Cranial and ventricular size following shunting or endoscopic third ventriculostomy (ETV) in infants with aqueductal stenosis: further insights from the International Infant Hydrocephalus Study (IIHS).

PURPOSE: The craniometrics of head circumference (HC) and ventricular size are part of the clinical assessment of infants with hydrocephalus and are often utilized in conjunction with other clinical and radiological parameters to determine the success of treatment. We aimed to assess the effect of endoscopic third ventriculostomy (ETV) and shunting on craniometric measurements during the follow-up of a cohort of infants with symptomatic triventricular hydrocephalus secondary to aqueductal stenosis. METHODS: We performed a post hoc analysis of data from the International Infant Hydrocephalus Study (IIHS)-a prospective, multicenter study of infants (< 24 months old) with hydrocephalus from aqueductal stenosis who were treated with either an ETV or shunt. During various stages of a 5-year follow-up period, the following craniometrics were measured: HC, HC centile, HC z-score, and frontal-occipital horn ratio (FOR). Data were compared in an analysis of covariance, adjusting for baseline variables including age at surgery and sex. RESULTS: Of 158 enrolled patients, 115 underwent an ETV, while 43 received a shunt. Both procedures led to improvements in the mean HC centile position and z-score, a trend which continued until the 5-year assessment point. A similar trend was noted for FOR which was measured at 12 months and 3 years following initial treatment. Although the values were consistently higher for ETV compared with shunt, the differences in HC value, centile, and z-score were not significant. ETV was associated with a significantly higher FOR compared with shunting at 12 months (0.52 vs 0.44; p = 0.002) and 3 years (0.46 vs 0.38; p = 0.03) of follow-up. CONCLUSION: ETV and shunting led to improvements in HC centile, z-score, and FOR measurements during long-term follow-up of infants with hydrocephalus secondary to aqueductal stenosis. Head size did not significantly differ between the treatment groups during follow-up, however ventricle size was greater in those undergoing ETV when measured at 1 and 3 years following treatment.

Pharmacokinetics of continuous once-a-week combination 17ß-Estradiol/Low- or high-dose levonorgestrel transdermal delivery systems in postmenopausal women.

Two open-label, randomized, two-period, crossover studies were performed to determine the safety, delivery rates, and pharmacokinetic properties of a combination estradiol (E2)/levonorgestrel (LNG) transdermal delivery system (TDS). Study 1 enrolled 24 postmenopausal women who received a single TDS containing 4.4 mg E2 and 1.39 mg of LNG (E2/LNG Low) or E2 0.050 mg/24 hours TDS and 0.090 mg LNG oral tablet. Study 2 enrolled 44 postmenopausal women who received either E2/LNG Low or TDS containing 4.4 mg E2 and 2.75 mg LNG (E2/LNG High) weekly for a period of 4 weeks. E2, estrone (E1), LNG, and sex hormone-binding globulin (SHBG) serum concentrations were determined. Overall, both E2/LNG TDS were well tolerated and had excellent adhesion properties. The average daily delivery for E2/LNG Low was 0.045 mg for E2 and 0.0132 mg for LNG. Following weekly delivery of E2/LNG Low or High for 4 weeks, the combination of E2 with two different strengths of LNG did not alter the pharmacokinetic profile of E2. SHBG, total cholesterol, and triglycerides concentrations significantly decreased compared to baseline. Both E2/LNG Low and High TDSs were well tolerated and provided continuous drug delivery over 7 days supporting the benefits of the transdermal route of administration in optimally delivering hormonal therapy.

Causes and types of precocious puberty in north-west iran.

OBJECTIVE: Precocious puberty is of concern because of the underlying disorders, the short adult stature, and the psychosocial difficulties. This study was carried out in order to evaluate the characteristics of children referred to pediatric endocrinology clinic with diagnosis of precocious puberty. METHODS: In a cross-sectional study between February 2007 and September 2009, all of the children referred to pediatric endocrinology clinic in North-West Iran with diagnosis of precocious puberty were recruited. FINDINGS: Data of 106 girls (82.2%) and 23 boys (17.8%) were analyzed. Mean age of the patients at the time of referral was 6.6±2.8 years (ranging 0.3-14 yr), which was 7±3.9 (ranging 0.3-14 yr) for boys and 6.6±2.5 (ranging 0.8-12 yr) for girls (P=0.6). Out of 129 subjects, 56(43.4%) had precocious puberty, 71.4% (35 cases) of them were due to central precocious puberty and 28.6% (16 cases) were pseudo-precocious puberty. 73 out of 129 subjects (56.6%) were due to normal variants of puberty, normal puberty, and no puberty. 87.5% of subjects with central precocious puberty were idiopathic. CONCLUSION: Most of children referred with diagnosis of precocious puberty have benign normal variants. Most of cases with precocious puberty are affected with central precocious puberty, especially with idiopathic form of it.

