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Biomedical subjects

B Fitzsimmons

Publications and source records attributed to B Fitzsimmons.

18 recordsLinked to original sources
PubMed1993

Parkinson's disease. Quality of life issues.

PD affects many dimensions of quality of life. This article has identified motor and nonmotor features of PD that are directly related to a patient's quality of life. Medication therapy can help to ameliorate some of the symptoms, yet side effects can be as disabling as the symptoms of PD. Nursing care should include assessment, intervention, and evaluation of both physical and psychosocial aspects of care for patients with PD to assist them in achieving maximum functioning.

Humans↗
PubMed1992

Development of 2,3-dihydro-6-(3-phenoxypropyl)-2-(2-phenylethyl)-5-benzofuranol (L-670,630) as a potent and orally active inhibitor of 5-lipoxygenase.

Leukotrienes are potent biological mediators of allergic and inflammatory diseases and are derived from arachidonic acid through the action of the 5-lipoxygenase. In this study, the syntheses and comparative biological activities of three series of 2,3-dihydro-2,6-disubstituted-5-benzofuranols with various substituents on position 3 are described. Compounds from each series were evaluated for their ability to inhibit the production of leukotriene B4 (LTB4) in human peripheral blood polymorphonuclear (PMN) leukocytes and the 5-lipoxygenase reaction in cell-free preparations from rat PMN leukocytes. The structure-activity relationships of each series in vitro and in vivo are presented. The bioavailability, metabolism, and toxicity profile of each series are discussed. The series with no substituent at position 3 was the most potent and among the compounds in that series 2,3-dihydro-6-(3-phenoxypropyl)-2-(2-phenylethyl)-5-benzofuranol (46, L-670,630) was chosen for further development.

Animals↗
PubMed1991

Depression in Parkinson's disease.

Approximately 50% of patients with Parkinson's disease experience clinical depression. Neurotransmitter deficits in depression and Parkinson's disease suggest a common lesion may be responsible for this high incidence. In addition to similar psychological profiles, the clinical features of Parkinson's disease and depression likewise overlap making the distinction difficult. Differentiating these two diseases is very important, as each is treatable. The neuroscience nurse is in a unique position to evaluate the patient with Parkinson's disease for signs and symptoms of depression.

Depressive Disorder↗
PubMed1988

The in vivo production of peptide leukotrienes after pulmonary anaphylaxis in the rat.

Inbred hyper-reactive rats, actively sensitized to OVA, were anesthetized, cannulated, and ventilated with room air. Tracheal instillation of Ag (OVA) resulted in an elevation of airways pressure (14.4 +/- 0.6 cm H2O). Measurement of biliary peptide leukotriene levels before and after Ag challenge using reverse phase HPLC and RIA techniques showed significant elevations in leukotriene (LT) levels, the amounts released being LTC4 (3.65 +/- 0.78), LTD4 (2.8 +/- 1.11), and N-Ac LTE4 (3.87 +/- 1.15) expressed as ng/100 g of body weight, n = 13. Identification of these metabolites were confirmed by HPLC/RIA techniques and LTC4 was further characterized by UV spectroscopy and its enzymatic conversion by gamma-glutamyl transpeptidase to LTD4. [3H]LTC4 (16 ng) administration by tracheal instillation resulted in a 31.4 +/- 4.3% recovery of radioactivity through the bile over 4 h (n = 3) with the major identified metabolite being N-Ac LTE4. [3H]LTC4 (16 ng) plus synthetic LTC4 (5 micrograms) showed a 30.8 +/- 3.1% recovery through the bile after tracheal instillation (3-h collection, n = 4) with significant amounts of LTC4 as well as N-Ac LTE4 present. [3H]LTC4 administration by the portal vein resulted in a 37.4 +/- 8.8% biliary recovery over 60 min (n = 6), the metabolites present in the bile being LTC4, LTD4, LTE4, and N-Ac LTE4. Pretreatment with the 5-lipoxygenase inhibitor L-656,224 (15 mg/kg, 3.5 h pre-p.o.) before Ag challenge resulted in a significant inhibition (greater than 90%, p less than 0.05) of biliary leukotriene levels in this model. Our study demonstrates that peptide leukotrienes are produced in the anesthetized rat after pulmonary anaphylaxis and that biliary leukotriene measurement is suitable for showing the biochemical efficacy of leukotriene inhibitors in vivo. In vivo tracer experiments suggest that the biliary metabolic profile of the peptide leukotrienes is dependent on the site and levels of release as well as the efficiency of the vascular clearance of the various metabolites.

