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Biomedical subjects

A McLellan

Publications and source records attributed to A McLellan.

At least 19 recordsLinked to original sources
PubMed2001

Urodynamic techniques.

Appropriate investigation is essential to a full evaluation of any patient with urinary incontinence, as accurate diagnosis leads to correct treatment. This paper describes the various investigations for lower urinary tract dysfunction, and their main indications. They include the pad test, uroflowmetry, subtracted cystometry, and more complex investigations such as videocystourethrography, ambulatory urodynamics, urethral pressure profilometry, magnetic resonance imaging and electromyography. Although not every patient requires extensive investigation, appropriate use of tests of lower urinary tract function provides useful information on which to base appropriate treatment.

Female↗
PubMed2001

Regionalisation of rural medical training in far north Queensland: a learning experience for medical educators and managers.

The need for an appropriate, dedicated vertically-integrated training pathway for rural doctors, provided by regional consortia of educational organisations, has been clearly identified by Rural Doctors Association of Queensland (RDAQ) and The Australian College of Rural and Remote Medicine (ACRRM) as a key strategy to resolve rural medical workforce issues. The opportunity to put the ideas into action is now here with rural doctors responding to the challenge of managing more reform in general practice all over Australia. In Far North Queensland, the ongoing reform of general practice education has been challenging, with many lessons learned by both educators and managers. This paper describes the management of change, and outlines key principles and characteristics of a successful regional rural medical training system, building on the lessons learned from the Rural and Remote Area Placement Program (RRAP) and other projects.

Cooperative Behavior↗
PubMed2001

A comparison of the objective and subjective outcomes of colposuspension for stress incontinence in women.

OBJECTIVES: To investigate the impact of colposuspension for stress incontinence on the symptoms and quality of life of women undergoing both primary and repeat surgery for genuine stress incontinence and in addition to assess the use of a condition specific quality of life questionnaire as an outcome measure following surgery. DESIGN: Prospective case series: videocystourethrography performed before and between six and twelve months after surgery. Validated condition specific quality of life (QoL) questionnaires completed by women before and six to twelve months after surgery. SETTING: A tertiary referral Urogynaecology Unit in a teaching hospital. PARTICIPANTS: A consecutive series of 83 women undergoing colposuspension between March 1995 and December 1997. Pre-operative assessment and surgery was performed by, or was under the direct supervision of, the unit director. INTERVENTION: Modified Burch colposuspension. MAIN OUTCOME MEASURES: Objective results of surgery assessed with videocystourethrography. Subjective results evaluated using a condition specific QoL tool, the Kings Health Questionnaire (KHQ). Symptom severity was evaluated as a component of the condition specific QoL questionnaire. RESULTS: Objective cure was demonstrated in 92% of women undergoing primary surgery with an 8% incidence of de-novo detrusor instability and a 10% incidence of voiding difficulties. In the group of women having repeat surgery the objective cure rate was 81% with no de-novo detrusor instability and a 6% incidence of post-operative voiding difficulties. QoL scores improved in 95% of women. Improvements of over 25% were seen in 70% of women and of over 50% in 28%. However, 2.4% of women recorded a deterioration in QoL scores. CONCLUSIONS: Colposuspension performed in this setting, assessed using both objective and standardised subjective measures, completed by women themselves, appears to produce good objective and subjective results and leads to enhanced quality of life in the great majority of women.

Adult↗
PubMed2000

Maturation of dendritic cells leads to up-regulation of cellular FLICE-inhibitory protein and concomitant down-regulation of death ligand-mediated apoptosis.

Dendritic cells (DCs) disappear from lymph nodes 1 to 2 days after antigen presentation, presumably by apoptosis. To evaluate the role of death ligands in elimination of DCs, we analyzed the sensitivity of human DCs to CD95 ligand (CD95L) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We found mature DCs to be resistant to killing via CD95L or TRAIL, whereas only immature DCs were partially sensitive. However, all DC populations expressed CD95, TRAIL-R2, and TRAIL-R3 at comparable levels, suggesting that sensitivity to death ligand-induced DC apoptosis is not regulated at the receptor level. Interestingly, mature DCs highly expressed the caspase 8 inhibitory protein cFLIP, whereas only low levels were detected in immature DCs. Thus, death ligand sensitivity proved to be dependent on DC maturation and inversely correlated with expression levels of cFLIP. Induction of apoptosis by TRAIL or CD95L does not seem to play a role in the elimination of mature DCs, but instead might serve to regulate immature DC populations.

