Poly-ε-caprolactone scaffold for the reinforcement of stapled small intestinal anastomoses: a randomized experimental study.

BACKGROUND: Anastomotic leakage is a severe complication in gastrointestinal surgery. Different methods have been evaluated for anastomotic reinforcement to prevent anastomotic leakage. The aim of this study was to investigate the effect of a poly-ε-caprolactone (PCL) scaffold incorporated in the staple-line, on the anastomotic strength and histological wound healing, of small intestinal anastomoses in piglets. METHOD: This randomized experimental trial included 17 piglets. In each piglet, three end-to-end anastomoses were performed in the small intestine with a circular stapler, i.e. one control and two interventional anastomoses. On postoperative day 5, the anastomoses were resected and subjected to tension stretch test and histological examination. RESULTS: No anastomotic leakage occurred. In the interventional anastomoses, the mean value for maximal tensile strength was 15.7 N, which was significantly higher than control anastomoses 12.7 N (p = 0.01). No statistically significant differences were found between the two groups in the histopathological parameters. CONCLUSION: To conclude, this study has shown that the incorporation of a PCL scaffold in the staple-line was feasible and significantly increased the maximal tensile strength of small intestine anastomoses in piglets on postoperative day 5. The difference in histological parameters was not significantly distinct.

Increased progesterone receptor A expression in labouring human myometrium is associated with decreased promoter occupancy by the histone demethylase JARID1A.

Progesterone regulates female reproductive function predominantly through two nuclear progesterone receptors (PRs), PR-A and PR-B. During human parturition myometrial PR expression is altered to favour PR-A, which activates pro-labour genes. We have previously identified histone H3 lysine 4 trimethylation (H3K4me3) as an activator of myometrial PR-A expression at labour. To further elucidate the mechanisms regulating PR isoform expression in the human uterus at labour, we have (i) determined the methylation profile of the cytosine-guanine dinucleotides (CpG) island in the promoter region of the PR gene and (ii) identified the histone-modifying enzymes that target the H3K4me3 mark at the PR promoters in term and preterm human myometrial tissues obtained before and after labour onset. Bisulphite sequencing showed that despite overall low levels of PR CpG island methylation, there was a significant decrease in methylated CpGs with labour in both preterm (P < 0.05) and term (P < 0.01) groups downstream of the PR-B transcription start site. This methylation change was not associated with altered PR-B expression, but may contribute to the increase in PR-A expression with labour. Chromatin immunoprecipitation revealed that the histone methyltransferase, SET and MYND domain-containing protein 3 (SMYD3), bound to the PR gene at significantly higher levels at the PR-A promoter compared with the PR-B promoter (P < 0.010), with no labour-associated changes observed. The H3K4 demethylase, Jumonji AT-rich interactive domain 1A (JARID1A), also bound to the PR-A, but not to the PR-B promoter prior to term labour, and decreased significantly at the onset of labour (P = 0.014), providing a mechanism for the previously reported increase in H3K4me3 level and PR-A expression with labour. Our studies suggest that epigenetic changes mediated by JARID1A, SMYD3 and DNA methylation may be responsible, at least in part, for the functional progesterone withdrawal that precipitates human labour.

Term myometrium is characterized by increased activating epigenetic modifications at the progesterone receptor-A promoter.

Term human myometrial expression of progesterone receptor (PR)-A is increased relative to PR-B, and as PR-A is a repressor of progesterone action mediated through PR-B, this increase may mediate the withdrawal of progesterone action and precipitate the onset of labour. PR-A and PR-B expression is regulated by two separate promoters of the PR gene. We hypothesized that epigenetic histone modifications at the two promoters contribute to the labour-associated regulation of PR-A and PR-B expression in term myometrium. PR total, PR-B and PR-A mRNA levels were determined using quantitative real-time PCR, and chromatin immunoprecipitation was used to determine the levels of activating and repressive histone modifications at the PR-A and PR-B promoters in human myometrial samples not in labour (n = 4) and in labour (n = 4). Chromatin extracts were immunoprecipitated with antibodies against activating (histone H3 and H4 acetylation and histone H3 lysine 4 trimethylation), and repressive (histone H3 lysine 9 trimethylation, histone H3 lysine 27 trimethylation and asymmetrical histone H3 arginine 2 dimethylation) histone modifications. PR-A mRNA levels increased during labour, while PR-B mRNA levels remained constant resulting in an increase of PR-A/PR-B mRNA ratio, as expected. Regardless of labour status, significantly higher levels of the activating histone modifications were found at the PR-A promoter compared with the PR-B promoter (P <0.001). H3K4me3 increased significantly at both promoters with labour onset (P =0.001). Low levels of the repressive histone modifications were also present at both promoters, with no labour-associated changes observed. Our data indicate that the PR-A promoter is epigenetically marked for activation in term myometrium more extensively than the PR-B promoter, and that labour is associated with an increase in H3K4me3 activating modification, consistent with the previously described increase in PR protein at this time.

