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Biomedical subjects

K Morris

Publications and source records attributed to K Morris.

At least 19 recordsLinked to original sources
PubMed2006

Direct characterization of Blastocystis from faeces by PCR and evidence of zoonotic potential.

In vitro propagation followed by PCR, and a PCR-based method capable of the direct detection of Blastocystis in faeces were utilized to detect Blastocystis from various hosts in Australia, including primates and their handlers from the Perth Zoo. In addition, Blastocystis isolates from dogs and humans living in a localized endemic community in Thailand were also characterized genetically. PCR-based detection directly from faeces was shown to be more sensitive compared with in vitro culture for the detection of Blastocystis. Moreover, phylogenetic analysis of Blastocystis isolates amplified utilizing in vitro techniques prior to PCR revealed that this method favoured the preferential amplification of Blastocystis subtype 5 over subtype 1. This study is the first to provide molecular-based evidence supporting the zoonotic potential of Blastocystis in dogs, possums and primates in a natural setting.

Animals↗
PubMed2006

Mice deficient in galectin-1 exhibit attenuated physiological responses to chronic hypoxia-induced pulmonary hypertension.

Pulmonary hypertension (PH) is characterized by sustained vasoconstriction, with subsequent extracellular matrix (ECM) production and smooth muscle cell (SMC) proliferation. Changes in the ECM can modulate vasoreactivity and SMC contraction. Galectin-1 (Gal-1) is a hypoxia-inducible beta-galactoside-binding lectin produced by vascular, interstitial, epithelial, and immune cells. Gal-1 regulates SMC differentiation, proliferation, and apoptosis via interactions with the ECM, as well as immune system function, and, therefore, likely plays a role in the pathogenesis of PH. We investigated the effects of Gal-1 during hypoxic PH by quantifying 1) Gal-1 expression in response to hypoxia in vitro and in vivo and 2) the effect of Gal-1 gene deletion on the magnitude of the PH response to chronic hypoxia in vivo. By constructing and screening a subtractive library, we found that acute hypoxia increases expression of Gal-1 mRNA in isolated pulmonary mesenchymal cells. In wild-type (WT) mice, Gal-1 immunoreactivity increased after 6 wk of hypoxia. Increased expression of Gal-1 protein was confirmed by quantitative Western analysis. Gal-1 knockout (Gal-1(-/-)) mice showed a decreased PH response, as measured by right ventricular pressure and the ratio of right ventricular to left ventricular + septum wet weight compared with their WT counterparts. However, the number and degree of muscularized vessels increased similarly in WT and Gal-1(-/-) mice. In response to chronic hypoxia, the decrease in factor 8-positive microvessel density was similar in both groups. Vasoreactivity of WT and Gal-1(-/-) mice was tested in vivo and with use of isolated perfused lungs exposed to acute hypoxia. Acute hypoxia caused a significant increase in RV pressure in wild-type and Gal-1(-/-) mice; however, the response of the Gal-1(-/-) mice was greater. These results suggest that Gal-1 influences the contractile response to hypoxia and subsequent remodeling during hypoxia-induced PH, which influences disease progression.

Animals↗
PubMed2006

Impaired vasoreactivity in bodybuilders using androgenic anabolic steroids.

BACKGROUND: Anabolic androgenic steroids are used by some bodybuilders to enhance performance. While the cardiovascular implications of supraphysiological androgen levels requires further clarification, use is associated with sudden death, left ventricular hypertrophy, thrombo-embolism and cerebro-vascular events. MATERIALS AND METHODS: To further understand the effect of androgenic anabolic steroid abuse on vascular function, this study assessed vascular stiffness (pulse-wave analysis) and cardiovascular risk factors in 28 male, bodybuilding subjects, of whom ten were actively receiving anabolic agents (group A; 26.4 +/- 7.2 years) and eight had undergone a 3-month "wash-out" period (group B; 32.1 +/- 7.1 years). The remaining ten bodybuilding subjects (group C; 24.4 +/- 4.4 years) denied any past use of anabolic steroids or other performance enhancing drugs. Comparisons were made with ten sedentary male controls (group D, 29.3 +/- 4.7 years). RESULTS: Endothelial independent dilatation in response to glycerol trinitrate was significantly impaired in the group currently using anabolic steroids (group A) compared with the other three groups [A (5.63 +/- 3.24%) versus; B (11.10 +/- 4.91%), C (17.88 +/- 9.2%) and D (14.46 +/- 3.9%), P < 0.0005, respectively], whereas no significant differences in endothelial-dependent dilatation were detected between the groups [A (5.0 +/- 3.0%), B (7.4 +/- 3.4%), C (9.6 +/- 4.5%) and D (8.2 +/- 3.3%), P < 0.059, respectively]. CONCLUSIONS: Previous studies described a decline in vascular reactivity occurring in bodybuilding subjects which is independent of anabolic steroid use and may result from smooth muscle hypertrophy with increased vascular stiffness. This study revealed impaired vascular reactivity associated with anabolic agents and that improvement in vascular function may occur following their discontinuation.