Antigens, CD↗
PubMed2000

Lectin ligands on human dendritic cells and identification of a peanut agglutinin positive subset in blood.

As only a few cell surface markers for dendritic cells (DC) have been identified to date, this study examined the expression of ligands for lectin on different human DC populations. The ability of Concanavalin A (Con A), Wheat Germ Agglutinin (WGA), peanut agglutinin (PNA), and Helix pomatia (HPA) to bind to cell lines and PBMC and DC populations was analyzed by flow cytometry and specificity of binding confirmed using inhibitory and noninhibitory sugars. The cell lines showed non-lineage-restricted binding with Con A and WGA, independent of sialidase treatment. HPA and PNA bound to a restricted number of lines, but showed broad reactivity after sialidase treatment. The peripheral blood mononuclear cells (PBMC) and directly isolated blood DC, activated CD83(+) blood DC, epidermal Langerhans cells (LC), and monocyte-derived DC (Mo-DC) showed strong binding of Con A and WGA, both before and after sialidase treatment. No HPA binding ligands were detected on PBMC populations, including directly isolated blood DC. Following sialidase treatment CD3(+), CD16(+), and a subset of CD19(+) lymphocytes bound HPA. The lectin PNA bound weakly to CD14(+) monocytes and a subpopulation of circulating DC that were HLA-DR(hi)CDw123 Dr(hi)CDw123(dim)/(neg)CD11c(+). The HLA-DR(mod)CDw123(hi)CD11c(neg) subpopulation did not bind PNA. Without sialidase treatment LC expressed both HPA and PNA ligands, but these were either absent on activated CD83(+) blood DC or weakly expressed on Mo-DC. Following sialidase treatment PBMC populations, activated CD83(+) blood DC, and Mo-DC became PNA positive. Thus human DC express several lectin ligands and PNA binding identifies a subset of blood DC. That may reflect discrete changes associated with stages of DC development or functional maturation.

Binding Sites↗
PubMed2000

MHC class II and CD40 play opposing roles in dendritic cell survival.

In contrast to very immature dendritic cells (DC), mature DC are largely resistant to death by CD95 (CD95/APO-1) ligation. Investigation of other potential death-inducing ligands showed that mature DC were instead highly susceptible to apoptosis induced by cross-linking of MHC class II. Thus, increasing DC maturity correlates with increased resistance to CD95 killing, but an increased susceptibility to class II-mediated killing. Anti-I-A/I-E monoclonal antibodies (mAb) induced rapid (<2 h) apoptotic cell death in mature epidermal, spleen and bone marrow-derived DC, as determined by annexin/propidium iodide staining, morphological changes, decreased diploidy and loss in mitochondrial membrane potential. Although full class II-mediated killing required DC cytoskeletal motion, divalent cations and phosphatase activity, neither caspase activation, respiration, RNA or protein synthesis, NO production, nor CD95:CD95L interactions were required. Strikingly, DC pretreated by CD40 mAb cross-linking, but not by lipopolysaccharide or TNF-alpha, were completely resistant to class II-mediated killing. CD40-mediated protection was reduced in the presence of the SB202190 inhibitor of the mitogen-activated protein kinase p38 pathway, but appeared to be independent of p42/44 extracellular signal-related kinase or NF-KB activation. Our findings show that in addition to its role as an activator of antigen-presenting cell function, CD40 provides an important counter-signal against class II-induced apoptosis. Thus, these data point to an important role of the T cell in regulating DC survival.

Animals↗
PubMed1999

Gilbert's syndrome is a contributory factor in prolonged unconjugated hyperbilirubinemia of the newborn.