Electronic structure calculations with GPAW: a real-space implementation of the projector augmented-wave method.

Electronic structure calculations have become an indispensable tool in many areas of materials science and quantum chemistry. Even though the Kohn-Sham formulation of the density-functional theory (DFT) simplifies the many-body problem significantly, one is still confronted with several numerical challenges. In this article we present the projector augmented-wave (PAW) method as implemented in the GPAW program package (https://wiki.fysik.dtu.dk/gpaw) using a uniform real-space grid representation of the electronic wavefunctions. Compared to more traditional plane wave or localized basis set approaches, real-space grids offer several advantages, most notably good computational scalability and systematic convergence properties. However, as a unique feature GPAW also facilitates a localized atomic-orbital basis set in addition to the grid. The efficient atomic basis set is complementary to the more accurate grid, and the possibility to seamlessly switch between the two representations provides great flexibility. While DFT allows one to study ground state properties, time-dependent density-functional theory (TDDFT) provides access to the excited states. We have implemented the two common formulations of TDDFT, namely the linear-response and the time propagation schemes. Electron transport calculations under finite-bias conditions can be performed with GPAW using non-equilibrium Green functions and the localized basis set. In addition to the basic features of the real-space PAW method, we also describe the implementation of selected exchange-correlation functionals, parallelization schemes, ΔSCF-method, x-ray absorption spectra, and maximally localized Wannier orbitals.

The Randomized Nitric Oxide Tocolysis Trial (RNOTT) for the treatment of preterm labor.

OBJECTIVE: This study was undertaken to assess the effectiveness of glyceryl trinitrate (GTN) patches in comparison with beta2 sympathomimetics (beta2) for the treatment of preterm labor. STUDY DESIGN: A multicenter, multinational, randomized controlled trial was conducted in tertiary referral teaching hospitals. Women in threatened preterm labor with positive fetal fibronectin or ruptured membranes between 24 and 35 weeks' gestation were recruited and randomly assigned to either beta2 or GTN with rescue beta2 tocolysis if moderate-to-strong contractions persisted at 2 hours. Obstetric and neonatal outcomes were assessed. RESULTS: Two hundred thirty-eight women were recruited and randomly assigned, 117 to beta2 and 121 to GTN. On a strict intention-to-treat basis, there was no significant difference in the time to delivery using Kaplan-Meier curves (P = .451). At 2 hours, 27% of women receiving beta2 had moderate or stronger contractions compared with 53% in the GTN group (P < .001). This led to 35% of women in the GTN group receiving rescue treatment. If delivery or requirement for beta2 rescue are regarded as treatment failure, then a significant difference was observed between the 2 arms (P = .0032). There were no significant differences in neonatal outcomes. CONCLUSION: GTN is a less efficacious tocolytic compared with ss2 sympathomimetics.

Rate of rise in maternal plasma corticotrophin-releasing hormone and its relation to gestational length.

