Biomedical subjects

Peter Thomas

Publications and source records attributed to Peter Thomas.

At least 19 recordsLinked to original sources

PubMed2007

Membrane progesterone receptor gamma: tissue distribution and expression in ciliated cells in the fallopian tube.

Non-genomic, rapid actions of steroids have long been known, suggesting the possible presence of non-classical steroid receptors. A membrane receptor for progestins (mPR) was recently described in the spotted seatrout, and transcripts of three related receptors (alpha, beta, and gamma) were subsequently identified in other species including human and mouse. To begin exploring the roles of mPRgamma in mammals, we have generated an antibody against this receptor. The specificity of the antibody was demonstrated by both overexpression and RNA interference experiments. Using the antibody, we show that mPRgamma is expressed in female mouse reproductive tissues such as ovary and fallopian tube, and also in the lung and liver of both sexes. Immunohistochemical studies revealed that mPRgamma is associated with the apical membrane of ciliated cells facing the lumen of the fallopian tube. The presence of mPRgamma in ciliated cells of the fallopian tube was also demonstrated in human samples. Rapid effects of progesterone on ciliary beat frequency in the fallopian tube have recently been reported. Together, this suggests a common role for mPRgamma in the regulation of ciliary activity in the fallopian tube and thus gamete transport in mammals. The presence of mPRgamma in lung and liver of mice suggests that the receptor mediates the actions of progesterone outside the reproductive tract as well.

Animals↗

PubMed2006

The role of Xenopus membrane progesterone receptor beta in mediating the effect of progesterone on oocyte maturation.

Rapid, nongenomic membranal effects of progesterone were demonstrated in amphibian oocytes more than 30 y ago. Recently, a distinct family of membrane progestin receptors (mPRs) has been cloned in fish and other vertebrate species. In this study we explore the role of mPR in promoting oocyte maturation in Xenopus laevis. RT-PCR analysis indicates that Xenopus oocytes contain transcripts for the mPRbeta ortholog, similar to what has been reported in zebrafish oocytes, and Western blotting shows that the protein is expressed on the oocyte plasma membrane. Microinjection of mPRbeta-specific antibodies into oocytes resulted in a dramatic inhibition of progesterone-dependent oocyte maturation, whereas microinjection of mRNA encoding Myc-Xenopus mPR (XmPR)beta resulted in an accelerated rate of progesterone-induced oocyte maturation, concomitant with membranal localization of the protein. Binding studies in mammalian cells expressing XmPRbeta confirmed specific binding of progesterone by the expressed protein. These results suggest that XmPRbeta is a physiological progesterone receptor involved in initiating the resumption of meiosis during maturation of Xenopus oocytes.

Animals↗

PubMed2006

Identification of membrane progestin receptors in human breast cancer cell lines and biopsies and their potential involvement in breast cancer.

Novel membrane progestin receptors (mPRs) coupled to G proteins recently identified in several species, including humans, are potential intermediaries in rapid, nongenomic progestin actions observed in a wide variety of tissues. Here we demonstrate mPR mRNA and protein expression and specific membrane-associated progestin binding in MCF-7 and SK-BR-3 human breast cancer cells. Interestingly, human mPRalpha mRNA expression was higher in breast tumor biopsies than in normal tissue from the same breast. Recent studies indicate intracellular signaling pathways initiated by the mPRs are broadly similar to those induced during breast cancer growth and development. Taken together these results suggest a potential involvement of mPRs during the development or progression of breast cancer.

Biopsy↗

PubMed2006

Is continuous infusion ceftriaxone better than once-a-day dosing in intensive care? A randomized controlled pilot study.

