Biomedical subjects

R Webb

Publications and source records attributed to R Webb.

At least 37 records · Page 2Linked to original sources

PubMed2004

The expression patterns of mRNA-encoding stem cell factor, internal stem cell factor and c-kit in the prepubertal and adult porcine ovary.

The receptor, c-kit, and its ligand, stem cell factor (SCF), are important regulators of ovarian follicle growth and development. The aim of this study was to identify the sites of expression of mRNA for c-kit and SCF in prepubertal and mature (pregnant and non-pregnant) animals. Ovaries were recovered from prepubertal animals, non-pregnant sows and five sows at approximately 3 months of gestation. Ovine SCF and c-kit DNA were cloned into plasmid vectors to produce RNA probes. Expression of mRNA encoding SCF and c-kit were detected via in situ hybridization. Both mRNA were detected throughout ovaries from all animals. This study provides evidence that the growth-factor complex is required throughout follicle development, and also for continued maintenance of the corpus luteum (CL) in the mature animal. SCF mRNA was localized to the granulosa cell layer and was also extensively expressed in endothelial tissue and throughout the CL. c-kit mRNA was detected in the theca layer, oocytes and also in CL. In conclusion, expression of SCF and c-kit mRNA in granulosa and theca cells, respectively, indicate an important interaction between somatic cells throughout follicle development and that in the mature animal, SCF and c-kit potentially have a role in maintaining progesterone secretion by the CL. The observations of continued expression of SCF and c-kit throughout development suggest that there may be differences in the role of this receptor-ligand complex between large mono- vs. poly ovulatory species, such as the pig.

Animals↗

PubMed2004

Determination of Cu environments in the cyanobacterium Anabaena flos-aquae by X-ray absorption spectroscopy.

Whole cells and peptidoglycan isolated from cell walls of the cyanobacterium Anabaena flos-aquae were lyophilized and used at pH 2 and pH 5 in Cu(II) binding studies. X-ray absorption spectra measured at the Cu K-edge were used to determine the oxidation states and chemical environments of Cu species in the whole-cell and peptidoglycan samples. In the whole-cell samples, most of the Cu retained at both pH values was coordinated by phosphate ligands. The whole-cell fractions contained significant concentrations of Cu(I) as well as Cu(II). An X-ray absorption near-edge spectrum analysis suggested that Cu(I) was coordinated by amine and thiol ligands. An analysis of the peptidoglycan fractions found that more Cu was adsorbed by the peptidoglycan fraction prepared at pH 5, due to increased chelation by amine and carboxyl ligands. The peptidoglycan fractions, also referred to as the cell wall fractions, contained little or no Cu(I). The Cu loading level was 30 times higher in the cell wall sample prepared at pH 5 than in the sample prepared at pH 2. Amine and bidentate carboxyl ligands had similar relative levels of importance in cell wall peptidoglycan samples prepared at both pH values, but phosphate coordination was insignificant.

Anabaena↗

PubMed2004

Associations between perinatal interventions and hospital stillbirth rates and neonatal mortality.

BACKGROUND: Previous studies suggest that high risk and low birthweight babies have better outcomes if born in hospitals with level III neonatal intensive care units. Relations between obstetric care, particularly intrapartum interventions and perinatal outcomes, are less well understood, however. OBJECTIVE: To investigate effects of obstetric, paediatric, and demographic factors on rates of hospital stillbirths and neonatal mortality. METHODS: Cross sectional data on all 65 maternity units in all Thames Regions, 1994-1996, covering 540 834 live births and stillbirths. Hospital level analyses investigated associations between staffing rates (consultant/junior paediatricians, consultant/junior obstetricians, midwives), facilities (consultant obstetrician/anaesthetist sessions, delivery beds, special care baby unit, neonatal intensive care unit cots, etc), interventions (vaginal births, caesarean sections, forceps, epidurals, inductions, general anaesthetic), parental data (parity, maternal age, social class, deprivation, multiple births), and birthweight standardised stillbirth rates and neonatal mortality. RESULTS: Unifactorial analyses showed consistent negative associations between measures of obstetric intervention and stillbirth rates. Some measures of staffing, facilities, and parental data also showed significant associations. Scores for interventional, organisational, and parental variables were derived for multifactorial analysis to overcome the statistical problems caused by high intercorrelations between variables. A higher intervention score and higher number of consultant obstetricians per 1000 births were both independently and significantly associated with lower stillbirth rates. Organisational and parental factors were not significant after adjustment. Only Townsend deprivation score was significantly associated with neonatal mortality (positive correlation). CONCLUSIONS: Birthweight adjusted stillbirth rates were significantly lower in units that took a more interventionalist approach and in those with higher levels of consultant obstetric staffing. There were no apparent associations between neonatal death rates and the hospital factors measured here.