OBJECTIVE: To assess the relationship between rate of increase in maternal plasma corticotrophin-releasing hormone and gestational length. DESIGN: A prospective observational study. SETTING: Department of Obstetrics and Gynaecology, Prince of Wales Hospital, Hong Kong. METHODS: Serial venous samples taken at four to six week intervals from 81 pregnant Chinese subjects were assayed for corticotrophin-releasing hormone concentrations. The investigators responsible for the laboratory assay were blinded to the obstetric outcome. RESULTS: A total of 380 blood samples were taken. Each subject provided three to seven samples (median = 5). Seven of the 81 subjects had preterm delivery. Maternal corticotrophin-releasing hormone levels increased exponentially as gestation advanced. A negative correlation between the rate of rise of logarithmic equivalence of corticotrophin-releasing hormone concentrations (Ln-corticotrophin releasing hormone) per week and the gestational age at delivery was demonstrated (r = -0.45, P < 0.001). The rate of increase of Ln-corticotrophin releasing hormone concentrations per week was also significantly greater for those who delivered preterm before 37 weeks compared with those with uncomplicated term deliveries (0.27 Vs 0.22, P = 0.018). CONCLUSIONS: The rate of increase in maternal plasma corticotrophin-releasing hormone is inversely proportional to gestational length. Results in a Chinese population confirm and extend results from previous caucasian populations. This study provides another piece of evidence on the close link between maternal plasma corticotrophin-releasing hormone and the timing of human parturition. As the hormone is synthesized by the placenta, it supports the suggestion that the human placenta has an important role in determining gestational length.

Characterization of urocortin in human pregnancy.

OBJECTIVE: To examine whether urocortin is produced locally to regulate utero-placental vascular tone during pregnancy. METHODS: We examined the distribution of urocortin in human placenta, fetal membranes and uterine tissue at term in the presence and absence of labor using a urocortin antibody produced in our laboratory and the immunoperoxidase staining method. Subsequently, we tested urocortin secretion from chorio-decidual cells in vitro using an immunoblot technique. Then, we tested whether urocortin is present in maternal plasma throughout gestation using a radioimmunoassay. A Sephadex G-50 column was used to examine whether immunoreactive urocortin (IR-urocortin) in maternal plasma is the same as synthetic urocortin. RESULTS: IR-urocortin was observed in vascular smooth muscle of myometrium decidual stromal cells, syncytiotrophoblast and amnion epithelium. No differences in staining intensity for urocortin were detected between tissues obtained in the absence or presence of labor. Staining intensity for IR-urocortin was greatest in the decidua, suggesting this may be the main site of urocortin production. Positive staining for urocortin was observed in 40% of chorio-decidual cells with 34% of these cells secreting urocortin under basal conditions. Urocortin was detectable in maternal plasma from 16 weeks gestation and concentrations did not change as gestation progressed. IR-urocortin in the maternal plasma eluted from a Sephadex G-50 column at the same site as synthetic urocortin and had a calculated retention co-efficient of 0.44. CONCLUSION: This study indicates that urocortin is produced by the decidua during human pregnancy and is detectable in maternal plasma. These data are consistent with the hypothesis that urocortin is produced locally by the decidua and may act to regulate utero-placental blood flow.

Localization and characterization of urocortin during human pregnancy.

Urocortin, a recently identified peptide of the corticotropin releasing hormone (CRH) peptide family, has potent vasodilatory effects in the human fetal placental circulation in vitro, promoting us to hypothesize that urocortin is produced locally to regulate uteroplacental vascular tone during pregnancy. In the present study, we examined the distribution of urocortin in the human placenta, fetal membranes and uterine tissue at term in the presence and absence of labour, using a urocortin antibody produced in our laboratory and the immunoperoxidase staining method. Immunoreactive (IR)-urocortin was observed in the vascular smooth muscle of the myometrium (n=5), decidual stromal cells, syncytiotrophoblast and amnion epithelium (n=10). No differences in staining intensity for urocortin were detected between tissues obtained in the absence (n=5) or presence (n=5) of labour. Staining intensity for IR-urocortin was greatest in the decidua suggesting this may be a site of urocortin production during pregnancy. Subsequently, we tested urocortin secretion from chorio-decidual cells in vitro, using an immunoblot technique. Positive staining for urocortin was observed in 40 per cent of chorio-decidual cells with 34 per cent of these cells secreting urocortin under basal conditions. Since urocortin was secreted by decidual cells we questioned whether urocortin was present in maternal plasma throughout gestation, using radioimmunoassay. Urocortin was detectable in maternal plasma from 7 weeks of gestation and concentrations did not change as gestation progressed. IR-urocortin in the maternal plasma eluted from a Sephadex G-50 column at the same site as synthetic urocortin and had a calculated retention coefficient (Kd) of 0.44. In summary, this study indicates that urocortin is produced by the decidua during human pregnancy and is detectable in maternal plasma. These data are consistent with the hypothesis that urocortin is produced locally by the decidua and may act to regulate uteroplacental blood flow.

