Biomedical subjects

D J Taylor

Publications and source records attributed to D J Taylor.

At least 55 records · Page 3Linked to original sources

PubMed2000

Endometrial protection from tamoxifen-stimulated changes by a levonorgestrel-releasing intrauterine system: a randomised controlled trial.

INTRODUCTION: Tamoxifen is currently the most commonly used adjuvant treatment for breast cancer, however, it frequently causes episodes of unscheduled uterine bleeding, which could be associated with proliferative changes of the endometrium, or even endometrial cancer. We aimed to assess whether a levonorgestrel intrauterine system could modulate the uterine responses to tamoxifen. We also aimed to assess women's tolerance of the screening procedures, the insertion, removal, and potential side-effects of the device. METHODS: We did a randomised controlled trial, in which postmenopausal women who had had at least 1 year of adjuvant tamoxifen treatment and who were undergoing regular follow-up for breast cancer were randomly assigned to either endometrial surveillance alone, or endometrial surveillance before and after insertion of the levonorgestrel intrauterine system for 12 months. We assessed tolerance of the surveillance procedures and the device with visual analogue scales. FINDINGS: Baseline assessment showed only benign uterine changes in all women (n=122). Hysteroscopic assessment indicated a uniform decidual response (confirmed histologically in 40 of 41 cases) in all women fitted with the intrauterine system; there were no new polyps in these women and 13% had fewer fibroids than in controls. Both screening procedures and device were well tolerated. There was an excess of bleeding in the women fitted with intrauterine systems but this resolved to a baseline similar to those receiving surveillance only. INTERPRETATION: The levonorgestrel-releasing intrauterine system had a protective action against the uterine effects of tamoxifen. The effectiveness of this device in preventing uterine changes in the endometrium needs to be assessed in the context of decreasing the need for repeated investigations of postmenopausal bleeding in women taking tamoxifen.

Aged↗

PubMed2000

Antimicrobial-resistance trends in bacterial isolates from companion-animal community practice in the UK.

We conducted a longitudinal, retrospective investigation of antimicrobial resistance in bacterial isolates obtained from canine and feline clinical cases in veterinary community practice in UK (1989-1997). Individual-drug resistance was examined using isolates of Escherichia coli and Staphylococcus spp. as Gram-negative and Gram-positive indicator organisms, respectively. The annual prevalence of resistance was calculated for each organism to each of nine (for E. coli) and 11 (for Staphylococcus spp.) selected antimicrobials. The annual prevalence of multiple-drug resistance (MDR) was calculated for E. coli, Proteus spp., Pseudomonas spp., staphylococci and streptococci. Using a chi-square test for trend, significant rising trends were identified in individual resistance of E. coli to clavulanate-amoxycillin and streptomycin, and in MDR of E. coli, Proteus spp. and Pseudomonas spp. Declining trends were identified in individual resistance of Staphylococcus spp. to ampicillin and penicillin. Comparison with previously reported results from a contemporaneous investigation of companion-animal hospital patients indicated that selection pressures acting on the two populations overlapped but were not identical.

Animals↗

PubMed2000

Sympathetic denervation of the upper limb improves forearm exercise performance and skeletal muscle bioenergetics.

BACKGROUND: Sympathetic activation may limit exercise performance by restraining muscle blood flow or by negatively affecting skeletal muscle metabolic behavior. To test this hypothesis, we studied the effect of thoracoscopic sympathetic trunkotomy (TST) on forearm exercise duration, blood flow, and muscle bioenergetics in 13 patients with idiopathic palmar hyperhidrosis. METHODS AND RESULTS: Heart rate and beat-by-beat mean arterial pressure were recorded at rest and during right and left rhythmic handgrip before and 4 to 7 weeks after right TST. Forearm blood flow was measured bilaterally at rest and on the right during exercise. Right forearm muscle phosphocreatine content and intracellular pH were assessed by (31)phosphorus magnetic resonance spectroscopy. After right TST, exercise duration increased from 8.9+/-1.4 to 13.4+/-1.8 minutes (P<0.0001) with the right forearm and from 5.7+/-0.4 to 7.6+/-0.9 minutes (P<0.05) with the left (P<0.05 for the interaction between treatment and side). Right forearm blood flow at rest was 66% higher (P<0.01) after right TST, but this difference decreased as the exercise progressed. After right TST, a significant reduction occurred in muscle acidification and phosphocreatine depletion during ipsilateral forearm exercise. This was associated with a significantly reduced mean arterial pressure response to right handgrip, whereas the pressor response to left handgrip did not change. CONCLUSIONS: Sympathetic denervation of the upper limb significantly improves forearm skeletal muscle bioenergetics and exercise performance in patients with idiopathic palmar hyperhidrosis.

