PubMed Health⌕ Search

Biomedical subjects

T Fitzpatrick

Publications and source records attributed to T Fitzpatrick.

At least 19 recordsLinked to original sources
PubMed2001

Subcellular localization and characterization of chorismate synthase in the apicomplexan Plasmodium falciparum.

The resurgence of drug-resistant apicomplexa, in particular Plasmodium falciparum, the most fatal human malarial parasite, has focused attention on the recent discovery of the shikimate pathway in these organisms, as it may provide the urgently required, novel drug targets resulting from the absence of this pathway in mammals. The direction of a parasiticidal drug design programme obviously requires knowledge of the subcellular localization and indeed full characterization of the possible enzyme targets. Here, we report the cloning and characterization of chorismate synthase from P. falciparum and present the first biochemical and immunological studies of an enzyme of the shikimate pathway from an apicomplexan parasite. We show that this chorismate synthase does not possess an intrinsic flavin reductase activity and is therefore monofunctional like the plant and bacterial chorismate synthases. Highest immunological cross-reactivity was found with a plant chorismate synthase. However, in contrast to the plant enzyme, which is located to the plastid, P. falciparum chorismate synthase is found in the parasite cytosol, akin to the fungal enzymes that possess an intrinsic flavin reductase activity (i.e. are bifunctional). Thus, P. falciparum chorismate synthase has a combination of properties that distinguishes it from other described chorismate synthases.

Amino Acid Sequence↗
PubMed2000

Antiproliferative actions of inhalational anesthetics: comparisons to the valproate teratogen.

The antiproliferative potential of the volatile anesthetics isoflurane, enflurane and sevoflurane was determined and compared to the valproate teratogen. The in vitro system employed, a G1 phase proliferative arrest endpoint in C6 glioma, has served previously to discriminate agents with known teratogenic potential in vivo. Based on estimated IC(50) values that were within twice the estimated minimum aveolar concentration value, the rank antiproliferative potency of the inhalational anesthetics employed was isoflurane=enflurane>>sevoflurane. Flow cytometric analysis of growth-arrested cell populations failed to reveal specific accumulation in any cell cycle phase and the lack of a G1 phase-specific effect was confirmed by the absence of a transient, time-dependent sialylation event in synchronized cells. The antiproliferative mechanism of volatile anesthetics, and valproate, was mediated at hydrophobic binding sites, as increasing the hydration sphere of the drug-micelle complex, using the hygroscopic qualities of the dimethylsulfoxide vehicle, completely reversed this effect. Our findings suggest inhalational anesthetics lack the specific in vitro characteristics of the valproate teratogen.

Anesthetics, Inhalation↗
PubMed1998

Pregnancy and delivery in a patient with recent peripartum cardiomyopathy.

We present a case of successful pregnancy and delivery in a patient with peripartum cardiomyopathy who conceived only 3 months after a vaginal delivery complicated by peripartum cardiomyopathy. Following the onset of labor, an arterial pressure catheter and pulmonary artery catheter were placed. A combined epidural spinal technique was performed without difficulty for labor analgesia. After a few hours of labor, the fetal heart rate tracing revealed repetitive variable decelerations, and a decision was made to proceed with operative delivery. The mother's hemodynamic changes are presented, and the specifics of the anesthetic care are outlined.

Journal Article↗
PubMed1998

Determinants of home health visit length: results of a multisite prospective study.

OBJECTIVES: The authors (1) compare visit length across four categories of skilled nursing home health visits which reflect recent changes in home health casemix-AIDS-related, hospice/terminal (HT), intravenous (IV) therapy, and maternal and child health (MCH)-with general adult medical/surgical (MS) visits and (2) identify factors influencing visit length. METHODS: The study sites were 12 nonproprietary Massachusetts home health agencies (HHAs). Staff nurses collected data concurrently on a sample of visits they provided between December 1, 1992 and November 30, 1993. The visits were stratified by agency, time of year, and visit category. The authors used analysis of variance to test for significant differences across visit categories in Home Length of Visit (the number of minutes between when the nurse entered and left the home) (HLOV). The authors used multivariate regression analysis to develop models identifying determinants of HLOV and adjusted R2 to measure the explanatory power of partial models. RESULTS: In univariate analysis, the categories differed significantly from each other in length (P < 0.0001). HT visits were the longest (median visit length = 60, 80, and 59 minutes for HT Only visits, visits in both the HT and AIDS categories (HT/AIDS), and HT/IV visits, respectively). MS visits were the shortest (median = 30 minutes). The remaining categories were intermediate in length (medians = 37 to 50 minutes). Almost half the variability in HLOV was explained by the full multivariate regression model, which includes all independent variables (adjusted R2 = .4486; P < 0.0001). Visit characteristics alone in a partial model explained 18% of the variability in HLOV. Three other variable sub-groups-agency, client characteristics, and nursing workload-each explained about 15% of the variability in HLOV. Nursing activities performed during the visit explained 11%; several of these related to teaching, education, or assessment. CONCLUSIONS: Accurate reimbursement reflecting casemix differences is important to protect the teaching, education, and assessment functions of nurses; measure nurse productivity and allocate caseloads; maintain access to services for clients with greater needs; and avoid creating economic disincentives to the agencies that serve them. Payers formulating prospective payment systems can adjust per visit reimbursement rates to reflect differences in visit length by category and incorporate functional limitations, clinical instability, and case coordination as classification variables. Developers of home health casemix systems can use factor analysis to improve the robustness of multivariate models and include nursing workload in predicting visit length. Home health agencies measuring productivity and caseload across complex client populations can classify visits into three groups-MS; HT; and AIDS, IV, and MCH-or use the regression results to develop more refined predictors of visit length and nursing caseload.