OBJECTIVE: Prolonged neonatal jaundice, beyond day 14 of life, is very common and of concern to the clinician. The aim of this study was to investigate whether a genetic mutation in the bilirubin UGT1A1 gene, which has been associated with Gilbert's syndrome in adults, is a contributory factor in prolonged neonatal jaundice. STUDY DESIGN: Blood was collected from 85 term newborns with unexplained hyperbilirubinemia, and DNA was prepared. The neonates were divided into 6 groups depending on whether they were breast-fed or bottle-fed and whether they had acute, prolonged, or very prolonged jaundice. UGT1A1 TATA promoter genotyping (DNA test for Gilbert's syndrome) was performed on all samples, and analysis of the entire UGT1A1 coding sequence was performed in a representative sample (11 of 26) of very prolonged cases. RESULTS: In addition to the known common UGT1A1 TATA alleles (TA6 and TA7), a novel TATA allele (TA5) in a neonate with very prolonged jaundice was identified. Statistical analysis of the TATA genotype distributions within the group of breast-fed neonates revealed significant differences among the acute, prolonged, and very prolonged subgroups (.05 > P >.01): the incidence of familial hyperbilirubinemia genotypes (7/7 and 5/7) is 5 times greater in very prolonged cases (31%) relative to acute cases (6%). Neonates with prolonged jaundice from family pedigrees were observed to demonstrate the Gilbert's phenotype as children or young adults. CONCLUSIONS: A genetic predisposition to develop prolonged neonatal hyperbilirubinemia in breast-fed infants is associated with TATA box polymorphism of the UGT1A1 gene and will be recognized as Gilbert's syndrome in adulthood.

Adolescent↗
PubMed1998

A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group.

BACKGROUND: Critically ill patients who require mechanical ventilation are at increased risk for gastrointestinal bleeding from stress ulcers. There are conflicting data on the effect of histamine H2-receptor antagonists and the cytoprotective agent sucralfate on rates of gastrointestinal bleeding, ventilator-associated pneumonia, and mortality. METHODS: In a multicenter, randomized, blinded, placebo-controlled trial, we compared sucralfate with the H2-receptor antagonist ranitidine for the prevention of upper gastrointestinal bleeding in 1200 patients who required mechanical ventilation. Patients received either nasogastric sucralfate suspension (1 g every six hours) and an intravenous placebo or intravenous ranitidine (50 mg every eight hours) and a nasogastric placebo. RESULTS: The patients in the two groups had similar base-line characteristics. Clinically important gastrointestinal bleeding developed in 10 of 596 (1.7 percent) of the patients receiving ranitidine, as compared with 23 of 604 (3.8 percent) of those receiving sucralfate (relative risk, 0.44; 95 percent confidence interval, 0.21 to 0.92; P=0.02). In the ranitidine group, 114 of 596 patients (19.1 percent) had ventilator-associated pneumonia, as compared with 98 of 604 (16.2 percent) in the sucralfate group (relative risk, 1.18; 95 percent confidence interval, 0.92 to 1.51; P=0.19). There was no significant difference between the groups in mortality in the intensive care unit (ICU) (23.5 percent in the ranitidine group and 22.9 percent in the sucralfate group) or the duration of the stay in the ICU (median, nine days in both groups). CONCLUSIONS: Among critically ill patients requiring mechanical ventilation, those receiving ranitidine had a significantly lower rate of clinically important gastrointestinal bleeding than those treated with sucralfate. There were no significant differences in the rates of ventilator-associated pneumonia, the duration of the stay in the ICU, or mortality.

Aged↗
PubMed1998

Severe sepsis caused by Mobiluncus curtisii subsp. curtisii in a previously healthy female: case report and review.

We present the case of a 54-year-old female with life-threatening septicaemia due to Mobiluncus curtisii subsp. curtisii. Her admission was complicated by septic shock, renal failure, disseminated intravascular coagulation, the adult respiratory distress syndrome and spontaneous splenic rupture. The patient survived with full intensive care support and intravenous ceftriaxone. Extra-genital infection with Mobiluncus species is rarely diagnosed and has been confined to breast abscesses and non-life-threatening bacteraemia. A review of extra-genital infections with Mobiluncus species is presented.

Bacteroidaceae Infections↗
PubMed1998

Embryonic lethality and tumorigenesis caused by segmental aneuploidy on mouse chromosome 11.

Chromosome engineering in mice enables the construction of models of human chromosomal diseases and provides key reagents for genetic studies. To begin to define functional information for a small portion of chromosome 11, deficiencies, duplications, and inversions were constructed in embryonic stem cells with sizes ranging from 1 Mb to 22 cM. Two deficiencies and three duplications were established in the mouse germline. Mice with a 1-Mb duplication developed corneal hyperplasia and thymic tumors, while two different 3- to 4-cM deficiencies were embryonically lethal in heterozygous mice. A duplication corresponding to one of these two deficiencies was able to rescue its haplolethality.

Aneuploidy↗
PubMed1994

Oxygen-induced retinopathy in the mouse.

