Search PubMed⌕ Search

Biomedical subjects

K Leslie

Publications and source records attributed to K Leslie.

At least 37 records · Page 2Linked to original sources

Anaesthetists' attitudes towards awareness and depth-of-anaesthesia monitoring.

Advances in technology have resulted in the development of several depth-of-anaesthesia monitors. Whether any of these monitors can reduce the incidence of awareness is an important issue for anaesthetists and their patients. We therefore surveyed a random selection of anaesthetists, asking for their opinions of awareness and depth-of-anaesthesia monitoring in current clinical practice. Approximately half (52%) of the anaesthetists surveyed had experienced a patient with awareness. Anaesthetists considered that they had a lower incidence of awareness in their own practice when compared with others, 1:5000 vs. 1:10 000 (p < 0.001). Anaesthetists rated awareness on an 11-point scale as only a moderate problem, median (interquartile range) 5 (2-7). Older anaesthetists were less likely to rate the importance of awareness highly (p = 0.009) and to use awareness monitoring (p = 0.001). Anaesthetists are prepared to use depth-of-anaesthesia monitoring more widely if it can be shown to prevent most cases of awareness in routine practice.

Adult↗

Cell shape and gene expression in human intervertebral disc cells: in vitro tissue engineering studies.

The objective of the present study was to examine the relation between gene expression and the shape of human intervertebral disc cells cultured in vitro in three-dimensional (3D) scaffolds. Disc cells from 19 subjects were seeded into either a collagen sponge or collagen gel and cultured for 10 days. In situ hybridization was performed on serial sections of paraffin embedded specimens and assessed for expression of selected genes important for extracellular matrix formation: Types I and II collagen, aggrecan and chondroitin-6 sulfotransferase. Rounded cells grown in collagen gel showed expression of Types I and II collagen, aggrecan and chondroitin-6 sulfotransferase; expression of these genes was absent in spindle shaped cells. Cells in the collagen sponge that lay on the sponge margin were frequently spindle shaped; these cells expressed type I collagen, but not type II collagen, aggrecan or chondroitin-6 sulfotransferase. Results presented here provide novel data concerning disc cell gene expression with collagen 3D constructs. This information is useful for future tissue engineering studies that have the challenging goal of selectively modulating gene expression.

Adult↗

Patients' knowledge of and attitudes towards awareness and depth of anaesthesia monitoring.

Awareness during anaesthesia is uncommon (approximately 0.1%), but causes significant anxiety, dissatisfaction and morbidity for patients. Several electroencephalographic monitors hold promise as monitors for awareness. We therefore conducted a survey to evaluate patients' knowledge of and attitudes towards awareness and monitors of anaesthetic depth. Two hundred consenting, preoperative patients completed a seven-item questionnaire. The median number of previous operations was 2 (inter-quartile range, 1-5). Thirteen patients reported an experience which they thought might be awareness (2% of operations performed on the cohort). Only 56% of patients had heard about awareness before and many (35%) of these had heard about it in the media. Many (35%) were uncertain about what might cause awareness. Many (42.5%) were anxious about awareness: female sex and not having heard about awareness before were significant predictors of anxiety. Nevertheless only 34% were willing to pay for a proven awareness monitor if they were at low risk and only 50% if they were at high risk. Perceived risk and a previous awareness experience were significant predictors of willingness to pay for awareness monitoring.

Adult↗

Target words for the Word Stem Completion test in Australian patients.

A robust test that reliably demonstrates implicit memory during general anaesthesia is required. The Word Stem Completion (WSC) test has been used as a measurement tool in a number of recent studies that have detected implicit memory during anaesthesia. However, target words used in the WSC test need to be culturally appropriate in order to maximize the sensitivity of the test. Therefore, fifty postoperative patients with English as a first language were recruited at The Royal Melbourne Hospital in order to assess the frequency of 98 target words in response to a word stem presentation. This generated a list of 32 target words that is suitable for use in studies of implicit memory during anaesthesia in Australian patients.

Aged↗

Effect of a monensin controlled release capsule on metabolic parameters in transition dairy cows.