Adolescent↗

PubMed2004

A population-based study of primary care predictors of non-attendance for cervical screening.

OBJECTIVE: To identify and estimate the population impact of primary care service delivery factors that independently predict non-attendance for cervical screening. SETTING: Screening records of all eligible women aged 30 years and over and resident in the former Manchester Health Authority area were analysed (n=72,613). METHODS: Practice-level and GP-level explanatory variables, along with area-level covariates, were obtained and merged to the study data set. Logistic regression models were used to identify factors associated with having no recorded history of attending NHS cervical screening services. A multivariate model was created to identify independent predictors of non-attendance with comprehensive adjustment for women's age, area-level socio-demographic factors, and other primary care factors. Attributable fraction estimates were used to assess the population impact of the independent predictors. RESULTS: Large practice size (>4,000 patients), single-handed practice, South Asian male GP, part-time GP employment status, older age and birthplace overseas, and area-level measures of deprivation and transience independently predicted non-attendance. Women born overseas and registered at larger practices were especially unlikely to have ever attended. The combined population attributable fraction estimate for the independent predictors reflecting primary care service delivery was almost 40%, and that for all variables in the final model was over 70%. CONCLUSIONS: Independent predictors of non-attendance reflecting general practice structure, workload and GP characteristics were identified. Although relative risks were modest, the collective population impact of these factors was considerable, which has implications for the implementation of informed targeting and the development of new screening services by Primary Care Trusts.

Adult↗

PubMed2004

Direct in vivo effects of leptin on ovarian steroidogenesis in sheep.

Leptin, the metabolic fat hormone, has been shown to have effects on reproduction in mice and to modulate steroid production by cultured ovarian somatic cells in a number of species. However, a direct role of leptin on normal ovarian function in vivo has not been shown. In this paper the effect of passive immunisation against leptin (experiment 1; 20 ml antiserum or non-immune plasma i.v.; n = 6/treatment) and direct ovarian infusion of leptin (experiment 2; 0, 2 or 20 mug recombinant ovine leptin; n = 4/treatment) during the early follicular phase was investigated in sheep with ovarian autotransplants, which allow recovery of ovarian venous blood and regular non-invasive scanning of the ovary. Passive immunisation against leptin resulted in an acute increase (P < 0.05) in ovarian oestradiol secretion but had no effect on gonadotrophin concentrations, ovulation or subsequent luteal function. Conversely, direct ovarian arterial infusion of the low dose of leptin resulted in an acute decline (P < 0.05) in ovarian oestradiol secretion whereas the high dose, which resulted in supra-physiological leptin concentrations, had no effect on oestradiol production compared with the controls. Neither dose of leptin had any effect on gonadotrophin concentrations or ovulation but both doses resulted in an increase (P < 0.05) in progesterone concentrations over the subsequent luteal phase. In conclusion, together these data provide strong in vivo evidence that leptin can modulate ovarian steroidogenesis directly and acutely in ruminants and suggest that leptin is an alternate regulatory system whereby nutritional status can regulate reproductive activity.

Animals↗

PubMed2004

Control of follicular growth: local interactions and nutritional influences.