OBJECTIVES: To compare the clinical and bacteriological outcome of critically ill patients with sepsis treated by ceftriaxone administered as a once-a-day intermittent bolus dose or by 24 h continuous infusion. PATIENTS AND METHODS: We conducted an open-label, randomized controlled pilot study in 57 patients clinically diagnosed with sepsis (suspected/proven infection and systemic inflammatory response syndrome) in a tertiary level intensive care unit. Patients were randomized to receive 2 g of ceftriaxone administered by once-daily intermittent bolus dosing or by 24 h continuous infusion. Clinical and bacteriological outcomes were assessed by blinded clinicians. RESULTS: Fifty-seven patients were enrolled in the study, 50 of whom fulfilled the a priori definition of treatment for 4 or more days. The infusion (n = 29) and bolus groups (n = 28) were similar in terms of demographics, although the median age of those receiving the infusion was younger. Intention-to-treat analysis found no statistically significant differences in the primary outcomes for clinical response (P = 0.17), clinical cure [infusion n = 13/29 versus bolus n = 5/28; adjusted odds ratio (AOR) = 3.74; 95% confidence interval (95% CI) = 1.11-12.57; P = 0.06], bacteriological response (P = 0.41) and bacteriological cure (infusion n = 18/29 versus bolus 14/28; AOR = 1.64; 95% CI = 0.57-4.70; P = 0.52). However, logistic regression in patients that complied with the a priori definitions who received ceftriaxone by continuous infusion (AOR = 22.8; 95% CI = 2.24-232.3; P = 0.008) or patients with a low Acute Physiology and Chronic Health Evaluation (APACHE) II score (AOR = 0.70; 95% CI = 0.54-0.91; P = 0.008) were associated with an improved clinical outcome when age and Sepsis Organ Failure Assessment (SOFA) score at time of study entry were controlled for. CONCLUSIONS: This pilot study suggests clinical and bacteriological advantages of continuous infusion of ceftriaxone over bolus administration in critically ill patients in patients requiring 4 or more days of treatment. This sets the scene for a large multicentre double-blind randomized controlled trial to confirm these findings.

APACHE↗

PubMed2006

Binding and activation of the seven-transmembrane estrogen receptor GPR30 by environmental estrogens: a potential novel mechanism of endocrine disruption.

A wide variety of environmental contaminants have been shown to exert estrogenic actions in wildlife and laboratory animals through binding to nuclear estrogen receptors (ERs) and subsequent transcription of estrogen responsive genes. We show here that several of these environmental estrogens also bind to the novel seven-transmembrane estrogen receptor, GPR30, to activate alternative estrogen signaling pathways in an ER-negative cell line (HEK293) stably transfected with the receptor. Genestein was the most effective competitor for the receptor (IC(50) 133 nM), with a relative binding affinity (RBA) 13% that of estradiol-17beta (E2). Bisphenol A, zearalonone, and nonylphenol also had relatively high binding affinities for GPR30 with RBAs of 2-3%. Kepone, p,p'-DDT, 2,2',5',-PCB-4-OH and o,p'-DDE had lower affinities with RBAs of 0.25-1.3%, whereas o,p'-DDT, p,p'-DDE, methoxychlor and atrazine caused less than 50% displacement of [(3)H]-E2 at concentrations up to 10 microM. Overall, the binding affinities of these compounds for GPR30 are broadly similar to their affinities to the ERs. Environmental estrogens with relatively high binding affinities for GPR30 (genestein, bisphenol A, nonylphenol and Kepone) also displayed estrogen agonist activities in an in vitro assay of membrane-bound adenylyl cyclase activity, a GPR30-dependent signaling pathway activated by estrogens. The results indicate that nontraditional estrogen actions mediated through GPR30 are potentially susceptible to disruption by a variety of environmental estrogens.

Adenylyl Cyclases↗

PubMed2006

Steroid and G protein binding characteristics of the seatrout and human progestin membrane receptor alpha subtypes and their evolutionary origins.