Endoscopic third ventriculostomy in patients with malfunctioning CSF-shunt.

OBJECTIVE: A less favorable outcome is usually claimed for ETV in formerly shunted patients, and continuous bias exists on using endoscopy in cases with malfunctioning CSF shunts. METHODS: A cohort of 60 patients with obstructive triventricular hydrocephalus (mean age 22 years, range 1-68) underwent an ETV instead of shunt revision. Fourteen patients had a history of multiple shunt-related surgeries (more than three times). Median follow-up lasted 2 years (range 1 month-8 years). Data on patients' preoperative condition and their history, including particularities of the surgery, were studied to define the impact of any given variable on the outcome. The Mann-Whitney U test was used to assess differences among groups. RESULTS: Sixteen patients did not improve and needed permanent shunts anyway. The remaining 44 patients improved and became free of shunt (72%). No reliable correlation has been found regarding final outcome and data, characterizing patients' profile, for example, etiology of hydrocephalus, the history of intraventricular bleeding and/or CNS infection, age at onset and age at the first shunting, number of shunt surgeries, the origin of shunt malfunction, and complicated ventricular anatomy. There were no deaths, and overall cases with morbidity comprised 20% (12 cases); among them, serious complications with neurologic deficit were noted in three (5%) patients. CONCLUSIONS: Patients with obstructive hydrocephalus could benefit from ETV in case of their shunt malfunction and if carefully selected have about 70% probability to become shunt free. In formerly shunted patients, endoscopy has somewhat greater risk of serious complications; thus a wider experience is essential when offering them an ETV.

Simultaneous estradiol and levonorgestrel transdermal delivery from a 7-day patch: in vitro and in vivo drug deliveries of three formulations.

A new drug-in-adhesive transdermal patch was developed to deliver both estradiol and levonorgestrel through the skin over a 7-day period, but at different rates. This report elucidates the in vitro and in vivo biopharmaceutical studies that were necessary during the development of this product. Three test patches had to be manufactured, all delivering estradiol at the same rate, but delivering levonorgestrel at three different rates so that a levonorgestrel dose response could be studied in the clinic. An in vitro hairless mouse skin model (HMS) using modified Franz diffusion cells was used to select the test products delivering levonorgestrel in the order of 1:2:3. HMS experiments also demonstrated that the presence of estradiol did not affect the flux of levonorgestrel. Two in vivo studies in postmenopausal women showed that at steady state (four weeks of once-weekly dosing) the three test products all delivered estradiol at comparable rates. Similarly, the levonorgestrel deliveries for the three test products were in the order expected. The target fluxes of both drugs were achieved in these three test products by varying the drug loads and patch size. That this approach was successful is evidence of the value of using the HMS penetration experiments in transdermal product development and should provide useful insights for other formulations having to develop complex systems. One of the test products is now marketed as Climara Pro.

The pharmacokinetics and pharmacodynamics of fludarabine phosphate in patients with renal impairment: a prospective dose adjustment study.

UNLABELLED: A significant number of chronic lymphocytic leukemia, follicular non-Hodgkin's lymphoma and Waldenström's macroglobulinemia patients, treated with fludarabine phosphate (fludarabine), are elderly with diminished renal function. Since the kidney eliminates approximately 60% of fludarabine's primary metabolite (F-ara-A), dose modification is necessary for all patients with impaired renal function including elderly patients. In this study, 22 patients with varying levels of renal function received a single intravenous dose of fludarabine (25 mg/m3), followed one week later by five (one per day) doses that were adjusted according to three predefined creatinine clearance (CLcr) levels. Relationships between renal function and F-ara-A clearance, F-ara-A exposure and F-ara-A--related toxicities were examined. The results demonstrate that total F-ara-A clearance correlated with CLcr and that F-ara-A exposure levels and patient toxicity profiles were similar across treatment groups. IN CONCLUSION: The CLcr-based fludarabine dose adjustments used in this study provided reasonably equivalent F-ara-A exposure with acceptable safety in patients with varying degrees of renal function.