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J Tierney

Publications and source records attributed to J Tierney.

At least 37 records · Page 2Linked to original sources
PubMed1997

Safety and pharmacokinetics of multiple doses of recombinant human CuZn superoxide dismutase administered intratracheally to premature neonates with respiratory distress syndrome.

OBJECTIVES: To examine the safety and pharmacokinetics of multiple intratracheal (IT) doses of recombinant human CuZn superoxide dismutase (rhSOD) in premature infants with respiratory distress syndrome who are at risk for developing bronchopulmonary dysplasia (BPD). Methods. Thirty-three infants (700 to 1300 g) were randomized and blindly received saline, 2.5 mg/kg or 5 mg/kg rhSOD IT within 2 hours of surfactant administration. Infants were treated every 48 hours (as long as endotracheal intubation was required) up to 7 doses. Serial blood and urine studies, chest radiographs, neurosonograms, SOD concentration and activity measurements, and tracheal aspirate (TA) inflammatory markers were assessed throughout the 28-day study. RESULTS: SOD concentrations in serum (0.1 [0.05/0.15] microg/mL-geometric mean with lower/upper confidence intervals), tracheal aspirates (TA) (0.2 [0.1/0.3] microg/mL) and urine (0.3 [0.2/0.4] microg/mL) were similar at baseline in all 3 groups and did not change significantly in the placebo group. In the rhSOD treatment groups, SOD concentrations were increased on day 3 and did not change significantly thereafter over the 14-day dosing period (also measured on days 5, 7, and 13). SOD concentrations averaged 0.4 [0.3/0.5] microg/mL in serum, 0.8 [0.6/1.2] microg/mL in TA and 1.1 [1.0/1.3] microg/mL in urine for the low-dose group and 0.6 [0.5/0.7] microg/mL in serum, 1.1 [0.9/1.5] microg/mL in TA, and 2.2 [1.6/2.9] microg/mL in urine for the high-dose group over the 14-day dosing period. Enzyme activity directly correlated with SOD concentration and rhSOD was active even when excreted in urine. TA markers of acute lung injury (neutrophil chemotactic activity, albumin concentration) were lower in the rhSOD agroups compared with placebo. No significant differences in any clinical outcome variable were noted between groups. CONCLUSIONS: These data indicate that multiple IT doses of rhSOD increase the concentration and activity of the enzyme in serum, TA and urine, reduce TA lung injury markers and are well-tolerated. Further clinical trials examining the efficacy of rhSOD in the prevention of BPD are warranted.

Analysis of Variance↗
PubMed1997

Two women honored.

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History, 19th Century↗
PubMed1996

Localization and activity of recombinant human CuZn superoxide dismutase after intratracheal administration.

Hyperoxia and mechanical ventilation cause acute lung injury which may be mitigated by prophylactic intratracheal (IT) administration of recombinant human CuZn superoxide dismutase (rhSOD). However, little is known about the localization, activity, and metabolism of rhSOD after IT administration by instillation or nebulization. Twenty-six newborn piglets were intubated, mechanically ventilated, and given either saline or fluorescently labeled rhSOD (5 mg/kg IT) by instillation or nebulization. Animals were killed 1, 6, or 12 h later. Intact rhSOD (% total fluorescence still associated with macromolecules) and total SOD activity in lung tissue were then determined. Results indicate that, after 1 and 6 h of administration, the majority of rhSOD present in the lung was still associated with the fluorescent label. By 12 h, most of the rhSOD was no longer fluorescently labeled. At 1 h, lung SOD activity increased by 100% compared with untreated control values, with activity remaining elevated at 6 and 12 h. Laser confocal microscopy of lung tissue showed that at 1 h, labeled rhSOD was found throughout the lung, inside a variety of cell types of airways, respiratory bronchioles, and alveoli. Deposition was more homogeneous after nebulization. Negative controls had minimal background fluorescence. These data indicate that after IT administration, rhSOD is rapidly incorporated into cells in the lung and significantly increases lung SOD activity. These observations have important implications for the clinical use of rhSOD in human trials.

Animals↗
PubMed1995

The effects of hyperoxia, mechanical ventilation, and dexamethasone on pulmonary antioxidant enzyme activity in the newborn piglet.