Regulation of ovarian activity is an integrated process encompassing both extraovarian signals and intrafollicular factors. Initiation of primordial follicle growth and the early stages of folliculogenesis can occur without gonadotropins, but FSH may affect the rate of preantral follicle growth. Antral follicle development from 1 to 4 mm in sheep and cattle is completely gonadotropin dependent. These recruited follicles express a range of mRNA encoding steroidogenic enzymes, gonadotropin receptors, and local regulatory factors and their receptors. As follicles continue to mature, there is a transfer of dependency from FSH to LH, which may be part of the mechanism involved in selection of follicles for continued growth. Locally produced growth factors, such as the IGF and members of the transforming growth factor-beta superfamily, work in concert with gonadotropins throughout the follicular growth continuum and can have significant effects on follicle selection. Environmental influences, such as changes in nutrition, also have an effect on ovarian activity. This can occur without significant variation in circulating gonadotropin concentrations and can be correlated with changes in circulating concentrations of metabolic hormones, including insulin, IGF-I, GH, and leptin. Nutrition can also affect the expression of mRNA encoding components of the ovarian IGF system to regulate the sensitivity/response of follicles toward gonadotropins. Hence, the roles of growth factors in follicular development and survival depend on gonadotropin status and differentiation state of the follicle. In conclusion, it is the integration of these extraovarian signals and intrafollicular factors that determine whether a follicle will continue to develop or be diverted into atretic pathways.

Animal Nutritional Physiological Phenomena↗

PubMed2003

Effects of circulating progesterone and insulin on early embryo development in beef heifers.

The aims of this study were to determine the effect on early embryo development of feeding a diet formulated to enhance circulating insulin concentrations and secondly to investigate the association between early embryo development and maternal progesterone concentrations in beef heifers. The study was carried out in 32 Simmental x Holstein Friesian heifers 22-25 months of age weighing 506+/-7kg and in condition score 3.1+/-0.1. Animals were fed two diets that were isoenergetic and isonitrogenous, but that would encourage either propionate (diet A) or acetate (diet B) production in the rumen. The rationale was that propionate would induce a greater insulin release in response to feeding. Animals were fed a 50:50 mix of the two diets for 14 days at 0.8x maintenance, with straw provided ad libitum. Animals were then fed one of the experimental diets for 3 weeks prior to synchronisation of oestrus and insemination and for a further 16 days following mating. All heifers were blood sampled daily from oestrus synchronisation and eight animals on each diet underwent daily transrectal real-time ultrasonography to determine the day of ovulation. All heifers were slaughtered at Day 16 after mating. While feeding of diet A (propionic) caused a significant (P<0.05) increase in the plasma insulin to glucagons ratio differences in insulin were not significantly different. This is probably due to the fact that insulin concentrations were quite high as the heifers used in the present study were in good body condition making further increases in insulin difficult to achieve. Diet did not affect size of ovulatory follicle (DIET A: 15.1+/-0.7mm; diet B: 14.6+/-0.7mm), day of ovulation (diet A: 3.5+/-0.2 days; diet B: 3.4+/-0.2 days), mean plasma progesterone concentration (diet A: 4.7+/-0.4ng/ml; diet B: 5.2+/-0.3ng/ml), corpus luteum weight (diet A: 6.0+/-0.2g; diet B: 6.0+/-0.2g) or pregnancy rate (diet A: 81.3%; diet B: 81.3%). However, the proportion of well-elongated (>10cm) embryos on Day 16 was higher in animals fed diet A than in those fed diet B (84.6% versus 38.5%; P<0.05). While progesterone concentration did not differ between pregnant and non-pregnant heifers, progesterone did show an earlier post-ovulatory rise in heifers with well-elongated (>10cm) embryos with levels in these animals significantly higher on Days 4 and 5 than in heifers with small (<10cm) embryos at slaughter. This study demonstrated an enhancement in early embryo development in animals fed a diet generating an increased insulin:glucagon ratio that was not related to circulating maternal progesterone concentrations. However, across diets, enhanced embryo development was associated with elevated plasma progesterone on Days 4 and 5 following mating.

Acetic Acid↗

PubMed2003

Prolactin, prolactin receptor and uncoupling proteins during fetal and neonatal development.

Uncoupling proteins (UCP) 1 and 2 are members of the subfamily of inner mitochondrial membrane carriers. UCP1 is specific to brown adipose tissue (BAT), where it is responsible for the rapid production of heat at birth. In fetal sheep UCP1 is first detectable at approximately 90 d of gestation; its abundance increases with gestational age and peaks at the time of birth. The mRNA and protein for both the long and short form of the prolactin (PRL) receptor (PRLR) are also highly abundant in BAT. Enhanced PRLR abundance in late gestation is associated with an increase in the abundance of UCP1. This relationship between PRLR and UCP is not only present in BAT. Similar findings are now reported in the pregnant ovine uterus, where PRLR abundance reaches a maximum just before that of UCP2. However, the role of PRLR in BAT remains undetermined. Rat studies have shown that PRL administration throughout pregnancy results in offspring with increased UCP1 at birth. Studies in newborn lambs have shown that administration of PRL (2 mg/d) causes an acute response, increasing colonic temperature in the first hour by 1 degrees. This increased colonic temperature is maintained for the first 24h of life, in conjunction with enhanced lipolysis. After 7 d of treatment there is no difference in the abundance of UCP1 but an increase in UCP1 activity; this effect may be mediated by an increase in lipolysis. Taken together these findings suggest that PRL could be an important endocrine factor during pregnancy and early postnatal life.

