The Role and Regulation of the 11 Beta-Hydroxysteroid Dehydrogenase Enzyme System in Patients with Inflammatory Bowel Disease.

INTRODUCTION: Glucocorticoids are known to modulate a number of immunological responses including counteracting inflammation. Within tissues expressing the glucocorticoid and mineralocorticoid receptors including the colon, glucocorticoid metabolism is regulated by the isoenzymes of 11ß-hydroxysteroid dehydrogenase (11ß-HSD). 11ß-HSD1 acts as an oxidoreductase converting inactive cortisone into active cortisol, while 11ß-HSD2 acts as a dehydrogenase converting active cortisol to inactive cortisone. Hexose-6 phosphate dehydrogenase (H6PDH) is a key regulator of 11ß-HSD1 activity via its generation of NADPH. Variations in the 11ß-HSD enzyme system in relation to levels of expression and regulation may have a role in IBD. The aim of this study was to investigate possible abnormalities of 11ß-HSD enzyme system in the colon of patients with IBD. METHODS: By using quantitative real-time PCR, we investigated the transcription levels of 11ß-HSD1 and 2 in colonic tissue from IBD patients and healthy controls undergoing a colonoscopy for disease assessment. Disease activity was recorded using clinical (Mayo Score/Harvey-Bradshaw Index), Biochemical (C-reactive protein), histological, and endoscopic parameters. In addition, transcription levels of H6PDH and the glucocorticoid receptor alpha (GR-α) as well as key pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, Rela (subunit for NF Kappa B)) were later examined among this group, and results were correlated with 11ß-HSD2 gene expression. Results and patient demographics were expressed as a mean (and SD), and differences between IBD patients and control groups were analyzed using a Student's t test or Mann-Whitney U test as appropriate, with a p value of ≤0.05 considered significant. Results were controlled for disease activity as outlined above. RESULTS: Results have demonstrated a significant downregulation in 11ß-HSD2 expression in IBD patients compared with controls (13.8 ± 17.1 au vs. 318.4 ± 521.1 au, p = 0.01), whereas levels of 11ß-HSD1 did not appear to vary across the two groups. Among IBD patients, there was a trend toward higher 11ß-HSD1 expression in inflamed tissue compared with matched non-inflamed tissue (422.1 ± 944 au vs. 102.2 ± 103.9, P = 0.09). Levels of H6PDH and the GR-α expression did not appear to vary among active inflamed IBD tissue and controls. As a result, we examined the association between pro-inflammatory cytokines and levels of 11ß-HSD2 expression. Results showed an upregulation of key pro-inflammatory cytokine mRNA expression (TNF-α, IL-1ß, IL-6) during inflammation with an associated downregulation of 11ß-HSD2 mRNA expression when compared to controls. Dysregulation in this pathway could have a potential role in IBD pathogenesis and may account for exogenous glucocorticoid resistance in IBD. Further work assessing the role of the 11ß-HSD enzyme system in steroid-resistant subjects is warranted.

Anti-TNFα antibody-induced psoriasiform skin lesions in patients with inflammatory bowel disease: an Irish Cohort Study.

AIM: To determine the prevalence of psoriasis in an IBD cohort with reference to clinical characteristics and anti-TNFα use. METHODS: Patients with psoriasis and IBD were retrospectively identified from the IBD database at Tallaght Hospital from 2000 to 2015. Pertinent clinical data were obtained from patients notes including anti-TNFα exposure. Prevalence rates of genuine and reactive psoriasis were calculated and compared using Student's T -test. A P values of <0.05 was considered significant. RESULTS: In total, 1384 IBD patients were identified. The overall prevalence rate of IBD and psoriasis was 2.4% ( n = 33), with 1.8% ( n = 25) in the Crohn's disease group and 0.6% ( n = 8) in the ulcerative colitis group. Within the psoriasis group, 24% ( n = 8 of 33) had reactive psoriasis. The prevalence rates of psoriasis in the non-biological and biological cohorts were similar 2.5% (25 of 981) and 2% (8 of 403), respectively. There was no significant association with reactive psoriasis and disease type. There was a trend towards higher rates of reactive psoriasis Adalimumab users, 3.6% (6 of 166) vs. 0.8% (2 of 237), OR = 4.283, P = 0.077, 95% CI 0.854-21.483 in infliximab users. In addition, in our cohort, smoking was not associated with any form of psoriasis in IBD, OR = 1.377, 95% CI 0.061-3.087, P = 0.437. CONCLUSION: In our large study, the prevalence rate of reactive psoriasis was similar to the background rate of psoriasis in the overall IBD cohort (2.0 vs. 2.4%). A 2% prevalence rate represents a common adverse event that clinicians should be aware of.

