Comparison of osseous healing after sagittal split ramus osteotomy and intraoral vertical ramus osteotomy.

The sagittal split ramus osteotomy (SSRO) is generally associated with greater postoperative stability than the intraoral vertical ramus osteotomy (IVRO); however, it entails a risk of inferior alveolar nerve damage. In contrast, IVRO has the disadvantages of slow postoperative osseous healing and projection of the antegonial notch, but inferior alveolar nerve damage is believed to be less likely. The purposes of this study were to compare the osseous healing processes associated with SSRO and IVRO and to investigate changes in mandibular width after IVRO in 29 patients undergoing mandibular setback. On computed tomography images, osseous healing was similar in patients undergoing SSRO and IVRO at 1year after surgery. Projection of the antegonial notch occurred after IVRO, but returned to the preoperative state within 1year. The results of the study indicate that IVRO is equivalent to SSRO with regard to both bone healing and morphological recovery of the mandible.

Mechanism of motor coordination of masseter and temporalis muscles for increased masticatory efficiency in mice.

The demand for the use of mice as animal models for elucidating the pathophysiologies and pathogeneses of oral motor disorders has been increasing in recent years, as more and more kinds of genetically modified mice that express functional disorders of the stomatognathic system become available. However, the fundamental characteristics of mouse jaw movements during mastication have yet to be fully elucidated. The purpose of this study was to investigate the roles of the masseter and temporalis muscles, and the mechanisms of motor coordination of these muscles for increasing masticatory efficiency in the closing phase in mice. Twenty-two male Jcl:ICR mice were divided into control (n = 8), masseter-hypofunction (n = 7) and temporalis-hypofunction groups (n = 7). Botulinum neurotoxin type A (BoNT/A) was used to induce muscle hypofunction. The masticatory movement path in the horizontal direction during the occlusal phase became unstable after BoNT/A injection into the masseter muscle. BoNT/A injection into the temporalis muscle decreased antero-posterior excursion of the late-closing phase corresponding to the power phase of the chewing cycle. These results suggest that the masseter plays an important role in stabilizing the grinding path, where the food bolus is ground by sliding the posterior teeth from back to front during the occlusal phase. The temporalis plays a major role in retracting the mandible more posteriorly in the early phase of closing, extending the grinding path. Masticatory efficiency is thus increased based on the coordination of activities by the masseter and temporalis muscles.

Effects of feeding a soft diet and subsequent rehabilitation on the development of the masticatory function.

It has been suggested that feeding a soft diet could possibly inhibit normal development of the masticatory function. However, the consequences of such changes in the alimentary habits have yet to be fully clarified. Therefore, the aim of this study was to determine whether a soft diet prevents the development of masticatory function and whether a critical period for programming the masticatory system exists. To examine these hypotheses, we used a three-dimensional jaw-movement tracking device and jaw muscle electromyography (EMG) to analyse masticatory function changes in mice. Jcl:ICR mice were divided into three groups, with the normal group fed a hard diet, the hypofunctional group fed a soft diet, and the rehabilitation group first fed a soft diet that was then changed to a hard diet. Our results showed that the excursion and duration of late-closing phase (occlusal phase) of the chewing cycle and EMG activity in the masseter muscle were not only reduced in the hypofunctional but also in the rehabilitation group as compared with the normal group. These results suggest that optimisation of the chewing pattern and acquisition of appropriate masticatory function are impeded by feeding a soft diet during the animal's growth period and that no catch-up effect of the masticatory function is observed when there is a prolonged period of time prior to changing the diet from soft to hard. In conclusion, masticatory function can only be fully developed through a learning process such as exposure to chewing various kinds of foods with different food textures.

Effect of epidermal growth factor on lung growth in experimental fetal pulmonary hypoplasia.