Administration, Sublingual↗
PubMed2006

Acute effects of caffeine and tobacco on arterial function and wave travel.

BACKGROUND: Caffeine and tobacco consumption are risk factors for heart failure, but their effects remain controversial. It has been hypothesized that they cause alterations in arterial stiffness and arterial wave travel which may increase ventricular loading. In this study the authors examined the influence of these widely used stimulants on wave intensity and arterial stiffness parameters using carotid wave intensity analysis. MATERIALS AND METHODS: A new Doppler-based ultrasound method was used to measure the acute effects of caffeine and tobacco on wave intensity in the right common carotid artery. The measurements enabled changes in arterial stiffness parameters to be recorded. RESULTS: In 17 subjects compared with 10 controls, caffeine increased blood pressure, early systolic wave intensity and wave speed, but late-systolic wave intensity and mid-systolic reflections were unchanged. In 11 smokers studied before and after smoking one cigarette, blood pressure and arterial stiffness increased but wave intensity was unchanged. No changes were observed in the controls. CONCLUSIONS: Increased wave intensity during ejection after caffeine suggested sympathomimetic effects on the left ventricular function. Increased wave speed in the common carotid artery implied augmented central loading after caffeine, but the absence of measurable changes in local arterial stiffness in the carotid artery suggested more complex and regional effects. Cigarette smoking acutely increased local arterial stiffness in the common carotid artery. These changes can be detected using wave intensity analysis.

Adult↗
PubMed2006

Prolonged deterioration of endothelial dysfunction in response to postprandial lipaemia is attenuated by vitamin C in Type 2 diabetes.

BACKGROUND: Endothelial dysfunction (ED) has been described in Type 2 diabetes (T2DM). We have described previously a diminution of flow-mediated arterial dilatation and, by implication, further ED in T2DM in response to postprandial lipaemia (PPL) at 4 h. This is possibly mediated by oxidative stress/alteration of the nitric oxide (NO) pathway. T2DM subjects tend to exhibit both exaggerated and prolonged PPL. We therefore studied the relationship of PPL to the duration of ED in T2DM subjects and oxidative stress with or without the antioxidant, vitamin C. METHODS: Twenty subjects with T2DM with moderate glycaemic control (mean HbA1c 8.4%) were studied. After an overnight fast, all subjects consumed a standard fat meal. Endothelial function (EF), lipid profiles, and venous free radicals were measured in the fasting, peak lipaemic phase (4 h) and postprandially to 8 h. The study was repeated in a double-blinded manner with placebo, vitamin C (1 g) therapy for 2 days prior to re-testing and with the fat meal. Oxidative stress was assessed by lipid-derived free radicals in plasma, ex vivo by electron paramagnetic resonance spectroscopy (EPR) and by markers of lipid peroxidation (TBARS). Endothelial function was assessed by flow-mediated vasodilatation (FMD) of the brachial artery. RESULTS: There was a significant decrease in endothelial function in response to PPL from baseline (B) 1.3 +/- 1.3% to 4 h 0.22 +/- 1.1% (P < 0.05) and 8 h 0.7 +/- 0.9% (P < 0.05) (mean +/- sem). The endothelial dysfunction seen was attenuated at each time point with vitamin C. Baseline EF with vitamin C changed from (fasting) 3.8 +/- 0.9-2.8 +/- 0.8 (at 4 h) and 2.9 +/- 1.3 (at 8 h) in response to PPL. Vitamin C attenuated postprandial (PP) oxidative stress significantly only at the 4-h time point [301.1 +/- 118 (B) to 224.7 +/- 72 P < 0.05] and not at 8 h 301.1 +/- 118 (B) to 260 +/- 183 (P = NS). There were no changes with placebo treatment in any variable. PPL was associated with a PP rise in TG levels (in mmol/l) from (B) 1.8 +/- 1 to 2.7 +/- 1 at 4 h and 1.95 +/- 1.2 at 8 h (P = 0.0002 and 0.33, respectively). CONCLUSION: PPL is associated with prolonged endothelial dysfunction for at least 8 h after a fatty meal. Vitamin C treatment improves endothelial dysfunction at all time points and attenuates PPL-induced oxidative stress. This highlights the importance of low-fat meals in T2DM and suggests a role for vitamin C therapy to improve endothelial function during meal ingestion.