Reverse shoulder arthroplasty as a salvage procedure after failed internal fixation of fractures of the proximal humerus: outcomes and complications.

Failed internal fixation of a fracture of the proximal humerus produces many challenges with limited surgical options. The aim of this study was to evaluate the clinical outcomes after the use of a reverse shoulder arthroplasty under these circumstances. Between 2007 and 2012, 19 patients (15 women and four men, mean age 66 years; 52 to 82) with failed internal fixation after a proximal humeral fracture, underwent implant removal and reverse shoulder arthroplasty (RSA). The mean follow-up was 36 months (25 to 60). The mean American Shoulder and Elbow Score improved from 27.8 to 50.1 (p = 0.019). The mean Simple Shoulder Test score improved from 0.7 to 3.2 (p = 0.020), and the mean visual analogue scale for pain improved from 6.8 to 4.3 (p = 0.012). Mean forward flexion improved from 58.7° to 101.1° (p < 0.001), mean abduction from 58.7° to 89.1° (p = 0.012), mean external rotation from 10.7° to 23.1° (p = 0.043) and mean internal rotation from buttocks to L4 (p = 0.034). A major complication was recorded in five patients (26%) (one intra-operative fracture, loosening of the humeral component in two and two peri-prosthetic fractures). A total of 15 patients (79%) rated their outcome as excellent or good, one (5%) as satisfactory, and three (16%) as unsatisfactory. An improvement in outcomes and pain can be expected when performing a RSA as a salvage procedure after failed internal fixation of a fracture of the proximal humerus. Patients should be cautioned about the possibility for major complications following this technically demanding procedure.

Deletion of the adenosine A(2A) receptor in mice enhances spinal cord neurochemical responses to an inflammatory nociceptive stimulus.

Knockout mice lacking the adenosine A(2A) receptor are less sensitive to nociceptive stimuli, and this may be due to the presence of pronociceptive A(2A) receptors on sensory nerves. In support of this hypothesis, we have recently shown that in A(2A) receptor knockout mice there are marked reductions in the changes of two markers of spinal cord neuronal activity, [(3)H]MK801 binding to NMDA receptors and uptake of [(14)C]-2-deoxyglucose, in response to formalin injection. We now report that following a more prolonged inflammatory stimulus, consisting of intraplantar injections of PGE(2) and paw pressure, there was in contrast an increase in [(3)H]MK801 binding and [(14)C]-2-deoxyglucose uptake in the spinal cords of the A(2A) receptor knockout mice which was much greater than in the wild-type mice. This increase suggests that when there is a pronounced inflammatory component to the stimulus, loss of inhibitory A(2A) receptors on inflammatory cells outweighs the loss of pronociceptive A(2A) receptors on peripheral nerves so that overall there is an increase in nociceptive signalling. This implies that although A(2A) antagonists have antinociceptive effects they may have only limited use as analgesics in chronic inflammatory pain.

Influence of host reproductive state on Sphaerothecum destruens prevalence and infection level.

Sphaerothecum destruens is an obligate intracellular parasite with the potential to cause high mortalities and spawning inhibition in the endangered cyprinid Leucaspius delineatus. We investigated the influence of L. delineatus's reproductive state on the prevalence and infection level of S. destruens. A novel real time quantitative polymerarse chain reaction (qPCR) was developed to determine S. destruens' prevalence and infection level. These parameters were quantified and compared in reproductive and non-reproductive L. delineatus. The detection limit of the S. destruens specific qPCR was determined to be 1 pg of purified S. destruens genomic DNA. Following cohabitation in the lab, reproductive L. delineatus had a significantly higher S. destruens prevalence (P<0.05) and infection levels (P<0.01) compared to non-reproductive L. delineatus. S. destruens prevalence was 19% (n=40) in non-reproductive L. delineatus and 41% (n=32) in reproductive L. delineatus. However, there was no difference in S. destruens prevalence in reproductive and non-reproductive fish under field conditions. Mean infection levels were 18 and 99 pg S. destruens DNA per 250 ng L. delineatus DNA for non-reproductive and reproductive L. delineatus respectively. The present work indicates that S. destruens infection in L. delineatus can be influenced by the latter's reproductive state and provides further support for the potential adverse impact of S. destruens on the conservation of L. delineatus populations.

