Surface hydrophilisation and antibacterial functionalisation for microporous polypropylene membranes.

The surface properties of polymer membranes are crucial to their separation performances. For the microporous polypropylene membranes, the high hydrophobicity and lack of functionality easily cause protein adsorption and subsequent microorganism attachment and biofilm formation, i.e. biofouling. Thus, their applications in water treatment, bioseparation and biomedical fields are largely limited. Surface hydrophilisation and antibacterial functionalisation are, therefore, reasonably necessary. This review provides a concise summarisation of related studies according to the surface modification strategies. Especially, the interfacial crosslinking approach developed in our previous studies is presented in detail.

Continuous dosing of a novel contraceptive vaginal ring releasing Nestorone® and estradiol: pharmacokinetics from a dose-finding study.

BACKGROUND: As part of a program to develop a novel estradiol-releasing contraceptive vaginal ring (CVR), we evaluated the pharmacokinetic (PK) profile of CVRs releasing segesterone acetate (Nestorone® (NES)) combined with one of three different estradiol (E2) doses. STUDY DESIGN: A prospective, double-blind, randomized, multi-centered study to evaluate a 90-day CVR releasing NES [200mcg/day] plus E2, either 10mcg/day, 20mcg/day, or 40mcg/day in healthy reproductive-age women with regular cycles. Participants provided blood samples twice weekly for NES and E2 levels during the first 60 days (ring 1) and the last 30 days (ring 2) of use. A subset underwent formal PK assessments at ring initiation, ring exchange (limited PK), and study completion. RESULTS: The main study enrolled 197 women; 22 participated in the PK substudy. Baseline characteristics between the main and PK participants were comparable, with an average BMI of 25.8 kg/m2 (SD 4.3). In the PK substudy, all three rings showed similar NES PK: mean area under the curve (AUC(0-72)) 34,181 pg*day/mL; concentration maximum (Cmax) 918 pg/mL; time to maximum concentration (Tmax) 3.5 h. For E2, the Cmax occurred at 2 h, and was significantly higher with the 20 mcg/day ring (mean 390 pg/mL); 10 mcg/day, 189 pg/mL, p=.003; 40 mcg/day, 189 pg/mL, p<.001), and declined rapidly to≤50 pg/mL for all doses by 24 h. For all subjects, the median E2 levels remained under 35 pg/mL during treatment. CONCLUSION: PK parameters of NES were not affected when paired with different doses of E2, but E2 levels from all three doses were lower than anticipated and no dose response was observed. IMPLICATIONS: While these novel estradiol-releasing combination contraceptive vaginal rings provided sustained release of contraceptive levels of Nestorone over 90 days, the E2 levels achieved were not consistent with bone protection, and a dose-response was not observed.

A review of the endometrial changes in Norplant users.

PIP: Prolonged exposure to levonorgestrel associated with use of Norplant contraceptive implants leads, in many acceptors, to menstrual irregularities. Endometrial biopsies collected from a group of Norplant acceptors with persistent or prolonged breakthrough bleeding indicated this side effect is associated with proliferative-type endometrium. The number of both proliferative and secretory endometrium was markedly reduced. The stroma showed edema, sloughing, and inflammatory infiltration. Despite chronic levonorgestrel exposure, only 31% of stroma showed poorly developed decidualization. There was no association between endometrial findings and levonorgestrel levels. Hysteroscopy revealed markedly engorged superficial vessels in long-term Norplant users. It is hypothesized that progestin-related bleeding abnormalities may be due to the changes in the vascular system (e.g., damaged vessels) and hemostatic factors. Confirmation of this hypothesis requires detection of the presence of hemostatic plugs in patients with and without abnormal bleeding, study of the perivascular expression of tissue factor, measurement of estrogen and progesterone receptors at bleeding and non-bleeding sites, and identification of factors that increase angiogenesis and the fragility of uterine vessels.^ieng

The effect of prostaglandin F2alpha on corpus luteal function in the rhesus monkey.

An experimental model was set up to show whether PGF2alpha caused luteolysis when adequate chorionic gonadotropin was administered. Four mature female rhesus monkeys were studied for two cycles each. HCG was given after ovulation until day 36. PGF2alpha was given on days 28 and 29 in one cycle, while the other served as control. In five out of the total eight cycles studied, the luteal function was maintained up to day 36. However, gradual decline of serum progesterone was noted after days 22 to 26 despite the continuous administration of hCG. Administration of PGF2alpha on days 28 and 29 did not accelerate CL regression. It was also noted that hCG in doses of 500 IU did not maintain CL function in three of four cycles when surgical stress was added.

Improved methods in the synthesis of 1 alpha-hydroxylated vitamin D.

Alternative methods that can be used to synthesize certain key intermediary compounds in the preparation of 1 alpha-hydroxylated vitamin D have been described. These methods are simple and give higher yields than the reported procedures.

Effects of acids and bases on salicylic acid-cetrimide systems.

