ABSTRACT: For decades, millions of mothers have been subjected to new obstetric procedures, but with little knowledge of the long term effects from such interventions. Such procedures might, however, be of importance for the infant's behavior as an adult. Jacobson and Bygdeman found that a traumatic birth was associated with an increased risk of the infant subsequently committing suicide by violent means, whereas giving opiates to the mother during labor seemed to reduce the risk. cases were matched with biological siblings to avoid confounding from genetic, socioeconomic, and environmental factors. Objective: To investigate any long term effects of traumatic birth and obstetric procedures in relation to suicide by violent means in offspring as adults. Design: Historic prospective case-control study. Setting: Stockholm, Sweden. Subjects: 242 adults who committed suicide by violent means from 1978 to 1995, and who were born in one of seven hospitals in Stockholm during 1945-80, matched with 403 biological siblings born during the same period and at the same group of hospitals. Main outcome measures: Adverse and beneficial perinatal factors expressed as relative risks (odds ratios) and 95% confidence intervals, derived from logistic regression of cases matched with their siblings. Results: For multiple birth trauma the estimated relative risks of offspring subsequently committing suicide by violent means were 4.9 (95% confidence interval 1.8 to 13) for men and 1.04 (0.2 to 4.6) for women. In mothers who received multiple opiate treatment during delivery, the estimated relative risk of offspring subsequently committing suicide was equal for both sexes (0.26, 0.09 to 0.69). Conclusion: Minimizing pain and discomfort to the infant during birth seems to be of importance in reducing the risk of committing suicide by violent means as an adult. INTRODUCTION For decades millions of mothers in developed countries have been subjected to new obstetric procedures, but with limited knowledge of the long term effects from those interventions. It does seem that long term effects are possible as one case-control study showed that suicide as an adolescent was associated with adverse perinatal conditions, and another study showed that suicide by violent means was associated with mechanical birth trauma.1·2 Neither of these studies, however, controlled for confounding factors. We tested whether traumatic birth could be associated with subsequent suicide by violent means in offspring, using a stringent study design. We also predicted that this association could be reduced by giving sedatives and analgesics to mothers during delivery, as the infants' perception of trauma would be reduced. We based our predictions on the hypothesis (presented to the ethics committee of the Karolinska Institute in advance) that, through a process of imprinting, certain individuals might subconsciously create a traumatic situation during the act of suicide that produces a sensation similar to that experienced during birth.2 Since such imprinting processes are facilitated by testosterone, we expected men to be affected more than women.3 We analyzed cases matched with siblings by logistic regression. Variables constituting a trauma score were selected by one of us (MB) before any access to birth records. SUBJECTS AND METHODS Cases and Controls Cases were included in the study if: (a) they were adults who had committed an unambiguous suicide by violent means, that is, using a firearm, jumping from a height, jumping in front of a train, laceration, hanging, and strangulation; (b) they were born at one of seven hospitals in Stockholm from 1945 to 1980; (c) they had been examined after death at the Department of Forensic Medicine, National Board of Forensic Medicine, Stockholm between January 1978 and June 1995; and (d) they were Swedish citizens at the time of death. Birth records could not be found for 22 (5. …

Objectives: This study was designed to evaluate the efficacy of Replens, a non-hormonal moisturizing vaginal gel, on symptoms of vaginal atrophy in postmenopausal women, in comparison with Dienoestrol (Cilag), an oestrogenic vaginal cream. Methods: Thirty-nine patients were randomly allocated to either of the two treatments. Replens was given three times a week during the 12 weeks of the study, while Dienoestrol was administred daily during the first 2 weeks and thereafter three times a week. Vaginal dryness index, itching, irritation, dyspareunia, pH and safety were evaluated every week the first month and every month thereafter. Results: Both treatments had a significant increase on vaginal dryness index as soon as the first week of treatment, and the hormonal compound was significantly better than the non-hormonal one. All symptoms such as itching, irritation and dyspareunia significantly decreased or disappeared without any difference between the two treatments. For pH, no significant difference was seen either in each group or between the two groups. No adverse events related with the two drugs were found. Conclusion: This study shows that Replens applied vaginally three times a week, is a full therapy for all symptoms of vaginal atrophy as well as local estrogen. No serious adverse event was related. Replens is an alternative treatment to local estrogen and perhaps a good complement of systemic HRT in patient suffering from vaginal dryness.