Adult↗

PubMed2000

The influence of endogenous dopamine levels on the density of [3H]SCH23390-binding sites in the brain of the honey bee, Apis mellifera L.

This paper examines the relationship between endogenous dopamine (DA) levels and the density of [3H]SCH23390-binding sites in the brain of the adult worker honey bee. DA levels were reduced pharmacologically using a single 10 microl injection of either alpha-methyl-DL-p-tyrosine (AMT; 250 microg or 500 microg) or alpha-methyl-DL-tryptophan (AMTP; 250 or 500 microg) into the haemolymph of the bee. In all cases, maximum depletion of DA was observed 3 h after treatment, but in bees treated with AMTP (250 or 500 microg) or with 250 microg AMT, DA levels returned to normal within 24 h of treatment. Neither AMT nor AMTP was selective for DA: both drugs also reduced serotonin (5-hydroxytryptamine, 5HT) levels in the brain. However, AMTP was more effective than AMT at depleting 5HT, whereas for DA, the reverse was true. Depletion of DA levels, using 250 microg AMT, led to a dramatic decline in the levels of specific binding of [3H]SCH23390, defined in this study as binding in the presence of 5x10(-6) M cis-(Z)-flupentixol (see Ref. [28] ). In contrast, naturally occurring diel fluctuations in DA levels, identified in the optic lobes of the brain, and changes in brain DA levels resulting from queenlessness, had no significant effect on the density of [3H]SCH23390-binding sites in the brain of the bee. Overall, these results indicate that under normal physiological conditions, there is no direct link in honey bees between changes in endogenous brain DA levels and the density of D(1)-like receptors labelled by [3H]SCH23390.

Animals↗

PubMed2000

Trends of antimicrobial resistance in bacterial isolates from a small animal referral hospital.

A longitudinal, retrospective investigation was made of antimicrobial resistance in bacterial isolates obtained from clinical cases in a small animal hospital between 1989 and 1997. Isolates of Escherichia coli and Staphylococcus species were used as Gram-negative and Gram-positive indicator organisms, respectively, and the annual prevalence of antimicrobial resistance was calculated for each organism to each of nine (for E coli) and 11 (for Staphylococcus species) appropriate antimicrobials, including enrofloxacin. Using a chi-square test for trend, statistically significant, rising trends were identified in the resistance of E coli to amoxycillin (P=0.04), clavulanate-amoxycillin (P<0.01) and streptomycin (P<0.01), and in the resistance of Staphylococcus species to erythromycin (P<0.01). There was an equivocal, rising trend for the resistance of Staphylococcus species to cephalexin. No significant trends were apparent for any of the other 15 organism/drug interactions. The annual prevalence of multiple drug resistance was calculated for E coli, Proteus species, Pseudomonas species, staphylococci and streptococci, but no statistically significant trends were identified.

Animals↗

PubMed2000

Evolution of parental care and ovulation behavior in oysters.