A novel progestin receptor (mPR) with seven-transmembrane domains was recently discovered in spotted seatrout and homologous genes were identified in other vertebrates. We show that cDNAs for the mPR alpha subtypes from spotted seatrout (st-mPRalpha) and humans (hu-mPRalpha) encode progestin receptors that display many functional characteristics of G protein-coupled receptors. Flow cytometry and immunocytochemical staining of whole MDA-MB-231 cells stably transfected with the mPRalphas using antibodies directed against their N-terminal regions show the receptors are localized on the plasma membrane and suggest the N-terminal domain is extracellular. Both recombinant st-mPRalpha and hu-mPRalpha display high affinity (Kd 4.2-7.8 nm), limited capacity (Bmax 0.03-0.32 nm), and displaceable membrane binding specific for progestins. Progestins activate a pertussis toxin-sensitive inhibitory G protein (G(i)) to down-regulate membrane-bound adenylyl cyclase activity in both st-mPRalpha- and hu-mPRalpha-transfected cells. Coimmunoprecipitation experiments demonstrate the receptors are directly coupled to the G(i) protein. Similar to G protein-coupled receptors, dissociation of the receptor/G protein complex results in a decrease in ligand binding to the mPRalphas and mutation of the C-terminal, and third intracellular loop of st-mPRalpha causes loss of ligand-dependent G protein activation. Phylogenetic analysis indicates the mPRs are members of a progesterone and adipoQ receptor (PAQR) subfamily that is only present in chordates, whereas other PAQRs also occur in invertebrates and plants. Progesterone and adipoQ receptors are related to the hemolysin3 family and have origins in the Eubacteria. Thus, mPRs arose from Eubacteria independently from members of the GPCR superfamily, which arose from Archeabacteria, suggesting convergent evolution of seven-transmembrane hormone receptors coupled to G proteins.

Animals↗

PubMed2006

Thyroid hormone status of Atlantic croaker exposed to Aroclor 1254 and selected PCB congeners.

Atlantic croaker (Micropogonias undulatus) were exposed to the polychlorinated biphenyl (PCB) mixture (Aroclor 1254) or one of three individual congeners (planar PCB 77 or ortho-substituted PCB 47 and PCB 153) in the diet for 30 days to investigate the effects of PCBs on circulating thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Aroclor 1254 (0.2 and 1.0 mg/kg body mass/day) decreased plasma T3 levels consistently, but the effects on T4 levels were inconsistent from year to year. Exposure to PCB 153 (0.1 and 1.0 mg/kg body mass/day) significantly lowered both T4 and T3, while PCB 47 at the same doses had no effect on thyroid hormone levels. The lower doses of PCB 77 (0.004, 0.01 and 0.02 mg/kg body mass/day) had no effect on T4 or T3, whereas the highest dose (0.1 mg/kg body mass/day) increased T4 levels significantly. The results of the present study demonstrate that exposure to PCBs at environmentally realistic concentrations can have profound effects on the thyroid status of Atlantic croaker. The ortho-substituted PCB 153 appears to contribute at least partially to the deleterious effects of Aroclor 1254 on thyroid status, whereas the planar PCB 77 at concentrations present in the mixture is unlikely to alter thyroid hormone levels.

Animals↗

PubMed2006

PCB congener-specific disruption of reproductive neuroendocrine function in Atlantic croaker.

Exposure of Atlantic croaker to Aroclor 1254 has been shown to impair reproductive neuroendocrine function in this species. In addition, we have identified hypothalamic tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin synthesis, as a target of PCB neuroendocrine toxicity. A previous study in rats has implicated di-ortho-substituted non-coplanar PCB congeners in the inhibition of a similar enzyme, tyrosine hydroxylase, which is the rate-limiting enzyme in dopamine synthesis. Therefore, the present study was designed to investigate whether di-ortho-substituted congeners (PCB 47, PCB 153) or a coplanar congener (PCB 77) present in Aroclor 1254 could be responsible for the reproductive impairment observed in croaker exposed to the PCB mixture. Fish were exposed to PCB 47 and PCB 153 in the diet (0, 0.2 and 1.0 mg/kg body weight/day) for 30 days and to PCB 77 (0.01 and 0.1 mg/kg body weight/day) for 15 days. Neither PCB 47 nor PCB 153 altered hypothalamic TPH activity or gonadal growth at doses similar to the effective doses of the Aroclor 1254 mixture. Therefore, these ortho-substituted PCB congeners known to be neurotoxic in mammalian systems are unlikely to contribute to Aroclor 1254-induced reproductive neuroendocrine disruption in croaker. In contrast, PCB 77 significantly inhibited hypothalamic TPH activity and gonadal growth at doses much lower than the effective doses of Aroclor 1254. The results provide the first evidence for PCB congener-specific disruption of reproductive neuroendocrine function in a vertebrate species.

