Search PubMedSearch

Biomedical subjects

J Rutledge

Publications and source records attributed to J Rutledge.

At least 19 recordsLinked to original sources

Antiphospholipid antibodies in predicting adverse pregnancy outcome. A prospective study.

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.

Abortion, Spontaneous

In vivo detection of a novel macrophage-derived protein involved in the regulation of nasal mucus-like glycoconjugate secretion.

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.

Adult

Treatment of neonatal lupus: case report and review of the literature.

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.

Betamethasone

Release of tissue-type plasminogen activator by activated rat eggs and its possible role in the zona reaction.

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.

Animals

Studies on zona hardening in rat oocytes that are matured in vitro in a serum-free medium.

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.

Animals

Liposomes with prolonged circulation times: factors affecting uptake by reticuloendothelial and other tissues.

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.

Animals

Self-disclosure in a clinical context by Asian and British psychiatric out-patients.

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.

Adult

Effect of intravenous enalaprilat in moderate and severe systemic hypertension.

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)

Antihypertensive Agents

Haemophilus influenzae type b lipooligosaccharide induces meningeal inflammation.

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.

Analysis of Variance

Sternal malformation/vascular dysplasia association.

Sternal defects associated with superficial craniofacial vascular lesions are rare. We report on two additional patients with a sternal cleft and cutaneous, craniofacial hemangiomata to emphasize that this unusual combination of findings represents a recognizable sternal malformation/vascular dysplasia association. In addition, internal vascular lesions were also identified in these individuals, in one instance involving the upper respiratory tract and in the other the viscera. Although the pathogenesis of these findings is unclear, an early disturbance affecting midline mesodermal structures leading to lack of complete fusion of lateral sternal bands and overlying cutaneous tissue, or deficient formation of a proposed medioventral unpaired structure which may be involved in the formation of the sternum, and persistence and proliferation of midline angioblastic tissue may be possible mechanisms during the sixth to ninth gestational weeks. To date, all but one of the 15 known cases have been sporadic and no teratogen has been identified as a cause for these clinical manifestations. The presence of this association should signal the need to search for potentially life-threatening internal hemangiomata.

Adult

Persistent hypertransaminasemia as the presenting finding of childhood muscle disease.

Four children with isolated, persistent elevations of serum transaminases were investigated for hepatic disease and followed for 4 to 24 months before serum creatine kinase determinations were obtained and found to be markedly elevated. Evidence of muscle disease was obtained by close questioning, retrospectively, and mild abnormalities were found on physical examination. Review of laboratory tests in our center for 6 months revealed 30 additional cases of anicteric hypertransaminasemia (20% of those with elevated enzymes), only two of which were unexplained by the admitting diagnosis. Serum transaminase values are elevated in a variety of diseases of different organ systems. Creatine kinase determinations may provide the clue to the diagnosis of occult muscle disease in some children with unexplained anicteric hypertransaminasemia.

Adolescent

Etiologic heterogeneity of fetal hydrocephalus diagnosed by ultrasound.

Increased use of fetal ultrasound imaging by obstetricians has led to an increased rate of in utero detection of fetal malformations. Eight patients referred for level II sonography for confirmation of suspected fetal hydrocephalus were found to have affected fetuses. Examination of the resulting fetuses and infants revealed remarkable etiologic heterogeneity for the hydrocephalus. The risk for recurrence of hydrocephalus and other malformations in future offspring of these mothers varies from negligible to 25%. This experience emphasizes that there are many causes of fetal hydrocephalus and that careful diagnostic studies must be performed on any fetus or infant found to have hydrocephalus, so that accurate genetic counseling can be provided to the family.

Female