Endometrial receptivity is a particular stage of maturation during the luteal phase to permit implantation. We have studied endometrial protein secretion and its patterns evaluated by SDS-PAGE, laser densitometry and Western blots. Uterine secretion electrophoresis (USE) permits highly sophisticated analyses of the intrauterine milieu and allows clinical determination of the receptive stage of the endometrium. This technique reveals direct parameters by patterns of numerous individual protein bands, mainly resolved between 68.0 and 6.5 kD. Characteristic bands appear during the typical functional states of the menstrual cycle presenting evidence on the diagnostic capacity of this method to identify stages of adequate (= normal) or inadequate (= defective) luteal phase maturation. Several individual protein bands appear as characteristic markers for the receptive stage of the luteal phase. We have isolated and molecularly identified several of these proteins: histones H2A, H2B, H3 and H4. In order to identify the endocrine dependency of the protein bands, which significantly contribute to the "receptive stage pattern," patients were treated with the progesterone antagonist RU 486 at day LH +2. The assessment 4 days later revealed deficient USE patterns, particularly diminished and missing bands of the H2A-, H2B-, and H3-histones. These results demonstrate progesterone-dependent components of the endometrium at the receptive stage, which can be used as useful markers for an improved precision in luteal phase diagnostics. On the other hand, essential parts of the protein pattern may serve as new targets for successful contraceptive interventions ("endometrial contraception").

The Swedish experience indicates that the combination of RU 486 and vaginal or intramuscular administration of different prostaglandin analogues such as Cervagem, Sulprostone, and 15- methyl PGF2 alpha is a highly effective and safe non-surgical method to terminate early pregnancy. The combined treatment may also be used during the second trimester. In mid- and late second trimester abortion this procedure represents a simple, non-invasive, highly effective method. There are several possibilities by which RU 486 can be used as a contraceptive. We have shown that post-ovulatory administration of RU 486 will effectively inhibit implantation. If the preliminary results are confirmed, treatment with RU 486 once a month on day LH+2 may be an attractive alternative to present contraceptive technology.

Human fetal brain tissue was obtained from first-trimester elective abortions of two women who also had schizophrenia. Portions of the embryonic hippocampus or cerebral cortex were transplanted into the anterior eye chamber of immunologically compromised athymic nude rats. In this environment, embryonic brain tissue derived from normal women generally continues organotypic growth and development for many months. Although initial survival after transplantation was normal, the tissue derived from schizophrenic women manifested less robust growth. However, cells in the transplants showed typical neuronal differentiation, with development of different neuronal types, such as pyramidal cells, granule cells, and gamma-aminobutyric acid (GABA)-containing interneurons. Rhythmic electrical activity was also observed, indicative of some local synaptic organization. The presence of messenger RNA (mRNA) for brain-derived neuronotrophic factor (BDNF) was observed using in situ hybridization. The reason for the decreased rate of growth of these transplants remains unknown and the significance of the finding cannot be assessed from only two fetuses. However, these preliminary findings suggest that fetal transplants may be a useful model system for the detection of developmental pathogenic processes in the expression and transmission of schizophrenia.

The cellular localization of mRNAs encoding the low affinity NGF receptor (here referred to as LANR) and the putative high affinity receptor for NGF, trk, have been studied in the human foetal spinal and sympathetic ganglia, and spinal cord, using in situ hybridization. The receptor mRNAs were highly expressed in the spinal and sympathetic ganglia, with most but not all neurons expressing both LANR and trk mRNA. Spinal nerve rootlets distal to the spinal ganglia expressed LANR but not trk mRNA, confirming the presence of the low affinity receptor in developing Schwann cells. In the spinal cord, LANR mRNA was found throughout the medial and lateral motor columns while, trk mRNA was detected in scattered cells in the dorsal aspect of developing grey matter.