Administration, Oral↗
PubMed2006

Hypothermia pediatric head injury trial: the value of a pretrial clinical evaluation phase.

BACKGROUND: The utility of a pretrial clinical evaluation or run-in phase prior to conducting trials of complex interventions such as hypothermia therapy following severe traumatic brain injury in children and adolescents has not been established. METHODS: The primary objective of this study was to prospectively evaluate the ability of investigators to adhere to the clinical protocols of care including the cooling and rewarming procedures as well as management guidelines in patients with severe traumatic brain injury (Glasgow Coma Scale<or=8) treated with 24 h of hypothermia therapy. A secondary objective was to evaluate the ability of study research assistants to complete the study case report form using a procedures manual. The study was conducted at 18 sites in Canada, the United Kingdom and France prior to proceeding to a randomized controlled trial (RCT). After 2 patients were enrolled at each center, an independent clinical evaluation committee examined the process of care and the completeness of data collection. Centers were permitted to enroll patients in the RCT once they met pre-established adherence criteria. RESULTS: Seventeen of the 18 centers completed the pretrial clinical evaluation phase demonstrating compliance with study procedures and proceeded to an RCT of hypothermia therapy. One center enrolled only 1 patient in the pretrial clinical evaluation phase due to small numbers of patients with traumatic brain injury, and therefore, did not proceed to the RCT. Three centers were required to enroll more than 2 patients in the pretrial clinical evaluation phase prior to proceeding to the RCT because of problems with adherence to the clinical protocols at two centers and the training of new study personnel at another center. Of the 39 patients enrolled during the pretrial clinical evaluation phase, 8 (20.5%) died and 22 (62.9%) had a good outcome defined as normal, mild or moderate disability assessed using the Pediatric Cerebral Performance Category score at 6 months following injury. DISCUSSION: The pretrial clinical evaluation phase was useful to ensure compliance with complex hypothermia therapy and consensus-based clinical management guidelines of care successfully implemented across 17 of 18 centers. This study maneuver allowed us to complete a subsequent RCT in 225 children following severe traumatic brain injury.

Algorithms↗
PubMed2005

The transcriptional landscape of the mammalian genome.

This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.

3' Untranslated Regions↗
PubMed2005

Smaller inner ear sensory epithelia in Neurog 1 null mice are related to earlier hair cell cycle exit.

We investigated whether co-expression of Neurog 1 and Atoh 1 in common neurosensory precursors could explain the loss of hair cells in Neurog 1 null mice. Analysis of terminal mitosis, using BrdU, supports previous findings regarding timing of exit from cell cycle. Specifically, we show that cell cycle exit occurs in spiral sensory neurons in a base-to-apex progression followed by cell cycle exit of hair cells in the organ of Corti in an apex-to-base progression, with some overlap of cell cycle exit in the apex for both hair cells and spiral sensory neurons. Hair cells in Neurog 1 null mice show cell cycle exit in an apex-to-base progression about 1-2 days earlier. Atoh 1 is expressed in an apex-to-base progression rather then a base-to-apex progression as in wildtype littermates. We tested the possible expression of Atoh1 in neurosensory precursors using two Atoh 1-Cre lines. We show Atoh 1-Cre mediated beta-galactosidase expression in delaminating sensory neuron precursors as well as undifferentiated epithelial cells at E11 and E12.5. PCR analysis shows expression of Atoh 1 in the otocyst as early as E10.5, prior to any histology-based detection techniques. Combined, these data suggest that low levels of Atoh 1 exist much earlier in precursors of hair cells and sensory neurons, possibly including neurosensory precursors. Analysis of Atoh 1-Cre expression in E18.5 embryos and P31 mice reveal beta-galactosidase stain in all hair cells but also in vestibular and cochlear sensory neurons and some supporting cells. A similar expression of Atoh 1-LacZ exists in postnatal and adult vestibular and cochlear sensory neurons, and Atoh 1 expression in vestibular sensory neurons is confirmed with RT-PCR. We propose that the absence of NEUROG 1 protein leads to loss of sensory neuron formation through a phenotypic switch of cycling neurosensory precursors from sensory neuron to hair cell fate. Neurog 1 null mice show a truncation of clonal expansion of hair cell precursors through temporally altered terminal mitosis, thereby resulting in smaller sensory epithelia.

Animals↗
PubMed2005

[Use of telepathology to provide rapid diagnosis of neurosurgical specimens].

