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Biomedical subjects

L Taylor

Publications and source records attributed to L Taylor.

At least 37 records · Page 2Linked to original sources
PubMed2001

Direct ESR dating of a Pliocene hominin from Swartkrans.

Two fragments of a hominin tooth (Australopithecus robustus) and two bovid teeth from the Hanging Remnant of the Swartkrans Formation were analysed with ESR. Research was complicated by the fact that the samples came from a curated collection and their precise provenance is unknown. The environmental dose rate was reconstructed by a series of in situ gamma spectrometric measurements and elemental analyses of a range of sediment samples. U-series isotopic analyses indicated that each of the teeth had a significantly different uranium uptake history, rendering the assumptive early U-uptake and linear U-uptake models ineffective. ESR and U-series data were combined to calculate open system ages, resulting in a best estimate of 1630+/-160 ka for the Hanging Remnant. An open-system model which provides the maximum age for given U-series and ESR measurements yielded an estimate of about 2100 ka. Two bovid teeth from Member 2, previously estimated to be between 1.0 and 2.0 Ma, yielded age estimates of between about 100 and 200 ka. No known geochemical processes are likely to explain this severe age underestimation. We conclude that these samples are of Middle to Upper Pleistocene age and their presence in Member 2 was either due to reworking or inadequate stratigraphical discrimination of these deposits.

Animals↗
PubMed2001

Intentional injury treated in community hospitals.

BACKGROUND: The impact of intentional injury in major metropolitan trauma centers has been established. Nonaccidental injury has become an increasingly important component of trauma care in mid-sized urban areas. To determine the medical and economic impact of personal violence in the Spokane, Washington, community we undertook a 5-year retrospective review. PATIENTS AND METHODS: Trauma registries were used to identify all victims of intentional injury admitted between May 1, 1994, and April 31, 1999. Demographic data, blood alcohol, mechanism, injury severity, hospital course, and outcome were abstracted from the registries. Financial data were obtained from hospital financial offices. SETTING: Spokane, Washington, has a population of 200,000 with 400,000 in the metropolitan area. Trauma patients are triaged to hospitals according to Washington Administrative Code guidelines, supervised by central medical control. The two level II and two level III facilities are staffed by private practice surgeons and serve a referral area of 650,000. RESULTS: Five hundred eighty-one intentional injury patients were admitted. This represented 15% of all significant injuries. Males accounted for 80% of the patients and 84%were Caucasian. The mean patient age was 30 years, only one quarter were listed as employed. Sixteen percent of the injuries were self-inflicted, gunshot was the most common mechanism (39%). Alcohol was involved in one half of the injuries. Sixty-three patients died, 39 died prior to intensive care unit admission. Hospital stay averaged 6.4 days, with a mean hospital charge of $18,000. Hospitals were reimbursed at 67%. Surgeons collected 31% of billed fees. Fewer than one third of patients had any form of private insurance. CONCLUSIONS: Intentional injury is a significant component of trauma care in our community. Patients are seriously injured and the fatality rate is high. Care is expensive and poorly funded.

Adolescent↗
PubMed2001

Muscarinic agonists and antagonists in the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment and personality changes. The development of drugs for the treatment of the cognitive deficits of AD has focused on agents which counteract loss in cholinergic activity. Although symptoms of AD have been successfully treated with acetylcholinesterase inhibitors (tacrine, donepezil. rivastigmine, galanthamine), limited success has been achieved with direct M1 agonists, probably due to their lack of selectivity versus other muscarinic receptor subtypes. Muscarinic M2 antagonists have been reported to increase synaptic levels of acetylcholine after oral administration to rats (e.g. BIBN-99, SCH-57790), but their selectivity versus other muscarinic receptor subtypes is modest. Exploration of a series of piperidinylpiperidines has yielded the potent and selective M2 antagonist SCH-217443. This antagonist has excellent bioavailability in rats and dogs and shows activity in a rat model of cognition.

Alzheimer Disease↗
PubMed2001

The Heartmate II: design and development of a fully sealed axial flow left ventricular assist system.