Fetal human brainstem tissue including the nucleus locus coeruleus was transplanted to the anterior eye chamber of athymic nude rats. Most transplants survived and grew in the anterior chamber of the eye. After 9-15 months, the host animals were anesthetized and electrophysiological or in vivo electrochemical recordings were performed. The brainstem transplants contained spontaneously active neurons with regular single-spike firing patterns. The neurons responded to ipsilateral light stimulation with an increase in firing rate and to the alpha 2-receptor agonist clonidine with significantly decreased firing rates. In vivo electrochemical studies demonstrated reproducible noradrenergic overflow after local application of potassium. Immunohistochemical evaluation of the brainstem transplants showed an abundance of tyrosine hydroxylase-positive neurons and neurites in all transplants and a dense network of neurofilament-, synapsin-, and glial fibrillary acidic protein-positive profiles throughout the grafts. Taken together, the present physiological and histochemical data indicate that it is possible to obtain transplants containing a specific monoaminergic population within the brainstem from human fetal fragments and to maintain these transplants in oculo in athymic nude rats for at least 15 months, during which time noradrenergic neurons develop.

In situ hybridization was used to study expression of beta-nerve growth factor receptor (NGF-R) mRNA in the early human fetus. In 8- to 12-week old fetuses, high labelling was found over motoneurons along the entire length of the lateral motor column. High levels of NGF-R mRNA were also seen over most developing nerve cell bodies in both the dorsomedial and ventrolateral part of the dorsal root ganglia. Lower, but clearly specific labelling was detected over a subpopulation of cells in Auerbach's plexus in the intestines. Evidence for a non-neuronal expression of NGF-R mRNA came from labelling over a subpopulation of cells in glomeruli of the kidney in a 12-week old human embryo. Myoblasts in skeletal muscle anlagen were labelled as well as cells along peripheral nerve. The widespread expression of NGF-R mRNA in the human fetus suggests that the NGF-R is important for development of a variety of different tissues of both neuronal and non-neuronal origin.

Solid pieces of human fetal mesencephalic tissue were grafted to the lateral ventricle adjacent to dopamine-depleted striata of rats immunosuppressed with cyclosporin A. Apomorphine-induced rotations were performed before and at monthly intervals after grafting. Reductions in rotations were seen at 2 months postgrafting and these reductions progressively increased. Spontaneously active dopaminergic cells were found within the grafts using extracellular single-unit recording techniques. Recordings of striatal cells ipsilateral to the graft revealed “normal” firing rates compared to those of neurons in the control striatum. In response to the local application of the dopamine antagonist cis-flupenthixol, both the dopaminergic and striatal neurons showed dose-dependant excitations. Potassium-evoked releases of electroactive species ipsilateral to the fetal human graft, measured using high-speed in vivo electrochemistry, revealed response amplitudes that were similar to control striatum when an electrode was placed adjacent to the graft; distal to the graft the responses showed smaller amplitudes but prolonged time courses. Much greater levels of dopamine and serotonin were detected in the grafts, compared to in normal rat substantia nigra, as measured with HPLC coupled to a 16-channel electrochemical array detector. Immunocytochemical studies using antibodies against tyrosine hydroxylase (TH), revealed not only TH-positive cells within the graft, but also a few positive neurons that migrated into the host striatum. Numerous TH-immunoreactive fibers penetrated into striatum and reinnervated its total volume. Taken together, these data suggest that intraventricular graft placement may be a highly efficacious technique for studying fetal brain tissues in terms of maturation, reinnervation, and function.

Publisher Summary Transplantation syngeneically of fetal brain tissue has become a powerful tool in studies of development, plasticity, and repair in the rodent central nervous system (CNS). This chapter demonstrates that human fetal catecholamine cells from CNS, sympathetic ganglia and adrenal medulla will survive cross-species transplantation into adult nude immunodeficient or immunosuppressed rodents. The approach presents the first opportunity to study in vivo the detailed morphological and functional development at the cellular level of human CNS. The chapter concludes that human fetal catecholamine containing cells can be retrieved from first trimester abortions and successfully transplanted into immunodeficient rodent hosts. Nigral dopamine neuroblasts and locus coeruleus noradrenaline neuroblasts survive in dopamine-denervated striatum, and nigral cells will form a functional reinnervation within four to six months. The chapter indicates that this new approach is the first opportunity to study in vivo development, plasticity, and repair of human CNS neurons and opens the possibility for future clinical treatment regimens.