The purpose of this study was (1) to compare the expression of epithelial growth factor receptor (EGFR) in the lung tissues of human fetuses with or without pulmonary hypoplasia, and (2) to investigate the effects of EGF on lung growth in experimental pulmonary hypoplasia in rabbits. Firstly, we investigated the expression of EGFR in lung tissues of human fetuses with or without pulmonary hypoplasia by immunohistochemistry. Secondly, the amniotic fluid was shunted into the maternal abdominal cavity in a group of 12 fetal rabbits, another group (n = 12) received EGF injection (5 microg, i.p.) at day 25 of gestation. The third group (n = 12) was only treated with EGF while littermates not operated on served as the control group (n = 12). On day 29 of gestation, fetuses were delivered by Cesarean section and the lungs removed. The body weight and wet lung and liver weights were measured. As a measure of fetal lung growth, we determined the size of lung acini, the number of terminal airspaces, and diameter of alveoli (n = 6, each groups). We also measured the concentration of phosphatidylcholine (PC) and the lecithin/sphingomyelin (L/S) ratio in lung lavage fluid at birth in some fetuses (n = 6, each groups). In human fetuses with pulmonary hypoplasia, there was a significant decrease in radial alveolar count and expression of EGFR compared with fetuses without pulmonary hypoplasia. Amniotic shunt significantly decreased fetal lung/body weight ratio compared with control. Injection of EGF in the shunted group significantly increased lung/body weight ratio to the control level. The concentration of PC and L/S ratio in lung fluid lavage from rabbit fetuses with hypoplastic lungs was significantly higher than the other three groups. Histopathological examination of fetuses with hypoplastic lungs treated with EGF showed no significant change in the size of acini, number of terminal airspaces or the diameter of alveoli compared with the control group. Our results suggested that EGF was associated with lung growth and maturation of human lung and that treatment of rabbit fetuses with hypoplastic lungs with EGF facilitated lung growth and development.

Immunohistochemical study of angiogenic factors in endometrium and endometriosis.

The proliferative activity and angiogenic factors of pelvic endometriosis and uterine endometrium and their correlation with different pigmented lesions are important throughout the menstrual cycle. The proliferative activity and/or expression of angiogenic factors appears to be different between endometrium and endometriosis, and also different in each pigmented lesion. Immunohistochemical studies using computerized image analysis have shown that in normal endometrium, the PCNA index shows cyclic variation, but no cyclic change is observed in endometriosis. In the pelvic peritoneum, the PCNA index is higher in red lesions compared to black and white lesions. There is no difference in VEGF expression among different pigmented lesions. However, a cyclic variation of VEGF concentration was found in the peritoneal fluid of patients with endometriosis. As a newly determined angiogenic factor, the number of endoglin-positive cells and the mean endothelial area were higher in red lesions than in black or white lesions. These results suggest that the pathogenesis and activity of endometriosis possibly depends on internal angiogenesis. The cellular activity of endometriotic lesions may not necessarily coincide with the regulation of angiogenesis, and may not be synchronized in each pigmented pelvic lesion of endometriosis. Copyrightz1999S.KargerAG, Basel

Involvement of parathyroid hormone-related peptide in cell proliferation activity of human uterine leiomyomas.

Uterine leiomyomas develop from uterine smooth muscle cells, which are known to be regulated by estrogen and other growth factors. The purpose of this study was to investigate the role of expression of parathyroid hormone related-peptide (PTHrP) in the growth of uterine leiomyomas treated or untreated with gonadotropin-releasing hormone agonist (GnRH-a). Thirty-nine leiomyoma tissues were obtained from 36 patients who had been treated with GnRH-a (n=10) or without GnRH-a (n=29). The intensity of PTHrP immunostaining was categorized into three grades; "negative", "weakly positive", and "positive". Leiomyoma cell growth was estimated by the proliferating cell nuclear antigen (PCNA) labeling index (LI) with an image analyser. We also investigated the correlation between PTHrP expression and cell proliferation or histopathological findings. In the GnRH-a-untreated group, LI of the PTHrP "positive" group was significantly higher than that of the PTHrP "negative" group, but the intensity of PTHrP immunostaining did not correlate with LI in the GnRH-a-treated group. PTHrP expression did not correlate with histological findings or clinical parameters (age and phase of menstrual cycle) in either the GnRH-a-treated or the -untreated group. In addition, the expression of mRNA for PTHrP and its receptor was detected in leiomyomas by reverse transcriptase-polymerase chain reaction (RT-PCR). Our results indicate that the expression of PTHrP in leiomyomas correlated positively with cell growth in the GnRH-a-untreated group, suggesting that PTHrP may act as a local cell growth modifier in an autocrine/paracrine fashion on uterine leiomyomas.

