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Biomedical subjects

J M O'Brien

Publications and source records attributed to J M O'Brien.

At least 19 recordsLinked to original sources

Taxol and colchicine increase LPS-induced pro-IL-1 beta production, but do not increase IL-1 beta secretion. A role for microtubules in the regulation of IL-1 beta production.

IL-1 beta is a proinflammatory cytokine secreted chiefly by monocytes and macrophages. Currently, much of its mechanism of processing and secretion is poorly understood, but there is increasing evidence that the microtubule system may be involved. For example, it is known that taxol and colchicine, two drugs that affect microtubule structure and function, increase LPS-induced IL-1 beta release. However, it is not known whether these drugs affect the synthesis of the 31-kDa precursor (pro-IL-1 beta) or the processing and release of mature IL-1 beta. To test this, an assay was used that allowed for the temporal separation of IL-1 beta synthesis and release. The addition of taxol or colchicine to the secretory phase of the assay resulted in no significant change in IL-1 beta release. However, when these drugs were added to the stimulus for IL-1 beta production, there was a significant increase in both IL-1 beta release and total IL-1 beta production, as measured by ELISA. These findings indicate that taxol and colchicine increase LPS-induced IL-1 beta release by an increase in the production of the precursor molecule. Thus, it is unlikely that microtubules are involved in the IL-1 beta secretory machinery in any significant manner, but they do play a role in the regulation of pro-IL-1 beta production.

Animals

Efficacy of outpatient induction with low-dose intravaginal prostaglandin E2: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Our purpose was to determine whether a protocol for outpatient induction is safe and effective for initiating labor. STUDY DESIGN: A randomized, double-blind, placebo-controlled trial was performed with 100 low-risk patients having well-dated pregnancies. Women with a Bishop score < or = 6 at 38 to 40 weeks' gestation were administered either 2 mg of intravaginal prostaglandin E2 gel or placebo for 5 consecutive days as outpatients while undergoing fetal monitoring. RESULTS: The median interval from randomization to delivery was 4 days in the prostaglandin E2 group (range 0 to 28 days) versus 10 days in the placebo group (range 0 to 26 days, p = 0.002). Twenty-seven of 50 patients (54%) in the prostaglandin E2 group were admitted for labor during the dosing interval compared with 10 placebo-treated patients (20%, p = 0.001). The mean gestational age at delivery was significantly reduced in the treatment group (39.9 +/- 1.0 weeks vs 40.5 +/- 0.99 weeks, p = 0.003) as was the incidence of postdates pregnancy (40% vs 66%, p = 0.016). Hyperstimulation was observed in one prostaglandin E2-treated patient, but no intervention was required. CONCLUSIONS: Outpatient low-dose prostaglandin E2 gel administration is effective for initiating labor in patients with an unfavorable cervix and appears safe if performed with adequate monitoring.

Administration, Intravaginal

The use of a modified vaginal pouch for the diagnosis and management of premature rupture of the membranes.

A modified Reality vaginal pouch (Wisconsin Pharmacal, Jackson, Wis.) was effective in assessing membrane integrity in patients evaluated for suspected premature rupture of the membranes and was useful for collecting fluid in patients requiring pulmonary maturity studies. This technique does not alter the incidence of infection and is beneficial in the management of selected patients.

Amniotic Fluid

Daily antenatal testing in women with severe preeclampsia.