Animals↗

PubMed2006

Reproductive endocrine dysfunction in Atlantic croaker exposed to hypoxia.

Although there is extensive evidence for impaired endocrine function in fishes exposed to environmental chemicals, information is currently lacking on reproductive endocrine effects of other environmental stressors such as hypoxia. The effects of ten weeks exposure to low dissolved oxygen (DO: 2.7 ppm and 1.7 ppm) on reproductive morphometric and endocrine responses in female Atlantic croaker (Micropogonias undulatus) were investigated in controlled laboratory studies, and compared to the effects observed in fish collected from hypoxic sites in Mobile Bay, Alabama. Exposure of croaker to moderate hypoxia during ovarian recrudescence, both in the laboratory and at the field sites, caused significant impairment of ovarian growth as well as decreased production of fully grown oocytes, resulting in dramatic reductions in the number of viable gametes (fecundity). Ovarian dysfunction was associated with significant decreases in endocrine indicators of the estrogen signaling pathway regulating production of vitellogenin, the yolk protein precursor sequestered by the growing oocytes. The results indicate that reproductive morphometric and endocrine biomarkers in croaker are sensitive to moderate hypoxia, and are potentially useful as early warning indicators of reproductive failure.

Animals↗

PubMed2006

Cross-sensitization between poppy seed and buckwheat in a food-allergic patient with poppy seed anaphylaxis.

The opium poppy, Papaver somniferum L., is the source of both poppy seeds and opium. The commercially available seeds are widely used as ingredients for various kinds of food. IgE-mediated sensitization to poppy seeds is rare, but, if present, clinical symptoms are usually severe. Cross-sensitizations between poppy seeds and other food allergens have been described with sesame, hazelnut, rye grain and kiwi fruit. We report the case of a 17-year-old female with an apparently food-allergic reaction after ingestion of a poppy seed cake. Allergological workup revealed a poppy seed anaphylaxis and led to the identification of a novel cross-sensitization with buckwheat.

Adolescent↗

PubMed2006

Gonadotropin regulation of testosterone production by primary cultured theca and granulosa cells of Atlantic croaker: II. Involvement of a mitogen-activated protein kinase pathway.

Previous investigations in Atlantic croaker ovaries and primary co-cultured theca and granulosa cells have identified multiple signal transduction pathways involved in the control of gonadotropin-induced steroidogenesis, including adenylyl cyclase- and calcium-dependent signaling pathways. In the present study, evidence was obtained for an involvement of a third signal transduction pathway, a mitogen-activated protein kinase (MAP kinase) signaling cascade, in the regulation of gonadal steroidogenesis in this lower vertebrate teleost model. Gonadotropin-stimulated testosterone synthesis was markedly attenuated by two antagonists of mitogen-activated protein kinase kinases 1/2 (MEK1/2, also known as Map2k1/Map2k2). Moreover, treatment with gonadotropin-induced MEK1/2-dependent phosphorylation of extracellular signal-regulated protein kinases 1/2 (ERK1/2, also known as Mapk3/Mapk1) in a concentration- and time-dependent manner in co-cultured croaker theca and granulosa cells. Active MEK1/2 was required for a complete steroidogenic response to activators of the adenylyl cyclase pathway, including forskolin and dbcAMP, suggesting that the target(s) of MAP kinase signaling are distal to cAMP generation and activation of cAMP-dependent protein kinase (PKA). Interestingly, dbcAMP caused a similar increase of ERK1/2 phosphorylation as was observed with gonadotropin treatment, although an inhibitor of PKA did not attenuate this response. Finally, there was no evidence of cross-talk between calcium-dependent signaling pathways and this MAP kinase cascade. While drugs that block calcium-dependent signal transduction, including inhibitors of voltage-sensitive calcium channels, calmodulin, and calcium/calmodulin-dependent kinases, significantly reduced gonadotropin-induced testosterone accumulation, these drugs had no apparent effect on hCG-induced ERK1/2 phosphorylation.

