Preimplantation teratology and the placenta.
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Biomedical subjects
Publications and source records attributed to J Rutledge.
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The purpose of this study was to review the emergency department management of children presenting in diabetic ketoacidosis (DKA) to determine if current recommendations for fluid therapy are practiced. A 5-year retrospective chart review was conducted of all pediatric patients admitted with DKA to the University of Alberta Hospital. Presenting clinical and laboratory data, the initial fluid therapy, and insulin dose were analyzed. The therapy was also compared between sites of initial presentation (primary, secondary, or tertiary hospital). A total of 49 cases of DKA in 37 patients were reviewed. There were no significant clinical or biochemical differences between patients presenting at the three levels of hospital. Forty-one cases (84%) were given a saline bolus and the mean fluid volume given by 1 hour was 18.3 mL/kg. In the first hour 82% of patients presenting at a primary or secondary centre and 67% of those at the tertiary centre received more than 10 mL/kg. This excessive fluid therapy was also evident after 4 hours. Fluid management of children in DKA is excessive and not in keeping with current recommendations. Education of emergency physicians is needed to reduce fluid therapy and the risk of neurologic complications.
OBJECTIVE: We observed two clusters of spontaneous pneumoperitoneums in extremely low birth weight infants during the use of a protocol for early dexamethasone prophylaxis (EDP) for bronchopulmonary dysplasia from 1996 to 1997. During surgery, focal small bowel perforation (FSBP) was found in eight of nine cases. A retrospective study was designed to identify risk factors for FSBP in these extremely low birth weight infants. METHODS: A case-controlled analysis was performed using all infants born weighing < 1001 gm and admitted to the University of Washington Medical Center Neonatal Intensive Care Unit during a 13-month period. A total of 51 infants were identified and divided into groups based on treatment or not with dexamethasone and indomethacin. These cohorts were homogeneous for gestational age, birth weight, and perinatal stability. Relative risk and confidence intervals were calculated for each of the comparisons. Routine pathology was performed on all surgical specimens and additional sections were cut and stained for further study. RESULTS: Infants who received EDP had a relative risk of perforation that was 12.3 times that of untreated infants. Those treated with indomethacin had a risk that was comparable with that for infants who did not receive indomethacin. Infants who received both EDP and indomethacin tended to have higher rates of pneumoperitoneum than infants who received EDP alone but comprised a cohort too small for valid analysis. The pathology of surgical specimens revealed FSBP with segmental loss of the muscularis externa. There was no evidence of fungal or bacterial infection in any of the surgical specimens. CONCLUSION: These findings implicate EDP, but not indomethacin, as a significant risk factor for FSBP.
Idiopathic dilation of the right atrium (IDRA) is a rare cardiac anomaly of unknown etiology. Whether it is an acquired or congenital lesion is controversial. A case of IDRA detected in utero and confirmed postnatally is reported. The postnatal course was complicated by the development of atrial flutter successfully treated with sotalol. A review of the literature concerning IDRA is presented.
Recent studies by Buhi et al. have demonstrated that estrogen (E2) is responsible for the induction of de novo synthesis and secretion of certain oviductal secretory proteins (OSP) and inhibition of other OSP in porcine oviductal explant cultures. The present work was undertaken to evaluate the effect of E2-treated oviductal epithelial cell coculture on the development of early porcine embryos derived from in vitro matured and fertilized oocytes. In vitro synthesis of secretory proteins by E2-treated oviductal cells used for coculture was also investigated by one-dimensional (1D) and two-dimensional (2D) sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE). The results showed that the cleavage rate was significantly enhanced by coculturing fertilized eggs with E2-treated oviductal epithelial cells. The in vitro protein synthetic pattern of oviductal secretory proteins was influenced by E2 treatment. These variations included the disappearance of one protein (82,000 M(r)) and the appearance of another (33,000 M(r)) in the E2-treated group as assessed by 1D-SDS-PAGE. Additional proteins of M(r) 97,000 and an M(r) 36,000-45,000 complex were increased in abundance by the E2 treatment. Analyses by 2D-SDS-PAGE revealed three major E2-dependent proteins, of M(r) 45,000 (pI 5.5), 43,000 (pI 5.5) and a 36,000-45,000 M(r) (pI 4.8) protein complex, whereas polypeptides of M(r) 97,000 (pI 5.1), 36,000 (pI 8.0) and 25,000 (pI 6.8) were inhibited by E2 treatment. The results demonstrated that porcine epithelial cell protein synthetic patterns are influenced by E2 treatment and that estradiol treatment of oviductal cells may increase the rate of zygote cleavage during early development in vitro in pigs.