OBJECTIVE: Our purpose was to determine whether daily antenatal testing in the expectant management of severe preeclampsia remote from term prevents stillbirth or neonatal compromise at birth. STUDY DESIGN: We reviewed the medical records of 68 women with severe preeclampsia remote from term who underwent expectant management with daily fetal testing until delivery. On admission each patient had reassuring nonstress testing (absence of persistent severe variable or late decelerations), biophysical profile (> or = 6), and amniotic fluid volume (> or = 2 cm maximal vertical pocket before 32 weeks or amniotic fluid index > or = 5 after 32 weeks). RESULTS: There were no stillbirths. Twenty-one patients (31%) had nonreassuring testing necessitating delivery. Two neonatal deaths occurred as a result of complications of prematurity. There were no statistical differences in the cord arterial pH (p = 0.93) or in the 1- and 5-minute Apgar scores (p = 0.18 and p = 0.88, respectively) between those with normal and abnormal antenatal testing. CONCLUSIONS: Because optimizing neonatal outcome is the only reason to prolong pregnancy in women with severe preeclampsia, confirmation of fetal well-being is mandatory. Because neither stillbirths nor fetal compromise at birth occurred in patients undergoing daily antenatal testing, we recommend daily testing in patients with severe preeclampsia managed expectantly.

Adolescent

Early versus late amniotomy for labor induction: a randomized trial.

OBJECTIVE: Our purpose was to determine the impact of early and late amniotomy on labor induction with continuous oxytocin infusion at term. STUDY DESIGN: A total of 209 women admitted for labor induction were randomized to early or late amniotomy. The early amniotomy group (n = 106) had membranes ruptured as soon as it was deemed safe and feasible. The late amniotomy group (n = 103) had membrane rupture performed at > or = 5 cm dilatation. The first 103 women received a continuous oxytocin infusion with incremental adjustments at 60-minute intervals as required. The next 106 women had adjustments every 30 minutes as required. Statistical analysis was confined to concurrent groups. RESULTS: Early amniotomy was associated with shorter labor (13.3 vs 17.8 hours, p = 0.001), chorioamnionitis (22.6% vs 6.8%, p = 0.002), and significant fetal umbilical cord compression (12.3% vs 2.9%, p = 0.017). The benefit regarding shortening of labor was limited to women having oxytocin increments every 30 minutes as required (13.3 vs 17.8 hours, p = 0.001). Alternatively, the increase in chorioamnionitis was confined to the 60-minute group (39% vs 11%, p < 0.001), which also demonstrated a trend toward increased moderate and severe variable decelerations (19.6% vs 6.4%, p = 0.08). CONCLUSIONS: When a protocol of 60-minute increments in oxytocin infusion rate is desired, amniotomy should be performed late in labor to reduce chorioamnionitis and significant umbilical cord compression. Alternatively, if early amniotomy is necessary, oxytocin should be adjusted every 30 minutes as tolerated.

Adolescent

The impact of initiating a human immunodeficiency virus screening program in an urban obstetric population.

OBJECTIVE: Our purpose was to describe the incidence of human immunodeficiency virus infection and to assess the cost/benefit ratio of universal antenatal human immunodeficiency virus screening. STUDY DESIGN: Medical records of women in this urban obstetrics population, from the years 1988 to 1993, were examined. The incidence of known human immunodeficiency virus seropositivity at delivery was determined. The costs of performing human immunodeficiency virus screening, evaluating the disease status, and administering therapy were calculated. These costs were compared with an averaged cost for care and follow-up of infants infected through vertical transmission. RESULTS: The incidence of known human immunodeficiency virus seropositivity at delivery approximately doubled since the initiation of a human immunodeficiency virus screening program (0.26% to 0.48%). Obstetric screening added an approximate $100,000 to medical costs. The calculated cost of pediatric follow-up of human immunodeficiency virus-seropositive infants for the first 18 months was estimated at $344,355. In our population, with universal screening and zidovudine therapy, the medical costs could be reduced by $175,500 per year. CONCLUSION: A program of voluntary human immunodeficiency virus screening increases the incidence of known human immunodeficiency virus infection. Offering screening and follow-up to all pregnant patients in an urban setting is both cost-effective and medically beneficial.

Adult

Common skin problems of infancy, childhood, and adolescence.

Common dermatological problems as a frequent presenting complaint are stratified by infancy, childhood, and adolescence. The common manifestations and questions asked by parents are discussed. Both infectious and noninfectious rashes are included. Convenient treatment modalities are listed.

Acne Vulgaris

Developing and implementing a self-learning packet on epidural analgesia.