Approximately half of all living oysters brood offspring in the inhalant chamber of their mantle cavities; the remainder are broadcast spawners which do not engage in parental care of young. Ostreid ovulation involves a complex behavioral sequence that results in the countercurrent passage of newly spawned eggs through the gills (ctenidia) and into the inhalant chamber. We constructed molecular and combined-evidence phylogenetic trees to test hypotheses concerning the directionality of parental care evolution, and the evolutionary significance of the trans-ctenidial ovulation pathway, in the Ostreidae. Representatives of all three ostreid subfamilies, together with gryphaeid and nonostreoidean pterioid outgroups, were sequenced for a 941-nucleotide fragment of the 28S ribosomal gene. Our phylogenetic analyses indicate that (1) the Ostreidae are robustly monophyletic, (2) broadcast spawning and larval planktotrophy are ancestral ostreid traits, (3) trans-ctenidial ovulation predates the evolution of parental care in ostreid lineages, and (4) brooding originated once in the common ancestor of the Ostreinae/Lophinae, involved a modification of the final behavioral step in the ancestral ovulation pathway, and has been retained in all descendent lineages. Our data permit an independent test of fossil-based ostreid phylogenetic hypotheses and provide novel insights into oyster evolution and systematics.

Animals↗

PubMed2000

The application of color power angiography to the longitudinal quantification of blood flow volume in the fetal middle cerebral arteries, ascending aorta, descending aorta, and renal arteries during gestation.

OBJECTIVE: This study was undertaken to determine by means of color power angiography the longitudinal changes in the diameters and the flow volumes of 4 major fetal arteries during gestation. STUDY DESIGN: The middle cerebral artery, the ascending aorta, the descending aorta, and the renal arteries in 81 appropriate-for-gestational-age fetuses were examined longitudinally between 24 and 38 weeks' gestation by means of color power angiography. In addition to measurement of the diameters of these arteries, Doppler velocimetry was performed. Flow volume was calculated from the cross-sectional areas of the arteries and the velocity integral of the Doppler waveforms. RESULTS: The mean (+/-SD) gestational age at delivery and birth weight were 39.8 +/- 1. 6 weeks and 3326 +/- 345 g, respectively. The diameters and flow volumes of all the arteries increased significantly as gestational age advanced. Flow volume increased from 39 +/- 19.0 mL/min to 140 +/- 63.9 mL/min in the middle cerebral artery, from 216.2 +/- 77.6 to 937.4 mL/min in the ascending aorta, from 124.4 +/- 76.6 to 390.0 mL/min in the descending aorta, and from 27.5 +/- 16.8 to 80.3 +/- 57.3 mL/min in the renal arteries. When blood flow volume was adjusted to milliliters per kilogram body weight, an initial significant fall in blood flow was seen in all the vessels to a minimal level at 30 weeks' gestation; blood flow rose thereafter, although not significantly, until term. The ratios of flow volume in the ascending aorta to those in the other vessels increased with gestation, with the highest ratio being that between the ascending aorta and the renal arteries. CONCLUSION: Identification of fetal arteries with color power angiography is easy and highly sensitive. The distributions of blood flow in various fetal arteries exhibited regional differences, with significantly more blood flow to the brain. These normative baseline values may be useful in the diagnosis of congenital cardiac anomalies and also in the diagnosis and monitoring of fetuses with intrauterine growth restriction.

Angiography↗

PubMed2000

Increased concentration of pro-matrix metalloproteinase 9 in term fetal membranes overlying the cervix before labor: implications for membrane remodeling and rupture.

