Reversible infantile respiratory chain deficiency is a unique, genetically heterogenous mitochondrial disease.

Objectives: Homoplasmic maternally inherited, m.14674T>C or m. 14674T>G mt-tRNA(Glu) mutations have recently been identified in reversible infantile cytochrome c oxidase deficiency (or 'benign COX deficiency').

Secondary post-partum haemorrhage: challenges in evidence-based causes and management.

Secondary postpartum haemorrhage (SPPH) is an important post-natal issue, whose significance is perceived differently between practices, settings and probably within cultures. It is generally less focussed upon, in contrast to its primary counterpart. Patients prefer that it is treated promptly, even when it is not life-threatening.

Pelvic pain in women: clinical and scientific aspects.

Purpose Of Review: Pelvic pain is a common complaint of women that is frequently poorly managed. This review considers the current understanding of the mechanisms of pain perception and the development of chronic pain in the context of three gynaecological pain conditions. Recent advances in the management of these conditions are then discussed.

The functions of microparticles in preeclampsia.

Circulating blood cells, trophoblast cells and endothelial cells release microparticles (MP) into the maternal blood by membrane shedding. This process occurs upon activation or apoptosis of these cells. Evidence is accumulating that MP play a role in the development of thrombotic diseases.

Information for genetic management of mtDNA disease: sampling pathogenic mtDNA mutants in the human germline and in placenta.

Background: Families with a child who died of severe, maternally inherited mitochondrial DNA (mtDNA) disease need information on recurrence risk. Estimating this risk is difficult because of (a) heteroplasmy-the coexistence of mutant and normal mtDNA in the same person-and (b) the so-called mitochondrial bottleneck, whereby the small number of mtDNAs that become the founders for the offspring cause variation in dose of mutant mtDNA. The timing of the bottleneck and of segregation of mtDNA during foetal life determines the management options.

Collated mutations in mitochondrial DNA (mtDNA) depletion syndrome (excluding the mitochondrial gamma polymerase, POLG1).

These tables list both published and a number of unpublished mutations in genes associated with early onset defects in mitochondrial DNA (mtDNA) maintenance including C10orf2, SUCLG1, SUCLA2, TYMP, RRM2B, MPV17, DGUOK and TK2. The list should not be taken as evidence that any particular mutation is pathogenic. We have included genes known to cause mtDNA depletion, excluding POLG1, because of the existing database (http://tools.

Effects of gonadotrophin releasing hormone analogues on human endometrial stromal cells and embryo invasion in vitro.

Background: Gonadotrophin releasing hormone (GnRH) analogues are widely used in IVF programmes as a method of suppressing the luteinizing hormone (LH) surge prior to ovarian stimulation, but their roles outside the pituitary remain relatively unknown. A 2002 Cochrane review (Al-Inany et al. Gonadotrophin-releasing hormone antagonists for assisted conception.

Depletion of mitochondrial DNA in fibroblast cultures from patients with POLG1 mutations is a consequence of catalytic mutations.

We investigated clinical and cellular phenotypes of 24 children with mutations in the catalytic (alpha) subunit of the mitochondrial DNA (mtDNA) gamma polymerase (POLG1). Twenty-one had Alpers syndrome, the commonest severe POLG1 autosomal recessive phenotype, comprising hepatoencephalopathy and often mtDNA depletion. The cellular mtDNA content reflected the genotype more closely than did clinical features.

Experimental models for investigating implantation of the human embryo.

Recently, significant advances in our understanding of embryo implantation have been made using animal models, notably in the mouse and nonhuman primates. However, the determination of the molecular and cellular events that underpin the early stages of implantation in the human remains an intractable problem, in part due to the inaccessibility of early human implantation sites. In the absence of in vivo implantation sites, several experimental in vitro model systems have been developed recently that mimic the different stages of human embryo implantation that occur in vivo during the first few weeks of pregnancy.

Endometrial cells from women with endometriosis have increased adhesion and proliferative capacity in response to extracellular matrix components: towards a mechanistic model for endometriosis progression.

Background: Endometriosis, classified as the presence of endometrial cells in ectopic sites, is a debilitating disease causing pain and infertility in approximately 10% of women of reproductive age. It is associated with the aberrant expression of extracellular matrix (ECM) components and their receptors, integrins.

Methods: We analysed the expression of integrins in stromal cells derived from peritoneal, ovarian and deeply infiltrating endometriotic lesions and from endometrium from women with and without endometriosis in vitro, using quantitative immunocytochemistry.

Meningioma mimicking puerperal psychosis.

Background: Meningiomas are slow-growing benign brain tumors. They can be sensitive to sex hormones, increasing in size with pregnancy and leading to clinical presentation either before or immediately after delivery. Initial symptoms and signs can present in the antenatal as well as the postnatal period.