Expression of estrogen and progesterone receptors in endometrium and peritoneal endometriosis: an immunohistochemical and in situ hybridization study.

OBJECTIVE: To clarify the role of ovarian steroids in the development and progression of endometriosis, estrogen receptors (ERs) and progesterone receptors (PRs) were localized by immunohistochemistry, and ER messenger RNA (mRNA) was detected by in situ hybridization in the uterine endometrium and in normal and altered pelvic peritoneum. DESIGN: Retrospective and prospective study. SETTING: Nagasaki University School of Medicine, Nagasaki, Japan. PATIENT(S): A retrospective study of 61 formalin-fixed uterine endometria and normal and altered pelvic peritonea from patients suffering from various gynecologic diseases was conducted. In addition, in 22 fresh frozen tissue specimens, ER mRNA expression was evaluated prospectively. MAIN OUTCOME MEASURE(S): In formalin-fixed tissues, ER and PR were localized immunohistochemically. The results of immunohistochemical staining were scored from 0 to 4, depending on the signal intensity and frequency of positive cells. In fresh frozen specimens, ER mRNA expression was assessed by nonradioactive in situ hybridization using thymine-thymine dimerized oligonucleotide probes. RESULTS: The highest score of ERs and PRs was observed in the epithelial and stromal cells of the normal uterine endometrium at the early proliferative phase of the menstrual cycle. The ER and PR scores declined throughout the secretory phase. In typical endometriotic lesions, the ER and PR scores were constantly high independent of the menstrual cycle. The expression pattern of ER mRNA was mostly in parallel with that of ERs. In typical endometriosis, ERs and PRs were found in both glandular epithelial cells and their surrounding stromal cells. Expression of ER mRNA was found in typical endometriotic peritonea and in pelvic peritoneum with columnar epithelial cells, but not in normal pelvic peritoneum (mesothelium). Estrogen receptors and PRs were negative in mesothelium, but were positive in the nuclei of fibroblasts in the connective tissue. CONCLUSION(S): We demonstrated the expression of ERs, ER mRNA, and PRs in the columnar cells in pelvic peritonea and typical endometriosis, but not in normal mesothelium. These results suggest that endometriosis may originate from the columnar cells with ERs and PRs in the pelvic peritoneal lining.

Influence of serum follicle stimulating hormone to luteinizing hormone ratio during buserelin acetate-induced pituitary desensitization on ovarian response to exogenous gonadotrophins in an in-vitro fertilization and embryo transfer programme.

We investigated the effect of endogenous gonadotrophins during pituitary desensitization with gonadotrophin-releasing hormone agonist (GnRHa) on ovarian responsiveness or the outcome of in-vitro fertilization (IVF) and embryo transfer. The results of 67 women who participated in the IFV programme at Nagasaki University Hospital, Japan, were analysed retrospectively. All women received GnRHa from the third day of menstrual cycle, and ovarian stimulation with exogenous gonadotrophins was initiated when the serum oestradiol concentration decreased to < 30 pg/ml. The serum follicle stimulating hormone (FSH)/luteinizing hormone (LH) ratio, rather than serum FSH or LH concentrations during GnRHa-induced pituitary desensitization, showed a significant positive correlation with age and the total dose of exogenous gonadotrophins. The FSH/LH ratio also showed a significant negative correlation with oestradiol response and the number of retrieved oocytes, and was significantly lower in pregnant women compared with the non-pregnant group during pituitary desensitization. Our results indicate that, even under pituitary desensitization with GnRHa, the serum FSH/LH ratio influences individual ovarian responsiveness and the state of the intra-ovarian hormonal environment. Our results suggest that the FSH/LH ratio may be a useful clinical predictor of the ovarian response to exogenous gonadotrophins under pituitary desensitization.

