Studying the factors that impact the dissolution characteristic of complex drug product.

This article summarizes the critical factors involved in product development of a single dosage form formulated by compacting ethyl cellulose (EC) coated controlled release pellets into a tablet. The greatest challenge associated with this type of complex system is to minimize the effect of compression on the drug release. The effects of compression on the drug release were optimized with combination of the following factors (1) particle size of the core pellets, (2) the selection of the coating polymer's viscosity grade, and (3) emergence of cushioning agents. The optimization of these factors provided superior protection for the controlled release coated pellets; therefore, the desired drug release from the tablet was successfully achieved as designed. However, the drug release rates from the coated pellets before and after the compression were minimized and exhibited only a slight difference.

Resistance to insulin-mediated glucose uptake and hyperinsulinemia in women who had preeclampsia during pregnancy.

Plasma glucose and insulin responses to a 75-g oral glucose load, and the steady-state plasma insulin (SSPI) and glucose (SSPG) concentrations after an infusion of somatostatin, insulin, and glucose, were determined 2 months after delivery in 26 women; 13 who had a normal pregnancy and 13 who developed preeclampsia. The plasma glucose response to oral glucose was not different in the two groups, but the plasma insulin response was significantly greater (P < .02) in those who had been preeclamptic. Although the mean (+/- SE) SSPI concentrations during the infusion study were similar in the two groups (51 +/- 2 v 56 +/- 2 microU/mL), the SSPG concentrations were significantly higher (P < .02) in those who developed preeclampsia (160 +/- 17 v 119 +/- 17 mg/dL). Thus, when studied 2 months after delivery, women who developed preeclampsia were relatively insulin resistant and hyperinsulinemic when compared to those who had an uncomplicated pregnancy.

The role of aggregation of platelets in pregnancy-induced hypertension: a comprehensive and longitudinal study.

Plasma 6-keto-prostaglandin F 1 alpha and thromboxane B2, the metabolites of prostacyclin and thromboxane A2 respectively, were measured in 12 women with pregnancy-induced hypertension, 12 age-matched normotensive pregnant women and 8 non-pregnant women as controls. Pregnancy was divided into 3 stages, namely: 22-27, 28-32 and 33-39 weeks. The concentrations of thromboxane B2 in the plasma of women with pregnancy-induced hypertension was 1.4-1.7 times greater than normotensive pregnant subjects at the same gestational stage, and 2 times higher than controls. Plasma levels of 6-keto-prostaglandin F 1 alpha in normotensive pregnant women was 1.8 times greater than in those with pregnancy-induced hypertension at 28-32 and 33-39 weeks, and was significantly higher than control. The ratio of thromboxane B2 to 6-keto-prostaglandin F 1 alpha was markedly increased in the group of patients with pregnancy-induced hypertension at 28-32 and 33-39 weeks gestation. The ratio of the two metabolites in normotensive patients at each stage of gestation was similar to the control group. The ratio of circulating aggregated platelets in subjects with pregnancy-induced hypertension was significantly lower than in normotensive pregnant subjects at 33-39 weeks, implying increased turnover of platelets in pregnancy-induced hypertension. There was no significant difference in count of platelets, adenosine diphosphate threshold concentration and variables of platelet aggregation induced by adenosine diphosphate among the 3 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of mullerian inhibiting substance binding on cervical carcinoma cells demonstrated by immunocytochemistry.

Müllerian inhibiting substance (MIS) is a glycoprotein released from Sertoli cells or follicular cells of gonads, responsible for the regression of Müllerian ducts and/or Müllerian-derived tumor cells. Binding of MIS to target cells is essential for initiating regression. A human cervical carcinoma CaSki cell was examined by quantitative immunocytochemistry detected by anti-avian MIS antibody for MIS binding ability. Various treatments of WGA-peroxidase conjugate, enzyme digestion, sodium periodate or exogenous estrogen before antibody recognition were performed. It was found that the WGA partially blocked MIS binding to CaSki cell surfaces. Protease digestion of CaSki cell surfaces prior to addition of MIS or an anticervical carcinoma monoclonal antibody 1H10 (MAb 1H10), blocked the binding of MIS but not MAb 1H10 to cell surfaces. Sodium periodate and overnight exposure of CaSki cells to estrogen or diethylstilbestrol before or after fixation of the cells, did not influence MIS binding ability in vitro. MIS binding was higher on avian Müllerian duct compared with MIS binding to CaSki cells by quantitative immuno-gold labeling analysis. MAb 1H10 immuno-gold complexes binding to CaSki cells was also obtained and compared with MIS immuno-gold bindings. MIS binding site could be a polypeptide which survived sodium periodate treatment. The 'critical window' period, in which developing Müllerian ducts respond to exogenous estrogen protection from MIS regression, is possibly lost in CaSki cell.

