addition, markers of bone resorption may be helpful.