OBJECTIVES: Regional structural alterations that develop before labor are important in the mechanisms of both physiologic and pathologic membrane rupture, because they are also detected in preterm prelabor rupture of the fetal membranes, the most common cause of preterm birth (as great as 60%). Matrix metalloproteinases are located in the fetal membranes and are the main mediators of extracellular matrix degradation. The objective of this study was to examine whether gelatinases (matrix metalloproteinases 2 and 9) could be involved in the development of these regional structural changes seen at term before labor. STUDY DESIGN: Fetal membranes from patients undergoing elective cesarean delivery were regionally sampled from over the cervix (cervical membranes) and midway between this area and the placental edge (midzone). Fetal membranes obtained after spontaneous labor and delivery at term were also regionally sampled. Matrix metalloproteinase 2 and 9 activities were assessed by gelatin zymography, whereas total matrix metalloproteinase 9 protein was determined by enzyme-linked immunosorbent assay. RESULTS: Zymography only detected activity corresponding to the pro-matrix metalloproteinase 2 (72 kd) and 9 (92 kd) forms in prelabor fetal membranes. Although the levels of pro-matrix metalloproteinase 2 showed no regional differences, the pro-matrix metalloproteinase 9 level was higher in the cervical area than in the midzone (2.5 +/- 0.98 vs 0.76 +/- 0.28 optical density units/20 microg protein; P <.01). The concentration of pro-matrix metalloproteinase 9 protein in the cervical area was also significantly higher than that in the midzone (6.69 +/- 4.8 vs 1.58 +/- 1.14 ng/mg protein; P <.01). After delivery both pro-matrix metalloproteinase 2 and 9 activities were elevated, whereas pro-matrix metalloproteinase 9 protein activity showed no regional difference between the rupture site and midzone (23.47 +/- 4.5 vs 25. 3 +/- 6.2 ng/mg protein). Active bands of matrix metalloproteinases 2 (66 kd) and 9 (83 kd) were also detected after delivery. CONCLUSION: This study suggests that a specific regional induction of pro-matrix metalloproteinase 9 occurs in the cervical area before labor and may play a role in "programming" this area for subsequent rupture after activation during labor.

Amnion↗

PubMed2000

How well do male latex condoms work? Pregnancy outcome during one menstrual cycle of use.

To evaluate the contraceptive effectiveness of male latex condoms, we assembled a cohort of 300 women relying on male latex condoms for contraception and followed them prospectively for one menstrual cycle. None of the 234 women who completed the study and reported at least one act of intercourse conceived (one cycle pregnancy rate 0%; 95% CI 0%--2%). Given the pattern of intercourse during the cycle and 3 different sets of conception probabilities for different days of the cycle, we would have expected between 32 and 36 pregnancies if no condoms had been used. Thus, the prevented fraction due to condom use (effectiveness) is 100% and the lower bounds of the 95% CI are between 89% and 90%. For this cohort, male latex condoms were an effective method of contraception. This cost-efficient approach of evaluating contraceptive effectiveness shows promise for post-marketing studies.

Adult↗

PubMed2000

The integration of digital camera derived images with a computer based diabetes register for use in retinal screening.

Exeter district provides a retinal screening service based on a mobile non-mydriatic camera operated by a dedicated retinal screener visiting general practices on a 2-yearly cycle. Digital attachments to eye cameras can now provide a cost effective alternative to the use of film in population based eye screening programmes. Whilst the manufacturers of digital cameras provide a database for the storage of pictures, the images do not as yet interface readily with the rest of the patient's computer held data or allow for a sophisticated grading, reporting and administration system. The system described is a development of the Exeter diabetes register (EXSYST) which can import digitally derived pictures from either Ris-Lite TM and Imagenet TM camera systems or scanned Polaroids Pictures can be reported by the screener, checked by a consultant ophthalmologist via the hospital network, and a report, consisting of colour pictures, map of relevant pathology and referral recommendations produced. This concise report can be hard copied inexpensively on a high resolution ink-jet printer to be returned to the patient's general practitioner. Eye images remain available within the hospital diabetes centre computer network to facilitate shared care. This integrated system would form an ideal platform for the addition of computer based pathology recognition and total paperless transmission when suitable links to GP surgeries become available.

Blindness↗

PubMed2000

Fetal heart rate in relation to its variation in normal and growth retarded fetuses.

OBJECTIVES: (1) to assess the relationship of basal fetal heart rate (FHR) with both long term (LTV) and short term (STV) FHR variation in low-risk pregnancies, longitudinally from 24 weeks gestation onwards and (2) to investigate the relationship of FHR with LTV and STV in intrauterine growth retarded (IUGR) fetuses. STUDY DESIGN: Computerised FHR recordings were made in twenty-nine uncomplicated pregnancies (n=224) and in twenty-seven IUGR fetuses who were selected retrospectively from three databases (n=135). Nomograms of FHR variation with FHR and GA were constructed using multilevel analysis. RESULTS AND CONCLUSIONS: There was a strong negative relationship of FHR with both LTV and STV in the control group (R2=53% and 52%, respectively). In the IUGR fetuses, FHR was generally higher than in normal fetuses whereas LTV and STV were lower. The relationship of FHR with LTV and STV in the IUGR group was less strong (for both: R2=18%). Correction of FHR variation for basal FHR in the IUGR fetuses only resulted in a slight reduction in the number of recordings with a variation below the normal range. As it does not improve the recognition of fetuses being considered at the highest risk, such a correction of FHR variation for basal FHR is therefore not necessary. Intrafetal consistency, known to be present in healthy fetuses, was also present in the IUGR fetuses with a low FHR variation.