Our group is developing the control and power transmission components required to implement a permanent and fully sealed left ventricular assist system (LVAS). Starting with the percutaneously powered HeartMate II blood pump, our development efforts are focused in the following areas: a complete redesign of the transcutaneous energy transmission system (TETS) to include a rectification network and autonomous voltage regulation within the secondary coil, a hermetically sealed electronics package containing a miniaturized implementation of the existing redundant drive and control electronics with several power-input options, an implanted rechargeable lithium ion battery pack capable of providing up to 1 h of untethered operation, implantable electrical connectors that allow components to be connected after placement in the body or to be replaced if needed, and a radio telemetry subsystem to transmit diagnostic information and to permit remote adjustment of selected parameters.

Electric Power Supplies↗
PubMed2001

The rate and cost of hospital-acquired infections occurring in patients admitted to selected specialties of a district general hospital in England and the national burden imposed.

Between April 1994 and May 1995 4000 adult patients admitted to selected specialties of a district general hospital were recruited to this study. Hospital-acquired infections presenting during the in-patient stay were identified using previously validated methods of surveillance, and information on daily resource use by both infected and uninfected patients was recorded and estimates of their cost derived. Linear regression modelling techniques were used to estimate how much of the observed variation in resource use and costs could be explained by the presence of an infection. Complete in-patient data sets were obtained for 3980 patients. Of these, 309 patients (7.8%; 95% CI; 7.0, 8.6) presented with one or more hospital-acquired infections during the in-patient period. Infected patients, on average, incurred hospital costs 2.9 (regression model estimate: 2.8; 95% CI; 2.6, 3.0) times higher than uninfected patients, equivalent to an additional pound3154 (regression model estimate pound2917). Both the incidence and the economic impact varied with site of infection and with admission specialty. Estimates of the burden of hospital-acquired infections occurring in adult patients admitted to similar specialties at NHS hospitals in England were derived from the results of this study. An estimated 320 994 (95% CI; 288 071, 353 916) patients per annum acquire one or more infections which present during the in-patient period, and these infections cost the hospital sector an estimated 930.62 million pounds (95% CI; 780.26 pounds; 1080.97 million pounds) per annum. The results presented represent the gross economic benefits that might accrue if these infections are prevented. Further research is required to establish the net benefits of prevention.

Adolescent↗
PubMed2001

The epic project: developing national evidence-based guidelines for preventing healthcare associated infections. Phase I: Guidelines for preventing hospital-acquired infections. Department of Health (England).

In 1998, the Department of Health (England) commissioned the first phase of national evidence-based guidelines for preventing healthcare associated infections. These focused on developing a set of standard principles for preventing infections in hospitals together with guidelines for preventing hospital-acquired infections (HAI) associated with the use of short-term indwelling ureteral catheters in acute care and with central venous catheters in acute care. These guidelines are systematically developed broad statements (principles) of good practice that all practitioners can use and which can be incorporated into local protocols. A nurse-led, multi-professional team composed of infection prevention practitioners, clinical microbiologists/retrovirologist, epidemiologists, and researchers developed the guidelines. A rigorous guideline development process was used to inform the systematic reviews, the clinical and critical appraisal of relevant evidence, and linking that evidence to evolving guidelines. Both general and specialist clinical practitioners were involved in all stages of developing these guidelines, as were representatives from relevant Royal Colleges, learned societies, other professional organisations and key stakeholders. The introduction to these guidelines describes a robust and validated guideline development model that can be used by others to develop future guidelines. This model is described in more detail in the associated technical reports that can be found on the project web site http://www.epic.tvu.ac.uk. Locating and appropriately using good quality evidence to inform guideline development in this field is challenging. Evidence from rigorously conducted experimental studies was frequently limited and consequently a range of other types of evidence were systematically retrieved and carefully appraised. The concluding discussion on implementation highlights potential issues for clinical governance and areas for future research and suggests issues that need to be addressed to allow practitioners to successfully incorporate these guidelines into routine clinical practice.

Acute Disease↗
PubMed2001

Outbreak of foetal infection with bovine pestivirus in a central Queensland beef herd.