No decline in preterm birth rate over three decades.

Low socioeconomic status has been associated with risk of preterm delivery. During the past 30 years, Taiwan has had tremendous economic growth and people have attained higher levels of education and living. It is thus not unreasonable to presume that the rate of preterm delivery would decline in response to these changes. The birth registry of Tri-Service General Hospital from 1957 to 1987 was reviewed. The rate of preterm delivery remained stable over the past 30 years, unaffected by these country-wide social changes.

Comparative study of Filshie clip and Pomeroy method for postpartum sterilization.

A prospective randomized comparison of the peri-operative complications and long-term sequelae between the Filshie clip and Pomeroy methods was undertaken in 200 postpartum women at Tri-Service General Hospital, Taipei, Taiwan. The peri-operative complications in either group were mild and infrequent. One pregnancy in the Pomeroy group was reported after follow-up for 24 months. No significant difference between the two groups was found in respect to long-term sequelae.

Transcervical flexible endoscopy for first trimester embryonic/fetal evaluation.

OBJECTIVE: The aim of the study was to investigate the efficacy of flexible embryofetoscopy for visualization of the first trimester human embryo and fetus. METHOD: Twelve pregnant women scheduled for legal termination of pregnancy at 6-12 weeks' gestation were included in the study. A flexible fiber optic endoscope with an eyepiece connected to a monitor was used. The sterile endoscope was passed transcervically under ultrasound guidance through the chorion into the chorionic cavity. Embryos/fetuses were observed directly through the intact amniotic membrane. RESULT: Successful embryofetoscopies with clear visualization of the embryo or fetus were accomplished in 50% of cases. There were no procedure-related complications. CONCLUSION: Preliminary experience employing transcervical flexible embryofetoscopy for direct visualization of the first trimester human embryo and fetus suggest that this technique may be used for the early identification of congenital anomalies suspected by ultrasound and is expected to offer opportunities for embryo/fetal tissue sampling as well as for gene and cell therapies.

Laparoscopic loop ligatures for bladder repair during laparoscopic surgery.

In this paper, we report a case where a bladder perforation occurred during a laparoscopically assisted vaginal hysterectomy and was repaired by laparoscopic loop ligatures. This is the first case report of using the laparoscopic loop ligatures to close the bladder perforations. The loop ligature is an easy and quick procedure, which can be performed by most surgeons who take the time to learn the endoscopic suturing techniques.

Neonatal gastric aspirates as a predictor of perinatal hepatitis B virus infections.

OBJECTIVE: To elucidate possible routes and predictors of perinatal transmission of hepatitis B virus (HBV). METHOD: This was a prospective follow-up study. One hundred and forty-seven out of 1762 pregnant women who were screened in the antenatal clinic of a university teaching hospital were HBsAg carriers. Enzyme immunoassay was used for determination of hepatitis B markers. Occurrence of HBsAg in newborns' gastric aspirates, newborns' and infants' blood, and maternal milk samples were determined. Their relationship with delivery routes and duration of the first stage of labor were analyzed by chi square test. RESULTS: The presence of HBsAg in newborns' gastric aspirates was strongly associated with the acquisition of HBsAg by the babies. There was no correlation between the rate of infant antigenemia and the duration of the first stage of labor, nor did cesarean section decrease the rate of vertical transmission of HBV. CONCLUSIONS: This is the first report to provide direct evidence for the major role of the oral route in vertical transmission of HBV during delivery. In addition to maternal serum HBeAg, HBsAg status in newborn's gastric aspirates is another important determinant for vertical transmission of HBV.

Hysteroscopic endometrial ablation without endometrial preparation.