Adipose Tissue, Brown↗

PubMed2003

The FecB (Booroola) gene acts at the ovary: in vivo evidence.

The aim of this study was to differentiate between pituitary and ovarian actions of the FecB gene by measuring the ovarian response to a standardized treatment with gonadotrophins designed to mimic the changes in FSH and LH that occur in the follicular phase of the ovarian cycle in ewes, with (Fec(B/-), n=6) and without (Fec(+/+), n=9) the gene, that were rendered hypogonadotrophic by pretreatment with a potent antagonist of GnRH. Ewes with ovarian autotransplants were used to facilitate the assessment of follicular function by the collection of ovarian venous blood and ultrasonography. The gonadotrophin regimen resulted in concentrations of FSH and LH that were similar to concentrations found in a normal cycle and did not differ between genotypes. Follicular development and ovulation occurred in all animals, and patterns of secretion of oestradiol, androstenedione and inhibin A were normal. Despite these endocrine similarities, the antral follicle population stimulated by FSH infusion retained the characteristic genotypic difference with the ovaries of Fec(+/+) animals containing a range of follicle sizes with decreasing proportions of small (<3.5 mm in diameter) and medium (3.5-4.5 mm in diameter) follicles as well as large follicles (> or =4.5 mm in diameter), whereas the ovaries of Fec(B/-) ewes contained no follicles of >4.5 mm in diameter. This genotypic difference was retained after ovulation with gene carriers having more preovulatory follicles/corpora lutea (3.8+/-0.3) of a smaller diameter (5.3+/-0.3 mm) than did non-gene carriers (1.7+/-0.3; 11.4+/-0.9 mm; P<0.05). As ewes carrying the FecB gene mutation were able to ovulate more follicles than non-gene carriers, despite identical concentrations and patterns of FSH and LH stimulation, the results of this study support the hypothesis that the FecB gene acts at the ovary to enhance ovarian sensitivity to gonadotrophic stimulation.

Androstenedione↗

PubMed2003

Interaction of bovine granulosa and theca cells in a novel serum-free co-culture system.

The objective of this study was to develop a defined culture system in which bovine follicular and granulosa cells are grown in close contact with each other and with the extracellular matrix (ECM) component laminin. Granulosa and theca cells from follicles 4-6 mm in diameter were cultured on either side of laminin-coated BioCoat cell culture inserts in a serum-free medium containing 10 ng insulin ml(-1) at plating densities of 10(5) and 3 x 10(5) cells per membrane side. The cells adopted a clumped arrangement, maintained steroidogenic activity for at least 7 days and demonstrated paracrine communication by increased steroidogenesis and enhanced cell survival compared with cells in mono-culture. Co-cultured theca cells secreted significantly more androstenedione compared with cells in mono-culture. Granulosa cell viability was doubled by co-culture with theca cells. Co-cultures at both cell plating densities were responsive to treatment with physiological combinations of either FSH, LH and LR3 insulin-like growth factor I (IGF-I) (treatment A) or FSH, LR3 IGF-I and androstenedione (treatment B). Significantly more androstenedione was secreted in the presence of treatment A compared with controls. In contrast, oestradiol secretion was increased only by treatment B. Progesterone secretion was unaffected by treatment and did not increase during culture. Co-cultures at the higher plating density demonstrated higher theca cell survival and better maintenance of the follicular cell phenotype. In conclusion, this novel co-culture system provides a unique model for the study of paracrine communication between ovarian somatic cells and cell-ECM interactions during follicle growth.

Androstenedione↗

PubMed2003

Mechanisms regulating follicular development and selection of the dominant follicle.