Epidural analgesia offers a highly effective route of providing acute pain relief. As this mode of medication delivery is used more frequently in the acute care setting, nurses must acquire theoretical knowledge, apply monitoring parameters, and demonstrate technical competency. Implementing a self-learning packet to educate nursing staff caring for patients receiving epidural analgesia is an effective teaching medium and can help improve clinical performance.

Analgesia, Epidural

Comparative genomic hybridization in the detection of DNA copy number abnormalities in uveal melanoma.

Genomic instability appears to play an important role in the development, growth, invasiveness, and eventual metastasis of the neoplastic cell. We have used a powerful new technique, comparative genomic hybridization, to evaluate genetic alterations in 10 fresh frozen uveal melanomas. Comparative genomic hybridization utilizes dual fluorescence in situ hybridization to characterize chromosome deletions and duplications, allowing for simultaneous evaluation of the entire human genome. Several consistent chromosomal abnormalities were detected. This study confirmed previous findings obtained using standard cytogenetic techniques but demonstrated an increased incidence in abnormalities of chromosomes 3 and 8; there was loss of chromosome 3 and duplication of 8q. In addition, we identified, although less frequently, other recurrent abnormal regions including alterations on chromosomes 6p, 7q, 9p, and 13q.

Chromosome Aberrations

Cervicovaginal prolactin: a marker for spontaneous preterm delivery.

OBJECTIVE: Our purpose was to determine whether the presence of prolactin in cervicovaginal washings is associated with preterm birth. STUDY DESIGN: A cohort of 80 patients underwent a washing of the ectocervix and vaginal fornices with a normal saline solution. The cohort consisted of two groups: 40 inpatients requiring tocolysis and 40 asymptomatic outpatients. The saline solution aspirates were centrifuged, the supernatant was stored at -70 degrees C, and a radioimmunoassay for prolactin was run in batch fashion. A prolactin concentration greater than the detection limit of the assay was considered a positive test result. RESULTS: Prolactin was identified in significantly more symptomatic patients than asymptomatic controls (50% vs 5%, p < 0.0001). In symptomatic patients cervicovaginal prolactin had an 80% positive predictive value and a 65% negative predictive value for delivery at < or = 34 weeks' gestation. Patients testing positive for prolactin had significantly shorter latency from testing to delivery (16 +/- 17 vs 34 +/- 24 days, p = 0.02) and had significantly lower birth weights (1985 +/- 729 vs 2583 +/- 696 gm, p = 0.01) compared with patients testing negative. Prolactin was also identified in two asymptomatic patients, both of whom were delivered before term. CONCLUSIONS: Cervicovaginal prolactin is a biochemical marker for preterm delivery, a shorter latency period to delivery, and lower birth weight in symptomatic patients. This test may also prove to be a valuable marker for preterm birth in asymptomatic women.

Adult

Tempting fate: control of communicable disease in England.

Recent changes in the NHS have left many defects in the systems for the control of communicable diseases and infection and their surveillance and the management of outbreaks. Clear, explicit legislation is needed, placing the responsibilities on health authorities. New teams led by consultants need to be set up to investigate and manage outbreaks of communicable diseases of all types.

Communicable Disease Control

Subcellular localization of Cdc42p, a Saccharomyces cerevisiae GTP-binding protein involved in the control of cell polarity.