Genetic deletion of the adenosine A(2A) receptor in mice reduces the changes in spinal cord NMDA receptor binding and glucose uptake caused by a nociceptive stimulus.

Mice lacking the adenosine A(2A) receptor are less sensitive to nociceptive stimuli, and A(2A) receptor antagonists have antinociceptive effects. We have previously shown a marked reduction in the behavioural responses to formalin injection in A(2A) receptor knockout mice. This may be due to the presence of pronociceptive A(2A) receptors on sensory nerves, and if so spinal cords from A(2A) receptor knockout mice may have altered neurochemical responses to a nociceptive stimulus. We tested this hypothesis by studying two parameters known to change with spinal cord activity, NMDA glutamate receptor binding and [(14)C]-2-deoxyglucose uptake, following intraplantar formalin injection in wild-type and A(2A) receptor knockout mice. In naïve untreated A(2A) knockout mice [(14)C]-2-deoxyglucose uptake in all regions of the spinal cord was significantly lower compared to the wild-type, similar to the reduced NMDA receptor binding that we have previously observed. Following formalin treatment, there was an decrease in [(3)H]-MK801 binding to NMDA receptors and an increase in [(14)C]-2-deoxyglucose uptake in the spinal cords of wild-type mice, and these changes were significantly reduced in the A(2A) knockout mice. In addition to altered behavioural responses, there are therefore corresponding reductions in spinal cord neurochemical changes induced by formalin in mice lacking adenosine A(2A) receptors. These observations support the hypothesis that activation of A(2A) receptors enhances nociceptive input into the spinal cord and suggests a possible role for A(2A) antagonists as analgesics.

A comparison between acoustic output indices in 2D and 3D/4D ultrasound in obstetrics.

OBJECTIVE: Three-dimensional (3D) ultrasound is gaining popularity in prenatal diagnosis. While there are no studies regarding the safety of 3D ultrasound, it is now widely performed in non-medical facilities, for non-diagnostic purposes. The present study was aimed at comparing the acoustic output, as expressed by thermal index (TI) and mechanical index (MI), of conventional two-dimensional (2D) and 3D/4D ultrasound during pregnancy. METHODS: A prospective, observational study was conducted, using three different commercially available machines (iU22, Philips Medical Systems; Prosound Alfa-10, Aloka; and Voluson 730 Expert, General Electric). Patients undergoing additional 3D/4D ultrasound examinations were recruited from those scheduled for fetal anatomy and follow-up exams. Fetuses with anomalies were excluded from the analysis. Data were collected regarding duration of the exam, and each MI and TI during 2D and 3D/4D ultrasound exams. RESULTS: A total of 40 ultrasound examinations were evaluated. Mean gestational age was 31.1 +/- 5.8 weeks, and mean duration of the exam was 20.1 +/- 9.9 min. Mean TIs during the 3D (0.27 +/- 0.1) and 4D examinations (0.24 +/- 0.1) were comparable with the TI during B-mode scanning (0.28 +/- 0.1, P = 0.343). The MIs during the 3D volume acquisitions were significantly lower than those in the 2D B-mode ultrasound studies (0.89 +/- 0.2 vs. 1.12 +/- 0.1, P = 0.018). The 3D volume acquisitions added 2.0 +/- 1.8 min of actual ultrasound scanning time (i.e. not including data processing and manipulation, or 3D displays, which are all post-processing steps). The 4D added 2.2 +/- 1.2 min. CONCLUSIONS: Acoustic exposure levels during 3D/4D ultrasound examination, as expressed by TI, are comparable with those of 2D B-mode ultrasound. However, it is very difficult to evaluate the additional scanning time needed to choose an adequate scanning plane and to acquire a diagnostic 3D volume.

Construction of a comparative RFLP map of Echinochloa crus-galli toward QTL analysis of flooding tolerance.