OBJECTIVE: To describe a significant outbreak of foetal infection and subsequent losses due to bovine pestivirus on a 5200 ha beef breeding and fattening property in central Queensland. DESCRIPTION OF THE HERD: The affected herd consisted of 656 cows, including 269 recently purchased cows, and 221 heifers that were joined in December/January 1995/96. There were approximately 2500 cattle on the property. INVESTIGATION: Following the purchase of 269 cows in October 1995, which were mingled with the existing cow herd, losses were experienced due to foetal infection with bovine pestivirus. These losses were recorded between 1996 and 1999 as: reduced pregnancy rates, losses between pregnancy testing (midpregnancy) and branding (calves averaged 3 months-of-age), losses due to pneumonia and ill-thrift between branding and approximately 12 months-of-age, and losses due to ill-thrift and the chronic wasting form of mucosal disease thereafter. All surviving calves were tested for bovine pestivirus in 1997 at an average of 10 months. Fifty-three calves were identified as persistently infected with bovine pestivirus. A further 110 calf losses could reasonably be attributed to bovine pestivirus infection. Persistently infected cattle were always unthrifty compared to their virus negative counterparts. Only one persistently infected calf was identified, on the basis of severe ill thrift, in the 1997 birth cohort and none in 1998. CONCLUSIONS: This outbreak of foetal infection with bovine pestivirus resulted in significant production losses. These losses were recorded over the three years subsequent to the outbreak. Significant numbers of persistently infected calves were not evident among calves born in the two years after this outbreak.

Age Factors↗
PubMed2001

Use of Neo-melubrina, a banned antipyretic drug, in San Diego, California: a survey of patients and providers.

BACKGROUND: Dipyrone is an antipyretic drug that has been associated with agranulocytosis. It is banned in the United States but is available in Mexico under the name Neo-melubrina. OBJECTIVES: To define the use of Neo-melubrina in the Hispanic population of 2 San Diego, California, community clinics and to determine local physicians' and nurse practitioners' awareness of the drug and its risks. DESIGN: Patient survey and provider survey. PARTICIPANTS PATIENTS: 200 parents of Hispanic pediatric patients. Providers: members of San Diego chapters of the American Academy of Pediatrics, the American Academy of Family Physicians, and the California Coalition of Nurse Practitioners. MAIN OUTCOME MEASURES: Self-reported use of Neo-melubrina by patients, and provider awareness of Neo-melubrina and its most significant side effects. RESULTS: Of the 200 patients, 76 (38.0%) reported a lifetime use of Neo-melubrina. Most (56%) used it for both pain and fever. Most providers were unable to correctly identify why Neo-melubrina might be used or its adverse effects. Physicians answered correctly more often than nurse practitioners and pediatric providers more often than family medicine providers. Providers who trained within 75 miles of the US-Mexico border, who reported a patient population of more than 50% Hispanic, and who were resident physicians at the time of the survey were most likely to answer correctly. CONCLUSIONS: Neo-melubrina has been used by a substantial percentage of Hispanic patients in the community clinics surveyed. Many San Diego health care providers are unaware of this medication and may, therefore, miss opportunities to educate patients about safer alternatives.

Adult↗
PubMed2001

C/EBPbeta contributes to cAMP-activated transcription of phosphoenolpyruvate carboxykinase in LLC-PK(1)-F+ cells.

Phosphoenolpyruvate carboxykinase (PEPCK) is a key regulatory enzyme in renal gluconeogenesis. Activation of various PEPCK(-2300)Luc reporter constructs in LLC-PK(1)-F+ cells, a gluconeogenic line of porcine renal proximal tubule-like cells, by protein kinase A (PKA) is mediated, in part, through the cAMP-response element (CRE)-1 of the PEPCK promoter. Incubation of a CRE-1 containing oligonucleotide with nuclear extracts from LLC-PK(1)-F+ cells produced multiple bands, all of which were blocked by antibodies that are specific for C/EBPbeta but not for C/EBPalpha or C/EBPdelta. Treatment of cells with cAMP did not affect the expression of C/EBPbeta, but the observed binding activity was increased nearly threefold. Mutation of CRE-1 to a Gal-4 binding site reduced the PKA-dependent activation of PEPCK(-2300)Luc to 40% of that observed with the wild-type construct. Coexpression of a chimeric protein containing a Gal-4 binding domain and the transactivation domain of C/EBPbeta, but not of C/EBPalpha or CRE binding protein (CREB), restored full activation by PKA. A deletion construct that lacks the activation domain of C/EBPbeta functions as a dominant negative inhibitor. Thus the binding of C/EBPbeta to the CRE-1 may contribute to the cAMP-dependent activation of the PEPCK promoter in kidney cells.