Reproductive function is an integrated process encompassing both extra-ovarian signals, such as gonadotrophins, and intrafollicular factors, such as locally produced growth factors. Initiation of primordial follicle growth and the early stages of folliculogenesis can occur without gonadotrophins. However, in vivo and in vitro studies indicate that FSH may stimulate the rate of preantral follicle growth and that it can take only 3 months for a primordial follicle to reach the ovulatory stage. Antral follicle development from 2 and 4 mm in diameter in sheep and cattle, respectively, is gonadotrophin dependent. During the oestrous cycle a transient increase in circulating FSH precedes the recruitment of a group of follicles. Recruited follicles are characterized by induction of expression of mRNAs encoding a range of steroidogenic enzymes, gonadotrophin receptors and local regulatory factors. As follicles continue to mature, there is a transfer of dependency from FSH to LH, which may be part of the mechanism involved in selection of follicles for continued growth. The mechanism of selection of the ovulatory follicle seems to be linked to the timing of mRNA expression encoding LHr and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in granulosa cells. Locally produced growth factors, such as the insulin-like growth factors (IGFs) and members of the transforming growth factor beta (TGFbeta) superfamily (inhibins, activins and bone morphogenetic proteins (BMPs)), work in concert with gonadotrophins throughout the follicular growth continuum. The roles of growth factors in follicular development and survival are dependent on gonadotrophin status and differentiation state, including morphology. In conclusion, it is the integration of extraovarian signals and intrafollicular factors that determine whether a follicle will continue to develop or be diverted into atretic pathways, as is the case for most of the follicles in monovulatory species, such as cattle.

Animals↗

PubMed2003

Interactions between nutrition and ovarian activity in cattle: physiological, cellular and molecular mechanisms.

The effects of acute changes in dietary intake on ovarian activity can be correlated with changes in circulating concentrations of metabolic hormones including insulin, insulin-like growth factor I (IGF-I), growth hormone and leptin. There is no corresponding change in circulating gonadotrophin concentrations and it is proposed that the dietary induced changes in ovarian activity, resulting from acute changes in dietary intake, are a result of direct actions of these metabolic hormones on the ovary. Changes in the peripheral concentrations of insulin, IGF-I and leptin were also associated with the initiation of a synchronized wave of follicle growth and it is hypothesized that oestrogen secreted by the developing follicle is involved in regulating the secretion of these metabolic hormones. At the cellular level, physiological concentrations of insulin and IGF-I interact to stimulate oestradiol production by granulosa cells. In contrast, leptin inhibits FSH-stimulated oestradiol production by granulosa cells and LH-stimulated androstenedione production by theca cells. At the molecular level, dietary energy intake affects the expression of mRNA encoding components of the ovarian IGF system and these changes can directly influence the bioavailability of intrafollicular IGF. This, in turn, can increase the sensitivity or response of follicles to FSH and is one mechanism through which nutrition can directly affect follicle recruitment. Dietary induced increases in intrafollicular IGF bioavailability also have a negative effect on oocyte quality, and diets that are optimal for follicle growth may not necessarily be optimal for oocyte maturation.

Animal Nutritional Physiological Phenomena↗

PubMed2003

Domestic ruminants as models for the elucidation of the mechanisms controlling ovarian follicle development in humans.

It is necessary to understand the basic physiology underlying the complex process of folliculogenesis to address common causes of infertility and to devise innovative strategies to increase the efficiency of assisted reproduction technologies. Availability of suitable ovarian tissue is a major constraint to research in this area in humans, and monovulatory domestic ruminants represent a physiologically relevant model to elucidate basic mechanisms before more focused clinical investigations. This paper reviews the development of several whole animal and cell culture models in ruminants that have allowed basic investigations into the endocrine and local mechanisms regulating preantral and antral follicle development in monovulatory species. Studies on preantral follicle development using the ovarian autograft model have shown, contrary to accepted dogma, that FSH may mediate the rate at which preantral follicles grow and have provided evidence to support the existence of local regulatory feedback mechanisms that influence the rate of primordial follicle initiation and preantral follicle development. Studies on the endocrine control of antral follicle development using the GnRH-antagonist model have shown that a pulsatile mode of LH delivery is not a requirement for normal patterns of follicle development and ovarian hormone secretion. Studies on the local control of somatic cell differentiation using physiological cell culture models have highlighted the essential relationship between somatic cell communication and expression of differentiative markers. We conclude that the domestic ruminant represents a valuable model system for the elucidation of the endocrine and local mechanisms controlling both early and terminal stages of follicle development in monovulatory species. The results of these investigations have direct strategic relevance within clinical medicine.