Adenylyl Cyclases↗

PubMed2006

Gonadotropin regulation of testosterone production by primary cultured theca and granulosa cells of Atlantic croaker: I. Novel role of CaMKs and interactions between calcium- and adenylyl cyclase-dependent pathways.

Theca and granulosa cells for in vitro primary culture were obtained by enzymatic digestion of mature ovarian tissue from Atlantic croaker (Micropogonias undulatus) and separation from the other cell types by Percoll density-gradient centrifugation. Histochemical staining and treatment with pregnenolone confirmed the presence in the cultured cells of enzymes involved in synthesizing the major sex steroids in croaker ovaries: testosterone, estradiol, and 17alpha,20beta,21-trihydroxy-4-pregnen-3-one (20beta-S). Croaker theca and granulosa cells maintained their steroidogenic response to gonadotropin when cultured with serum-supplemented media and produced high levels of testosterone for up to 5 days, although estradiol production was low. Multiple signal transduction pathways mediating gonadotropin stimulation of androgen production were identified in Atlantic croaker ovarian theca and granulosa cells in primary co-culture. Inhibitors of voltage-sensitive calcium channels (VSCCs) and calmodulin decreased the steroidogenic response to gonadotropin, whereas activators of adenylyl cyclase and protein kinase A (PKA) increased testosterone production, indicating that both calcium and PKA-dependent signaling pathways are involved in the regulation of follicular steroid production. In addition, the first evidence in vertebrates for an involvement of calcium/calmodulin-dependent protein kinases (CaMKs) in gonadal steroidogenesis was obtained, since the stimulatory effects of gonadotropin on testosterone media accumulation were attenuated by specific inhibitors of CaMKs. Some interactions among the signaling pathways were observed as demonstrated by the positive effect of elevated intracellular calcium on adenylyl cyclase activity and the reduction of forskolin- and dbcAMP-induced testosterone production by inhibitors of VSCCs, calmodulin, and CaMKs.

3-Hydroxysteroid Dehydrogenases↗

PubMed2006

Progesterone signaling in human myometrium through two novel membrane G protein-coupled receptors: potential role in functional progesterone withdrawal at term.

Progestin withdrawal is a crucial event for the onset of labor in many mammalian species. However, in humans the mechanism of a functional progestin withdrawal is unclear, because progestin concentrations do not drop in maternal plasma preceding labor. We report the presence of two novel functional membrane progestin receptors (mPRs), mPRalpha and mPRbeta, in human myometrium that are differentially modulated during labor and by steroids in vitro. The mPRs are coupled to inhibitory G proteins, resulting in a decline in cAMP levels and increased phosphorylation of myosin light chain, both of which facilitate myometrial contraction. Activation of mPRs leads to transactivation of PR-B, the first evidence for cross-talk between membrane and nuclear PRs. Progesterone activation of the mPRs leads also to a decrease of the steroid receptor coactivator 2. Our data indicate the presence of a novel signaling pathway mediated by mPRs that may result in a functional progestin withdrawal, shifting the balance from a quiescent state to one of contraction.

Acetyltransferases↗

PubMed2006

Psychological responses to the sniper attacks: Washington DC area, October 2002.

