The effect of cross-linked hyaluronate hydrogel on the reduction of post-surgical adhesion reformation in rabbits.

The effects of cross-linked hyaluronate hydrogel and liquid sodium hyaluronate on post-surgical adhesion reformation were examined using a rabbit model. Primary adhesions in the ileocaecal region of Japanese white rabbits were induced by mechanical and chemical irritants during laparotomy. After 1 month the primary adhesions were lysed by microsurgery and cross-linked hyaluronate hydrogel or liquid sodium hyaluronate was applied to the lysed lesions. After 10-14 days the area of adhesion reformation was measured to assess any inhibitory effect of the test materials. Rabbits treated with cross-linked hyaluronate hydrogel showed a significant reduction in adhesion reformation area compared with liquid sodium hyaluronate or physiological saline treatment, and the area reduced to (mean +/- standard deviation) 0.6 +/- 1.95% of the original lesion. In a separate study, histological evaluation of rabbits treated with cross-linked hyaluronate hydrogel revealed a better healing pattern and a lower inflammatory response compared with controls. All these findings suggest cross-linked hyaluronate hydrogel may be a valuable anti-adhesion material to prevent post-surgical adhesion in abdominal or pelvic surgery.

The effect of hyaluronic acid-carboxymethylcellulose in reducing adhesion reformation in rabbits.

The effect of hyaluronic acid-carboxymethylcellulose film (Seprafilm) in reducing postoperative adhesion formation was examined in a rabbit induced-adhesion model. During laparotomy, the ileocaecal region was mechanically and chemically abraded to induce lesions. After a 28-day recovery period, adhesions were lysed by microsurgery and Seprafilm was applied to the lysed lesion in 10 rabbits and six rabbits received physiological saline. A third laparotomy was performed 10-14 days later and the area of adhesion reformation was compared to that found prior to application of test materials. The area of adhesion reformation with Seprafilm decreased to (mean +/- standard deviation) 11.71 +/- 10.97% of the originally lysed lesion and, the area was significantly reduced compared with controls treated with physiological saline. These results suggest that the use of Seprafilm may be a valuable new anti-adhesion material for abdominal or pelvic surgery and may be superior to existing anti-adhesion materials and techniques.

Clinical evaluation of a haemostatic and anti-adhesion preparation used to prevent post-surgical adhesion.

TachoComb consists of equine collagen in a sponge-like form coated on one side with human fibrinogen and bovine thrombin. This product functions as a haemostatic and physical barrier to inhibit post-surgical adhesion. In this study, we investigated TachoComb to control oozing in 16 patients who required haemostasis. Evaluation of post-surgical adhesion by second-look laparoscopy was performed at 3 months and 7 months after initial surgery. Observation via laparotomy during Caesarean section was also performed at 13 months, 3 years and 4 years after initial surgery. In all but one patient, no macroscopic evidence of TachoComb persistence was found. Furthermore, no de novo adhesions were detected at the TachoComb application site. We have thus demonstrated that TachoComb can be used to control oozing haemorrhage effectively from surgical sites and can prevent adhesion formation at the application site, and may thus be an effective method of preventing adhesion-induced infertility.

The Clinical Significance of TachoComb, a Fibrin Adhesive in Sheet Form.

Recent improvements in surgical techniques and procedures have been accompanied by attempts to develop adhesives to seal wounds. In the 1940s, Young et al., in animal studies, attempted to connect nervous tissue with a fibrin adhesive, however, as separation and purification of blood constituents were still in a primitive state, their efforts did not progress to clinical usage.

Stimulation of early embryonic development in cattle by coculture with surfactant.

PURPOSE: Our purpose was to determine the efficacy of Surfacten, a bovine pulmonary surfactant, on the maturation of in vitro bovine ova. METHODS: We used Surfacten as a supplement to the coculture media both at the onset of coculture and after cleavage in bovine ova had been determined. The controls received no Surfacten. RESULTS: The maturation rate in bovine embryos to the blastocyst stage statistically improved (P < 0.05) in the series in which Surfacten was added to the media at the onset of coculture, compared with the controls and the series in which Surfacten was added after cleavage had been determined. CONCLUSIONS: Surfacten, a commercially available surfactant which is a naturally occurring phospholipid that dramatically increases in the cervical mucus and the ampullaris of the oviduct at or near the time of ovulation, improves the maturation of bovine embryos in vitro by making the coculture medium approach the conditions found in the oviducts.

The effects of postural changes of baroreflex gain in normal and hypertensive pregnancies.

In order to understand the changes of baroreflex gain due to postural changes in normal pregnancies, we measured percentage changes (% changes) in blood pressure (SBP, DBP), heart rate (HR), stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) as well as cardiac autonomic nervous function (HF as an index of parasympathetic and LF/HF as an index of sympathetic function) and compared these parameters in normal pregnancies with those found in hypertensive pregnancies, such as chronic hypertensive (CHP) and severe preeclamptic pregnancies (PE), in late pregnancy (after 32 wks). When the position was changed from supine to standing in normal and non-pregnant women, the % changes of HR, DBP, TPR and LF/HF were increased and SBP, SV, CO and HF were decreased. The % changes of these parameters, however, were gradually decreased as pregnancy progressed, especially after 20-24 wks of gestation. In hypertensive pregnancies, however, even in late pregnancy, the decreased SBP and increased TPR was still observed and the profound decrease of CO and SV and increase of TPR were characteristic in PE when compared to CHP.