Anaphylaxis↗
PubMed1988

The lipoxins.

Explore the source record for details and available documents.

Arachidonic Acid↗
PubMed1987

Evidence of in-vivo omega-oxidation of peptide leukotrienes in the rat: biliary excretion of 20-CO2H N-acetyl LTE4.

In a previous study in our laboratory it was observed that after [3H] LTC4 administration (luCi/kg i.v.) to the anesthetized rat, significant amounts of injected radioactivity (approximately 25%) were associated with previously unidentified biliary polar metabolite(s). In the present study we describe the isolation and characterization of the predominant polar metabolite. Rats were injected with synthetic LTC4 (20 microgram/kg i.v.) and bile collected over 30 min. After extraction and purification (2 step RP-HPLC procedure), the retention time of the metabolite was compared (plus coinjections) and found to be identical with synthetic 20-CO2H N-Ac LTE4 in two RP-HPLC systems. Also, the UV spectrum of the biologically derived metabolite was compared and found identical to the synthetic material, giving a characteristic conjugated triene absorption in the UV with a max of 281 nm and shoulders at 270 and 290 nm. Further, the trimethyl ester derivative of the metabolite showed identical chromatographic behaviors in 2 reverse and 2 normal phase HPLC systems compared with synthetic 20-CO2H N-Ac LTE4 trimethyl ester. We conclude omega-oxidation of peptide leukotrienes occurs in the rat and that 20-CO2H N-Ac LTE4 is an in vivo product of LTC4 metabolism.

Animals↗
PubMed1987

Metabolism and excretion of peptide leukotrienes in the anesthetized rat.

The metabolism and excretion of the peptide leukotrienes C4, D4, E4 and N-acetylleukotriene E4 have been studied in the anesthetized rat. The intravenous administration of [3H]leukotriene C4 (2.6 X 10(-11) mol/kg) showed a rapid clearance of radioactivity from the blood and a time-related biliary excretion, recovering 69 +/- 1.6% (n = 6) over 60 min. Less than 1% of total radioactivity was recovered in the urine over the same time period. Similarly, the intravenous administration of [3H]leukotriene D4 (2.5 X 10(-11) mol/kg), [3H]leukotriene E4 (2.5 X 10(-11) mol/kg) and N-acetyl[3H]leukotriene E4 (2.1 X 10(-11) mol/kg) showed a 62 +/- 7.5% (n = 4), 52 +/- 1.5% (n = 4) and 37 +/- 4.6% (n = 5) biliary recovery of radioactivity, respectively, after 60 min. Examination of bile identified leukotriene D4 and N-acetylleukotriene E4 as the main products, although substantial radioactivity, which probably represents unidentified polar products, was present at the solvent fronts of the reverse-phase HPLC. Time course studies indicated a relatively rapid conversion of leukotriene C4 to leukotriene D4, while leukotriene D4 metabolism appeared to be much slower. Leukotriene E4 was a minor product, suggesting that the N-acetylation process is rapid. Incubation of [3H]leukotriene C4 in rat plasma and whole blood in vitro resulted in a slow conversion of leukotriene C4 to leukotriene D4 and leukotriene E4 only. These data suggest that the majority of the leukotriene metabolism and excretion in vivo in the anesthetized rat occurs predominantly in the hepatic system. We conclude that this model is suitable for the measurement of in vivo production of peptide leukotrienes.