Female↗

PubMed2000

Transglobal comparisons of nuclear and mitochondrial genetic structure in a marine polyploid clam (Lasaea, Lasaeidae).

Existing genetic studies have proposed that the intertidal clam, Lasaea, is one of a few animal groups with asexual lineages that has persisted for an evolutionarily significant time. This proposal is based on the exceptional mitochondrial genetic divergence between studied sexual and asexual lineages. Nevertheless, a conclusion of long-lived asexuality awaits a more comprehensive sampling of the collective global range of this taxon. We assessed the breeding system and phylogeography of geographically divergent Lasaea populations using nuclear and mtDNA genetic markers. The allozyme genetic structure of five populations (from Japan, New Zealand, South Africa, Florida and Bermuda) showed marked deviation from expected random mating patterns (within and among loci), frequent fixed heterozygosity, and reduced genotypic diversity. This pattern and the finding of multiple asymmetric allozymic heterozygotes, indicated a clonal structure consistent with allopolyploid origins for each population. Spatial analysis of mtDNA and allozyme markers revealed strong geographical structure and yielded no cosmopolitan clonal lineages. Australian sexual species formed sister taxa to a minority of the clonal lineages, but pronounced mitochondrial genetic divergence levels and developmental differences precluded their identification as convincing parental species to any of the clones. A majority of asexual lineages may have originated in areas where no sexual congeners are presently known. The observed nuclear and mtDNA genetic structure is consistent with Lasaea clonal diversity being enriched by local mutational derivatives but infrequent recombination cannot be ruled out.

Animals↗

PubMed2000

Myofibroblast differentiation in the connective tissues of the amnion and chorion of term human fetal membranes-implications for fetal membrane rupture and labour.

An area of the fetal membranes, within the rupture tear after spontaneous delivery at term, exhibits altered morphology compared to more distal sites. It is characterized by marked swelling of the amniotic and chorionic connective tissue layers, consistent with structural weakness, and a marked reduction of the thickness of both the cytotrophoblast and decidual layers. These features, albeit less extreme, have been identified in fetal membranes in the lower uterine pole in patients prior to labour. In this study of pre-labour, labour-affected and post-labour term fetal membranes, we report that these regions are associated with an alteration in the phenotype of the vimentin positive mesenchymal cell population of the chorionic connective tissue reticular layer, and are consistent with myofibroblastic differentiation, i.e. alpha-smooth muscle actin (alpha-sma) expression. In the reticular layer of the lower uterine pole biopsies in the labour-affected group the numbers and densities of alpha-sma immunoreactive positive cells were 17-fold (P=0.04) and 8.5-fold (P=0.02) higher than in mid-zone biopsies. After delivery, in rupture line biopsies the numbers and densities were 50-fold (P=0. 002) and 36-fold (P=0.003) higher compared to mid zone biopsies. The percentage of the vimentin positive population positive for alpha-sma was 2-5 per cent in mid-zone biopsies compared to 49 per cent (P=0.03) in the labour-affected 'cervical' biopsies and 69 per cent (P=0.05) in the rupture line biopsies. Within the tear sites, alpha-sma positive cells were also detected within the fibroblastic layer of the amniotic connective tissue. Although there was no significant difference between the numbers and density of alpha-sma cells in the reticular layers between mid and lower uterine pole biopsies in the pre-labour group, in a proportion of patients the biopsies were similar to labour-affected biopsies indicating that this alteration occurs prior to clinically apparent labour in these patients. The incidence of alpha-sma positive cells in the reticular layer correlated with morphological changes within the fetal membranes, for example thickness of reticular (r(2)=0.349, P=0.0006) and amniotic connective tissue layers (r(2)=0.389, P=0.0002). This suggests that cellular activities associated with myofibroblastic differentiation in the reticular layer of the chorion may be associated with the observed connective tissue changes, fetal membrane rupture and labour.