A prospective field study involving 251 Holstein cows and heifers from five dairy farms near Guelph, Ontario, Canada, was conducted to measure the effect of monensin delivered in a controlled release capsule 3 wk precalving on metabolic function in dairy cows immediately pre- and postcalving. At 3 wk before expected calving, cows were randomly assigned to receive either a controlled release capsule containing monensin or to serve as negative controls. Cows were blood sampled once per week precalving and once in the week following calving, at the same time of day and the same day of the week. Serum was evaluated for beta-hydroxybutyrate (BHBA), nonesterified fatty acids (NEFA), cholesterol, urea, glucose, calcium, and phosphorus. Monensin-treated cows had significantly decreased NEFA and BHBA and significantly increased concentrations of serum cholesterol and urea in the week immediately precalving. No effect of treatment was observed for calcium, phosphorus, or glucose in the precalving period. After calving, concentrations of phosphorus were lower and BHBA tended to be lower, and cholesterol and urea were higher in monensin-treated cows. There was no effect of treatment on NEFA, glucose, or calcium in the first week postcalving. Monensin treatment administered precalving significantly improved indicators of energy balance in both the immediate precalving and postcalving periods. The findings indicate better energy metabolism in monensin-treated cows as they approach calving. Improvement of energy balance before calving is important for the prevention of energy associated metabolic diseases, such as retained placenta, clinical ketosis, and displaced abomasum, which might occur immediately postcalving.

3-Hydroxybutyric Acid↗

A meta-analysis review of the effects of recombinant bovine somatotropin. 1. Methodology and effects on production.

This manuscript presents the results of a review of the effects of recombinant bovine somatotropin (rBST) on milk production, milk composition, dry matter intake, and body condition score that was carried out by an expert panel established by the Canadian Veterinary Medical Association (CVMA). The panel was established by the CVMA in response to a request from Health Canada in 1998 and their report was made public in 1999. A series of meta-analyses was used to combine data on production and nutrition related parameters that were extracted from all randomized clinical trials, which had been published in peer-reviewed journals or which were provided by Health Canada, from the submission by Monsanto for registration of rBST in Canada. A companion paper will present the results of the effects of the drug on measures of health, reproductive performance, and culling parameters. Recombinant bovine somatotropin was found to increase milk production by 11.3% in primiparous cows and 15.6% in multiparous cows; although there was considerable variation from study to study. While some statistically significant effects on milk composition (% butterfat, protein, and lactose) were found, they were all very small. Treatment increased dry matter intake by an average 1.5 kg/day during the treatment period and dry matter intake remained elevated on into the first 60 days of the subsequent lactation. Despite the increase in dry matter intake, treated animals had lower body condition scores at the end of the treatment period, and the reduced scores persisted through until the start of the subsequent lactation.

Animals↗

A meta-analysis review of the effects of recombinant bovine somatotropin. 2. Effects on animal health, reproductive performance, and culling.

This manuscript presents the results of a review of the effects of recombinant bovine somatotropin (rBST) on dairy cattle health, reproductive performance, and culling, that was carried out by an expert panel established by the Canadian Veterinary Medical Association (CVMA). The panel was established by the CVMA in response to a request from Health Canada in 1998 and their report was made public in 1999. A series of meta-analyses was used to combine data on health-related parameters that were extracted from all randomized clinical trials that had been published in peer-reviewed journals or which were provided by Health Canada from the submission by Monsanto for registration of rBST in Canada. A companion paper (1) presents the estimates of the effect of the drug on production parameters. Recombinant bovine somatotropin was found to increase the risk of clinical mastitis by approximately 25% during the treatment period but there was insufficient data to draw firm conclusions about the effects of the drug on the prevalence of subclinical intra-mammary infections. Use of rBST increased the risk of a cow failing to conceive by approximately 40%. For cows which did conceive, there was no effect on services per conception and only a small increase in average days open (5 days). Use of the drug had no effect on gestation length, but the information about a possible effect on the risk of twinning was equivocal. Cows treated with rBST had an estimated 55% increase in the risk of developing clinical signs of lameness. Few studies reported data on culling, but based on those that did, there appeared to be an increase risk of culling evident in multiparous cows. Use of the drug in 1 lactation period appeared to reduce the risk of metabolic diseases (particularly ketosis) in the early period of the subsequent lactation.

Animals↗

Evaluation of the repeatability of a crude adult indirect Ostertagia ostertagi ELISA and methods of expressing test results.