Animals↗
PubMed1987

Stereochemical requirements for substrate specificity of LTB4 20-hydroxylase.

LTB4 20-hydroxylase (P-450LTB) is the cytochrome P-450 in the microsomes of human polymorphonuclear leukocytes that catalyzes the omega-oxidation of leukotriene B4 (LTB4) to 20-OH LTB4. The activity of P-450LTB for LTB4 compared to isomers and analogs of LTB4 at a concentration of 0.3 microM revealed a preference of P-450LTB for both the triene bond configuration of LTB4 and for the chirality of the 5S and 12R hydroxyl groups. 15S-Hydroxyeicosatetraenoic acid, 8(R/S), 15S-dihydroxy-5-cis-9,11,13-trans-eicosatetraenoic acid, 8R,15S-dihydroxy-5,13-cis-9,11-trans-eicosatetraenoic acid, and 5S,15S-dihydroxy-6,13-trans-8,11-cis-eicosatetraenoic acid were each not subject to omega-oxidation, indicating a negative effect of the presence of a 15-hydroxyl group on substrate recognition. At a concentration of 1.5 microM, 12R- and 12S-hydroxyeicosatetraenoic acid were converted to their respective 20-OH derivatives at rates that were 34.2 +/- 11.6% (mean +/- S.D., n = 3) and 3.5 +/- 4.3% (mean +/- S.D., n = 4), respectively, of that of LTB4 to 20-OH LTB4, further indicating that P-450LTB can distinguish the chirality of the 12-hydroxyl group. The lower Km of LTB4 (2.0 microM), as compared to those of its 6-trans-12-epi isomer (3.8 microM) and 5-epi-LTB4 (6.6 microM) confirmed the preference of P-450LTB for the specific triene bond structure of LTB4 and its preference for the chirality of the hydroxyl groups of LTB4 within this structurally related class of molecules. At equal 1.5-microM concentrations, LTB4 completely inhibited the omega-oxidation of all other substrates and partially suppressed that of leukotriene B5, consistent with the lower Km of LTB4 and indicating that P-450LTB catalyzed the omega-oxidation of all substrates. Thus, P-450LTB is a novel cytochrome P-450 of human polymorphonuclear leukocytes with substrate recognition determined by the triene bond configuration and the chirality of the hydroxyl groups.

Cytochrome P-450 Enzyme System↗
PubMed1986

The synthesis of N-acetyl-leukotriene E4 and its effects on cardiovascular and respiratory function of the anesthetized pig.

The effects of the putative biliary metabolite of the peptido-leukotrienes, N-acetyl-leukotriene (LT) E4 has been investigated in the anesthetized pig. Intravenous bolus doses of synthetic N-acetyl-LTE4 produced minimal respiratory and cardiovascular actions in the pig. N-acetyl-LTE4 was approximately 100-fold less active than LTC4. The actions of N-acetyl-LTE4 were not blocked by pretreatment of the animals with indomethacin (5 mg/kg iv) or with a selective LTD4 antagonist L-649,923 (5 mg/kg plus 2 mg/kg/hr iv). In summary, N-acetyl-LTE4 exerts weak actions in the pig which is consistent with the acetylation process being a mechanism of detoxification.

Animals↗
PubMed1986

Association of fetal growth with elevated maternal plasma zinc concentration in human pregnancy.

This report consists of two separate studies. Study I was a prospective one in which 23 pregnant women ultrasonically diagnosed as having small fetuses were compared with 22 women with large fetuses. Maternal plasma zinc concentrations pre- and post-35 weeks gestation were significantly higher in mothers of small than in mothers of large infants. Twelve women with normal pregnancies participated in study II. Biochemical data obtained in maternal plasma during the third trimester of pregnancy, including total, albumin-bound and alpha 2-macroglobulin-bound plasma zinc concentrations and plasma copper concentration were compared with infant anthropometric data at birth. The results indicated significant negative correlations between maternal plasma zinc and albumin-bound zinc concentrations and plasma copper concentration in the third trimester of pregnancy and mid-arm circumference and ponderal index. The results of these studies, in the light of other data reported for primates and humans, suggest the need for a more extensive investigation of the relationship between maternal circulating zinc and copper concentrations and fetal growth.

