Precipitation casting of drug-loaded microporous PCL matrices: incorporation of progesterone by co-dissolution.

Microporous, poly(epsilon-caprolactone) (PCL) matrices were loaded with progesterone by precipitation casting using co-solutions of PCL and progesterone in acetone. Progesterone loadings up to 32% w/w were readily achieved by increasing the drug content of the starting PCL solution. The kinetics of steroid release in PBS at 37 degrees C over 10 days could be described effectively by a diffusional release model although the Korsmeyer-Peppas model indicated the involvement of multiple release phenomena. The diffusion rate constant (D) increased from 8 to 24 microg/mg matrix/day0.5 as the drug loading increased from 3.6 to 12.4% w/w. A total cumulative release of 75%-95% indicates the high efficiency of steroid delivery. Increasing the matrix density from 0.22 to 0.39 g/cm3, by increasing the starting PCL solution concentration, was less effective in changing drug release kinetics. Retention of anti-proliferative activity of released steroid was confirmed using cultures of breast cancer epithelial (MCF-7) cells. Progesterone released from PCL matrices into PBS at 37 degrees C over 14 days retarded the growth of MCF-7 cells by a factor of at least 3.5 compared with progesterone-free controls. These findings recommend further investigation of precipitation-cast PCL matrices for delivery of bioactive molecules such as anti-proliferative agents from implanted, inserted or topical devices.     

Proximal femoral focal deficiency: radiologic analysis of 49 cases

Proximal femoral focal deficiency, an uncommon congenital anomaly, necessitates early radiologic classification for surgical planning and treatment. Objective radiographic criteria, including femoral length index, acetabular depth index, acetabular angle index, and shape of the proximal femur were determined in 49 patients before cartilaginous ossification of the femoral capital epiphysis; final classification was based on follow-up radiographs or findings at arthrography or surgery. These parameters were analyzed to determine the accuracy and contributions of each in classification. Correct classification into one of three groups was possible in 86% of cases with use of three of the parameters: femoral length index, acetabular depth index, and shape of the proximal femur. The acetabular angle was found to contribute insignificantly to classification. Magnetic resonance imaging, used in only one case, depicted the nonossified cartilaginous femoral capital epiphysis, thus obviating the need for invasive diagnostic procedures and facilitating early classification.     

Acute and chronic pharmacokinetics of asymmetrical doses of slow release choline theophyllinate in asthma.

The day and night pharmacokinetics of assymetrical doses of slow release choline theophyllinate (Sabidal SR 270) were compared at day 1 and at day 4 of treatment when steady state had been achieved. Ten patients with chronic asthma were given oral choline theophyllinate 424 mg at 09.00 h and 848 mg at 21.00 h for 4 days. At regular intervals during day 1 and day 4 of treatment theophylline concentrations were measured in plasma and dried blood spots by fluorimmunoassay. Theophylline concentrations measured from dried blood spots were slightly lower than those in plasma, the difference remaining constant at all time points during day 1 and day 4 of treatment. On day 1 the mean peak plasma theophylline concentration was 5.4 +/- 1.0 (+/- s.e. mean) micrograms ml-1 4 h after the morning dose and 11.2 +/- 1.6 micrograms ml-1 4 h after the evening dose which were significantly (P less than 0.01) different. Similarly the areas under the plasma theophylline concentration-time curves at night were significantly (P less than 0.001) greater than those observed during the day. During day 4 mean peak plasma concentrations of theophylline after the morning and larger evening dose were 13.2 +/- 1.3 and 12.1 +/- 1.4 micrograms ml-1 respectively, which were not significantly different. No significant difference was observed between the areas under the plasma theophylline concentration-time curves during the day and at night. However the post-dose time to peak was significantly delayed at night (6 h) compared to the morning (2 h, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

44Sacral extracorporeal magnetic stimulation is an effective treatment for pelvic floor dyssynergia; Comparative study with biofeedback therapy

Background: Recent development of extracorporeal magnetic stimulation (ECMS) which uses current‐changing magnetic fields allows the induction of electrical stimulation in the desired deep tissue. Recent study showed the sacral nerve stimulation reduces corticoanal excitability that may play a functional role in anal continence mechanisms. Preliminary study shows that ECMS of sacral nerve can modify pelvic floor function and expel rectal balloon in patients with pelvic floor dyssynergia (PFD). Aims: To evaluate the effect of ECMS compared with biofeedback therapy (BF) in patients with PFD. Methods and Materials: Thirty‐eight patients who fulfilled Rome II criteria for PFD by colon transit time and anorectal function tests, were randomly treated with 8 sessions of ECMS (2/weeks; n = 19) at prone position or BF (2/weeks; n = 19) at sitting position. Stimulation parameters were set at 50–80% of maximum intensity, 10 and 50 Hz frequency, 3 s burst length with 3 and 6 s off using arm‐typed stimulator (BioCom‐1000, Mcube Co., Korea). Symptom scores for constipation with/without anorectal function test were repeatedly measured after each treatment. Response was defined as 50% or more decreased symptom score after treatment (partial response: 30–50%, poor: <30%). Results: Fifteen patients (age 49.1 ± 13.4 years, mean ± SD; 4 men) completed 8 session of BF and 14 patients (54.5 ± 17.6 years, 3 men) completed 8 session of ECMS. Four patients of BF group discontinued treatment due to unsatisfactory therapeutic effect (n = 1) and withdrew consent (n = 3) and 5 patients of ECMS group discontinued treatment because of same reasons (n = 1, 4). Total symptom scores were significantly decreased after treatment of 8 session in both treatment groups (13.4 ± 6.6 vs. 4.3 ± 4.0 for BF, p = 0.009; 14.9 ± 5.6 vs. 3.4 ± 4.0 for ECMS, p < 0.001). Bowel movements per week were also significantly increased after treatment in both groups (median 2 vs. 7 for BF, p = 0.035; median 2 vs. 7 for ECMS, p = 0.008). Thirteen out of 15 patients showed response in BF group and 12 out of 14 showed good response in ECMS group. No adverse effects in both groups. Conclusions: ECMS is as effective as BF for the treatment of PFD. Long‐term effect of ECMS for the patients with pelvic floor dyssynergia need to be evaluated in the near future.