Animals↗

PubMed2002

The effect of increased dietary intake on superovulatory response to FSH in heifers.

We have previously shown that the number of ovarian follicles <4 mm in diameter can be increased by enhanced dietary intake in heifers. This study investigated the effect of the same dietary treatment on superovulatory response. The estrous cycles of 24 mature Hereford x Friesian heifers were synchronized by a standard progesterone plus prostaglandin protocol. The animals were fed with either 100% (group M, n = 12) or 200% (group 2M, n = 12) maintenance requirements for a 3-week period. Starting from day 4 of the synchronized estrous cycle, all the animals were superovulated using a standard 4-day FSH regime followed by an injection of GnRH analogue (GnRHa) to induce ovulation. Rectal ultrasound scanning was carried out to assess ovarian follicular populations at the start of FSH treatment and on the day of GnRHa injection, and to determine the number of corpora lutea 5 days after GnRHa injection. The body weight (BW) and body condition score (BCS) were recorded weekly and plasma samples were collected throughout the experimental period. There were no differences in either BW or BCS between two groups at the start of the experiment. The BW and BCS were maintained during the experiment in the group M, whilst animals in the group 2M showed a non-significant (P > 0.05) increase in BW and BCS. Circulating concentrations of insulin were significantly (P < 0.01) higher in heifers from the group 2M throughout the controlled feeding period. The group 2M had significantly (P < 0.05) more follicles 2-4 mm in diameter at the start of FSH treatment and more (P < 0.01) follicles >9 mm in diameter on the day of GnRHa injection, when compared with the group M. Similarly, 5 days after GnRHa injection there were significantly (P < 0.01) more corpora lutea in the group 2M (18.1+/-2.2) than in the group M (10.6+/-3.0). In addition, plasma progesterone concentrations following GnRHa injection were significantly (P < 0.01) higher in heifers from the group 2M. In conclusion, these results confirm that increased dietary intake can enhance the recruitment of ovarian follicles in heifers. This treatment may provide a valuable approach to improving superovulatory response in cattle.

Animals↗

PubMed2002

Corpus luteum (CL) function: local control mechanisms.

LH and PGF(2alpha) are the principal luteotrophic and luteolytic hormones in domestic animals, however, it is becoming increasingly apparent that intra-ovarian factors can modulate luteal function. For example, the insulin-like growth factors (IGF-I and -II) can regulate ovarian function, and have direct effects on ovarian cells. An important role for the IGFs in regulating ovarian function is suggested by the multiple effects of IGFs on both follicular and luteal steroidogenesis. Expression of mRNA encoding IGF-I, IGF-II and the type 1 IGF receptor has also been detected in the ruminant CL and is suggestive of autocrine/paracrine roles for both IGF-I and -II in the regulation of luteal function. The actions of the IGFs are further modulated by their association with specific binding proteins (IGFBPs), which regulate the transport of IGFs and their presentation to specific receptors. IGFBPs have been detected in the CL of domestic animals, and inhibitory effects on IGF-I-stimulated progesterone production have been demonstrated. The rapid cyclical changes in luteal growth and regression are associated with rapid changes in vasculature. The principle angiogenic factors include the fibroblast growth factors (FGFs), vascular endothelial growth factor (VEGF) and the angiopoietins (Ang). Other locally produced factors include cytokines such as TNF-alpha and IL-1beta. One such factor is monocyte chemoattractant protein (MCP-1), which increases after exogenous PGF(2alpha). An influx of macrophages takes place in the CL around luteolysis, possibly in response to MCP-1 release, but these changes are not observed in cattle when luteolysis is inhibited. In conclusion locally produced factors are important in the control of luteal function, although their roles have yet to fully elucidated.

Animals↗

PubMed2002

Adjusted mortality rates: a tool for creating more meaningful league tables for stillbirth and infant mortality rates.