Adult↗
PubMed1996

A model of blast overpressure injury to the lung.

Despite decades of animal experiments, data on blast injury to the lung cover only a limited number of circumstances and are in a fragmented form. This paper develops a mathematical model of the chest wall dynamics and the subsequent generation of strong pressure waves within the lung, which have been hypothesized as the mediator of injury. The model has been compared to an extensive database of observed pathologies from animal tests. The incidence of injury and lethality is found to follow a log-normal correlation with the computed total energy in these waves and, when the energy is normalized by the lung volume, the lethality correlation applies to all large animal species. Small animals also correlate with the normalized energy, but at a different value, and it is speculated that structural differences, other than lung volume, may be involved. This relatively simple model allows the potential for blast injury to the lung to be determined from measured or computed pressure traces without additional animal testing. Improved occupational exposure criteria should follow from this methodology.

Animals↗
PubMed1986

Linkage, evolution, and expression of the rat apolipoprotein A-I, C-III, and A-IV genes.

The genes coding for three of the proteins of the lipid transport system, apolipoproteins A-I (apoA-I), C-III (apoC-III), and A-IV (apoA-IV), are closely linked and tandemly organized as a multigene family in the human genome. The evolution of this multigene family was studied by cloning and extensive restriction mapping analysis of an approximately 20-kilobase genomic DNA fragment containing the rat apoA-I gene. Low stringency hybridization blotting analysis of this DNA fragment using human apoC-III and apoA-IV cDNA probes revealed that the apoA-I, apoC-III, and apoA-IV genes are also closely linked and tandemly organized in the rat genome. Complete characterization of the rat apoA-I, apoC-III, and apoA-IV genes showed that their relative location, size, direction of transcription, and intron-exon organization are remarkably similar to those of the corresponding human genes. The relative steady state apoA-I, apoC-III, and apoA-IV mRNA levels in various rat tissues were determined by quantitative dot blot hybridization of tissue total RNA using the corresponding gene probes. Adult liver and intestine, but not colon, brain, spleen, muscle, heart, lung, and kidney, contain apoA-I, apoC-III, and apoA-IV mRNAs. Fetal liver and intestine contain apoA-I but not apoC-III or apoA-IV mRNAs. During neonatal development the liver contains apoA-I and apoC-III but not apoA-IV while the intestine contains apoA-I, apoC-III, and substantial amounts of apoA-IV mRNAs. In adulthood and during aging both liver and intestine contain all three apoA-I, apoC-III, and apoA-IV mRNAs. These results indicate that the apolipoprotein A-I/C-III/A-IV multigene family was established before mammalian radiation and suggest that these genes are similarly organized in the genomes of all mammals. In addition, these results indicate that expression of the rat apoA-I, apoC-III, and apoA-IV genes is liver- and intestine-specific and regulated by fetal-, neonatal-, and aging-related factors.

Amino Acid Sequence↗
PubMed1984

Responses to leukotriene C4 in the perfused rat lung.

The isolated rat lung was used to study both the effect of leukotriene C4 on pulmonary perfusion pressure and the synthesis and release of cyclooxygenase products in the pulmonary circulation. A cell-free perfusate was passed only once through the pulmonary circulation or was recirculated. During single transit, leukotriene C4 produced dose-dependent increases in pulmonary perfusion pressure that were abolished by FPL-55712, a leukotriene receptor antagonist, but were not altered significantly by indomethacin. The duration of the pulmonary pressor response to leukotriene C4 was markedly prolonged during recirculation compared to single transit. Leukotriene C4 also induced dose-dependent increases in effluent levels of 6-keto-prostaglandin F1 alpha and thromboxane B2 that were attenuated by indomethacin or FPL-55712 pretreatment. We conclude that leukotriene C4 directly constricts the pulmonary vasculature independent of cyclooxygenase products, is not rapidly degraded by the pulmonary circulation and stimulates the release of cyclooxygenase products in the pulmonary circulation that can be attenuated by pretreatment with indomethacin or FPL-55712.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Quantitative criteria for prediction of the results after displaced fracture of the ankle.

In a series of 146 displaced ankle fractures, the effects of age, sex, side of injury, mechanism of injury, severity as determined by the Lauge-Hansen classification, type of injury (open or closed), open or closed treatment, and internal fixation of one or both malleoli were analyzed using subjective, objective, and radiographic parameters. Statistically significant prognostic features were identified and a prognostic scale was developed using multiple linear-regression analysis. The significant parameters were age, adequacy of the post-reduction positions of the medial and lateral malleoli, and completeness of the restoration of the deltoid ligament and distal tibiofibular syndesmosis. Open reduction proved superior to closed reduction, and in bimalleolar fractures open reduction of both malleoli was better than fixing only the medial side. Using the data on the first 109 fractures, a multiple linear-regression equation was formulated and used to predict the outcomes of the last thirty-seven fractures in the study. The accuracy of the predictions in them was 81 per cent.

Adolescent↗