To investigate the role of the germinal vesicle (GV) on in vitro maturation (IVM) of rat oocytes, we examined protein synthesis during IVM by comparing polypeptide patterns in control and enucleated oocytes using one and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Separation of polypeptides extracted from the cytoplasm of GV by one-dimensional SDS-PAGE revealed that a 55 kDa polypeptide was present only in the GVs of rat oocytes. At 0, 12, 24, 36, and 44 hr after PMSG injection, prior to the initiation of maturation, enucleated oocytes synthesized the same major polypeptides as cumulus intact (CI) oocytes. During meiotic maturation, no major changes were detected in protein synthesis from prophase (GV stage) to prometaphase I (0-6 hr IVM). However, after entry into prometaphase I (7 hr IVM), striking changes were seen; a 24 kDa polypeptide disappeared and expression of a 34 kDa polypeptide became stronger. This pattern lasted until metaphase II. We detected no major differences in the pattern of protein synthesis between CI and enucleated oocytes using two-dimensional PAGE. These results indicate that protein synthesis in the maturing rat oocyte is controlled by cytoplasmic regulators rather than intrinsic nuclear components.
OBJECTIVE: To examine serum concentrations of hyaluronic acid (HA) in patients with rheumatoid arthritis (RA) and to investigate the relationship between clinical measures of disease activity and serum HA concentrations in these patients. METHODS: Sixty-five patients with established RA were enrolled and RA disease activity was measured by clinical variables. Serum samples obtained at the time of the clinical evaluation were assayed for serum HA, erythrocyte sedimentation rate (ESR), and C reactive protein (CRP), and correlations between these laboratory variables and clinical disease activity were sought. RESULTS: Concentrations of serum HA were higher in patients with RA than in healthy controls. There was statistically significant correlation between patient age and serum HA and between serum HA and disease activity measured by physician assessment and number of swollen joints. Correction for age strengthened the correlation between serum HA and measures of disease activity. ESR did not correlate with any measure of clinical disease activity. CRP concentrations correlated with physician assessment of disease activity, and number of swollen joints and tender joints, but the correlation was not as strong as the correlation between serum HA and disease activity variables. CONCLUSION: Measurement of serum HA may be a useful measure of disease activity in patients with RA. Measurement of serum HA appears to be a better correlate of clinical disease activity in patients with RA than ESR or CRP.
OBJECTIVE: To determine if the presence of antiphospholipid antibody (aPL) in healthy pregnant women is associated with adverse pregnancy outcome, including 1) intrauterine fetal loss, 2) maternal pregnancy complications, 3) low birth weight, and 4) low 5-minute Apgar scores. DESIGN: Prospective cohort study in women with normal pregnancies. SETTING: Obstetrics clinic at the University of Colorado Health Sciences Center. PATIENTS: Eligible patients included 451 low-risk, nulliparous pregnant women who came to the obstetrics clinic before 25 weeks gestation; 408 were enrolled and 389 had blood drawn at the first prenatal visit and completed clinical follow-up. MEASUREMENTS: Blood for six aPL measures was drawn at the first prenatal visit and for 239 patients at delivery. RESULTS: Ninety-five patients (24.4%) had elevated aPL levels by one or more measures at the first prenatal visit: 15.8% of the aPL-positive and 6.5% of the aPL-negative patients experienced fetal loss (relative risk, 2.44; 95% CI, 1.29 to 4.62). However, an elevated IgG anticardiolipin antibody level at the first prenatal visit was the only aPL measurement that was significantly associated with fetal loss (relative risk, 3.5; CI, 1.56 to 8.07). Adjustment for confounding variables decreased the relative risk of aPL for fetal loss slightly, but the difference remained statistically significant. Neither a positive aPL result at the initial visit nor a positive result at delivery was associated with maternal complications of pregnancy, low birth weight, or low Apgar scores. CONCLUSIONS: Patients with elevated aPL levels at their initial prenatal visit had an increase in fetal loss but no increase in maternal pregnancy complications, low birth weight, or low Apgar scores. Immunoglobulin G anticardiolipin antibody was the only single test of aPL significantly associated with fetal loss.