Molecular genetic evidence that endometriosis is a precursor of ovarian cancer.

Histopathology and epidemiology studies have consistently demonstrated a strong link between endometriosis and endometriosis-associated ovarian cancers (EAOCs)--in particular, the endometrioid and clear cell subtypes. However, it is still unclear whether endometriosis is a precursor to EAOCs, or whether there is an indirect link because similar factors predispose to both diseases. In order to search for evidence of clonal progression, we analyzed 10 EAOCs (endometrioid=4; clear cell=6) with coexisting endometriosis for common molecular genetic alterations in both the carcinoma and corresponding endometriosis.

Stromal cells from endometriotic lesions and endometrium from women with endometriosis have reduced decidualization capacity.

Objective: To evaluate the phenotype, proliferative, and differentiation capacities in vitro of stromal cells derived from peritoneal, ovarian, and deeply infiltrating endometriosis.

Design: Experimental study using phase contrast microscopy, immunocytochemistry, and functional bioassays.

Setting: University-based laboratory.

Does a first trimester dating scan using crown rump length measurement reduce the rate of induction of labour for prolonged pregnancy? An uncompleted randomised controlled trial of 463 women.

Objective: To evaluate the effect of a first trimester ultrasound dating scan on the rate of induction of labour for prolonged pregnancy.

Design: Randomised controlled trial to include 400 women in each arm of the trial.

Setting: Participating general practices and a district general teaching hospital.

Fetal and neonatal exposure to AZT and low-protein diet affects glucose homeostasis: a model with implications for AIDS prevention.

Zidovudine (AZT) lowers the perinatal transmission of HIV but can impair mitochondrial function by depleting mitochondrial DNA (mtDNA). AZT therapy and perinatal nutritional deprivation affect the body fat distribution, which influences glucose tolerance. We sought to model intrauterine exposure to AZT in humans to determine whether it interacts with low-protein diet (LPD) to impact on birth weight and glucose homeostasis in the offspring.

A common mitchondrial DNA variant is associated with thinness in mothers and their 20-yr-old offspring.

A common mitochondrial (mt)DNA variant that is maternally inherited, the 16189 variant, is associated with type 2 diabetes and thinness at birth. To elucidate the association of the variant with thinness, we studied the 16189 variant in a well-characterized Australian cohort (n = 161) who were followed up from birth to age 20 yr. PCR analysis and mtDNA haplotyping was carried out on DNA from 161 offspring from consecutive, normal, singleton pregnancies followed from birth to age 20 yr.

Tocolysis for repeat external cephalic version in breech presentation at term: a randomised, double-blinded, placebo-controlled trial.

Background: External cephalic version (ECV) reduces the incidence of breech presentation at term and caesarean section for non-cephalic births. Tocolytics may improve success rates, but are time consuming, may cause side effects and have not been proven to alter caesarean section rates. The aim of this trial was to determine whether tocolysis should be used if ECV is being re-attempted after a failed attempt.

Expression profiling of murine intestinal adenomas reveals early deregulation of multiple matrix metalloproteinase (Mmp) genes.

Initiation of intestinal tumours occurs as a consequence of aberrant Wnt signalling. This causes altered expression of a number of genes which provides the mechanistic basis of neoplastic change in normal epithelium. In order to identify these genes, expression profiles of normal intestinal mucosa and intestinal adenomas from multiple intestinal neoplasia (Min) mice were compared.

Assisted reproductive technologies in europe encompass diverse and complex ethical viewpoints: issues to be considered in reporting research in human reproduction.

The many dimensions of the field of reproduction (clinical, scientific, social, ethical, legal) must be addressed by those with editorial responsibility for the major journals in the field. As the editorial team of the leading reproductive journal Human Reproduction, we have evolved processes that attempt to ensure a transparent but robust approach to complexities whose impact varies across international boundaries.

Why is there a modifying effect of gestational age on risk factors for cerebral palsy?

Objective: To investigate risk factors for cerebral palsy in relation to gestational age.

Design: Three case-control studies within a geographically defined cohort.

Setting: The former Oxfordshire Health Authority.

Adrenomedullin: multiple functions in human pregnancy.

Adrenomedullin is a 52 amino acid peptide originally isolated from human phaeochromocytoma in 1993. It was initially demonstrated to have profound effects on the vasculature including vasodilatation and subsequently promotion of angiogenesis. Since then it has become apparent that it has a wide range of other biological actions including regulation of cell growth and differentiation.

Amielle vaginal trainers-a patient evaluation.

Ten consecutive patients presenting to a gynaecology clinic with a principal diagnosis of secondary vaginismus and superficial dyspareunia were given a set of Amielle vaginal trainers and instructed in their use. They were subsequently sent a questionnaire asking for their evaluation of the efficacy of the trainers. Nine patients (90%) reported a substantial improvement or complete cure of their symptoms.