It has been previously shown that prophylactic, intravenous dexamethasone (DEX) and intratracheal recombinant human Cu/Zn superoxide dismutase (SOD) ameliorate lung injury in newborn piglets treated with 48 hr of hyperoxia and mechanical ventilation. DEX has many pharmacologic effects, including the possible induction of antioxidant enzyme systems. To investigate whether the effects of DEX are mediated by an increase in endogenous antioxidant enzyme activity, 5 groups of term newborn piglets were studied: Group 1 piglets were ventilated with room air for 48 hr; Group 2 animals were ventilated with 100% O2 for 48 hr; Group 3 animals were ventilated with room air for 48 hr and received DEX (0.7 mg/kg) every 12 h; Group 4 were ventilated with 100% O2 for 48 hr and also received DEX; Group 5 animals were no ventilated and were sacrificed at time 0. At the conclusion of the studies, bronchoalveolar lavage (BAL) was performed and the lungs were removed and homogenized. Lung tissue and BAL were analyzed for SOD, catalase, GPX activities, and total protein concentration. No significant differences in any of these assays were seen in either lung tissue or BAL in the 5 groups. These observations indicate that 48 hr of hyperoxia, mechanical ventilation, or dexamethasone treatment does not induce activity of SOD, catalase, or glutathione peroxidase (GPX) in the lungs of newborn piglets. Thus postnatal DEX appears to minimize neonatal lung injury by mechanisms that are independent of these enzymes.

Analysis of Variance↗
PubMed1995

The role of ciprofloxacin in a patient with delirium due to multiple etiologies.

A 40-year-old female with a lumbar drain was admitted to the neurosurgery service with a bacterial meningitis. During the course of her treatment with multiple central nervous system (CNS) active medications, the patient became disoriented and agitated with visual hallucinations and generalized myoclonus. A psychiatric consultation was requested. The case is presented and discussed within the context of the importance of understanding etiological mechanisms in treating and reversing delirium. The fluoroquinolone agent ciprofloxacin was considered to be the primary etiology of the patient's delirium. This class of medication as a cause of altered mental status is discussed.

Adult↗
PubMed1992

Psychopharmacology in the elderly.

By the year 2030, it is estimated that 17% of the population (52 million people) will be over age 65. Most of these individuals will be taking several medications, and one or more of these medications may be a psychotropic, that is, an antidepressant, anxiolytic, antipsychotic, or lithium. This article summarizes the pharmacokinetic changes that accompany aging and highlight how these changes impact the elderly.

Age Factors↗
PubMed1989

Protooncogene structure in the cancer family syndrome.

Protooncogene loci in constitutional DNA from affected members of a kindred with the cancer family syndrome were studied by Southern blot hybridization analysis. No structural rearrangements or amplification of 16 protooncogenes were detected. These studies demonstrated that gross structural alteration of the tested protoocongenes is not responsible for cancer susceptibility in this syndrome.

Chromosome Mapping↗
PubMed1988

The secreted and somatic antigens of the third stage larva of Anisakis simplex, and antigenic relationship with Ascaris suum, Ascaris lumbricoides, and Toxocara canis.

The in vitro-released 'excretory/secretory' (ES) and somatic antigens of the third stage (infective) larva of Anisakis simplex were characterised by radioiodination, immunoprecipitation, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Oral infection with the parasite elicited a substantial IgG antibody response to ES in infected rabbits and humans, with a minimal response to somatic materials. Serial serum sampling in experimental infection showed that there was a sequential recognition of distinct ES components. In contrast to oral infection, intraperitoneal exposure of rats with living parasites induced a strong response to both ES and somatic antigen preparations. Sequential recognition of ES antigens, and differential responses to somatic components, might, therefore, have application in the estimation of the age and degree of penetration by the nematodes in human infection. Extensive antigenic relationships were found between A. simplex and three other species of ascaridoid nematodes, namely Ascaris lumbricoides, Ascaris suum, and Toxocara canis, but none with a panel of non-ascaridoid nematodes. Evidence is presented that a Mr 14,000 component of A. simplex has a homologue in all of the ascaridoids examined, but does not elicit an antibody response in anisakiasis. Finally, the ES of A. simplex is shown to contain two proteinase activities, of approximately Mr 23,400 and 46,100, as revealed by separation on gelatin substrate gels, although the antigenicity of the enzymes remains to be established.

Animals↗