The effects of acids and bases on the viscosity of salicylic acid-cetrimide systems were investigated. A viscosity reduction was produced by the addition of acids and was independent of the degree of saturation of the cetrimide solution with salicylic acid. The incorporation of base followed by that of acid increased and decreased the viscosity, respectively. This viscosity behavior was demonstrated in undersaturated systems and was not goverened by the relative amounts of base or acid used. In oversaturated systems, only a lowering of viscosity was observed.

Viscosity and surface tension of dilute salicylic acid-cetrimide systems.

The viscosity and surface tension of systems containing small amounts of salicylic acid in aqueous solutions of cetrimide were determined. An abrupt increase in viscosity was observed, and the molar ratio of salicylic acid to certrimide at which this viscosity increase occurred was 1:2. The surface tension of these systems also increased sharply after an initial lowering. The salicylic acid concentration at which this behavior was demonstrated was almost the same as that at maximum solubility in the surfactant solution.

Surfactant effect on the dissolution of sulfanilamide granules.

Polysorbate 80 incorporated in sulfanilamide granules was found to depress the dissolution of sulfanilamide. The largest decrease corresponded to the lowest concentration of surfactant used. Sulfanilamide granules formulated with either starch or microcrystalline cellulose also decreased the release of the drug. The effect of starch depressing sulfanilamide dissolution was greater with higher starch content in the granules. However, addition of polysorbate 80 improved the dissolution of sulfanilamide granules containing starch but not those with microcrystalline cellulose. This difference was found to be related to the ability of starch to swell and cause granule disintegration. The inclusion of polysorbate 80 in starch-containing granules produced softer and more densely packed granules which were more responsive to the swelling effect of starch.

Termination of very early pregnancy by vaginal suppositories-(15S)-15-methyl prostaglandin F2 alpha methyl ester.

A new approach to terminate very early pregnancy was tried on 49 healthy women who were proven to be pregnant from 31 to 47 days from their last menstrual period. All pregnancies were confirmed either by UCG or serum HCG-B subunit. (15S)-15-Methyl PGF2 alpha Methyl Ester in a suppository form was administered in two separate doses: 1.0 mg initial dose followed by 3.0 mg one hour later. Patients were kept under observation for 8 hours. Blood sampling for progesterone, HCG-B, and prostaglandin levels were assayed at 0 degree, 30', 1 degree, 4 degrees, 8 degrees and 14 days. Patients were re-examined at a two week follow-up visit. Pelvic examination and pregnancy tests were performed to confirm whether the pregnancy was successfully terminated. There were no significant changes in serums progesterone and HCG-B levels during the 8-hour observation period. Both levels declined significantly to very low levels at 14 days post-therapy, confirming the clinical impression of successful termination of pregnancy. Plasma prostaglandin levels rose as early as 30 minutes after initiation of therapy, peaked at 4 hours and declined gradually afterwards. Most side effects such as nausea, vomiting, diarrhea and cramps, although clinically manageable, were still bothersome. One patient experienced an episode of vasovagal syncope. The majority of patients required medical observation up to 6 hours. Clinical implications of this new approach of termination of very early pregnancy are discussed.

Pituitary response to LHRH stimulation in women on oral contraceptives: a followup dose response study.

Gonadotropic response to bolus intravenous injection of LHRH was measured in 36 women. Thirty of them were taking five different oral contraceptive preparations with six women in each category, and the remaining six served as controls. 150 micrograms LHRH was given during cycle days 20-25. Serum samples were obtained prior to the bolus injection and at 20 minute intervals for two hours. Five different oral contraceptive agents were selected to compare different progestins with same type and dose of estrogen, and different type or dose of estrogen with same type and dose of progestins. Significant suppression of LH response to LHRH stimulation ws observed in the agents containing 50 mcg of ethinyl estradiol or mestranol. No such suppression was noted in the product containing only 20 mcg of ethinyl estradiol. In comparing the different type of estrogenic or progestational components, no statistically significant differences in LH response were demonstrated. This finding suggests that it is not the individual component alone, but the combined action of estrogenic and progestational components which determines the potency of an oral contraceptive agent.

Effects of the Progestasert on the menstrual pattern, ovarian steroids and endometrium.

PIP: 193 women were fitted with a progesterone-releasing IUD (Progestasert) and followed for a total of 1823 woman-months (minimum 1 year use); 108 were nulliparous and 84 parous. Patients were examined at 1, 6, and 12 months and were interviewed to assess length of cycle, duration of flow, amount of flow, pain associated with menstruation, and intermenstrual bleeding and pain. Endometrial biopsies were performed on 45 patients and serum estrogens and progesterone measurements were made. There were .5 pregnancies/100 woman-years during the first 12 months of use. Overall expulsion rate was 7.4/100 woman-years; 4.8 and 10.7 corresponding to nulliparous and parous, respectively. 77% of expulsions occurred within 1 month of insertion. Intermenstrual bleeding occurred in small amounts and during the first 2 months of use. Menstrual flow and dysmenorrhea were significantly reduced. The overall continuation rate was 76.0 + or -3.2. Normal ovulatory function continued after insertion. Endometrial biopsies demonstrated glandular atrophy and decidual reaction after 12 months use.^ieng

Endometrial biopsy using the Tao Brush method. A study of 50 women in a general gynecologic practice.