Analysis of mid-trimester corticotrophin-releasing hormone and alpha-fetoprotein concentrations for predicting pre-eclampsia.

The aims of this study were firstly to examine if corticotrophin-releasing hormone (CRH) concentrations in maternal plasma were significantly elevated in Chinese pregnancies complicated by pre-eclampsia, secondly to assess if this elevation could be detected in the mid-trimester before onset of clinical signs of the disease, and thirdly to evaluate the performance of using maternal CRH and/or alpha-fetoprotein (AFP) concentrations in the mid-trimester for prediction of pre-eclampsia. The first part of this study was tested in a cohort of 39 subjects. The CRH concentrations were significantly elevated in pregnant women complicated by pre-eclampsia. The second and third parts of the study involved a different cohort of 1021 subjects. Both CRH and AFP concentrations in the mid-trimester were significantly elevated in those who subsequently developed pre-eclampsia. However, when used for prediction of pre-eclampsia, neither the CRH nor AFP concentrations alone in the mid-trimester had strong predictive value. Although the combination of both tests improved the detection rate compared to the use of CRH alone, the small increase in the likelihood ratio from 1.9 to 2.6 did not suggest that the combination would be of great clinical value.

Development of pectin matrix tablets for colonic delivery of model drug ropivacaine.

The objective of this work was to develop pectin-based matrix tablets for colonic delivery of the model drug ropivacaine, with the future perspective of radiolabelling the system by neutron activation technique for a gamma-scintigraphic study. The aim was to investigate some formulation factors that could reduce the release of the drug in the simulated gastric and intestinal fluids, increase the release in the simulated cecal fluid (with pectinolytic enzymes) and improve the poor compactibility of pectins. For dissolution studies, the flow-through apparatus with sequential dissolution liquids simulating the mouth-to-colon conditions was used. The effect of two pectin types, the incorporation of ethylcellulose as a dry matrix-additive and water or ethanol as granulation liquids were investigated in a study designed as a D-optimal mixture. Amidated pectin (Am.P) produced harder tablets than the calcium salt of pectin (Ca.P) and was more susceptible to enzymatic degradation. Addition of ethylcellulose increased the tablet strength and the dissolution rate. Furthermore, directly compressed Am.P tablets were produced by addition of coarse or micronised qualities of ethylcellulose. The latter improved the crushing strength markedly imposing a marginal release-reducing effect. Coating this formulation with Eudragit((R)) L 100 reduced the release in the simulated upper GI conditions without interference with the subsequent enzymatic activity.

The effect of fetal fibronectin testing on admissions to a tertiary maternal-fetal medicine unit and cost savings.

OBJECTIVE: Fetal fibronectin bedside testing has been proposed as a diagnostic tool for the accurate diagnosis of preterm labor. The study objective was to determine whether the introduction of routine fetal fibronectin bedside testing affected costs and transfer rates from referral district hospitals to a tertiary obstetric hospital, as well as direct admissions to a tertiary referral hospital. STUDY DESIGN: We performed an 18-month prospective audit of fetal fibronectin use in 9 referral hospitals and one university maternal-fetal medicine unit. Data collected were delivery details and cervical dilatation at admission. Cost savings in terms of transport costs for patients with a negative fetal fibronectin result who were not transferred or admitted to the tertiary center were calculated for interhospital transfer (road ambulance or fixed-wing retrieval). RESULTS: One hundred fifty-one patients had a presumptive diagnosis of threatened preterm labor. Forty-five patients had a positive fetal fibronectin result and 106 had a negative fetal fibronectin result (3 with cervical dilatation >/=3 cm). Eleven (24%) patients with a positive fetal fibronectin result were delivered within 7 days, and 5 (5%) with a negative fetal fibronectin result were delivered within 7 days. One patient was delivered at 34 weeks, and the remaining patients were delivered at or after 36 weeks' gestation. All 3 patients with negative fetal fibronectin results with cervical dilatation of >/=3 cm were delivered within 5 days, leaving 2 (1.9%) patients (with closed cervices and negative fetal fibronectin results) being delivered 5 days after the fetal fibronectin testing. Ninety percent of the patients admitted to a referral hospital with threatened preterm labor who had a negative fetal fibronectin result were not transferred; thus an unnecessary transfer was avoided, with cost savings ranging from $30,297 for road and fixed-wing transport. CONCLUSION: A negative fetal fibronectin result is not helpful if cervical dilatation is present, and these patients should be treated as having a high risk of preterm delivery. The use of a fetal fibronectin test was associated with a 90% reduction in maternal transfer and can substantially reduce the costs and inconvenience associated with unnecessary transfer.