PURPOSE: To develop oxygen-induced retinopathy in the mouse with reproducible and quantifiable proliferative retinal neovascularization suitable for examining pathogenesis and therapeutic intervention for retinal neovascularization in retinopathy of prematurity (ROP) and other vasculopathologies. METHODS: One-week-old C57BL/6J mice were exposed to 75% oxygen for 5 days and then to room air. A novel fluorescein-dextran perfusion method has been developed to assess the vascular pattern. The proliferative neovascular response was quantified by counting the nuclei of new vessels extending from the retina into the vitreous in 6 microns sagittal cross-sections. Cross-sections were also stained for glial fibrillary acidic protein (GFAP). RESULTS: Fluorescein-dextran angiography delineated the entire vascular pattern, including neovascular tufts in flat-mounted retinas. Hyperoxia-induced neovascularization occurred at the junction between the vascularized and avascular retina in the mid-periphery. Retinal neovascularization occurred in all the pups between postnatal day 17 and postnatal day 21. There was a mean of 89 neovascular nuclei per cross-section of 9 eyes in hyperoxia compared to less than 1 nucleus per cross-section of 8 eyes in the normoxia control (P < 0.0001). Proliferative vessels were not associated with GFAP-positive astrocyte processes. CONCLUSIONS: The authors have described a reproducible and quantifiable mouse model of oxygen-induced retinal neovascularization that should prove useful for the study of pathogenesis of retinal neovascularization as well as for the study of medical intervention for ROP and other retinal angiopathies.

Animals↗
PubMed1992

Plasma endothelinlike immunoreactivity levels in IDDM patients with microalbuminuria.

OBJECTIVE: To determine whether plasma endothelin, a potent vasoconstrictor and growth factor for vascular smooth muscle, is elevated in microalbuminuric insulin-dependent diabetes mellitus patients. RESEARCH DESIGN AND METHODS: Plasma endothelinlike immunoreactivity was measured by radioimmunoassay in 15 microalbuminuric diabetic patients, 12 normoalbuminuric diabetic patients, and 12 control subjects. RESULTS: The mean levels of plasma endothelinlike immunoreactivity were raised in the normoalbuminuric patients (8.4 pM [range 4.8-12.7 pM]; P less than 0.01) and the microalbuminuric patients (10.2 pM [range 5.6-31.1 pM]; P less than 0.001) compared with control subjects (6.1 pM [range 4.5-7.6 pM]). Plasma endothelinlike immunoreactivity was also higher in the microalbuminuric patients compared with the normoalbuminuric patients (P less than 0.05). CONCLUSIONS: The increase in plasma endothelinlike immunoreactivity further confirms endothelial dysfunction in diabetes and this increase in plasma endothelin may contribute to the vascular disease prevalent in diabetes.

Adult↗
PubMed1989

A double-blind comparison of conventional and controlled-release carbamazepine in healthy subjects.

1. Eight healthy subjects took part in a balanced, double-blind, crossover comparison of conventional carbamazepine (Tegretol, Ciba-Geigy Ltd, CBZ-C) and a novel controlled-release formulation (Tegretol CR Divitabs, Ciba-Geigy Ltd; CBZ-CR). An initial single dose of either preparation was followed 1 week later by a 2 week course of 200 mg twice daily. 2. Following the single dose, CBZ-CR produced a concentration plateau from 6-56 h at 50-60% of the CBZ-CR peak. 3. After 2 weeks' treatment, CBZ daytime levels measured as area under the concentration-time curve over a dosage interval were 7% lower with CBZ-CR, but this difference was not statistically significant. 4. CBZ-CR showed less diurnal fluctuation (12%) of CBZ than CBZ-C (24%; P less than 0.025) with less rapid changes in concentration (P less than 0.02). 5. Diurnal fluctuation of free CBZ and of CBZ 10,11 epoxide, the active metabolite, did not differ significantly between the two preparations. 6. Auto-induction of CBZ metabolism resulted from the administration of both formulations. The mean elimination half-life was 23 h (CBZ-C) and 25 h (CBZ-CR) after dose 29 compared with a base-line value of 37 h (both P less than 0.02). Antipyrine metabolism was also induced to a similar extent in both legs of the study (P less than 0.01). 7. No significant alteration in psychomotor function was demonstrated with either preparation. 8. CBZ-CR fulfils the criteria for a controlled-release preparation with comparable apparent bioavailability to CBZ-C. Further pharmacokinetic and, more importantly, pharmacodynamic studies are required in epileptic patients to confirm a clinical advantage over the currently available formulation.

Adult↗