Search for the Pair Production of Dark Particles X with K_{L}

We present the first search for the pair production of dark particles X via K_{L}^{0}→XX with X decaying into two photons using the data collected by the KOTO experiment. No signal was observed in the mass range of 40-110 MeV/c^{2} and 210-240 MeV/c^{2}. This sets upper limits on the branching fractions as B(K_{L}^{0}→XX)<(1-4)×10^{-7} and B(K_{L}^{0}→XX)<(1-2)×10^{-6} at the 90% confidence level for the two mass regions, respectively.

Increased levels and activity of cathepsins B and D in kainate-induced toxicity.

Administration of kainic acid induces acute seizures that result in the loss of neurons, gliosis and reorganization of mossy fiber pathways in the hippocampus resembling those observed in human temporal lobe epilepsy. Although these structural changes have been well characterized, the mechanisms underlying the degeneration of neurons following administration of kainic acid remain unclear. Since the lysosomal enzymes, cathepsins B and D, are known to be involved in the loss of neurons and clearance of degenerative materials in a variety of experimental conditions, we evaluated their potential roles in kainic acid-treated rats. In parallel, we also measured the levels and expression of insulin-like growth factor-II/mannose 6-phosphate (IGF-II/M6P) receptors, which mediate the intracellular trafficking of these enzymes, in kainic acid-treated rats. Our results showed that systemic administration of kainic acid evoked severe loss of neurons along with hypertrophy of astrocytes and microglia in the hippocampus of the adult rat brain. The levels and activity of cathepsins B and D increased with time in the hippocampus of kainic acid-treated rats compared to the saline-injected control animals. The expression of both cathepsins B and D, as evident by immunolabeling studies, was also markedly increased in activated astrocytes and microglia of the kainic acid-treated rats. Additionally, cytosolic levels of the cathepsins were enhanced along with cytochrome c and to some extent Bax in the hippocampus in kainic acid-treated rats. These changes were accompanied by appearance of cleaved caspase-3-positive neurons in the hippocampus of kainic acid-treated animals. The levels of IGF-II/M6P receptors, on the other hand, were not significantly altered, but these receptors were found to be present in a subset of reactive astrocytes following administration of kainic acid. These results, taken together, suggest that enhanced levels/expression and activity of lysosomal enzymes may have a role in the loss of neurons and/or clearance of degenerative materials observed in kainic acid-treated rats.

Endoscopic surgery for mature teratoma of the ovary.

BACKGROUND: This study was undertaken to assess the value of laparoscopic surgery as treatment for benign mature teratomas of the ovary. METHODS: A total of 70 patients treated exclusively with laparoscopic surgery for ovarian mature teratoma were studied. The tumors were either enucleated with preservation of the ovary or removed by salpingo-oophorectomy. RESULTS: Ovary-preserving surgery was performed in 60 cases; salpingo-oophorectomy was accomplished in 10 cases. All tumors removed were histologically benign. No surgical complications were encountered throughout the series. In eight patients who underwent primary ovary-preserving surgery, a second-look laparoscopy was undertaken with virtually no pathological findings noted. CONCLUSIONS: Our findings confirm those of other authors- when performed by experienced surgeons, laparoscopic removal of ovarian mature teratomas is a safe and recommendable alternative to laparotomy. Preoperative diagnosis and intraoperative inspection of the tumor must be as thorough as possible.

Reduction of postoperative adhesion formation after laparoscopic ovarian cystectomy.

The purpose of this randomized, open-label study was to assess the efficacy of the product Interceed absorbable adhesion barrier in the prevention of adhesion formation on the ovary after laparoscopic ovarian cystectomy. A total of 25 patients requiring laparoscopic bilateral ovarian cystectomy were enrolled into this study. After removal of ovarian cysts, peri-adnexal adhesions, and peritoneal irrigants, and the attainment of meticulous haemostasis, the random assignment of one ovary for wrapping with Interceed was revealed to the surgeon. The other ovary served as the untreated control. A follow-up laparoscopy was performed 8-30 weeks after the initial procedure in 17 patients. Significantly fewer adhesions formed at the Interceed treated ovaries compared with the control (untreated) ovaries (P < 0.05). In terms of adhesion-free outcome, 76% (13/17) of Interceed treated ovaries and 35% (6/17) of control ovaries were free of adhesions. A significant reduction was observed in the area of the sutured ovaries involved with adhesions when Interceed (6%) was used, compared with controls (20%). The reduction of adhesion formation was not related to the size of the cysts at the initial procedure. No adverse events were reported by any patient during the study. In conclusion, Interceed was found to be safe and effective in reducing the incidence of postoperative adhesion formation in patients undergoing laparoscopic ovarian cystectomy.