Fimbrial capture of the ovum and tubal transport of the ovum in the rabbit, with emphasis on the effects of beta 2-adrenoreceptor stimulant and prostaglandin F2 alpha on the intraluminal pressures of the tubal ampullae.

PURPOSE: Our purpose was to elucidate the roles of the ampullar and isthmic portions of the oviduct and the effects of drugs on oviductal contractility. METHODS: Prostaglandin F2 alpha (PGF2 alpha; Ono Pharmaceuticals, Osaka) and oxytocin (Atonin-O; Teikoku Hormone Manufacturing Co. Ltd., Tokyo) were used to stimulate oviductal contractility, and ritodrine hydrochloride (Utemerin; Solvay-Duphar Corp., Denmark) to inhibit the contractility. RESULTS: Both PGF2 alpha and Atonin-O were involved in ovum capture by the ampullar oviduct by stimulating contractility, thus altering the intraductal pressures. Utemerin is effective in inhibiting the enhanced contractility induced by PGF2 alpha and Atonin-O. CONCLUSIONS: Variations in pressure of the ampullar portion of the oviduct seem necessary for the capture of ova expelled from the ovary. Once in the isthmic portion of the oviduct, transport appears to be under the influence of ciliary activity rather than variations in contractility.

Termination of early pregnancy by ONO-802 suppositories (16,16-dimethyl-trans-delta2-PGE1 methyl ester).

ONO-802 was used in the form of vaginal suppositories for the termination of early pregnancy in 63 healthy volunteers. Fifty-four (86%) of the 63 cases had complete abortions and remaining 9 (14%) had incomplete abortions. One (1.6%) of the 63 cases complained of nausea and vomiting, and 3 (4.8%) complained of headaches. No other side effects were observed. These results suggest that ONO-802 is acceptable in the form of vaginal suppositories for the termination of early pregnancy.

PIP: 63 pregnant women (aged 20-35 years) with a parity range from 0-3 (average 1.6+-.8) were treated in vaginal suppository form with ONO-802 at either .5 or 1 mg. Pregnancy-stage range was from 11-66 days beyond last expected menstrual period. Patients were instructed to insert 1 suppository every 3 hours for a maximum of 5 applications. Estradiol and progesterone levels were assayed from venous blood samples before (control) administration and 3, 6, and 24 hours postadministration. No changes were present at onset of contractions, but all fractions decreased by 48 hours postadministration. 63/63 responded with hemorrhage. 54/63 (86%) had complete abortions (89% with 1 mg, 84% with .5 mg). 9/63 were incomplete (14%), but there was sufficient dilatation for subsequent uterine content removal. With the 1-mg dose, uterine contractions and hemorrhage occurred about 1.5 hours sooner. 1/63 (1.6%) complained of nausea and vomiting, and 3 (4.8%) complained of headache. No other side effects were observed.

The effects of intramyometrial injection of prostaglandin F2alpha on severe post-partum hemorrhage.

Effectiveness of prostaglandin F2alpha (PGF2alpha) in controlling postpartum uterine hemorrhage was evaluated with the following results. (1) Systemic administration, whether by continuous i.v. infusion or by gluteal i.m. injection, was not a completely adequate method for hemostasis. (2) Local administration by directly injecting into the uterine musculature, whether transabdominally or transvaginally, resulted in a dramatic reduction of the rate of bleeding. Routine clinical application of the direct intramyometrial injection of PGF2alpha for severe post-partum hemorrhage is recommended in view of its easy performance, excellent hemostatic effect, minimal side effects and good prognosis.

Effects of paternal lymphocyte immunization on peripheral Th1/Th2 balance and TCR V beta and V gamma repertoire usage of patients with recurrent spontaneous abortions.

PROBLEM: The mechanism of immunotherapy for patients with recurrent spontaneous abortions is not well understood. In order to investigate the suppressor mechanism of paternal lymphocyte immunization, we examined peripheral blood lymphocyte subpopulations and the repertoire of T-cell receptor (TCR) gene segments. METHOD OF STUDY: Twelve patients with recurrent miscarriage were treated with immunization with paternal lymphocyte vaccinations three times during 12-14 weeks. Before and 2 weeks after the final inoculation, lymphocyte subsets and intra-cellular interferon (IFN)-gamma and/or interleukin (IL)-4 production were examined by flow cytometry. TCR V beta and V gamma repertoires were examined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: We found no significant difference in CD4/CD8 ratios, prevalence of CD56+CD3+ or CD57+CD3+ cells (possible extrathymic T cells), gamma(delta)T cells, and CD5+ CD19+ (B-1) cells. However, by in vitro activation with phorbol 12-myristate 13-acetate (PMA) and ionomycin, peripheral CD4 cells demonstrated a significant decrease of IFN-gamma-producing T helper 1 (Th1) cells and an increase of IL-4-producing T helper 2 (Th2) cells after immunotherapy. Seven of nine patients who exhibited remarkable decreases in Th1/Th2 ratios became pregnant within 6 months after three courses of immunotherapy, and four women delivered healthy babies, while none of the three patients who exhibited an increased or unchanged Th1/Th2 ratio had full-term pregnancies (chi2 < 0.0001). Further, changes in usage of TCR V beta and V gamma gene segments were observed after immunotherapy in six patients examined. CONCLUSION: Our findings suggest a shift of Th1-dominant to Th2-dominant status by vaccination might play important roles in maintaining successful pregnancies. Induction of some T cells that utilize different TCR repertoires possibly suppresses maternal rejection reactions.