Actins↗

PubMed2000

Clinical utility of muscle MR spectroscopy.

31Phosphorus (31P) magnetic resonance spectroscopy (MRS) is well suited for gathering data on skeletal muscle energetics in vivo. The technique has evolved to the point where it has become an important tool in the study of the pathophysiology both of rare primary disorders of muscle such as the mitochondrial myopathies and of more common systemic diseases such as renal failure, which also influence muscle metabolism. 31P-MRS is used for providing information about the biochemical composition of tissue without invasive sampling, and it has the unique ability to measure intracellular pH. In some conditions it can be used as an aid to diagnosis. Because MRS is well tolerated and examinations are easily repeated, the technique can also be employed in longitudinal studies of disease progression or the effects of treatment. Magnetic resonance spectroscopy is being increasingly used in conjunction with other noninvasive technologies to investigate effects of gene function on metabolism.

Energy Metabolism↗

PubMed2000

A new method for simultaneous immunodetection and morphologic identification of individual sources of pollen allergens.

BACKGROUND: Exposure to outdoor allergens has commonly been estimated by collecting airborne particles with a Hirst-type spore trap and then using morphologic criteria to identify the intact pollen grains and fungal spores that are recognized as allergen sources. Several antibody-based blotting or fixation methods have also been developed that enable the counting of amorphous airborne particles carrying allergen, but none of these methods allow the ready association of the released allergen with the morphologically identifiable particle of origin. A method has been developed that uses pressure-sensitive adhesive tape to sample the airborne particles and then allows the immunoidentification of the specific particles that are the allergen sources. OBJECTIVE: Our purpose was to visualize and immunostain the particles carrying pollen allergen that are collected with a volumetric spore trap. METHODS: A Burkard sampler was used to collect airborne particles onto pressure-sensitive adhesive tapes. The particles were permanently fixed between the tape and a protein-binding membrane when the tape was laminated with the membrane. Allergens that elute from the particles onto the membrane were detected with a range of antibodies. Both the particle and associated immunostained allergen were viewed through the transparent tape for final microscopic identification. RESULTS: Polyclonal and monoclonal antibodies and IgE from allergic patients stained allergens in the periphery of particles collected on the tapes. Individual pollen grains and paucimicronic particles were seen with halos of immunostained allergen surrounding them. When IgE was used, the density of immunostaining in the halo surrounding Lolium perenne pollen grains was found to be proportional to the level of Lolium-specific IgE. The method is highly sensitive and can be used to detect different airborne particles that carry allergen. Both the particle and the immunostaining can be subjected to a range of simple measurement techniques. CONCLUSION: Individual particles carrying allergens and antigens were visualized. These particles included intact pollen grains, paucimicronic particles, and fungal spores.

Air Pollutants↗

PubMed2000

Birth weight and 24-hour ambulatory blood pressure in nonproteinuric hypertensive pregnancy.

OBJECTIVE: The aim of this study was to examine the relationship between maternal ambulatory blood pressure monitor measurements during pregnancy and birth weight in a population of women considered to have hypertension according to conventional antenatal clinic measurement. STUDY DESIGN: A prospective observational study was carried out within the obstetric departments of Leicester Royal Infirmary and Queen Charlotte's Hospital. A total of 237 women were found to have hypertension (blood pressure >/=140/90 mm Hg) without significant proteinuria during examination in the antenatal assessment area. Sequential-day unit blood pressure recordings and a 24-hour automated ambulatory blood pressure recording were performed, and the results were compared with the principal outcome measure of birth weight. RESULTS: A significant inverse association (gradient, -13.5; 95% confidence interval -23.4 to -3.6) was found between daytime ambulatory diastolic blood pressure measurement and birth weight. An increase of 5 mm Hg in daytime mean diastolic blood pressure was associated with a fall in birth weight of 68.5 g. This association remained after adjustment for potential confounders that included maternal age, maternal weight, smoking status, ethnicity, and gestational age at delivery. No such association was found between obstetric day unit assessment of blood pressure and birth weight. CONCLUSION: There is a significant association between blood pressure and birth weight in nonproteinuric hypertensive pregnancies. The best predictor of this association is the daytime mean ambulatory diastolic blood pressure measurement. This is further evidence that maternal blood pressure may be an important confounding and potentially genetic variable in the association between birth weight and subsequent adult hypertension.