BACKGROUND: We recently described a novel 68 kd mucus secretagogue (MMS-68) derived from human monocytes, pulmonary macrophages, and a macrophage hybridoma, clone 63. We detected MMS-68 in monocyte culture supernatants from patients with steroid-dependent asthma and in bronchoalveolar lavage fluid from patients with chronic bronchitis by antigen capture ELISA and in normal lung tissue by immunohistochemistry. METHODS: To determine a role for MMS-68 in the regulation of nasal mucus, we labeled human nasal turbinates with tritiated glucosamine and assayed for the ability of the previously purified MMS-68 (stock solution) to induce mucus-like glycoconjugate release (MLGC). We also performed immunohistochemistry stains with an anti-MMS-68 antibody (1-D-10) on frozen sections (n = 5) of nasal turbinates from patients with allergic and nonallergic rhinitis who were undergoing rhinoplasty and measured MMS-68 levels in nasal lavages from patients who were undergoing topical nasal histamine or methacholine challenge. RESULTS: MMS-68 is a potent nasal MLGC secretagogue causing a dose-dependent increase in MLGC release in vitro. Staining revealed a subepithelial distribution for MMS-68. Antigen capture ELISA of nasal lavages demonstrated mean MMS-68 levels from saline control challenge of 0.9 +/- 0.5 micrograms MMS-68 per milligram of protein (n = 5), 8.6 +/- 1.4 micrograms MMS-68 per milligram of protein from histamine challenge and 20.7 +/- 2.3 micrograms MMS-68 per milligram of protein (n = 5) after methacholine challenge. CONCLUSION: Taken together these data suggest that MMS-68 may play a role in the normal regulation of mucus secretion.
A critically ill infant with congenital complete heart block and neonatal lupus was treated with pulse steroids, exchange transfusion and intravenous gammaglobulin. Transient improvement in clinical status and laboratory results occurred, although the infant died. Based on this report and review of prior experience with immunosuppressive therapy, prenatal treatment of the mother with betamethasone or dexamethasone has been successful in resolving the cardiomyopathy/myocarditis associated with neonatal lupus. Postnatal treatment of the infant with steroids appears to be beneficial for persistent hepatic and hematologic manifestations. The evidence for exchange transfusion is less certain.
The resumption of meiosis results in synthesis of tissue-type plasminogen activator (tPA) in the rat and mouse oocytes (Haurte et al., Cell 43:551-558, 1985). The present study demonstrates that freshly ovulated rat oocytes released their tPA into the surrounding medium upon in vitro activation by sperm penetration or treatment with a calcium ionophore. The presence of a neutralizing monoclonal anti-tPA antibody during in vitro activation by the calcium ionophore inhibited the activation-induced zona hardening and also preserved the ability of the oocyte to be penetrated by sperm subsequent to activation. Rat oocytes undergo zona hardening during in vitro maturation in the absence of serum, presumably as a result of spontaneous cortical granule release, based on findings in mice and hamsters. In the present study, the anti-tPA antibody prevented the zona hardening and enhanced partition by spermatozoa of rat oocytes that were matured in vitro without serum. Collectively, the observations reported have suggest a possible role of tPA released during the cortical granule reaction in the zona reaction, which contributes to the block to polyspermy.
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The present study confirms that zona pellucidae of rat oocytes became resistant to chymotrypsin digestion (zona hardening) after undergoing in vitro maturation (IVM) in a serum-free medium. However, zona hardening did not occur when empty zonae without oocytes were cultured in the same IVM conditions, suggesting that oocyte-derived factor(s) is responsible for zona hardening in oocytes matured in the serum-free medium. Zona hardening occurred primarily after dictyate oocytes were cultured for 6-8 hours in the IVM medium without serum. Zona hardening could be prevented or alleviated if oocytes were cultured in the IVM medium containing bovine foetal calf serum, a soybean trypsin inhibitor, or beta-mercaptoethanol, and in vitro fertilization rates for such oocytes were normal. Possible mechanisms of the phenomenon of zona hardening in oocytes matured in serum-free conditions are discussed in relation to its possible relevance to the cortical reaction and the physiological block to polyspermy.