Local injection of methotrexate dissolved in saline versus methotrexate suspensions for the conservative treatment of ectopic pregnancy.

To compare the local injection of methotrexate (MTX) dissolved in saline and MTX suspensions for the laparoscopic treatment of ectopic pregnancy in terms of success rate and postoperative tubal patency. A total of 26 patients with unruptured ectopic pregnancies were selected from among 60 women with ectopic pregnancies admitted to the Nagasaki University clinic. Of these patients, 12 were treated with MTX dissolved in saline solution (solution group) and 14 with MTX suspensions consisting of lipiodol (LPD) with phosphatidylcholine (PC) added as a dispersing stabilizer (suspension group). Except for one case treated under transvaginal guidance, all the patients were treated by laparoscopy. Persistent ectopic pregnancy was recognized in seven cases (58%) in the solution group but in only two cases (14%) in the suspension group. Moreover, rupture occurred in two cases in the solution group but in no case in the suspension group. A patent treated tube was found in seven of 10 cases in the saline group and in 10 of 12 cases in the suspension group. During the follow-up period of 6-31 months, five women in the saline group and three women in the suspension group had an intrauterine pregnancy. In this study, the local injection of MTX is considered to be a reasonable method for the treatment of unruptured ectopic pregnancy, and the MTX suspension seems to be more effective and useful than MTX solution.

A new approach to methotrexate and lipiodol suspensions for ectopic pregnancy: preliminary in vitro and animal experiments.

OBJECTIVES: To measure and evaluate the in vitro release of MTX from suspensions of methotrexate (MTX) and lipiodol (LPD), and to investigate the MTX concentration and fertility rate using an animal model. METHODS: This study was divided into three components: a) An in vitro Release Study, b) Animal Study No. 1 (concentration of tissue and plasma levels), and c) Animal Study No. 2 (fertility rate after MTX suspension). RESULT: The releasing rate in vitro was more rapid with MTX-S (MTX dissolved in saline) than with either MTX-LPD (MTX dissolved in lipiodol) or MTX-LPD-PC (MTX suspended in lipiodol and phosphatidylcholin, i.e., MTX suspension). The tissue concentration tended to be higher with an MTX suspension than with MTX-S. There was no significant difference in the fertility rate or the nidation index among the 3 groups (Groups 1, 2, and 3). CONCLUSION: The injection of an MTX suspension is useful for increasing the tissue concentration and maintaining the long-term effectiveness of MTX, and this technique might offer a new approach in the treatment of ectopic pregnancy (EP) or in second-line therapy for persistent EP.

Establishment of functional imprinting of the H19 gene in human developing placentae.

We have found that the imprinted H19 gene can be expressed either biallelically or monoallelically in the developing human placentae. H19 biallelic expression is confined to the placenta until 10 weeks of gestation, after which it becomes exclusively maternal, and does not affect allele-specificity or levels of IGF2 expression. The promoter region of H19 is hypomethylated at all stages of placental development, while the 3' portion shows progressive methylation of the paternal allele with gestation. Our observations demonstrate that the establishment of functional H19 imprinting occurs during the early development of the placenta and provide an opportunity to understand the mechanism by which the H19 primary imprint is manifested in somatic cells.

[The evaluation of ovarian tumor associated with pregnancy by the ultrasonographical method and serum CA125 levels].