A number of problems associated with league tables of performance indicators have been discussed in the literature. This paper attempts to address these problems for stillbirth and infant mortality rates in order to produce meaningful and useful information for the government, general public and health professionals. Composite stillbirth and infant mortality rates, low birth-weight and very low birth-weight rates were determined for the 100 English Health Authorities for 1996-1997. Townsend deprivation scores for these districts were also obtained. The mortality rates were adjusted by multiple regression for very low birth-weight and Townsend score separately and together. Confidence intervals were calculated for the dual-adjusted rates. Almost 60% of the variability in mortality rates were explained by Townsend score and very low birth-weight rates together. Adjusted league tables showed how the individual and combined predictors affect the individual mortality rates for each Health Authority. There was considerable overlap in the confidence intervals for the adjusted rates although there were a few Health Authorities whose mortality rates were clearly below most others. We conclude that fairer and more useful information is provided by geographically based league tables which give both crude rates and rates adjusted for single and multiple predictor variables. The inclusion of confidence intervals aids interpretation of annual random variations and knowledge of differences in the effects of the individual predictors enables better resource targeting.

England↗

PubMed2002

Value of mesothelial and epithelial antibodies in distinguishing diffuse peritoneal mesothelioma in females from serous papillary carcinoma of the ovary and peritoneum.

AIMS: To evaluate the role of mesothelial markers (calretinin, thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers (polyclonal and monoclonal carcinoembryonic antigen, Leu-M1, CA-125 and Ber-EP4) in distinguishing diffuse peritoneal malignant mesothelioma from primary serous papillary adenocarcinoma of the ovary and peritoneum. METHODS AND RESULTS: Paraffin-embedded formalin-fixed blocks from 32 diffuse peritoneal mesotheliomas of epithelial subtype (all females), 20 serous papillary ovarian carcinomas and three primary peritoneal serous papillary carcinomas were studied. Calretinin and Ber-EP4 appeared to be the best positive mesothelial and carcinoma marker, respectively. Nuclear calretinin expression was identified in 28 of 32 malignant mesotheliomas with no nuclear immunoreactivity in the cohorts of serous papillary ovarian and peritoneal carcinomas, thus yielding 88% sensitivity and 100% specificity. Ber-EP4 showed 95% sensitivity and 91% specificity for serous papillary ovarian carcinoma. Thrombomodulin, cytokeratin 5/6 and CD44H immunoreactivities were seen in 18 (56%), 17 (53%) and 15 (47%) of peritoneal mesotheliomas, respectively, and in six (30%), five (25%) and five (25%) of the ovarian tumours, respectively. None of the three primary peritoneal serous papillary carcinomas expressed calretinin, thrombomodulin, cytokeratin 5/6 or CD44H. Polyclonal and monoclonal CEA, and Leu-M1 were expressed by two (10%), one (5%) and seven (35%) serous papillary ovarian carcinomas, respectively. None of the serous papillary peritoneal carcinomas expressed polyclonal CEA, monoclonal CEA or Leu-M1. CA-125 was positive in 19 (95%) and two (67%) ovarian and peritoneal carcinomas, respectively, and in eight (25%) peritoneal mesotheliomas. CONCLUSIONS: Calretinin and Ber-EP4 are useful discriminant markers in distinguishing peritoneal mesothelioma in women from serous papillary ovarian and peritoneal carcinoma. The other mesothelial markers (thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers (polyclonal and monoclonal CEA, and Leu-M1) yielded a too low sensitivity for practical use.

Antigens, Neoplasm↗

PubMed2002

Predictors of obstetric intervention rates: case-mix, staffing levels and organisational factors of hospital of birth.

We performed a cross-sectional study of all Thames maternity units, 1994-96, including 540,834 live and stillbirths. In contrast to recent media speculation, no association of caesarean section rates with midwifery staffing levels was found after adjustment for confounders. The only association with staffing was with levels of junior obstetric staffing, which could be a reflection of less experienced management of labour. Caesarean section rates were also associated positively with the levels of delivery beds, which could be a reflection of the closer monitoring of labour that may result from increased bed availability. Both caesarean section and instrumental vaginal delivery rates were associated with epidural rates, which was expected from the literature. Variations in epidural rates were mainly associated with variations in demographic case-mix, due possibly to patient demand. Demographic case-mix was also associated with instrumental vaginal deliveries but not the caesarean section rate.

Analgesia, Epidural↗