Animals↗
PubMed2001

Presumed common source outbreaks of hepatitis A in an endemic area confirmed by limited sequencing within the VP1 region.

Hepatitis A virus isolates from anti-HAV IgM positive sera of 70 hepatitis cases in two outbreaks and 216 other cases in Central America, 136 sporadic cases and 53 cases from an hyper-endemic region in Costa Rica, were compared by phylogenetic analyses within the VP1 region. The outbreaks in all 531 cases, in 1992 and 1999, respectively, were presumed water borne. In the first outbreak, HAV RNA could be detected in 70% of the cases sampled during 6 weeks after onset of jaundice. In the hyper-endemic region of San Ramón in Costa Rica, 1,932 cases were registered between 1972 and 1985. All isolates belonged to subtype 1A. Background isolates from Costa Rica and El Salvador tended to form separate subclusters in the phylogenetic tree construction and were mostly unrelated to subtype 1A strains from other parts of the world. Based on their amino acid sequences, four HAV strains, all related to CR326 sampled in Costa Rica in 1960, were found to have circulated in the area during the last three decades. However, on the basis of nucleotide variability the isolates from the outbreaks could be distinguished from the strains from sporadic cases and sequence analysis could confirm the epidemiological homogeneity of both outbreaks. In the hyper-endemic region, 16 different sequences were encountered forming one single subcluster. Thus, limited sequencing within the VP1 region proved useful to identify outbreaks of hepatitis A in a highly endemic area, where most strains were local and only one subtype was prevalent.

Adolescent↗
PubMed2000

Evaluation of transdermal fentanyl patches for analgesia in cats undergoing onychectomy.

OBJECTIVE: To evaluate efficacy and safety of using transdermal fentanyl patches (TFP) for analgesia in cats undergoing onychectomy. DESIGN: Randomized controlled clinical trial. ANIMALS: 45 client-owned cats weighing > or = 2.7 kg (5.9 lb) undergoing onychectomy, onychectomy and ovariohysterectomy, or onychectomy and castration. PROCEDURE: Cats were randomly assigned to be treated with a TFP (25 micrograms/h) or butorphanol; TFP were applied a minimum of 4 hours before surgery (approx 8 hours prior to extubation). Rectal temperature, heart rate, respiratory rate, force applied by the forelimbs, and serum fentanyl concentration were measured, and temperament, recovery, degree of sedation, severity of pain, severity of lameness, and appetite were scored before and periodically for up to 40 hours after surgery. RESULTS: Cats treated with a TFP had better recovery scores at 2 of 4 evaluation times, lower sedation scores at 2 of 8 evaluation times, and lower pain scores at 6 of 8 evaluation times, compared with cats treated with butorphanol. Use of a pressure-sensitive mat to evaluate force applied by the forelimbs did not reveal any differences between groups but did reveal a significant difference between preoperative and postoperative values. Mean +/- SD serum fentanyl concentrations were 1.56 +/- 1.08, 4.85 +/- 2.38, 4.87 +/- 1.56, and 4.35 +/- 2.97 ng/ml approximately 8, 24, 32, and 48 hours, respectively, after TFP placement. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that use of a TFP (25 micrograms/h) for postoperative analgesia in cats undergoing onychectomy with or without surgical sterilization is safe and effective.

Administration, Cutaneous↗
PubMed2000

The shc adaptor protein forms interdependent phosphotyrosine-mediated protein complexes in mast cells stimulated with interleukin 3.