Adult↗

PubMed2000

Practice observed: is speculum examination on admission a necessary procedure in the management of all cases of antepartum haemorrhage?

The objective of the study was to determine the justification or otherwise of admission speculum examination in women presenting with antepartum haemorrhage and the outcome/ benefits of the practice on women with antepartum haemorrhage presenting to the delivery suite of a UK teaching hospital. Factors studied included gestational age at presentation, associated factors with the bleeding, grade of medical/ midwifery staff performing the admission speculum examination, findings on speculum examination and ultrasound scan and the overall pregnancy outcome. Of the 564 (4.9%) women who presented with antepartum haemorrhage; 521 had an admission speculum examination; 94.4% of these were by senior house officers (SHOs). The findings were a normal cervix (69%) and ectopy (21.3%). Of the women, 14.4% had recurrent bleeding and 8.5% went into preterm labour. The complications of the pregnancies, timing of delivery and management were independent of speculum examination. Admission speculum examination did not influence the management of pregnancies and the complications thereafter. These results suggest that such an intrusive procedure may not be justifiable in women presenting with antepartum haemorrhage.

Journal Article↗

PubMed2000

Prostaglandin E(2)-dependent production of latent matrix metalloproteinase-9 in cultures of human fetal membranes.

Studies in our laboratory have shown that structural changes in cervical biopsied fetal membranes, prior to labour, coincide with differences in the expression of the gelatinase enzyme, latent matrix metalloproteinase-9 (MMP-9). Concurrently, in vivo, there is an increase in the expression of prostaglandins, notably prostaglandin E(2) (PGE(2)), which has been shown to regulate the expression of MMPs in other systems. The aim of this study was to test the hypothesis (using an in-vitro culture model) that endogenously produced PGE(2) has a role in the elevation of MMP-9 described in vivo. Non-infected fetal membranes sampled from women undergoing elective Caesarean section were stimulated with 10% (v/v) fetal bovine serum (FBS), a known inducer of prostaglandins. This activation resulted in a time-dependent increase in the secretion of PGE(2) into the media, as determined by enzyme-linked immunosorbent assay (day 1: 19 +/- 9 pg/ml/24 h to 358 +/- 54 pg/ml/24 h by day 4). A similar pattern of secretion of latent MMP-9 was observed in parallel with the increase in PGE(2) in the same culture media (day 1: 1.63 +/- 0.17 ng/ml/24 h to 4.2 +/- 1.4 ng/ml/24 h by day 4). When both molecules were compared, a significant (P: < 0.01) positive correlation (r = 0.623) was observed. Secretion of the tissue inhibitor of MMPs-9 (TIMP-1) was not significantly different between untreated (3.07 +/- 0.266 microg/ml/24 h) and FBS-treated (3. 85 +/- 0.24 microg/ml/24 h) cultures during the first 4 days in culture. Prostaglandin synthesis inhibition studies using indomethacin (100 micromol/l) resulted in a 70-80% reduction in the activated secretion of latent MMP-9. Direct PGE(2) stimulation of cultures resulted in the bell shaped dose-response curve with concentrations of 1-100 nmol/l (which are within the range secreted in culture in response to FBS), stimulating significant latent MMP-9 secretion. These results suggest a link between endogenous PGE(2) and latent MMP-9 production in human fetal membranes, raising the possibility that PGE(2) has a role in the mechanism of fetal membrane structural changes and, hence, in parturition-associated membrane rupture.

Cell Survival↗