An indirect enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against Ostertagia ostertagi using a crude adult worm antigen was evaluated using serum and milk samples from adult cows, as well as from bulk tank milk. Within and between plate repeatabilities were determined. In addition, the effects of factors such as antigen batch, freezing, preserving of the samples and somatic cell counts (SCCs) of the samples were evaluated. Raw optical densities (ODs) and normalized values were compared using the concordance correlation coefficient (CCC), the coefficient of variation (CV), Bland-Altman plots (BA). Based on raw OD values, there was a high repeatability within a plate (CCC approximately 0.96 and CV<10%). Repeatability between plates was evaluated following normalization of OD values by four methods. Computing normalized values as (OD-Nt)/(Pst-Nt), gave the most repeatable results, with the CCC being approximately 0.95 and the CV approximately 11%. When the OD values were higher than 1.2 and 0.3 for the positive and the negative controls, respectively, none of the normalization methods evaluated provided highly repeatable results and it was necessary to repeat the test. Two batches of the crude antigen preparation were evaluated for repeatability, and no difference was found (CCC=0.96). The use of preservative (bronopol) did not affect test results, nor did freezing the samples for up to 8 months. A significant positive relationship between ELISA OD for milk samples and SCC score was found. Therefore, the use of composite milk samples, which have less variable SCC than samples taken from each quarter, would be more suitable when the udder health status is unknown. The analytical methods used to evaluate repeatability provided a practical way to select among normalization procedures.

Animals↗

Reproducibility of the blood lactate threshold, 4 mmol.l(-1) marker, heart rate and ratings of perceived exertion during incremental treadmill exercise in humans.

The aim of this study was to investigate the reproducibility of blood lactate measurements, heart rate (HR) and ratings of perceived exertion (RPE) during treadmill exercise at speeds corresponding to the lactate threshold ( v(Th,la)-) and a fixed blood lactate concentration of 4 mmol.l(-1)( v(la)-(,4)). Possible differences in reproducibility related to fitness levels were also investigated. A group of 20 men [mean (SD)] [age 20.5 (1.4) years] and 16 women [age 21.2 (0.9) years] took part in the study. The subjects performed two identical incremental exercise tests consisting of at least six 4 min stages. Blood lactate concentrations, HR and RPE were recorded at the end of each stage. Limits of agreement (LoA), correlation coefficients and 95% confidence intervals for the mean difference between tests were employed to investigate the level of agreement and reproducibility of blood lactate concentration, HR and RPE. For the group as a whole, the sample correlation coefficient for speed at v(Th,la)- was r=0.88, and was r=0.92 for the speed at v(la)-(,4). At v(Th,la) -, the correlation coefficients for the moderately fit and unfit were r=0.94 and r=0.36, respectively, and at v(la)-(,4) r=0.93 and r=0.68, respectively. The LoA for the moderately fit group indicated that a change of 1.62 km.h(-1) in v(Th,la)- would be necessary to be considered a change in training status. For HR and RPE, relationships between the tests were generally poor. The LoA suggested that changes in scores must be unacceptably large. These findings cast doubt on the sensitivity of testing for change of blood lactate concentration, HR and RPE in this population.

Adult↗

Closed loop control of sedation for colonoscopy using the Bispectral Index.

Sixteen patients undergoing colonoscopy were sedated with propofol using a closed-loop control system guided by the Bispectral Index (BIS). Propofol administration, via a target-controlled infusion, was controlled by a proportional-integral-differential control algorithm. The median (range) propofol target concentration during closed-loop control was 2.3 (1.7-3.6) microg.ml(-1). The performance characteristics of the system were excellent, with a median absolute performance error of 7 (1-15). Patients were drowsy yet rousable, with a median (range) BIS set-point of 80 (75-85). No patient became apnoeic, required airway support or became haemodynamically unstable whilst sedated. Eight patients moaned or moved during colonoscopy and four had recall. Median (range) time to full consciousness was 4 (2-20) min after the end of closed-loop control. Patient and surgeon satisfaction were high. We conclude that BIS may be a suitable control variable for closed-loop control of sedation with propofol.

Adult↗

Remifentanil concentration during target-controlled infusion of propofol.