OBJECTIVE: To study the effectiveness of endometrial ablation by hysteroscopic resection without prior medical preparation for the treatment of women with persistent menorrhagia. METHOD: From January 1996 to January 1997, a total of 170 women with persistent menorrhagia and/or dysmenorrhea and who underwent hysteroscopic endometrial resection were included in the study. A thorough suction curettage was done before the procedure. The operation was conducted through a continuous flow hysteroscopic resectoscope with electrosurgery while the patient was under intravenous general anesthesia. The distention fluid used was 5% dextrose with a gravity feed infusion system consisting of a 2-1 bag between 1 and 1.5 m above the uterine cavity. After the procedure, the patients' conditions were followed for at least 6-18 months by telephone interview or at our clinic. RESULTS: A total of 127 women were available for a follow-up period of at least 6 months. Operative complications were 3%; three women had fever and received oral antibiotics; no uterine perforation occurred; one case of post-operative bleeding was controlled by intrauterine balloon inflation; the average operation time was 21 min; The mean fluid deficit was 435 ml. Ninety-nine out of 127 women (78%) had adequately controlled menorrhagia (18.1% had amenorrhea, 42.5% hypomenorrhea and 17.3% had normal menstrual flow), while 27 women (21.2%) were failed due to unchanged or heavier menstrual flow after surgery. Eleven (40%) out of the 27 failed cases had myoma with menorrhagia, whereas only five women (5%) out of the 99 adequately treated women had myomas (P < 0.05). Thirty-eight (54%) out of the 70 women with severe dysmenorrhea reported either lessening dysmenorrhea or no dysmenorrhea after the surgery. A total of 76 women (60%) were satisfied with the procedure. A second surgical procedure, either a resection or hysterectomy, was necessary in 13 women (10%) after ablation (seven received repeated ablations and six underwent hysterectomy). CONCLUSION: Endometrial ablation without endometrial suppression is a cheap, effective and acceptable procedure for treatment in women with persisted persistent menorrhagia.

Genital human papillomavirus infections in Taiwan.

OBJECTIVES: Identification and typing of HPV infections in genital condyloma and normal cytological cervix. METHODS: Cervical cells from 289 Pap cases with normal cytological findings were examined for HPV infection by slot blot hybridization. Fifteen condyloma biopsy specimens were studied by Southern blot hybridization. RESULTS: Thirty-six cases (12.5%) with normal cervical cytology were HPV positive. The predominant HPV type in women with normal cytology is HPV-16. Risk factors for HPV infection in women with normal cytology depend on age and history of pregnancies. Twelve cases (80%) of condyloma contained HPV-6 or -11 sequences. The predominant HPV type in genital condyloma is HPV-11. CONCLUSIONS: HPV detection in population-based screening programs for cervical neoplasia can be an important tool in identifying women who are at risk of developing dysplasia and cervical cancer.

Unsuccessful treatment of fetal immunologic thrombocytopenia with dexamethasone.

Corticosteroid therapy near term for mothers with immunologic thrombocytopenia has recently been suggested as a clinically useful method to prevent neonatal thrombocytopenia. The unreliability of this approach is illustrated by the case of an infant with a low platelet count delivered after the maternal administration of dexamethasone.

Rectal administration of misoprostol for the management of retained placenta--a preliminary report.

BACKGROUND: Retained placenta is one of the serious complications of childbirth, and misoprostol is known to be a potent uterotonic agent. Therefore, we proposed that rectal misoprostol also may facilitate placental separation in women with retained placenta by its ability to increase uterine contractility. METHODS: The placenta was diagnosed as retained if it was not expelled within 40 minutes after vaginal birth. Then, 800 microg of misoprostol was inserted rectally and the patient observed thereafter. RESULTS: A total of 18 parturients who had retention of the placenta were studied; all the placentas were spontaneously expelled within 35 minutes. The side effects involved included nausea 17%, vomiting 11%, diarrhea 22%, shivering 33%, and pelvic cramping pain 44%. All these discomforts resolved within 24 hours. CONCLUSIONS: Our study demonstrated that misoprostol per rectum is a safe and effective technique and may be a useful alternative to manual removal of retained placentas.

Psychosocial risk factors of teenage pregnancy in eastern Taiwan.

BACKGROUND: Teenage pregnancy is a growing worldwide problem, associated with adolescents' social and health problems and poor perinatal outcome. This study was conducted to investigate psychosocial factors predisposing to the high teenage pregnancy rate in Hualien, eastern Taiwan. METHODS: A regional hospital-based study was conducted with a retrospective analysis of hospital records and questionnaires to collect personal and family data regarding the perinatal outcome of 100 pregnant teenagers and 100 pregnant adults, who had normal deliveries at the Buddhist Tzu-Chi General Hospital between 1994 and 1995. RESULTS: A significantly higher percentage of teenage mothers were of aboriginal origin than adult mothers (63% vs 25%; p < 0.05) and lived in rural areas (80% vs 19%; p < 0.05). There was also a higher incidence of late antenatal care (31% vs 11%; p < 0.05) drinking (36% vs 9%; p < 0.05) and a greater history of smoking (34% vs 7%; p < 0.05) among teenage mothers. About 86% of teenage mothers did not use any contraception. The preterm birth rate was not significantly higher in the adult group, but teenage mothers tended to have significantly lower birth weight infants (19% vs 9%; p < 0.05) and a decreased incidence of cesarean section (19% vs 33%; p < 0.05). About 20% of the teenage mothers had their first coitus before the age of 13, while none of the adult mothers had sexual coitus before the age of 13. CONCLUSIONS: In this hospital-based study, teenage mothers tended to be of aboriginal origin, lived in rural areas, had early sexual exposure without contraception, had drinking and smoking habits, were late seeking antenatal care and gave birth to low birth weight infants.