Elevated mid-trimester maternal corticotrophin-releasing hormone levels in pregnancies that delivered before 34 weeks.

OBJECTIVE: To test whether maternal corticotrophin-releasing hormone levels are elevated in the mid- trimester for those women who subsequently had spontaneous preterm delivery and to assess the clinical utility of the measurement in the prediction of preterm delivery. DESIGN: A prospective observational study. SETTING: Department of Obstetrics and Gynaecology, Prince of Wales Hospital, Hong Kong. POPULATION: 1047 low risk pregnant women recruited at 15-20 weeks of gestation. METHODS: Venous samples were assayed for levels of corticotrophin-releasing hormone. The investigators responsible for the laboratory assay were blinded to the obstetric outcome. MAIN OUTCOME MEASURES: Incidence of preterm, term and post-term pregnancies. RESULTS: Those who were delivered spontaneously at a preterm gestational age (before 34 weeks) had significantly higher corticotrophin-releasing hormone levels in the mid-trimester, compared with those who were delivered at term or post-term. There was a trend towards lower corticotrophin-releasing hormone levels with more advanced gestational age at delivery. When the measurement of corticotrophin- releasing hormone was used to predict delivery before 34 weeks, the best cut off was 1.9 MoM, which produced a sensitivity of 72.7% and specificity of 78.4%. This translated to a positive predictive value of 3.6%, negative predictive value of 99.6% and relative risk of 9.4 when the background prevalence of spontaneous preterm delivery before 34 weeks was 1.1%. The likelihood ratio was 3.4. CONCLUSIONS: Mid-trimester maternal corticotrophin-releasing hormone levels are elevated in pregnancies destined to deliver preterm before 34 weeks. When used alone in a low risk population, the measurement has a low predictive power for preterm delivery. However, the likelihood ratio of 3 4 implies that in high risk populations the test may be considerably more valuable.

Corticotropin-releasing hormone in chimpanzee and gorilla pregnancies.

In humans, the length of gestation and the onset of parturition have been linked to the exponential production of placental CRH and a late gestational decline in maternal plasma CRH-binding protein (CRH-BP). CRH has been shown to have direct effects on the myometrium and on the fetal adrenal, where it stimulates production of the estrogen precursor dihydroepiandrosterone sulfate. In vitro placental CRH production is stimulated by cortisol and inhibited by progesterone. To determine whether this mechanism might operate in other apes, we sampled eight chimpanzees and two gorillas through their pregnancies for CRH, CRH-BP, cortisol, estradiol, progesterone, and alpha-fetoprotein. We show that both chimpanzee and gorilla maternal plasma CRH concentrations rise exponentially as observed in the human. The gorillas exhibited a human-like antepartum fall in CRH-BP, whereas CRH-BP in the chimpanzee remained stable. Pregnancy-associated changes in cortisol, estradiol, progesterone, and alpha-fetoprotein were qualitatively similar to those observed in humans. Maternal plasma cortisol correlated with plasma CRH in both gorillas (r = 0.60; P < 0.05) and chimpanzees (r = 0.36; P < 0.02). Further, there was a strong correlation between plasma estradiol and the log of plasma CRH in the gorilla (r = 0.93; P < 0.0001) and in the chimpanzee (r = 0.72; P < 0.001), which is consistent with the hypothesis that placental CRH determines the placental production of estradiol by stimulating the production of fetal adrenal dehydroepiandrosterone sulfate. Plasma CRH and progesterone were positively correlated providing no in vivo support for progesterone inhibition of CRH release.