To analyze quantitative trait loci (QTLs) affecting flooding tolerance and other physiological and morphological traits in Echinochloa crus-galli, a restriction fragment length polymorphism (RFLP) map was constructed using 55 plants of the F(2) population ( E. crus-galli var. praticola x E. crus-galli var. formosensis). One hundred forty-one loci formed 41 linkage groups. The total map size was 1,468 cM and the average size of linkage groups was 35.8 cM. The average distance between markers was 14.7 cM and the range was 0-37.2 cM. Early comparisons to the genetic maps of other taxa suggest appreciable synteny with buffelgrass ( Pennisetum spp.) and sorghum ( Sorghum spp.). One hundred ninty-one F(2) plants were used to analyze QTLs of flooding tolerance, plant morphology, heading date, number of leaves, and plant height. For flooding tolerance, two QTLs were detected and one was mapped on linkage group 24. Other traits, including plant morphology, heading date, number of leaves, and plant height were highly correlated. Three genomic regions accounted for most of the mapped QTLs, each explaining 2-4 of the significant marker-trait associations. The high observed correlation between the traits appears to result from QTLs with a large contribution to the phenotypic variance at the same or nearby locations.

Reversal of dormancy in switchgrass with low-light photoperiod extension.

Some switchgrass (Panicum virgatum L.) cultivars originating in the northern USA show limited late-summer and fall growth when grown in more southerly locations despite adequate temperature and moisture. Our objective was to determine the effects of low-light photoperiod extension on the dry matter yield of switchgrass cultivars originating from contrasting latitudes. Seedlings of the four cultivars (Cave-in-Rock, 'Caddo', 'Kanlow', and 'Alamo') were grown for 100 d in a greenhouse in winter under ambient (11.2-12.2 h) and extended (18 h) photoperiods. Photoperiod extension was with 7 micromol m(-2) s(-1) photosynthetic photon flux density. Cultivars responded differently to photoperiod extension (P<0.05). Large increases in dry matter yield at extended photoperiods were observed in Cave-in-Rock (+98%) and Caddo (+129%). The dry matter yield of Kanlow increased by 31%, whereas dry matter yield of the southernmost cultivar Alamo was not affected by photoperiod extension. Yield increases for Cave-in-Rock and Caddo were associated with increased tiller number and weight. A reversal of dormancy for some cultivars with a photoperiodic signal verified that dormancy was not simply a result of a low radiant input.

Segmental allotetraploidy and allelic interactions in buffelgrass (Pennisetum ciliare (L.) Link syn. Cenchrus ciliaris L.) as revealed by genome mapping.

Linkage analyses increasingly complement cytological and traditional plant breeding techniques by providing valuable information regarding genome organization and transmission genetics of complex polyploid species. This study reports a genome map of buffelgrass (Pennisetum ciliare (L.) Link syn. Cenchrus ciliaris L.). Maternal and paternal maps were constructed with restriction fragment length polymorphisms (RFLPs) segregating in 87 F1 progeny from an intraspecific cross between two heterozygous genotypes. A survey of 862 heterologous cDNAs and gDNAs from across the Poaceae, as well as 443 buffelgrass cDNAs, yielded 100 and 360 polymorphic probes, respectively. The maternal map included 322 RFLPs, 47 linkage groups, and 3464 cM, whereas the paternal map contained 245 RFLPs, 42 linkage groups, and 2757 cM. Approximately 70 to 80% of the buffelgrass genome was covered, and the average marker spacing was 10.8 and 11.3 cM on the respective maps. Preferential pairing was indicated between many linkage groups, which supports cytological reports that buffelgrass is a segmental allotetraploid. More preferential pairing (disomy) was found in the maternal than paternal parent across linkage groups (55 vs. 38%) and loci (48 vs. 15%). Comparison of interval lengths in 15 allelic bridges indicated significantly less meiotic recombination in paternal gametes. Allelic interactions were detected in four regions of the maternal map and were absent in the paternal map.

Prospective evaluation of two-dimensional transthoracic echocardiography in emergency department patients with suspected pulmonary embolism.