Elective cesarean section for macrosomia?

BACKGROUND: Fetal macrosomia is associated with increased risk of dystocia and birth trauma. Elective Cesarean section has been recommended for macrosomic fetus to prevent the associated complications. However, the cost/benefit ratio of such practice should be known before it can be considered appropriate. METHODS: The record of 6230 women delivered consecutively at Tri-Service General Hospital were reviewed retrospectively. The occurrence rates of dystocia and birth trauma were compared between normal birthweight group (2500-3999 gm) and macrosomic group (> or = 4000 gm). The complication rates were calculated specifically among those macrosomic infants delivered vaginally. RESULTS: Of the 6230 singleton pregnancies, 207 had an infant weighing at least 4000 gm. One hundred and three macrosomic infants were delivered by Cesarean section. The indication for Cesarean section was dystocia in 25, estimated fetal macrosomia in 30 and other, 48. If only those pregnancies with macrosomic infant allowing an adequate trial of labor were considered, the frequency of Cesarean section for dystocia was 19.1% in the 4000-4999 gm group and 21.4% in the 4500 gm group, compared with 4.4% in the normal birthweight group. No birth trauma occurred in the macrosomic infants delivered by Cesarean section. Of those macrosomic infants delivered vaginally, the frequency of clavicle fracture was 11.8% in the 4000-4499 gm group and 18.2% in the > or = 4500 gm group, compared with 1.2% in the normal birthweight group. Two infants (18.2%) weighing greater than 4500 gm sustained brachial plexus injury. CONCLUSIONS: Elective Cesarean section on macrosomic infants to prevent dystocia is not recommended because most of them can be delivered vaginally. For the very macrosomic infants (> or = 4500 gm), elective Cesarean section is suggested to prevent birth trauma.

Pregnancy in patients with systemic lupus erythematosus.

Ten pregnancies in patients with systemic lupus erythematosus were reviewed. Preterm delivery occurred in 4 cases (40%), fetal growth retardation in 2 (20%) and intrauterine death in 2 (20%). Preeclampsia developed in one case, which was the only found maternal complication. The most important factor associated with poor outcome was lack of antenatal care. Most of the SLE-complicated pregnancies can anticipate a favorable outcome if, and only if, there is a well-planned management with close cooperation among the patient, obstetrician, rheumatologist and neonatologist.

Lectin bindings and diethylstilbestrol effects on the recognition of mullerian inhibiting substance (MIS) on chick mullerian ducts by MIS-antiserum.

A high intensity of lectin bindings was demonstrated on the epithelial cells and serosa cells of the regressing right Mullerian ducts (Mds) in the female chick embryos. The strong lectin bindings occurs on, or in the regressing Md cells along with marked surface MIS bindings at the age of day 13. However, at the age of days 5-7 1/2, bindings of lectins were weak. Neither Wheat-germ agglutinin (WGA) or Concanavalin A (Con-A) labelings before MIS-antiserum (MIS-Ab) incubation can block antibody recognitions to the antigens, including MIS and growth hormone at the age of day 13. Our previous studies indicated that after WGA labeling on the surfaces of Md epithelial cells prior to the incubation of MIS-Ab at day 10 did not prevent the recognition of MIS-Ab (Wang 1989). On the contrary, at day 7 1/2, the specific binding of MIS was eliminated after preincubations with lectins and prenatal diethylstilbestrol (DES) treatment at the age of day 5. It is suggested that DES provides a protection to the Mds from MIS-induced regression by preventing the MIS binding to its specific membrane receptors. An increase of extra- and intracellular glycoproteins or carbohydrates of regressing Md epithelial cells were suggested. Internalization of WGA but not MIS molecules was found in Md epithelial cells. The Golgi saccules were negative of lectin bindings.

Postcoital hemoperitoneum without identifiable bleeding source: a case report.

Spontaneous intra-abdominal bleeding has been called abdominal apoplexy. It has been so named because its nature and spontaneity closely resemble those of its more common cerebral counterpart. The bleeding source commonly came from a ruptured branch of celiac axis or superior mesenteric artery. Rarely, hemoperitoneum occurs spontaneously post coitus without evident vaginal injury. There were only twelve cases reported in the medical literature to date. Nearly, all of them showed injury of pelvic organs including round or broad ligaments, ovarian cysts or adhesion bands. A case of massive hemoperitoneum after coitus, with no definite bleeding source, is reported.