The measurement of endometrial perfusion in norplant users: a pilot study

The use of progestogens without oestrogen is commonly associated with irregular menstrual bleeding. Oestrogens and progestogens are both thought to influence endometrial perfusion; changes in endometrial perfusion may contribute to vascular fragility and breakdown. In this study, endometrial perfusion was measured using laser-Doppler fluxmetry in women in the secretory phase of the menstrual cycle before and 4-6 weeks after insertion of the low-dose long-acting levonorgestrel contraceptive implant system, Norplant. Endometrial perfusion was also measured in women exposed to Norplant for up to 19 months. There was no significant difference between endometrial perfusion in control cycles (27.2 flux units +/- 5.5, SEM) and at 4-6 weeks after Norplant insertion (16.3 flux units +/- 5.0), a time when irregular bleeding and spotting are common. Endometrial perfusion was no different from controls after longer periods of Norplant exposure (35.7 flux units +/- 7.2). No direct relationships between endometrial perfusion and plasma concentrations of ovarian steroid hormones were demonstrated. Short-term endometrial vasomotion was largely abolished during Norplant exposure.     

The structure of endometrial microvessels

Recent studies have provided substantial evidence to highlight abnormalities in the structure of endometrial microvessels in users of progestogen-only contraception. Structural changes alone are unlikely to lead to breakthrough bleeding, but appear to be associated with a reduction in vessel integrity, and may reflect alterations in the control and growth of endometrial microvessels in those exposed to exogenous progestogens. In users of low-dose progestogens, immunohistochemical studies have demonstrated changes in superficial endometrial vascular morphology, density and in endometrial migratory cell populations. In Norplant users the endometrial endothelial basal lamina is deficient in the initial months of exposure, when bleeding problems are most common. The basal lamina refers to the very thin structure consisting mostly of collagen IV and laminin seen underlying endothelial and epithelial cells at the electron microscope level. In addition, hysteroscopic studies have demonstrated increased fragility of superficial vessels. Changes in endometrial microvascular anatomy associated with normal menstruation have been reviewed, and are compared with those seen following contraceptive steroid exposure. Likely mechanisms of breakthrough bleeding such as increased superficial vascular fragility and the possible alterations in endometrial vascular structure leading to this are discussed.     

Recurrence risk for sibs of children with "sporadic" achondroplasia

Because of gonadal mosaicism, the risk of recurrence of achondroplasia in the sibs of achondroplastic children with unaffected parents is presumably higher than twice the mutation rate, but it has not been measured. Data from 11 Canadian genetics centers provide an estimate of 1/443, or 0.02%.     

Action research to improve the pre-registration midwifery curriculum--Part I: An appropriate methodology

OBJECTIVE: To improve the pre-registration midwifery curriculum locally and influence national policy and guidelines for these programmes. DESIGN: Action research provided the framework for the study where a multi-method approach was largely qualitative to attempt to capture the context and complexity in which the midwifery programme operates. The study comprises a synthesis of two separate but interwoven research projects: a national study about the effectiveness of midwifery education (the EME project) and an evaluation and re-design of the three year pre-registration midwifery programme in a large multi-sited university in England. SETTING: A large university in England. PARTICIPANTS: The EME project 39 case study students, their teachers, practice-based mentors/assessors, preceptors and supervisors of midwives or managers; 50 students from the local university's midwifery programme, their teachers and practice-based mentors/assessors from six sites; 41 women who gave birth to their babies in a large teaching hospital in the East Midlands; and a professional network of experienced midwives whose role is to advise the statutory body regulating midwifery programmes in England. FINDINGS: Overall the three-year, pre-registration route into midwifery was found to be an effective preparation for contemporary midwifery practice as judged against a model of a competent midwife at the point of registration. However, there was evidence to suggest that not all students are equipped to practise competently and confidently in contexts of uncertainty and change in the National Health Service. Factors which emerged as influencing curriculum effectiveness related to: recruitment and selection; curriculum structure, appropriateness; and robustness of assessment schemes; the preparation of and support for assessors; and the role of the midwife teacher in assessment in practice settings. CONCLUSION AND IMPLICATIONS FOR PRACTICE: Diagnosing problems and initiating actions as a collaborative process formed an important part of designing and implementing an 'ideal' curriculum in constrained health and higher education contexts. The need for on-going dialogue, critical reflection, and research to facilitate and assess learning more effectively in the 'caring' professions emerged as necessary to ensure that only competent practitioners have a license to practise.     

Action research to improve the pre-registration midwifery curriculum Part. 2: Case study evaluation in seven sites in England

OBJECTIVE: To identify factors which facilitate and inhibit the effectiveness of current pre-registration midwifery programmes. DESIGN: The case study part of an action research project. SETTING: Seven case study institutions in England. PARTICIPANTS: Student midwives, midwives, midwifery managers/supervisors of midwives, midwife teachers, collaborators in the study. FINDINGS: It emerged, following a synthesis of all data, that the pre-registration midwifery curriculum should have five key outcomes: students should feel confident and competent as midwives; students must have achieved the statutory requirements for registration; students should be committed to undertaking the whole role and responsibilities of a midwife; students must be equipped to take responsibility and accept accountability for their actions; students must recognise the need for career long learning. Whilst overall these new programmes were considered to be effective in preparing students for their role as midwives, there was variability in the degree to which these five key outcomes were achieved by the case study students. IMPLICATIONS FOR PRACTICE: There needs to be agreement as to what constitutes fitness for practice at the point of registration; assessment schemes, particularly those relating to practice capabilities, need to be valid, reliable and robust with the benefit of the doubt being given in favour of childbearing women when students are 'borderline'; fitness for purpose requires clarification to avoid employers having unreal expectations of new qualifiers which may result in attrition due to excessive stress; review of curricula should take account of the importance of personal qualities and learning strategies which enable students to cope with complexity, uncertainty, decision making and 'being a midwife' before course completion.     

Infection and establishment of latency in the dog brain after direct inoculation of a nonpathogenic strain of herpes simplex virus-1

A number of diseases affecting the CNS occur in the dog and can be used as models for gene therapy in a large brain. HSV-1 has several potential advantages as a vector to transfer genes into the CNS. However, the ability of HSV-1 to infect CNS cells varies among species and no information was available for the dog. When the nonpathogenic 1716 strain of HSV-1 was injected into the brains of normal dogs it established a latent infection without signs of pathology. Thus, it appears to be suitable as a vector for therapeutic, or marker genes, in this species.     

B cell- and monocyte-activating chemokine (BMAC), a novel non-ELR alpha-chemokine

A novel alpha-chemokine, designated KS1, was identified from an EST database of a murine immature keratinocyte cDNA library. The EST has 94% similarity to a recently cloned human gene, BRAK, that has no demonstrated function. Northern analysis of mouse and human genes showed detectable mRNA in brain, intestine, muscle and kidney. Tumour panel blots showed that BRAK was down-regulated in cervical adenocarcinoma and uterine leiomyoma, but was up-regulated in breast invasive ductal carcinoma. KS1 bound specifically to B cells and macrophages, as well as two B cell lines, CESS and A20, and a monocyte line, THP-1. KS1 showed no binding to naive or activated T cells. In addition, KS1 stimulated the chemotaxis of CESS and THP-1 cells but not T cells. The s.c. injection of KS1 creates a mixed inflammatory response in Nude and C3H/HeJ mice. The above data indicates that KS1 and its human homologue represents a novel non-ELR alpha-chemokine that may have important roles in trafficking of B cells and monocytes. We propose the name B cell- and monocyte-activating chemokine (BMAC) for this molecule to reflect the described biological functions.