OBJECTIVE: To test whether the Tao Brush can retrieve sufficient endometrium for diagnosis and also to observe patients' tolerance of its use. STUDY DESIGN: Fifty women underwent Tao Brush sampling: 25 were sampled by Tao Brush alone, and the remainder were sampled by Pipelle immediately following. Patients' reactions to each method were observed. RESULTS: Pipelle currettes larger pieces of endometrium; the Tao Brush obtains smaller pieces. There was no discrepancy between Tao Brush and Pipelle except that Pipelle sampled two of five endometrial polyps, while the Tao Brush sampled none. There was less tissue insufficient for diagnosis with the Tao Brush (2%) than Pipelle (12%). Most patients did not show signs of distress during Tao Brush sampling but grimaced during Pipelle suction curettage. For each of the 16 patients in the second group, the Tao Brush was significantly less painful than Pipelle (P < .01). CONCLUSION: Our data suggest that the Tao Brush is an effective alternative endometrial sampler, causes less pain and produces less tissue insufficient for diagnosis than does the Pipelle. The CPT billing codes (58100) are the same for both the Pipelle and Tao Brush.

Low dosage megestrol acetate application as contraceptive.

PIP: A review of the development of low dose progesterone is presented. Continuous low-dose megestrol acetate therapy data from 43 patients is presented. When short cycle lengths, breakthrough bleeding, and amenorrhea occurred, a lower dose of megestrol acetate was substitute. 78% of the cycles varied between 21 and 38 days a breakthrough bleeding occurred in 19.6% cycles, and average flow was 5.2 days. There were no breakthrough pregnancies in this group. A majority of the cycles with megestrol acetate were ovulatory, but the cervical mucus was hostile and vaginal smears showed a definite progestational effect.^ieng

Endometrial brush biopsy for the diagnosis of endometrial cancer.

OBJECTIVE: To evaluate a new technique for processing endometrial cytology for the diagnosis and exclusion of endometrial cancer. STUDY DESIGN: All women at risk for endometrial cancer with clinical indications for endometrial biopsy were evaluated by endometrial brush biopsy (Tao Brush, Cook OB-GYN, Bloomington, Indiana) and Pipelle (Cooper Surgical, Shelton, Connecticut) endometrial biopsies during one office visit. Patients were followed longitudinally for the development of endometrial cancer or until undergoing dilatation and curettage or hysterectomy. All comparisons were analyzed using the chi 2 or t test. RESULTS: One hundred one women (mean age, 58; range, 35-86) had endometrial biopsies performed. Median follow-up was > 21 months (range, 3-29). Twenty-two had cancer or atypia, while the remaining had benign diagnoses. When correlated with the final diagnosis, the Tao Brush had 95.5% sensitivity and the Pipelle, 86% sensitivity. Both devices had 100% specificity, positive predictive value of 100% and negative predictive value of 98%. When the results of the two biopsy devices are considered together, the positive and negative predictive value for detecting or excluding endometrial cancer was 100%. Based on 1998 Medicare reimbursements, a simultaneous second office biopsy using the Tao brush could save approximately $67 per case as compared to a sonohistogram and much more when compared to dilatation and curettage. CONCLUSION: Endometrial cancer can be reliably detected and excluded using these two distinct office biopsy devices simultaneously during one office visit. In patients with an indication for endometrial biopsy, no further diagnostic test may be necessary to exclude or diagnose endometrial cancer or atypia.

Compact cell blocks. Use for body fluids, fine needle aspirations and endometrial brush biopsies.

OBJECTIVE: To obtain an ideal cell block wherein the maximal number of cells are displayed within the smallest area on the block surface. STUDY DESIGN: Cyto-Rich Red (AutoCyte, Inc., Elon College, North Carolina, U.S.A.) is added to fresh cellular sediment in a centrifuge tube at a ratio of 1:1. After two minutes, three to four drops of plasma and topical thrombin (5,000 U/10 mL) is added. The tube is then gently agitated for two minutes, until a gelatinous clot is obtained. The clot is then slid onto a lens tissue on top of paper towels. The lens tissue is folded once over the clot. By gently squeezing the excess fluid from it through the lens tissue into the paper towels, the clot is transformed into a flat, compact, densely cellular aggregate, which is painted with mercurochrome prior to fixation in formaldehyde. RESULTS: From each of the 495 cases, including 250 body cavity fluids, 170 fine needle aspirates and 75 endometrial brush biopsies, processed with the above protocol, there was a compact cell block containing packed cells or tissue fragments in a clean background devoid of red blood cells. CONCLUSION: The compact cell block is about 10-20% the size of a conventional cell block, yet more cells are on display, thus reducing the need for deeper cuts and screening time while increasing the efficiency of cytodiagnosis. The compact cell block technique is particularly helpful for endometrial brush biopsies.