OBJECTIVE: To prospectively examine the diagnostic accuracy of two-dimensional transthoracic echocardiography (2-D echo) in emergency department (ED) patients being evaluated for acute pulmonary embolism (PE). METHODS: This was a 14-month prospective observational trial of a convenience sample of ED patients undergoing evaluation for suspected PE at a suburban teaching hospital. The 2-D echo was defined as positive if any two of the following were noted: right ventricular dilation, abnormal septal motion, loss of right ventricular contractility, elevated pulmonary artery or right ventricular pressures, moderate to severe tricuspid regurgitation, or visualization of a clot seen in the right ventricle or pulmonary artery. The patient was considered to have a PE if one of the following was positive: a pulmonary angiogram, contrast helical computed tomography, a magnetic resonance angiogram, a high-probability ventilation/perfusion (V/Q) scan without contradictory evidence, or an intermediate-probability V/Q scan with ultrasonic evidence of deep venous thrombosis. RESULTS: Of 225 cases identified, 39 met the defined criteria for PE (17%). A 2-D echo was performed on 124 patients (55%), of whom 27 (22%) had PE. In 20 patients the 2-D echo had at least two indicators of right ventricular strain; however, only 11 of these patients had confirmed pulmonary embolus. The 2-D echo had a sensitivity of 0.41 (95% CI = 0.32 to 0.49) and a specificity of 0.91 (95% CI = 0.86 to 0.96). The likelihood ratio positive was a moderately strong 4.4, with a weak likelihood ratio negative of 0.6. CONCLUSIONS: Bedside 2-D echo is not a sensitive test for the diagnosis of PE in ED patients. Positive findings moderately increase the suspicion for PE but are not diagnostic.

The long-term fluctuation of the visual field in stable glaucoma.

PURPOSE: To determine, in stable glaucoma, the characteristics of the between-examination variability of the visual field recorded with the Humphrey Field Analyser (HFA; Humphrey Systems, Dublin, CA) using the homogeneous, LF(Ho), and heterogeneous, LF(He), components of the long-term fluctuation (LF), thereby providing a technique for separating progressive loss from fluctuation in sensitivity. METHODS: The LF components were calculated using a two-factor analysis of variance (ANOVA) with replications and were determined between each pair of three successive HFA program 30-2 fields for each patient from two groups, each containing 30 patients with primary open-angle glaucoma. The interval between examinations for the first group was 6 to 9 months and for the second group was 3 weeks. RESULTS: The group mean values for LF(Ho) ranged from 1.50 to 2.19 dB and for LF(He) from 1.70 to 2.05 dB. The average difference between examinations was within +/-0.35 dB for each component, and the 95% limits of agreement for the two groups, respectively, were +/- 2.31 and +/- 2.39 dB for the LF(Ho) and +/- 2.36 and +/- 2.09 dB for the LF(He). The estimate of the 90% confidence limit for the LF(Ho) was 3.30 dB and for the LF(He), 3.60 dB. Little relationship was present between the LF components and the modulus differences in mean deviation (MD), the corrected pattern SD (CPSD), or the mean MD, mean short-term fluctuation, and mean CPSD, of the two fields. CONCLUSIONS: Estimation of the LF components and of the corresponding confidence limits yields an expression of the normal between-examination variability of two consecutive fields that can be used as a reliability index. A value outside the confidence limits indicates the necessity for a confirmatory follow-up field.

Striking findings concerning the variability in the measurement of the fetal renal collecting system.

OBJECTIVE: Using strict thresholds of normality, investigators have reported associations between fetal pyelectasis and aneuploidy, obstructive uropathy, postnatal pyeloplasty and vesicoureteral reflux. Although evidence continues to mount regarding the importance of fetal pyelectasis, little is known of the variability of collecting system measurements. To investigate the short-term variability and its relationship to bladder dilatation, the following study was conducted. DESIGN: During May and June 1996, 20 mid- and late-trimester patients with varying degrees of fetal pyelectasis were recruited into this study. Each consented to undergo periodic (every 15 min for 2 h) ultrasound measurements of the fetal renal collecting systems and bladder. To account for anatomic and technical variability in measurement, we used both the sum of the transverse and anterior-posterior (AP) measurements of the collecting systems, and AP measurement alone for comparison. The variability of the collecting system measurements was assessed based upon gestational age, magnitude of pyelectasis and fetal bladder size. RESULTS: We investigated 38 renal units in 20 patients (eight in the second trimester and 12 in the third). The mean(SE) AP diameter of all kidneys was 5.89(2.49) mm (range 15 (2-17) mm), and the sum of transverse and AP renal collecting system diameters was 13.91(5.73) mm (range 26 (4-31) mm). These data were normally distributed. When assessing the variability in individual kidneys over time, we found the mean variation (minimum to maximum) for the sum of the AP and transverse measurement to be 7.61(4.26) mm and for the AP measurement alone to be 3.80(2.49) mm. No relationship was found between variability of dilatation, magnitude of dilatation or fetal bladder size. Cyclic dilatation of the fetal bladder was observed in all cases. The mean time from maximal to minimal dilatation was 20 min (1.34 observations; range 12-30 min). CONCLUSIONS: We found the size of the fetal renal collecting system to be highly variable over the course of a 2-h period. Seventy per cent of cases (14 of 20) had both normal (< 4 mm) and abnormal values (> or = 4 mm) during the 2-h study period. Significant caution should be used when considering the implications of renal collecting system dilatation based upon a single AP measurement.