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Many of the applications of liposomes drug-delivery systems have been limited by their short circulation half-lives as a result of rapid uptake into the reticuloendothelial (mononuclear phagocyte) system. We have recently described liposomes formulations with long circulation half-lives in mice (Allen, T.M. and Chonn, A. (1987) FEBS Lett. 223, 42-46). A study of the principal factors important to the attainment of liposomes with prolonged circulation half-lives is presented in this manuscript. Liposomes with the longest circulation half-lives, in mice, had compositions which mimicked the outer leaflet of red blood cell membranes (egg phosphatidylcholine/sphingomyelin/cholesterol/ganglioside GM1, molar ratio 1:1:1:0.14). Several other gangliosides and glycolipids were examined, but none could substitute for GM1 in their ability to prolong circulation half-lives. However, other negatively charged lipids with bulky headgroups, i.e., sulfatides and phosphatidylinositol, had some effect in prolonging circulation half-lives, but GM1 was clearly superior in this regard. Bilayer rigidity, imparted by sphingomyelin or other high-phase-transition lipids, acted synergistically with the negatively charged components, especially GM1, in extending circulation times. Circulation half-lives of liposomes increased with decreasing size, but even larger (0.2-0.4 microns) liposomes of the optimum formulations had significantly prolonged half-lives in circulation. Uptake of liposomes into tissues other than liver and spleen increased with increasing circulation times of the liposomes for i.v. and for i.p. injections. Liposomes appeared to move from the circulation into the carcass between 6 and 24 h post-injection. Our ability to achieve significant prolongation in circulation times of liposomes makes possible a number of therapeutic applications of liposomes which, until now, have not been achievable.
A study is described in which self-reported self-disclosure levels of Asian and British out-patients to psychiatrists are examined as a function of racial and gender match to psychiatrist. Analysis of self-disclosure scores for 77 subjects revealed no overall differences between Asian and British subjects, or between men and women. Asian subjects, however, reported being prepared to disclose significantly more to a psychiatrist of the same sex as themselves, regardless of race; no such effect was found for British subjects. British women reported being prepared to reveal significantly more to a psychiatrist of the same race as themselves; this effect was not observed in any of the other three subgroups. Implications of these findings for clinical practice are discussed.
The antihypertensive effect and tolerability of enalaprilat, an intravenously administered angiotensin converting enzyme inhibitor, was studied in 65 patients with moderate or severe hypertension. In this randomized, double-blind study, enalaprilat was compared with placebo in 42 (22 enalaprilat, 20 placebo) moderate hypertensive (diastolic blood pressure [BP] 100 to 114 mm Hg) patients. It was compared with furosemide in 23 (12 enalaprilat, 11 furosemide) severe hypertensive (diastolic BP 115 to 130 mm Hg) patients. Enalaprilat (1.25 or 5.0 mg), placebo (5% dextrose) or furosemide (40 or 80 mg) was given every 6 hours intravenously up to 48 hours. In the moderate hypertension stratum, the mean supine diastolic BP was significantly (p less than or equal to 0.01) reduced from baseline at all timepoints in the enalaprilat group. These diastolic BP reductions were significantly (p less than or equal to 0.01) greater in the enalaprilat group than the placebo at 1 to 24 hours (-12 vs -4 mm Hg), with 59% of the patients responding to enalaprilat compared with 30% of the patients responding to placebo. An even greater reduction (p less than or equal to 0.01) was seen at 25 to 48 hours (-14 vs -7 mm Hg, with 73% enalaprilat vs 58% placebo responders). Significant (p less than or equal to 0.01) reductions in mean, supine systolic BP were also seen at 1 to 24 hours (-22 vs -2 mm Hg) and 25 to 48 hours (-24 vs -8 mm Hg) during the 48 hours of the double-blind treatment phase in the enalaprilat group compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
We evaluated the ability of two Haemophilus influenzae type b (Hib) components, lipooligosaccharide (LOS) and capsular polysaccharide, to provoke meningeal inflammation in rabbits. Intracisternal inoculation of 2 fg-200 ng of LOS produced a dose-dependent increase in concentrations of white blood cells and protein in cerebrospinal fluid, whereas 4 micrograms of Hib capsular polysaccharide did not provoke meningeal inflammation. Preincubation of LOS with a murine monoclonal antibody to Hib LOS did not reduce the potency of the LOS. Incubation of LOS with polymyxin B (which neutralizes LOS by binding to its lipid A region) and deacylation of the LOS with acyloxyacyl hydrolase (a neutrophil enzyme that removes nonhydroxylated fatty acyl chains from lipid A) reduced meningeal inflammation. We demonstrated that purified Hib LOS induced meningeal inflammation in this model and suggest that the lipid A moiety of Hib LOS is principally responsible for this host response.