BACKGROUND: This study assessed the psychological and behavioral responses of residents of the Washington DC metropolitan area to the October 2002 sniper shootings, as well as the association between measures of exposure to the shootings and elevated traumatic stress symptoms. METHODS: Random-digit-dial telephone survey of 1205 adults living in Washington DC and two surrounding counties during the shootings, conducted May 2003. Main outcome measures included self-reports regarding traumatic stress symptoms, perceptions of safety, behavioral responses, and exposures to incidents. RESULTS: Forty-five percent of residents reported going to public spaces such as parks and shopping centers less than usual, and 5.5% reported missing at least 1 day of work because of the sniper attacks. Women who reported living within 5 miles of any shooting incident were significantly more likely to report elevated traumatic stress symptoms-consistent with a probable diagnosis of post-traumatic stress disorder-than women who reported living farther from incidents (odds ratio = 4.2, 95% confidence interval = 1.9-9.3). Among men, there was no significant association between reported residential proximity and elevated traumatic stress symptoms. CONCLUSIONS: These results suggest the substantial behavioral and psychological impact that traumatic events such as these sniper shootings can have on communities. They support the importance of clinicians and community leaders addressing psychological functioning in the setting of such events that threaten a population. The results further suggest that women who report residing closest to such incidents are at greatest risk for experiencing elevated symptoms of traumatic stress, and perhaps warrant special attention.

Absenteeism↗

PubMed2006

Sub-Tenon's anesthesia with aspirin, warfarin, and clopidogrel.

PURPOSE: To review the frequency of hemorrhagic complications with sub-Tenon's anesthesia in patients on aspirin, warfarin or clopidogrel. SETTING: St. James's University Hospital, Leeds, United Kingdom. METHODS: Data were collected prospectively for patients having elective phacoemulsification under sub-Tenon's anesthesia. Seventy-five patients were on aspirin, 65 were on warfarin, and 40 were on clopidogrel. Seventy-five patients on no anticoagulants were used as the control group. No changes in the anticoagulant regimen were made prior to surgery. RESULTS: No sight-threatening hemorrhagic complications were noted, and no surgery was postponed or cancelled due to an anesthesic complication. Subconjunctival hemorrhage occurred in 19% in the control group, 40% in the clopidogrel group, 35% in the warfarin group, and 21% in the aspirin group. The warfarin and clopidogrel groups had the highest incidence of subconjunctival hemorrhage (P<.05). The incidence of hemorrhages involving more than 1 quadrant was highest in these 3 groups; however, this did not achieve statistical significance (P = .37, Fisher exact test). CONCLUSION: Data from this study support the continued use of anticoagulant agents among routine users during cataract surgery using a sub-Tenon's block.

Adult↗

PubMed2006

A prospective, randomized trial of rifampicin-minocycline-coated and silver-platinum-carbon-impregnated central venous catheters.

OBJECTIVE: Central venous catheters are the predominant cause of nosocomial bacteremia; however, the effectiveness of different antimicrobial central venous catheters remains uncertain. We compared the infection rate of silver-platinum-carbon (SPC)-impregnated catheters with rifampicin-minocycline (RM)-coated catheters. DESIGN: A large, single-center, prospective randomized study. SETTING: Twenty-two-bed adult general intensive care unit in a large tertiary metropolitan hospital in Brisbane, Australia (2000-2001). PATIENTS: Consecutive series of all central venous catheterizations in intensive care unit patients. INTERVENTIONS: Randomization, concealment, and blinding were carefully performed. Catheter insertion and care were performed according to published guidelines. Blood cultures were taken at central venous catheter removal, and catheter-tip cultures were performed by both roll-plate and sonication techniques. Pulsed field gel electrophoresis was used to establish shared clonal origin for matched isolates. MEASUREMENTS AND MAIN RESULTS: Central venous catheter colonization and catheter-related bloodstream infection were determined with a blinded technique using the evaluation of the extensive microbiological and clinical data collected and a rigorous classification system. Six hundred forty-six central venous catheters (RM 319, SPC 327) were inserted, and 574 (89%) were microbiologically evaluable. Colonization rates were lower for the RM catheters than SPC catheters (25 of 280, 8.9%; 43 of 294, 14.6%; p=.039). A Kaplan-Meier analysis that included catheter time in situ did not quite achieve statistical significance (p=.055). Catheter-related bloodstream infection was infrequent for both catheter-types (RM 4, 1.4%; SPC 5, 1.7%). CONCLUSIONS: The SPC catheter is a clinically effective antimicrobial catheter; however, the RM catheter had a lower colonization rate. Both catheter types had low rates of catheter-related bloodstream infection. These results indicate that future studies will require similar rigorous methodology and thousands of central venous catheters to demonstrate differences in catheter-related bloodstream infection rates.