After institutional approval and with written informed consent, eight surgical patients were infused intravenously with remifentanil at 250 ngkg lean body mass (LBM)(-1) x min(-1) for 30 min. Cardiovascular and respiratory parameters were recorded and arterial blood samples were taken at regular intervals. In each patient, the same protocol was repeated 40 min later during propofol infused to a target concentration of 3.0 microg x ml(-1). Blood concentrations of remifentanil and propofol were assayed using capillary gas chromatography and high performance liquid chromatography techniques respectively. The number of subjects enrolled was determined by testing the successive areas under the remifentanil time-concentration curve (AUC) for significant difference or non-difference using sequential analysis. The median measured propofol concentration was 3.5 (range: 2.6-4.5) microg x ml(-1) which did not change significantly during the second remifentanil infusion. The median AUC during propofol infusion was greater than control in all subjects, although there was considerable variation of 94.4 (64.3-129.6) versus 64.6 (34.8-126.9) ng x ml(-1) x min; P=0.008, n=8. After 30 min, there was no significant difference in remifentanil concentration during propofol infusion when compared with remifentanil alone of 4.6 (3.2-5.7) versus 3.8 (1.6-4.9) ng x ml(-1); P=0.73, n=8. Co-administration of propofol and remifentanil may result in greater remifentanil concentrations than when remifentanil is infused alone.

Adolescent↗

The structure of the negative transcriptional regulator NmrA reveals a structural superfamily which includes the short-chain dehydrogenase/reductases.

NmrA is a negative transcriptional regulator involved in the post-translational modulation of the GATA-type transcription factor AreA, forming part of a system controlling nitrogen metabolite repression in various fungi. X-ray structures of two NmrA crystal forms, both to 1.8 A resolution, show NmrA consists of two domains, including a Rossmann fold. NmrA shows an unexpected similarity to the short-chain dehydrogenase/reductase (SDR) family, with the closest relationship to UDP-galactose 4-epimerase. We show that NAD binds to NmrA, a previously unreported nucleotide binding property for this protein. NmrA is unlikely to be an active dehydrogenase, however, as the conserved catalytic tyrosine in SDRs is absent in NmrA, and thus the nucleotide binding to NmrA could have a regulatory function. Our results suggest that other transcription factors possess the SDR fold with functions including RNA binding. The SDR fold appears to have been adapted for other roles including non-enzymatic control functions such as transcriptional regulation and is likely to be more widespread than previously recognized.

Amino Acid Sequence↗

Experimental infection of European red foxes (Vulpes vulpes) with canine herpesvirus.

We report on the pathogenicity of canine herpesvirus (CHV) for European red foxes. In the first experiment, we inoculated 10 adult foxes intravenously with a canine isolate of CHV. All foxes became infected and shed CHV in saliva and genital secretions for up to 14 days post-inoculation (p.i.) as evaluated by PCR and/or by virus isolation. All foxes developed clinical signs such as fever, lethargy and evidence of respiratory tract disease. Two foxes died on day 6 p.i., one on day 7 p.i., and one fox was euthanased on day 6 p.i. Tissues taken from the four dead foxes were positive for CHV by PCR. The remaining six foxes recovered after approximately 14 days p.i. Virus particles with morphology typical of herpesviruses were found by electron microscopy in the liver of an infected animal. All surviving foxes developed serum anti-CHV antibodies. In a second experiment, six foxes were dosed perorally with CHV and paired with six untreated controls. Neither the perorally dosed nor the in-contact control foxes developed clinical signs of disease. Infectious CHV was not isolated from any of the dosed or the in-contact foxes but all perorally-infected foxes and one of the in-contact foxes tested PCR-positive for CHV on several occasions p.i. All perorally-infected foxes, but none of the in-contact foxes, seroconverted. In summary, intravenous CHV inoculation caused a clinical disease in adult foxes much more severe than observed in experimentally-infected adult dogs. No clinical disease or virus spread was observed after peroral dosing although viral infection occurred as evidenced by seroconversion.

Administration, Oral↗

Clinical and demographic prognostic indicators for human disc cell proliferation in vitro: pilot study.