The Saccharomyces cerevisiae Cdc42 protein, a member of the Ras superfamily of low-molecular-weight GTP-binding proteins, is involved in the control of cell polarity during the yeast cell cycle. This protein has a consensus sequence (CAAX) for geranylgeranyl modification and is likely to be associated, at least in part, with cell membranes. Using cell fractionation and immunolocalization techniques, we have investigated the subcellular localization of Cdc42p. Cdc42p was found in both soluble and particulate pools, and neither its abundance nor its distribution varied through the cell cycle. The particulate form of Cdc42p could be solubilized with detergents but not with NaCl or urea, suggesting that it is tightly associated with membranes. An increase in soluble Cdc42p was observed in a geranylgeranyltransferase mutant strain (cdc43-2ts) grown at the restrictive temperature. In addition, Cdc42p from a cdc42C188S mutant strain (that has an alteration at the prenylation consensus site) was almost exclusively in the soluble fraction, suggesting that membrane localization is dependent on geranylgeranyl modification at Cys-188. Immunofluorescence and immunoelectron microscopy experiments demonstrated that Cdc42p localizes to the plasma membrane in the vicinity of secretory vesicles that were found at the site of bud emergence, at the tips and sides of enlarging buds, and within mating projections (shmoo tips) in alpha-factor-arrested cells. These results indicate that Cdc42p is localized to the bud site early in the cell cycle and suggest that this localization is critical for the selection of the proper site for bud emergence and for polarized cell growth.

Amino Acid Sequence

Amniotic fluid index in hospitalized hypertensive patients managed expectantly.

OBJECTIVE: To determine the relationship between low amniotic fluid (AF) index and fetal growth retardation (FGR), fetal distress, and cesarean delivery in patients hospitalized for hypertensive disease, and to describe changes in AF status in relation to the severity of maternal disease. METHODS: The AF index in 142 hospitalized hypertensive patients was followed per an inpatient protocol with semi-weekly testing; medical records were reviewed to obtain delivery data. RESULTS: Fetal growth retardation was significantly associated with an AF index of 5.0 cm or less or 7.0 cm or less (P < .001) at initial assessment, with positive predictive values of 86 and 52%, respectively. However, the sensitivity of an AF index of 5.0 cm or less or 7.0 cm or less to detect FGR was limited (21 and 46%, respectively). Fetal distress and cesarean delivery were not associated with an AF index of 5.0 cm or less or 7.0 cm or less throughout observation in this cohort. Based upon a definition of oligohydramnios as an AF index of 7.0 cm or less, the AF status worsened from an initial normal value in 39% of patients whose final diagnosis was severe preeclampsia, versus only 14% of patients who were diagnosed as having mild disease. The AF index also normalized in ten patients who were originally diagnosed with oligohydramnios and admitted for expectant management. Only one of these women was diagnosed with severe preeclampsia. CONCLUSIONS: 1) Depending on the definition, the incidence of oligohydramnios ranges from 10-30% in hypertensive patients requiring hospitalization; 2) an AF index of 5.0 cm or less at initial evaluation predicts FGR but lacks sensitivity; 3) the AF status frequently changes with serial assessment, and these changes appear to be related to the severity of hypertensive disease; and 4) the frequency of the obstetric complications studied depends more upon the severity of hypertensive disease than on its potential effect of inducing oligohydramnios.

Cesarean Section

Investigation of the role of the ras protooncogene point mutation in human uveal melanomas.

PURPOSE: Genetic alterations have been observed in a wide variety of neoplastic processes, including Burkitt's lymphoma, chronic myelogenous leukemia, promyelocytic leukemia, and solid tumors of the colon, skin, and breast. The polymerase chain reaction (PCR), dot blotting, and direct double-stranded DNA sequencing were used to assess ras gene activation in human uveal melanomas for three candidate genes: c-Ha-ras1, c-Ki-ras2, and N-ras at codons 12, 13, and 61. METHODS: Samples of 49 human uveal melanomas were obtained. Amplifiable high molecular weight DNA was obtained from 39 of these. PCR amplification of regions centering on three candidate ras genes was performed. PCR-amplified DNA was evaluated by dot blot and double-stranded DNA sequencing utilizing standard methods. RESULTS: No point mutations were identified in screening the c-Ha-ras gene nor were any genetic alterations found in the c-Ki-ras2 gene at codons 12 and 13. Only wild-type sequences were found at codon 61. No ras mutations were detected in any uveal melanomas studied. CONCLUSIONS: This study provides no evidence to support an association between ras protooncogene mutations and human uveal melanomas at codons 12, 13, or 61.

Adult