Anti-Infective Agents, Local↗

PubMed2006

Risk factors for hospital admission related to excessive and/or prolonged postpartum vaginal blood loss after the first 24 h following childbirth.

A population case-control study was used to determine risk factors for excessive and/or prolonged vaginal bleeding (described collectively as vaginal loss problems) and uterine infection from 24 h to 3 months postpartum. Data were obtained from women whose maternity care took place in one of two health districts in the south of England. The cases were women remaining in or admitted to hospital with excessive or prolonged vaginal blood loss from 24 h to 3 months postpartum. Two controls for each case were identified; these were women whose delivery was the nearest in time and in the same location as the case delivery. Medical and midwifery records were searched retrospectively to cover hospital admissions for vaginal blood loss problems or uterine infection in postpartum women from 1 January 1994 to 31 December 1995. Data were analysed for 243 cases and 486 controls. Univariable analysis identified 28 variables associated with being a case. Using multivariable analysis, nine factors remained in the final model, with a history of secondary postpartum haemorrhage (PPH) being the most strongly predictive (OR [95% confidence interval] 6.0 [2.1, 16.8]). Vaginal bleeding prior to 24 weeks' gestation (OR 3.0 [1.6, 5.9]), third trimester hospital admission (OR 2.0 [1.4, 2.8]), maternal smoking (OR 2.7 [1.8, 3.9]), a prolonged (OR 3.1 [1.2, 7.5]) or incomplete third stage (OR 2.1 [1.0, 4.4]), and primary PPH (OR 4.7 [1.9, 11.6]) for blood loss >500 mL, were predictive of becoming a case. No significant association was identified for parity (OR 1.1 [0.8, 1.5]) or method of delivery, spontaneous (OR 1.0 [0.7, 1.3]), instrumental (OR 1.4 [0.9, 2.2]) or operative (OR 1.2 [0.8, 1.9]). This is a neglected area of women's health after childbirth, and the value of this study is in the identification of potential risk factors for postpartum morbidity related to vaginal blood loss. Where morbidity occurs, early diagnosis, management and treatment are likely to reduce its extent or duration. It is considered that raising awareness about these factors, both among healthcare professionals and women themselves, may play an important part in the recognition and treatment of postpartum morbidity.

Adolescent↗

PubMed2006

Low mannose-binding lectin function is associated with sepsis in adult patients.

Mannose-binding lectin (MBL) is an innate immune system pattern recognition molecule that kills a wide range of pathogens via the lectin complement pathway. MBL deficiency is associated with severe infection but the best measure of this deficiency is undecided. We investigated the influence of MBL functional deficiency on the development of sepsis in 195 adult patients, 166 of whom had bloodstream infection and 35 had pneumonia. Results were compared with 236 blood donor controls. MBL function (C4b deposition) and levels were measured by enzyme-linked immunosorbent assay. Using receiver-operator characteristics of MBL function in healthy controls, we identified a level of <0.2 U microL(-1) as a highly discriminative marker of low MBL2 genotypes. Median MBL function was lower in sepsis patients (0.18 U microL(-1)) than in controls (0.48 U microL(-1), P<0.001). MBL functional deficiency was more common in sepsis patients than controls (P<0.001). MBL functional deficient patients had significantly higher sequential organ failure assessment (SOFA) scores and higher MBL function and levels were found in patients with SOFA scores predictive of good outcome. Deficiency of MBL function appears to be associated with bloodstream infection and the development of septic shock. High MBL levels may be protective against severe sepsis.

Adolescent↗