Laparoscopic creation of a neovagina: modified Vecchietti method.

A new surgical technique for the treatment of vaginal aplasia is described. It consists of a modification of Vecchietti's method, allowing laparoscopic performance of the operation. 9 patients have been treated in this way since January, 1991 with good results. No complications were seen. Being virtually atraumatic, this method requires only brief hospitalisation, which is of vital importance in view of the psychological and physical problems this particular condition entails. Results are identical, so that this technique should always take precedence over the conventional Vecchietti method.

[The effect of different anesthetic procedures on hormone levels in women. Studies during an in vitro fertilization-embryo transfer (IVF-ET) program]. / Der Einfluss unterschiedlicher Anästhesieverfahren auf den Hormonhaushalt der Frau. Untersuchungen im Rahmen eines in vitro-Fertilisations-Embryotransfer-(IVF-ET-)Programms.

Different anaesthetic procedures that were used during an in vitro fertilisation and embryo transfer (IVF-ET) program have been analysed in order to determine their influence on plasma levels of estradiol, progesterone, prolactin, and beta-endorphin and results of IVF-ET. METHODS. Fifty-four patients awaiting transvaginal oocyte aspiration were randomised into three groups: (1) anaesthesia with ketamine as an induction agent and analgesic (n = 20); (2) general intubation anaesthesia using thiopentone for induction and enflurane for maintenance (n = 18); and (3) no anaesthesia (n = 16). Estradiol, progesterone, prolactin, and beta-endorphin were measured from day 3 to 14 referring to follicle aspiration. Differences between preoperative hormone levels and their intra- and postoperative peaks were analysed using the Kruskal-Wallis test (P < 0.03). The results were corrected using the Holms method (alpha = 0.05). RESULTS. No differences were observed in estradiol and progesterone levels (Figs. 1, 2). Prolactin levels were 1.4 times higher (P < 0.001) when ketamine was used and 2.2 times higher (P < 0.001) after short general anaesthesia than in the control group (Fig.3). Similar results were observed with respect to beta-endorphin: in comparison with the control group we found significant elevation by a factor of 2.1 when ketamine was used (P < 0.001). The discrepancy became even more marked with general anaesthesia: beta-endorphin was 3.9 times higher compared to the controls (P < 0.001) (Fig.4). Comparing the two groups who were given anaesthetics, prolactin and beta-endorphin levels were also significantly different (P < 0.001). The IVF procedure itself did not appear to be affected by different anaesthetic procedures during oocyte aspiration (Table 2). CONCLUSIONS. The increased prolactin and beta-endorphin plasma levels associated with ketamine and general anaesthesia reflect a significant alteration of the observed hormone levels. When anaesthesia is indicated, we try to avoid general intubation anaesthesia in favor of ketamine.

Endoscopic Nd:YAG Laser Coagulation of Intramural Endometriosis of the Bladder

Treatment of intramural endometriosis of the bladder using the Nd:YAG laser is described. An operative cystoscope fitted with a 600 µ fibre is introduced into the bladder. At a power setting of 50 W, superficial coagulation of the visible lesion is performed. The coagulation technique corresponds to that used for the treatment of superficial bladder carcinomas. Three patients were managed in this way. In all patients dysuria and hematuria either significantly decreased or disappeared altogether. No intraoperative complications were observed. This new technique appears to be superior to surgical excision techniques, especially in cases where the lesion is situated on the roof of the bladder. Further studies need to be conducted to compare results obtained from this technique with those of the CO2 laser or excision technique.

