Elimination and biochemical responses to intravenous alendronate in postmenopausal osteoporosis.

Postmenopausal women with established vertebral osteoporosis were studied for 2 years to determine the terminal elimination half-life and the duration of response to treatment with intravenous alendronate (30 mg) given over 4 days. The urinary excretion of alendronate followed a multiexponential decline. Approximately 50% of the total dose was excreted over the first 5 days, and a further 17% was excreted in the succeeding 6 months. Thereafter, there was a much slower elimination phase with an estimated mean terminal half-life of greater than 10 years (n = 11). Urinary excretion of hydroxyproline and calcium decreased significantly from pretreatment values by day 3, reaching a nadir by 1 week (40% and 67% decrease, respectively). Thereafter, hydroxyproline remained suppressed for the following 2 years. In contrast, urinary calcium excretion returned gradually toward pretreatment values over the first year and during the second year was comparable to pretreatment values. Serum activity of alkaline phosphatase activity decreased over 3 months (23% reduction), increased gradually thereafter, and returned to pretreatment values at month 24. Bone mineral density measured at the spine increased by approximately 5% during the first year and remained significantly higher than pretreatment values at 2 years. We conclude that a short course of high doses of intravenous alendronate is associated with a prolonged skeletal retention of the agent. This open study also suggests that this regimen has a sustained effect on bone turnover persisting for at least 1 year.

Urinary urge incontinence: randomised crossover trials of penthienate versus placebo and propantheline.

OBJECTIVE: To compare the efficacy of penthienate with that of propantheline and placebo for treatment of primary idiopathic detrusor instability. DESIGN: Two prospective, randomised, crossover trials (double-blind for penthienate versus placebo and non-blinded for penthienate versus propantheline). SETTING: Urology Clinic of Prince Henry Hospital, Sydney, NSW (an outpatient clinic of a tertiary referral hospital), in 1993-1994. PARTICIPANTS: Neurologically intact patients with urodynamically proven detrusor instability, urgency and urge incontinence, but no stress incontinence (20 participated in the penthienate/placebo trial and 23 in the penthienate/propanthelin trial). OUTCOME MEASURES: Cystometrography results before and after treatment; frequency and volumes of urine voided in weeks 1 and 4 of treatment; and patient scores for degree of continence, side effects, efficacy and acceptability of treatment. INTERVENTIONS: Penthienate (5 mg), propantheline (15 mg) or placebo (all three times a day) for 4 weeks. RESULTS: Penthienate produced significantly greater improvements than placebo in frequency (daytime, P = 0.002; and night-time, P = 0.02), incontinence scores (P = 0.002) and amplitude of unstable detrusor contractions, when present (P = 0.01), and significantly increased diurnal and nocturnal bladder capacity, both on cystometrography (P = 0.003) and by voiding-diary records (P < 0.001). It also increased residual urine volume over the baseline level, but not significantly. Side effects, especially dry mouth, were common with penthienate, and one patient developed urinary retention. Penthienate was significantly better than propantheline in improving cystometric capacity (P = 0.03), and reducing the amplitude of unstable detrusor contractions (P = 0.01), and was perceived as more effective by patients for frequency, nocturia and incontinence. CONCLUSIONS: Penthienate (5 mg three times a day) was objectively and subjectively significantly better than both placebo and propantheline (15 mg three times a day) for treatment of primary idiopathic detrusor instability.

Mycobacterium xenopi--an unusual presentation as tenosynovitis of the wrist in an immunocompetent patient.

Mycobacterium xenopi is an atypical acid-fast bacillus which may colonize tap water supplies. It typically causes pulmonary infection, particularly in patients with pre-existing lung damage, and non-pulmonary involvement is rare. We describe the first reported case of tenosynovitis due to this organism in an immunocompetent male patient.

Duration of response with oral clodronate in Paget's disease of bone.

We studied retrospectively 51 patients with Paget's disease of bone treated with oral clodronate, 1600 mg daily given for 1 (n = 23), 3 (n = 13), or 6 months (n = 15), to compare the effect of a variable length of treatment on the response rate to treatment and the duration of disease suppression. Activity of alkaline phosphatase and urinary hydroxyproline excretion were measured before treatment at monthly intervals for a year and every 3 months thereafter until biochemical relapse. Before treatment, patients given the three regimens had similar disease activity as judged by serum alkaline phosphatase and urinary hydroxyproline values. There was no significant difference in the time to response between groups (median = 2 months). The proportion of patients attaining normal values of alkaline phosphatase activity was significantly higher in patients treated for 6 months (71%, p < 0.03) compared with those treated for 1 or 3 months (23% and 39%, respectively). The time to relapse from the start of treatment was significantly shorter in patients treated for 1 month compared with those treated for 3 or 6 months (median = 11, 18, and 23 months, respectively). Thus, at 2 years all patients treated for 1 month had relapsed, whereas 31% and 40% were still relapse-free in patients receiving treatment for 3 and 6 months, respectively. The length of treatment was the only variable identified by stepwise linear regression that significantly affected the duration of response. We conclude that oral clodronate (1600 mg daily) suppresses disease activity in the vast majority of patients with Paget's disease of bone. The magnitude of the response and its duration depend on the duration of treatment or the total dose administered, so that several months of treatment with oral clodronate are required when a durable response is desired.

The accuracy of portable ultrasound scanning in the measurement of residual urine volume.

The accuracy of 2 successive models of a portable (2.5 kg.) ultrasound unit in determining residual urine volumes in 100 patients was assessed. Ultrasound measurements were compared to post-scan bladder volumes obtained by catheterization and fluoroscopic screening in the same patients. The first ultrasound unit (group 1, 50 patients) showed correlation with residual volumes of 0.86 (R2 = 0.73) and a mean difference from the true residual volume of 41 ml. (95% confidence interval 26 to 55 ml.). The second ultrasound unit (group 2, 50 patients) showed correlation with residual volumes of 0.97 (R2 = 0.94) and a mean difference from the true residual volume of 24 ml. (95% confidence interval 17 to 31 ml.). The differences in volumes were significantly lower with scanner 2 (t = 2.02, p = 0.047). The mean difference between catheter volume estimate and true bladder volume was 25 ml. (95% confidence interval 16 to 34 ml.). The accuracy of the BladderScan BVI 2500+ scanner is as good as catheter estimations of true residual volume and is sufficient to recommend its use as an alternative to catheterization for the determination of residual urine volume.