STUDY DESIGN: Human anulus cells were cultured under control and experimental conditions to study associations between proliferation and clinical-demographic features of subjects from which cells were obtained. Statistical multiple regression analyses were applied to develop mathematic models relating proliferation to age, gender, Thompson score (denoting stage of disc degeneration), and status (control donor [postmortem]; surgical patient). OBJECTIVES: To identify the effect of donor characteristics on proliferative capacities of human disc cells. SUMMARY OF BACKGROUND DATA: As therapeutic options for disc degeneration increase, novel biologic options are important future considerations. Little is known about the influence of clinical-demographic features on cell proliferation. METHODS: Anulus cells were studied in two designs: 1) Cells from 12 individuals were grown in monolayer with 50 ng/mL interleukin growth factor-1 (IGF-I), 100 ng/mL insulin, or control conditions. 2) Cells from nine individuals were grown in three-dimensional culture with 10 ng/mL IGF-I or control conditions. Cell proliferation data and data on age, gender, Thompson score, and status were collected. Standard statistical analyses were used to develop correlation models. RESULTS: Data from monolayer experiments produced significant models fitting proliferation in the presence of low serum, 50 ng/mL IGF-I, or insulin, with age, gender, Thompson score, and status (respective R2: 0.827, 0.680, 0.850). Three-dimensional cultures exposed to 10 ng/mL IGF-I resulted in proliferation that correlated in a significant negative manner with Thompson score (r = -0.798). CONCLUSIONS: Clinical-demographic prognostic indicators may help predict levels of proliferation. Greater age, greater disc degeneration, female gender, and surgical derivation had deleterious effects on proliferation potential in this model.

Adolescent↗

Extracutaneous angiosarcomas metastatic to the lungs: clinical and pathologic features of twenty-one cases.

Angiosarcomas are rare malignant vascular tumors with a high rate of metastasis involving lungs (most commonly), liver, regional lymph nodes, bone, and other sites. In this study, we have reviewed the clinical presentation and histopathology of 21 cases of extracutaneous angiosarcoma metastatic to the lungs. Tumors with exclusively pleural involvement were excluded. Patients presented with dyspnea, chest pain, and/or hemoptysis lasting a few weeks to months. Radiologically, the most common finding comprised multiple peripheral lung nodules (57%), often accompanied by infiltrates. For 11 cases (52%), the primary tumor was not identified at the time of presentation. Vasoformative areas were identified in 15 cases (71%). Nine cases comprised spindle cells (43%), two contained epithelioid cells (9.5%), and 10 consisted of both spindle and epithelioid cells (48%). Nuclear pleomorphism was at least moderate in all cases. However, five tumors contained regions of minimal nuclear atypia. Hemorrhage, siderophages, and fibrosis were commonly present. Immunohistochemical staining (IHS) was performed on 14 cases. Thirteen tumors showed reactivity for vascular markers. Tumor cells reacted for Von Willebrand factor in 13 of 14 cases, and CD31 and CD34 were each positive in 2/2 cases. Two cases (of nine examined) also expressed cytokeratins. Because the tumor often first presented in the lungs before the primary sarcoma was identified, the clinical impression included both benign and malignant entities. For patients with primary cardiac tumors, symptoms referable to the primary tumor complicated the clinical presentation, and radiologic evaluation supported a clinical diagnostic impression of non-neoplastic pericarditis. Thus, angiosarcoma in the lung may elude diagnosis until histopathologic evaluation of the lung biopsy.

Adult↗

Nerve blocks versus subcutaneous infiltration for stereotactic frame placement.

In this unblinded, randomized controlled trial, we compared supraorbital and greater occipital nerve blocks with subcutaneous infiltration for anesthesia during the placement of a stereotactic head-frame. Twenty consecutive patients scheduled for functional surgery to treat Parkinson's disease were studied. Each patient received supraorbital and greater occipital nerve blocks on one side of the head and subcutaneous infiltration on the other, thereby acting as their own control. Pain was assessed by visual analog scale pain scores (scale: 0-100) for both local anesthetic injection and stereotactic pin placement. Supplementary subcutaneous infiltration was also recorded. Results are presented as mean +/- SD. Nerve blocks were significantly less painful than subcutaneous infiltration of local anesthetic at both the frontal (34 +/- 24 vs 49 +/- 25) and occipital (34 +/- 21 vs 49 +/- 23) sites. Neither technique was superior in preventing pain associated with pin placement, at either the frontal site (48 +/- 27 vs 46 +/- 24) or occipital site (33 +/- 27 vs 32 +/- 24). Supraorbital nerve blocks required significantly more supplementation than either greater occipital nerve blocks or subcutaneous infiltration. Visual analog scale pain scores were greater at local anesthetic injection and pin placement than at any subsequent time. We conclude that supraorbital and greater occipital nerve blocks are an alternative to subcutaneous infiltration for the placement of a stereotactic frame.

Administration, Cutaneous↗