Laparoscopic Treatment of Distal Tubal Occlusion-Reocclusion and Pregnancy Rate

There is still controversy about the question of which approach is best to treat tubal infertility: microsurgery, laparoscopic treatment, or in vitro fertilization. Our study comprised 161 patients with distal tubal occlusion. Various instruments (argon laser, CO2 laser, Nd:YAG laser, monopolar electrical needle, scissors) were used for laparoscopic salpingostomy, and a variety of techniques applied for tubal wall eversion (flowering technique according to Bruhat with and without suturing, suturing alone, or no eversion at all). Thirty-seven women with a total of 63 laparoscopically treated tubes were followed over a period of 2-72 months. Tubal patency was 38.9%. The reocclusion rate correlated with severity of tubal wall pathology and state of reduction of the tubal mucosa. After laser treatment tubal patency proved to be higher (41.1%) compared with treatment with conventional instruments. The Argon laser scored best results. The majority of patent tubes in the follow-up were found in the cohort with "perfect" and "good" eversion (95.8%), whereas none of the tubes where eversion was classed "insufficient" remained patent. The technique according to Bruhat without the use of additional suturing yielded better results regarding tubal patency (66.6%) than the other eversion methods described (33.4%). The pregnancy rate could be assessed in 81 out of 161 laparoscopically treated cases. A total of 19 patients (23.3%) became pregnant. In 9.8% pregnancy was intrauterine and in 13.5% extrauterine. The highest intrauterine and lowest extrauterine pregnancy rate was seen in the group with "mild" distal tubal occlusion (according to AFS classification). In 84.2% of women who had conceived postoperatively, tubal wall eversion had been done by the Bruhat technique without suturing. Taking into account tubal wall pathology, tubal patency, eversion techniques, and rate of intrauterine pregnancies, it can be concluded that patients with thin-walled tubes allowing "perfect" or "good" eversion will benefit most from laparoscopic salpingostomy.

Laser techniques in gynaecology.

Lasers have been in use for 15 years in laparoscopic surgery. The CO2-laser in particular has become very popular in the field of gynaecology for the treatment of endometriosis and adhesions. Results achieved with the CO2-laser seem to be superior to those of conventional instruments, although only a small number of randomised prospective studies exist. Fibre lasers, such as the Nd:YAG-, KTP, and Argon-lasers combine vaporisation- and/or coagulation-effects within the same operating instrument. Time-consuming changes of instruments during the procedure are unnecessary. Nevertheless, technical problems and high costs of these laser systems on the one hand, and unfulfilled and unrealistic expectations by physicians and patients alike on the other hand hinder wide-spread use of this technique.

[Effect of different follicle puncture methods on hormone homeostasis in the woman. Studies within the scope of an in vitro fertilization-embryo transfer program]. / Der Einfluss unterschiedlicher Follikelpunktionsmethoden auf den Hormonhaushalt der Frau. Untersuchungen im Rahmen eines In-vitro-Fertilisation-Embryotransfer-Programmes.

Different methods for follicular puncture which were used in an in vitro fertilization-embryo transfer program have been analyzed in order to determine their influence on plasma levels of estradiol, progesterone, prolactin and beta-endorphins. Thirty-eight patients awaiting oocyte aspiration were randomized into a laparoscopic (n = 20) and an ultrasound-guided oocyte aspiration group (n = 18). No differences were observed as far as estradiol and progesterone levels and embryo transfer rates were concerned. When using the laparoscopic technique, prolactin levels were found to be elevated 1.5 times in comparison with the ultrasound-guided aspiration procedure, which is highly significant (p < 0.001). Also, beta-endorphins peaked at a significantly higher level during laparoscopy (27.8 vs. 20.7 mol/l, p < 0.001). The enhanced prolactin and beta-endorphin levels reflect an increased stress response during laparoscopy. With respect to less trauma and shorter duration of the procedure, we now perform the sonographically guided transvaginal aspiration technique in our program almost exclusively.

[Cytogenetics of unfertilized or uncleaved oocytes within the scope of in vitro fertilization: correlation with maternal age]. / Zytogenetik unbefruchteter oder ungeteilt gebliebener Eizellen im Rahmen der In-vitro-Fertilisation: Beziehungen zum Alter der Patientinnen.

A cytogenetic analysis could be performed on 343 out of 566 oocytes, which remained unfertilized or uncleaved during our IVF programme. The results were analysed with relation to the women's age by classifying the patients into two age groups (< or = 35 years and > 35 years). There was no significant difference for the corresponding total rates of abnormal oocytes (27.7% vs. 42.4%), the rates of aneuploidy (14.5% vs. 18.2%), and the rates of hyperhaploidy (4.8% vs. 3.0%). These results do not support the assumption of an increase in (numerically) abnormal gametes with increasing maternal age, which is of special interest in cases of trisomy 21. However, it is not possible to draw any definite conclusions, because of the low number of gametes, which were analysed in the upper age group.

[Cytogenetics of unfertilized or undivided oocytes within the scope of in vitro fertilization: relation to the kind of hormonal stimulation]. / Zytogenetik unbefruchteter oder ungeteilt gebliebener Eizellen im Rahmen der In vitro-Fertilisation: Beziehungen zur Art der hormonellen Stimulation.