A successful approach to immunizing men who have sex with men against hepatitis B.

This paper reports the success of outreach efforts to immunize adults at high risk of acquiring hepatitis B virus (HBV) infection. Local health department testers recruited clients when they sought anonymous HIV testing. Interested clients were serologically tested for HBV infection. Susceptibles were offered a free hepatitis B vaccine. Of 189 clients who were tested, 161 (86%) were susceptible to HBV infection and 140 (74%) were men who have sex with men (MSM). Of the susceptibles, 82 (51%) started the hepatitis B vaccine series. Sixty-five (80%) received three doses of hepatitis B vaccine and an additional 10 (12%) received two doses. Completing the hepatitis B vaccine series was associated with being a MSM (odds ratio [OR] 8.8, confidence interval [CI] 1.5-56.0) and with not being an injection drug user (IDU) (OR 0.2, CI 0.02-1.0). One way to provide hepatitis B vaccine to MSM is to attach an immunization program to a successful anonymous HIV testing program. The feasibility of implementing such programs would increase if public vaccine policymakers made more federally purchased hepatitis B vaccine available for adults.

Spontaneous closure of atrial septal defects in premature vs. full-term neonates.

Our hypotheses were that the following factors influenced closure of atrial septal defects (ASDs) detected in neonates: estimated gestational age (EGA), the presence of a persistent ductus arteriosus (PDA), severity of pulmonary disease, gender, and the initial size of the ASD. Our population consisted of 82 newborns (38 premature and 44 term) who were found before the age of 1 month to have an ASD. Closure of ASDs was analyzed using both Kaplan-Meier survival analysis and the Cox proportional hazards model, each with the five covariates. The hazard ratio (or ratio of instantaneous closure rates) of term vs preterm infants was 3.60 (95% CI = 1.80-7.20), whereas the hazard ratio for infants with a PDA (compared to infants with no PDA) was 2.41 (95% CI = 1.28-4.54). Multivariate analysis showed that each of these terms (PDA and EGA) were independent predictors of ASD closure. The hazard ratio of ASD closure for each of four levels of pulmonary disease was 0.632 [95% CI = 0.453-0.881]. We conclude that the majority of neonatal ASDs will close, with EGA and PDA acting as important influences on closure.

Transmission of varicella to a gravida via close contacts immunized with varicella-zoster vaccine. A case report.

BACKGROUND: Varicella-zoster is a highly contagious DNA virus, transmitted by direct contact and respiratory droplets. An attenuated live-virus vaccine has recently become available and is of value for susceptible, nonimmunized people. As with other attenuated vaccines, such as measles, mumps and rubella virus, there is no evidence of transmission by those immunized, and it is generally recognized that these vaccines can be given to the close contacts of pregnant women. CASE: A 32-year-old woman at 39 weeks of gestation presented with generalized pruritic vesicles and pustules. Diagnosis of primary varicella infection was made and confirmed by serologic studies. The patient denied recent or past exposure. The only significant history that the patient could recall was her exposure to her two children, who were vaccinated with the varicella-zoster vaccine eight days prior to her admission but were asymptomatic. CONCLUSION: This is the first report of a pregnant woman contracting the primary varicella infection from exposure to close contacts vaccinated with the varicella vaccine. It may not be as safe as previously thought for seronegative gravidas to be in close contact with people vaccinated with the varicella vaccine.

Doppler velocity and flow through the aortic isthmus in normal term neonates.