Women uranium workers: a case study of perceived hazardous exposures and health effects.

An exploratory study of seventy-four women uranium workers employed in the western United States (miners, millers, truck haulers, and office workers) was conducted. These uranium industry workers were employed primarily during the 1970s and 1980s. It was found that approximately 60 percent perceived overall moderate to high levels of dust during their employment, and about 50 percent reported the likelihood of having past, present, or future health problems related to their uranium work. Two of the most-often-identified health problems were respiratory symptoms or illnesses and cancer. Issues regarding public policy, research, and worker rights are discussed.

On the electronic nature of low-barrier hydrogen bonds in enzymatic reactions.

The electronic nature of low-barrier hydrogen bonds (LBHBs) in enzymatic reactions is discussed based on combined low temperature neutron and x-ray diffraction experiments and on high level ab initio calculations by using the model substrate benzoylacetone. This molecule has a LBHB, as the intramolecular hydrogen bond is described by a double-well potential with a small barrier for hydrogen transfer. From an "atoms in molecules" analysis of the electron density, it is found that the hydrogen atom is stabilized by covalent bonds to both oxygens. Large atomic partial charges on the hydrogen-bonded atoms are found experimentally and theoretically. Therefore, the hydrogen bond gains stabilization from both covalency and from the normal electrostatic interactions found for long, weak hydrogen bonds. Based on comparisons with other systems having short-strong hydrogen bonds or LBHBs, it is proposed that all short-strong and LBHB systems possess similar electronic features of the hydrogen-bonded region, namely polar covalent bonds between the hydrogen atom and both heteroatoms in question.

A corticotropin-releasing hormone type I receptor antagonist delays parturition in sheep.

In sheep, corticotropin-releasing hormone (CRH) can stimulate the fetal release of ACTH to produce a cortisol surge which leads to the onset of parturition. We tested the hypothesis that fetal CRH is a primary factor in the onset of parturition in sheep by using a Type I CRH receptor antagonist, antalarmin, to block the endogenous action of CRH. Pregnant ewes were cannulated at 130-135 days of gestation. Five catheters were placed into the amniotic sac, fetal femoral artery, fetal tarsal vein, maternal jugular vein and carotid artery. After 5 days' recovery, blood samples from maternal and fetal vessels were collected at the following times: a day before the start of infusion, at [-1, 0, 1, 2, 4, 8 and 24]h, on the first day of infusion, and thereafter daily throughout a 10-day infusion. Animals (n=6 per group) received infusions into a fetal vein of either a vehicle comprising 1:1 mixture of ethanol and polyethoxylated castor oil (Cremophor EL) or antalarmin (50 g/L) in the vehicle at a rate of 0.3 mL/h. The plasma samples were assayed for ACTH and cortisol using commercial RIA kits. Fetuses infused with vehicle delivered at a mean gestational age of 141.8 +/- 0.9 days compared with antalarmin-infused sheep at 148.8 +/- 1.6 days (P = 0.0036, unpaired Student's t-test). Fetal ACTH and cortisol did not change in the antalarmin-infused sheep after 3 days' infusion compared to significant increases in vehicle-infused sheep (P=0.004 and P = 0.016 respectively, ANOVA). These data show that CRH receptor antagonism in the fetus can delay the onset of parturition. It supports the hypothesis that hypothalamic CRH drives fetal production of ACTH and is essential for the onset of parturition triggered by a surge in fetal cortisol.

Corticotropin-releasing hormone: a biochemical predictor of preterm delivery in a pilot randomized trial of the treatment of preterm labor.