A cytogenetic analysis could be performed on 343 out of 566 oocytes which remained unfertilized or uncleaved during our in vitro fertilization (IVF) programme. The results were analyzed in relation to the kind of ovarian stimulation by classification of the patients into two groups: treatment with human menopausal gonadotropin (hMG) or treatment with clomiphene citrate (CC). There was no significant difference for the total rates of abnormal oocytes (hMG: 28.6%, CC: 32.2%), the rates of aneuploidy (hMG: 14.4%, CC: 16.9%), and the rates of hyperhaploidy (hMG: 3.9%, CC: 8.5%). These results suggest that the kind of medication for induction of multiple follicular growth does not influence the rate of cytogenetic anomalies in human oocytes.

[Type and incidence of cytogenetic abnormalities in unfertilized or uncleaved human oocytes within the scope of in vitro fertilization]. / Art und Häufigkeit zytogenetischer Anomalien in unbefruchtet oder ungeteilt gebliebenen menschlichen Eizellen im Rahmen der In-vitro-Fertilsation.

Human oocytes remaining unfertilized or uncleaved during in vitro fertilization (IVF) yield valuable information on the kind and frequency of numerical and structural chromosome aberrations after their fixation. This enables us to assess the maternal contribution to perturbations in the course of fertilization and early embryonic development. Therefore, 566 unfertilized or uncleaved oocytes from our IVF programme were processed for cytogenetic examination. 223 gametes were not analyzable. 260 oocytes were completely karyotyped and chromosome counts could be established for 83 cells. 243 eggs had the normal haploid chromosome complement whereas 100 cells (29.2%) were abnormal. In detail, we found the following aberrations: hypohaploidy = 10.2%, hyperhaploidy = 4.7%, diploidy = 9.0%, tetraploidy = 1.2%, structural anomalies = 2.6%, prematurely condensed sperm chromosomes = 3.2%. Six cells had to be considered in two of these categories. Our results and comparisons with other publications imply that the total rate of anomaies in human oocytes from stimulated cycles amounts to 20 to 30%. This high frequency might be one of the limiting factors for the success rate of IVF.

The contact Nd:YAG laser: a new technique for conservation of the fallopian tube in unruptured ectopic pregnancy.

Between August 1986 and April 1988, 22 women with unruptured tubal pregnancy were treated by laparoscopy in the Department of Gynaecology and Obstetrics at the University of Ulm. Linear salpingotomy was performed using the contact Nd:YAG laser technique. The laser beam was delivered by special sapphire probes attached to a standard optical fibre for incision and coagulation. Two different shapes of sapphire probes were used. The specific laser properties and the application of vasopressin enabled treatment without any other incision instruments or coagulation agents. In one patient subsequent laparoscopy became necessary due to persisting trophoblastic tissue. Sixteen women were assessed subsequently by second-look laparoscopy or hysterosalpingography for tubal patency and possible formation of adhesions. In 14 (88%) women the tubes were patent, and in two women adhesions were seen.

Doppler sonographic findings and their correlation with implantation in an in vitro fertilization program.

In 45 women from an in vitro fertilization (IVF) program, the uterine and ovarian blood flows were investigated by vaginal Doppler sonography. The resistance index was used to evaluate the blood pattern. When comparing the patients who became pregnant after embryo transfer (ET [group I, n = 12]) with those who did not conceive (group II, n = 33), it is evident that in group I the vascular resistance of the uterine arteries is significantly lower on the day of follicular aspiration. No differences could be detected in the ovarian vessels. The data obtained so far suggest that the receptivity of the endometrium is a crucial factor for successful implantation. In the final analysis, this can be appraised not only on the basis of morphological but also of hemodynamic parameters.

A new variation of in-vitro fertilization: intravaginal culture of human oocytes and cleavage stages.

In this study, we present further experiences with the intravaginal culture (IVC) of oocytes and cleavage stages. IVC is a new technique for in-vitro fertilization, its principle consisting of fertilization of oocytes in an air-free plastic capsule which is placed into the maternal vagina. In a total of 45 patients, 22 were treated by IVC and 23 by a conventional in-vitro fertilization technique (IVF). The pregnancy rates for IVC and IVF amounted to 22.7% (5/22) and 17.4% (4/23), respectively. Our results indicate that IVC is a valuable new method for treatment of special cases of sterility. Furthermore, extracorporal stress factors such as light and low temperature can be minimized by IVC. We also consider the psychological factor for the patients as very important since the mother can actively participate in the early development of the conceptus.