Adult↗
PubMed1985

Actions of synthetic leukotrienes on platelets and blood vessels in the anesthetised pig: the release of a platelet derived vasodilator.

The actions of leukotrienes (LT's) C4, D4, E4 and F4 have been investigated in the perfused hind-limb of the anesthetized pig. In the blood perfused hind limb LTC4, D4 and E4 increased the perfusion pressure in a dose-dependent fashion whereas LTF4 decreased perfusion pressure. In the Tyrode perfused hind limb all LT's increased perfusion pressure (rank order potency LTC4 = LTD4 much greater than LTF4). The actions of LTF4 were not affected by a wide variety of pharmacological treatments, including indomethacin, methysergide and FPL-55712. The LT's aggregated porcine platelets (rank order potency LTC4 greater than LTF4 greater than LTD4) and induced the release of a platelet-derived vasodilatory mediator. The results provide pharmacological evidence of specific leukotriene receptors in vivo and that leukotrienes can independently modulate blood flow. These data suggest that important interactions may occur between platelets, the arachidonate lipoxygenase products and platelet-derived substances in response to inflammatory stimuli in the cardiovascular system.

Animals↗
PubMed1984

Biological activities of isomers of 8,15-dihydroxyeicosatetraenoic acid.

Chemically synthesized 8(S), 15(S)-dihydroxy-5,11-cis-9, 13-trans-eicosatetraenoic acid and 8(R), 15(S)-dihydroxy-5,11-cis-9,13-trans-eicosatetraenoic acid were inactive, in comparison to leukotriene B4, in a human polymorphonuclear leukocyte chemokinetic assay and a rat polymorphonuclear leukocyte aggregation assay.

Animals↗
PubMed1978

Clinical study of mianserin, imipramine and placebo in depression: blood level and MHPG correlations.

1. The clinical efficacy of mianserin, a tetracyclic compound, was compared with imipramine and placebo in 47 hospitalized depressed patients. 2. The clinical ratings showed that the three treatment groups improved equivalently during hospitalization. 3. Plasma levels of mianserin correlated with changes in the Hamilton Rating Scale for depression, total score and two of its factors (anxiety/somatization, and retardation) and the item 'late insomnia'. 4. Drowsiness was a more frequent side-effect among mianserin patients on day 4; no other side-effect distinguished the treatments. 5. No relationship between MHPG levels and treatment or treatment outcome were observed.

Adjustment Disorders↗
PubMedDate not supplied

Intrathecal vincristine: an analysis of reasons for recurrent fatal chemotherapeutic error with recommendations for prevention.

PURPOSE: Accidental intrathecal vincristine instillation is usually a fatal error. The authors report an analysis of a patient and suggest means with which to reduce such errors. PATIENTS AND METHODS: A 7-year-old girl with recurrent acute lymphoblastic leukemia was inadvertently injected intrathecally with 1.5 mg vincristine. A detailed analysis of the events leading to this error and a review of all reported cases in the English literature were undertaken. RESULTS: Reasons for errors reported by us and other institutions included mistaking vincristine for an intended intrathecal drug, assuming vincristine was an additional drug to be injected, not checking physician orders, mistaken route of administration, and mislabeling of syringes. CONCLUSION: Intrathecal injection of vincristine may be the end-result of a series of systems errors. Protocol recommendations to reduce the likelihood of this error are presented.

Antineoplastic Agents, Phytogenic↗
PubMedDate not supplied

Nurse educator performance standards.

In this article, the authors highlight the process by which one staff education department developed performance standards. These standards facilitate orientation of new educators, assist with the planning of developmental goals, and guide the evaluation process. This process can serve as a prototype for nurse educators faced with the challenge of developing performance standards.

Education, Nursing, Continuing↗