Our hypothesis was that the relationship between the internal aortic diameter and the Doppler flow velocity across the aortic isthmus could be modeled by applying the principle of conservation of mass flow. The aortic diameter decreased at the isthmus by a mean of 18% (t = 11.02, p < 0.0001), while the flow velocity increased by a mean of 44% (t = 10.09, p < 0.0001). The mean peak mass flow rate was 34. 5 ml/s preisthmus and 32.9 ml/s at the isthmus with excellent correlation (r = 0.830). We conclude that the increase in Doppler velocity observed in the descending aorta can be explained by the normal narrowing observed at the aortic isthmus and application of the continuity equation for conservation of mass flow.

Relationship of fetal growth to duration of heat stress in an ovine model of placental insufficiency.

OBJECTIVE: Intrauterine growth restriction in an ovine model occurs after exposure to environmental heat stress for 80 days beginning at 35 days' gestation. Our objective was to determine whether intrauterine growth restriction is reversible on removal of the heat stress after only 55 days of exposure; that is, does a brief exposure at a critical point of development suffice? STUDY DESIGN: Five pregnant ewes were exposed to heat stress beginning at 35 days' gestation and were removed after 55 days of exposure. Five ewes in a control group were studied as contemporaneous controls and added to data from 37 ewes in a control group previously studied. Serial fetal biometric ultrasonographic measurements (biparietal diameter, abdominal circumference, femur length, and tibia length) were obtained beginning at 50 days' gestation. Growth curves were calculated for each parameter, and comparisons were made between fetuses in the group exposed to heat stress for 55 days and 42 fetuses in the control group and 4 fetuses from a previous study that were exposed to heat for 80 days. Regression lines, 95% confidence intervals, and slopes were determined for each study group. RESULTS: Both the 55-day and the 80-day heat exposure groups showed a significant reduction in fetal and placental weights compared with the control group. Animals in the 80-day group had significantly lower fetal and placental weights than the animals in the 55-day group (P <.05). Indexes of somatic growth (abdominal circumference, femur length, and tibia length) for the control group were significantly greater than those of either the 55-day group or the 80-day group (P <.001). Asymmetric growth restriction was evident in both heat groups by a biparietal diameter/abdominal circumference ratio that was significantly higher than in the control group (P <.004 for the 55-day group and P <.001 for the 80-day group). The slopes for somatic parameters (abdominal circumference, femur length, and tibia length) versus time became significantly different between the control and 55-day groups at 77, 101, and 80 days' gestation, respectively. The 55-day group had abdominal circumference and femur length measurements that were significantly greater than those in the 80-day group. CONCLUSION: The fetuses in the 55-day and 80-day groups reflect a pattern of asymmetric intrauterine growth restriction. Our findings suggest that the initial insult affecting fetal and placental growth occurs early in gestation, but removal of fetuses after only 55 days of exposure significantly reduces the degree of fetal growth restriction compared with that found in those fetuses exposed for 80 days.

Evaluating rapid diagnostic tests of intra-amniotic infection: Gram stain, amniotic fluid glucose level, and amniotic fluid to serum glucose level ratio.

OBJECTIVE: The aim of the study was to compare the diagnostic utility of the Gram stain, the amniotic fluid glucose level, and the ratio of amniotic fluid glucose level to serum glucose level in detecting intra-amniotic infection. STUDY DESIGN: We conducted a prospective study of 127 patients with preterm labor and 26 patients with preterm premature rupture of the membranes (153 total). All patients underwent amniocentesis to diagnose intra-amniotic infection. The diagnostic criterion for intra-amniotic infection was a positive amniotic fluid culture result. RESULTS: The Gram stain is 80% sensitive and 91% specific when a positive is considered the presence of white blood cells or bacteria. Amniotic fluid glucose level and the ratio of amniotic fluid glucose level to serum glucose level are significantly lower when amniotic fluid culture results are positive, but as diagnostic tests they are inferior to the Gram stain. Logistic regression models that combine predictors yield superior accuracy with respect to individual tests. The most accurate combination was amniotic fluid glucose level and Gram stain with white blood cells or bacteria. Although the number of patients with preterm premature rupture of the membranes was small in this study (n = 26), analysis of our data suggests that the diagnostic performance levels of these tests were similar when used in patients with preterm labor and intact membranes and in patients with premature rupture of the membranes. CONCLUSIONS: The amniotic fluid glucose level and the ratio of amniotic fluid to serum glucose level have equivalent diagnostic utility and are inferior to the Gram stain. The combination of Gram stain with amniotic fluid glucose level is superior to any individual test.