OBJECTIVE: We assessed the ability of maternal plasma corticotropin-releasing hormone measurements to predict preterm delivery in the setting of a pilot study comparing transdermal glyceryl trinitrate with standard beta-mimetic therapy for preterm labor and to determine the effect of these tocolytics on maternal plasma corticotropin-releasing hormone concentrations. STUDY DESIGN: Twenty-six consecutive patients with preterm labor were randomized to tocolytic treatment with transdermal glyceryl trinitrate (n=13) or intravenous albuterol (n=13). RESULTS: Plasma corticotropin-releasing hormone immunoreactivity levels were higher in women who were delivered within 7 days (41.4+/-13.5 pmol/L) than in those continuing to term (14.2+/-2.4 pmol/L, p=0.011) and were not altered by treatment. Two women in each of the treatment groups delivered within 7 days of the initiation of treatment, two women in the glyceryl trinitrate group were changed to albuterol because of persistence of contractions. Glyceryl trinitrate treatment was associated with significantly fewer maternal side effects. Neither treatment altered umbilical artery Doppler ultrasonographic findings. CONCLUSION: Transdermal glyceryl trinitrate is better tolerated than intravenous albuterol but may be no more efficacious than albuterol for the treatment of preterm labor. Biologic markers such as plasma corticotropin-releasing hormone levels may be an important method of identifying women at high risk of preterm delivery.

Decreased tumor necrosis factor-alpha and interleukin-1alpha production from intrahepatic mononuclear cells in chronic ethanol consumption and upregulation by endotoxin.

The relationship between the changes in liver pathology and the production of interleukin (IL)-1alpha, IL-6, and tumor necrosis factor-alpha (TNF-alpha) by intrahepatic mononuclear cells was studied in rats fed alcohol and subsequently exposed to lipopolysaccharide (LPS). Rats were fed 40% ethanol in drinking water, whereas control rats were provided with a chow diet with isocaloric or 2% sucrose drinking solutions for up to 20 weeks. Decreased IL-1alpha and TNF-alpha production in 24-hr culture supernatants of mononuclear cells isolated from liver perfusate was detected while IL-6 remained unchanged over 20 weeks. When animals were injected with LPS (1.0 microg/kg body weight), there was a 5-fold rise in ALT levels in the ethanol-fed group, but not in control groups. Increased IL-6 and TNF-alpha levels in the serum and supernatant of cultured intrahepatic mononuclear cells stimulated with or without LPS or concanavalin A was observed. There was a correlation between levels of ALT and TNF-alpha, but not IL-6. T cells and Kupffer cells were the major source of TNF-alpha in culture supernatants of hepatic perfusate mononuclear cells from ethanol-consuming rats injected LPS. In addition, pathological liver injury was evident, which suggests a pathogenic role for TNF-alpha in alcohol-induced liver disease.

The carbohydrate-deficient transferrin test in hospital practice.

We report an experience in two hospital populations of the use of a commercially available kit for the detection of carbohydrate-deficient transferrin (CDT). Patients from a drug and alcohol unit and a gastroenterology clinic at two hospitals were selected for the study. Sera were used from blood samples collected for routine biochemical assays. All patients had a specific alcohol history taken by one clinician and CDT results were correlated with reported alcohol intake by the patient and where relevant by their relatives. Sensitivity and specificity of the CDT assay were calculated using an alcohol intake of 60 g/day as the cut-off point for detection of heavy drinking. The CDT assay had a specificity of 95%; a sensitivity of 80% and a 90% positive and 89% negative predictive value. The severity and type of liver disease had little influence on the CDT result and a high alcohol intake was the only predictor of a raised CDT concentration. The assay provided information not available from routine investigations in some patients and also proved useful in monitoring patients over periods of up to 4 years. The test has a role in the evaluation of patients in a hospital practice where routine histories of alcohol intake may lack sensitivity and where other diseases may cause routine liver tests to be unreliable.

The role of emergency medical services in primary injury prevention. Consensus workshop. Arlington, Virginia, August 25-26, 1995.

Injury is a leading cause of death and disability. Preventing injuries from ever occurring is primary injury prevention (PIP). The objective of this statement is to present the consensus of a 16-member panel of leaders from the out-of-hospital emergency medical services (EMS) community on essential and desirable EMS PIP activities. Essential PIP activities for leaders and decision makers of every EMS system include: protecting individual EMS providers from injury; providing education to EMS providers in PIP fundamentals; supporting and promoting the collection and utilization of injury data; obtaining support for PIP activities; networking with other injury prevention organizations; empowering individual EMS providers to conduct PIP activities; interacting with the media to promote injury prevention; and participating in community injury prevention interventions. Essential PIP knowledge areas for EMS providers include: PIP principles; personal injury prevention and role modeling; safe emergency vehicle operation; injury risk identification; documentation of injury data; and one-on-one safety education.