The Shc adaptor protein possesses 2 distinct phosphotyrosine (pTyr) recognition modules-the pTyr binding (PTB) domain and the Src homology 2 (SH2) domain-and multiple potential sites for tyrosine (Tyr) phosphorylation (Tyr residues 239, 240, and 317). On stimulation of hematopoietic cells with interleukin 3 (IL-3), Shc becomes phosphorylated and may therefore contribute to IL-3 signaling. We investigated the interactions mediated by the Shc modular domains and pTyr sites in IL-3-dependent IC2 premast cells. The Shc PTB domain, rather than the SH2 domain, associated both in vitro and in vivo with the Tyr-phosphorylated beta subunit of the IL-3 receptor and with the SH2-containing 5' inositol phosphatase (SHIP), and it recognized specific NXXpY phosphopeptides from these binding partners. In IL-3-stimulated mast cells, Shc phosphorylation occurred primarily on Tyr239 and 317 and was dependent on a functional PTB domain. Phosphorylated Tyr317, and to a lesser extent, Tyr239, bound the Grb2 adaptor and SHIP. Furthermore, a pTyr317 Shc phosphopeptide selectively recognized Grb2, Sos1, SHIP, and the p85 subunit of phosphatidylinositol 3' kinase from mast cells, as characterized by mass spectrometry. These results indicate that Shc undergoes an interdependent series of pTyr-mediated interactions in IL-3-stimulated mast cells, resulting in the recruitment of proteins that regulate the Ras pathway and phospholipid metabolism.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Regulation of inducible bradykinin B1 receptor gene expression through absence of internalization and resensitization.

Rapid induction and down-regulation of bradykinin B1 receptor (BKB1R) gene expression is tightly regulated at the transcriptional and mRNA levels (Zhou et al. [1998] Biochem. J. 330:361-366; Zhou et al. [1999] Mol. Cell Biol. Res. Commun. 1:29-35). Here we explore regulation of BKB1R expression at the protein level. To make this inducible gene express constitutively, we utilized a bicistronic mammalian expression vector (pCMin) for stable transfection of the BKB1R gene into human lung fibroblasts, IMR90SV40. The BKB1R displayed a high affinity and specificity (K(d) = 0.5 nM) for desArg(10)-kallidin. The receptor mediated such signaling events as arachidonic acid (ARA) release, phosphoinositide (PI) turnover and Ca(2+)-flux. The receptor function proved differentially desensitized. For example, after initial exposure to desArg(10)-kallidin, a second stimulation with desArg(10)-kallidin did not induce further Ca(2+)-flux or ARA-release while PI-turnover continued unabated. Unlike most of the G-protein coupled receptors, the BKB1R did not internalize within 60 min of exposure to 10 nM desArg(10)-kallidin. It also did not resensitize. Thus, the duration and signal capacity of the BKB1R at the protein level is regulated through lack of internalization, an absence of resensitization and a lack of desensitization for certain events such as PI turnover. In fact, the absence of BKB1R resensitization is likely a very important contributor to the rapid disappearance of this inducible receptor.

Arachidonic Acid↗
PubMed2000

Isolation, characterization and expression of a human brain mitochondrial glutaminase cDNA.

Various cDNAs that encode overlapping portions of the full-length human brain glutaminase (GA) cDNA were cloned and sequenced. The overall nucleotide sequence of hGA has a very high degree of identity with that of the rat kidney-type GA cDNA (77.4%) and the known portion of the cDNA that encodes the 5.0-kb porcine GA mRNA (81.1%). The identity is even more remarkable at the amino acid level, particularly in the C-terminal half where the three proteins share a 99.7% sequence identity. The hGA cDNA encodes a 73,427-Da protein that contains an N-terminal mitochondrial targeting signal and retains the primary proteolytic cleavage site characterized for the cytosolic precursor of the rat renal mitochondrial glutaminase. The entire coding region was assembled through the use of unique restriction sites and cloned into a baculovirus. Sf9 cells infected with the recombinant virus express high levels of properly processed and active glutaminase. Thus, expression of the isolated hGA cDNA should provide a means to purify large amounts of the mitochondrial glutaminase, a protein that catalyzes a key reaction in the metabolism of glutamine and the synthesis of important excitatory and inhibitory neurotransmitters.

Amino Acid Sequence↗