Publisher Summary Syngeneic grafting of brain tissue has emerged as a valuable approach in studying the development and regeneration of neural connections in the central nervous system (CNS) of mammals. This chapter describes the electrophysiological studies of human fetal cerebellar and cortical brain tissue grafted to the anterior chamber of the eye of athymic nude rats. The results demonstrate that human fetal cerebellar and cerebral cortex grafts survive in athymic nude rat recipients, and continue their development in the anterior chamber of the eye. It has also been shown that several different human fetal central nervous system areas can survive and develop, when grafted to the anterior chamber of the eye of cyclosporin A-treated host rats. However, in spite of rigorous immunosuppression, only some of the grafted material survives intraocularly. Thus, the athymic nude rat offers an alternative model for xenogeneic brain tissue grafting with several advantages. The chapter concludes that this technique uniquely permits the study of human brain development, connectivity, and pharmacological properties in an otherwise immunologically incompatible host species.

An overall constancy in the total protein profile of human seminal plasma (HSP) as determined by gel filtration chromatography and high-resolution electrophoresis was found in six healthy volunteers. Thirteen different proteins were identified by double immunodiffusion in five individual HSP samples each previously subjected to gel filtration. It was also found that comparatively large amounts of yet unidentified low-molecular-weight (less than 12,000) compounds occurred in all HSP samples. Of eight specific proteins in consecutive samples collected from one individual, large intra-individual variations were found in some of the proteins. The largest variations (about 100%), for both concentration and total amount, were noted for alpha 1-antitrypsin, transferrin, IgA, and secretory IgA. Albumin and lactoferrin were rather stable and varied less than 20% between samples. It is suggested that HSP-albumin may be used as a reliable marker of transudation of serum proteins to the genital tract. Likewise, lactoferrin could be used as a marker for the secretion of seminal vesicle proteins, since it reflects the functional status of these glands.

Abstract Beta 2 -microglobulin and CEA-like protein are normal constituents of human seminal plasma (HSP). Both occur in high concentrations:4.4-109.9 mg/l and 26-640 ng/ml for b 2 m and CEA, respectively. Studies with split ejaculates showed that the level of both proteins in HSP is a composite from the different secretions of the male genital tract. A portion of b 2 m is in some way attached to the spermatozoa but free b 2 m is not easily taken up by the spermatozoa. In terms of b 2 m and CEA levels in HSP, no significative difference was found between the morphologically normal males and patients with defects in sperm appearence or performance. However, we have to await the final outcome in terms of conceptions in our patients before the usefulness of b 2 m and CEA can be finally evaluated.

Labor was induced for medical reasons at or near term in altogether 200 patients. The women were randomly assigned to low amniotomy and either oral PGE2 or intravenous infusion of oxytocin. The initial PGE2 dose was 0.5 mg, followed by 1.0 mg every hour for up to 24 hours. Oxytocin was given as an intravenous pump infusion, starting with 5 mIU/min and rising stepwise to 20 mIU/min. Uterine contractility and fetal heart rate (FHR) were recorded by cardiotocography in 61 women receiving oxytocin and in 63 given prostaglandin E2. A detailed analysis of the contractility pattern was performed in 16 women, eight from each group. Labor was established slightly earlier in the oxytocin group than in the prostaglandin group of patients. When in labor, frequency and amplitude of contractions as well as uterine contractility were the same in both treatment groups. The frequency of atypical contractility patterns was higher in labor induced with PGE2 than with oxytocin. One period of hypertonus was observed in one patient treated with PGE2 but it was not associated with alterations in FHR and disappeared without additional therapy. Both mild and more severe variations in FHR occurred but were equally common on both treatment groups. There was no perinatal mortality among the newborns and the Apgar score 5 minutes after delivery was 8 or more.

Acta Physiologica ScandinavicaVolume 95, Issue 1 p. 142-144 Noradrenaline Release Following Nerve Stimulation and its Modification by Prostaglandin E2 in Human and Rabbit Oviduct Atef Moawad, Atef Moawad Department of Physiology, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorPer Hedqvist, Per Hedqvist Department of Physiology, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorMarc Bygdeman, Marc Bygdeman Department of Physiology, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this author Atef Moawad, Atef Moawad Department of Physiology, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorPer Hedqvist, Per Hedqvist Department of Physiology, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorMarc Bygdeman, Marc Bygdeman Department of Physiology, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this author First published: September 1975 https://doi.org/10.1111/j.1748-1716.1975.tb10036.xCitations: 15AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume95, Issue1September 1975Pages 142-144 RelatedInformation