We examined and evaluated ovarian tumor during pregnancy using ultrasonography. The CA 125 level was measured in 21 cases in the first and second trimesters. For a total of 65 cases of ovarian tumor considered to be tumor-like lesions (corpus luteum cyst, etc) the longitudinal and transverse diameters were measured, and the shape was assumed to be ellipsoid. Disappearance of the tumor was confirmed in 40 of the 65 cases. The disappearance occurred by the 16th week of gestation (mean time = 13 weeks and 2 days) in 32/39 (82%) cases, and the maximum diameter (size) did not exceed 10cm (50cm2) at any gestational week. Also the diameter (size) did not exceed 7cm (30cm2) after 15 weeks of gestation in the tumor-like lesions. Surgery performed during pregnancy (9-24 weeks) in 22 cases revealed 19 tumors (16 benign, one borderline malignant and two malignant tumors). The remaining 3 were chocolate cysts and did not require surgery because the diagnosis had been confirmed before pregnancy. There was no difference in the CA 125 level in benign and malignant tumors (15 were benign, 3 were chocolate cysts, one was borderline malignant and two were malignant tumors). Cases in which the maximum diameter (size) of an ovarian tumor increases or remains unchanged during the gestational period may need surgery for benign or occasionally malignant ovarian tumors.

Influence of ovarian endometrioma on fertility.

OBJECTIVE: This study examines the influence of ovarian endometrioma on fertility. STUDY DESIGN: For 117 infertile women who were diagnosed as having endometriosis by laparoscopy and who underwent danazol therapy, we examined (1) the relationship between ovarian endometrioma and level of bead-phagocytotic macrophages in ascites and the interleukin-1 beta level, (2) the relationship between ovarian endometrioma and pregnancy rate during the 36 months after danazol therapy, and (3) the relationship between ovarian endometrioma and pregnancy rate, considering the severity of the lesion on the bilateral tubes and the pelvic peritoneum. RESULTS: (1) The levels of bead-phagocytotic macrophages in patients with or without ovarian endometrioma were 68% and 67%, respectively (not significant). Similarly, no significant difference was seen in the interleukin-1 beta positive rate between the two groups. (2) The pregnancy rates of the former group and the latter group were 36% and 43%, respectively (not significant). (3) The existence or absence of ovarian endometrioma made no significant difference in the pregnancy rate in a group of patients with no lesions in the bilateral tubes or in another group with no lesions and scattered endometriotic implants on the peritoneum. CONCLUSIONS: It seems unlikely that ovarian endometrioma itself significantly impedes fertility after danazol therapy.

PIP: In Japan, physicians prescribed 300-400 mg danazol to 117 women, 21-37 years old, diagnosed with endometriosis and followed them for 3 years. Prior to danazol therapy, laparoscopy had identified ovarian endometriosis in at least 1 ovary in 86% of the 49 patients. Danazol therapy resolved only 1 of these ovarian endometrioma cases. The 3-year pregnancy rates of women with and without ovarian endometrioma were not significantly different (36% vs. 43%). Even when the researchers compared endometriosis cases with completely intact tubes and with a completely intact pelvic peritoneum or with scattered endometriotic implants on the peritoneum, the absence or existence of ovarian endometrioma did not affect the pregnancy rate. The researchers compared the bead-phagocytotic macrophage activity of 34 women with endometriosis with that of 20 controls and found a significantly higher level among endometriosis cases than controls (66% vs. 34%; p .01). The activity level was not significantly different, however, between those with and without ovarian endometrioma (68% vs. 67%). The interleukin-1 beta positive rate in 53 endometriosis cases was significantly higher than it was in the 29 control cases (36% vs. 7%; p .01). It was the same in cases with ovarian endometrioma and those without ovarian endometrioma, however (36% for both groups). These results suggest that ovarian endometrioma itself does not impede conception after danazol therapy.

Association between chlamydial infections and pelvic lesions.

Chlamydia trachomatis usually causes asymptomatic cervicitis, but it sometimes ascends into the uterine cavity, fallopian tubes, or peritoneal cavity, causing pelvic inflammatory disease and infertility. In this study, we examined endocervical chlamydial antigens and serum chlamydial antibodies in infertile women and laparoscopically evaluated pelvic lesions according to our pelvic scoring system. In patients testing positive for a chlamydial infection, the total pelvic score was significantly higher than in patients testing negative. When each area examined was assessed separately, however, only the tubal score was significantly higher in the chlamydia infected patients. These findings may indicate that tubal lesions are the major cause of infertility in women with chlamydial infections.