To determine whether still digital images of neurosurgical specimens sent by e-mail are an effective and safe way of obtaining an emergency pathological diagnosis, representative images from 48 neurosurgical smear specimens were digitized, compressed and sent by electronic mail to our consultant neuropathologist with relevant clinical and radiological information. The time to select, digitize, compress and send the images for each case was recorded. Comparison was made between diagnosis made from digital images (DI) and historical smear (HS) using the original permanent section (PS) diagnosis as the gold standard. A diagnosis of normal vs. abnormal, neoplastic vs. non-neoplastic, primary vs. secondary and tumor grade was made in each case. The mean time for selection and digitalization of each case was 9.51 minutes. The number of correct pathological diagnosis was 41/48 using DI and 48/48 using HS, giving an accuracy rate of 85.4% and 100% respectively. DI was 100% sensitive in recognizing neoplastic tissue but only 98% specific. Most inaccuracies were in grading and caused by problems with field selection and familiarity with the technique. We conclude that static digital images are reliable and safe method of interpreting tissue during neurosurgical procedures. This corresponds with the findings of previous studies.

Brain Neoplasms↗
PubMed2005

Detection of HCV and HIV-1 antibody negative infections in Scottish and Northern Ireland blood donations by nucleic acid amplification testing.

BACKGROUND AND OBJECTIVES: To reduce the risk of transfusion-transmissible viruses entering the blood supply, the nucleic acid amplification testing (NAT) was implemented to screen Scottish and Northern Irish blood donations in minipools. After 5 years of NAT for hepatitis C virus (HCV) and 2 years for human immunodeficiency virus-1 (HIV-1), the yield of serologically negative, nucleic acid positive 'window donations' and cost-benefit of NAT is under review. MATERIALS AND METHODS: When the Scottish National Blood Transfusion Service (SNBTS) implemented NAT in 1999, a fully automated 'black box' system was not available. Therefore, an 'in-house' assimilated NAT assay was developed, validated and implemented. The system is flexible and allows testing for additional viral markers to be introduced with relative ease. RESULTS: The HCV and HIV NAT assays have 95% detection levels of 7.25 IU/ml and 39.8 IU/ml, respectively, as determined by probit analysis. One HCV (1 in 1.9 million) and one HIV (1 in 0.77 million) window donation have been detected in 5 and 2 years, respectively, of NAT. CONCLUSION: The SNBTS NAT assays are robust and have performed consistently over the last 5 years. The design of the in-house system allowed HIV NAT to be added in 2003 at a relatively small additional cost per sample, although for both assays, the royalty fee far exceeds the cost of the test itself. Clearly NAT has a benefit in improving the safety of the blood supply although the risks of transfusion-transmitted viral infections, as reported in the Serious Hazards of Transfusion (SHOT) report, are extremely low. Also, in UK the yield of HCV antibody negative, NAT positive donations is far lower than predicted although the early detection of an HIV window period donation and the increase of HIV in the blood donor and general populations may provide a stronger case for HIV NAT. SUMMARY SENTENCE: The yield of HCV and HIV NAT in UK is significantly less than that anticipated from statistical models.

Adult↗
PubMed2004

Prevalence and clonality of Burkholderia cepacia complex genomovars in UK patients with cystic fibrosis referred for lung transplantation.

BACKGROUND: It has previously been reported that patients infected with Burkholderia cenocepacia (genomovar III) before lung transplantation have a poorer outcome than those with other B. cepacia complex infections. METHODS: An extensive study was conducted to determine the prevalence and clonality of B. cepacia complex genomovars isolated from patients referred for transplant assessment between 1989 to the present and, where appropriate, whether strain type was related to transplant outcome. RESULTS: Isolates from 29 patients were identified as B. cepacia complex organisms by molecular analysis. Thirteen patients (45%) were infected with the highly transmissible ET-12 strain of B. cenocepacia recA lineage III-A, while all remaining patients were infected with genetically unique B. cenocepacia, B. multivorans, and B. vietnamiensis strains. All previously reported deaths following transplantation were associated with ET-12 infection. CONCLUSIONS: The ET-12 strain is the predominant cause of B. cenocepacia infections in patients with cystic fibrosis referred to our pulmonary transplant centre and is associated with poor transplant outcomes using standard treatment regimens.

Burkholderia Infections↗
PubMed2003

False positive Kleihauer tests and unnecessary administration of anti-D immunoglobulin.

This obstetric case shows two false negative Kleihauer tests and two persistently positive Kleihauer tests leading to unnecessary administration of anti-D immunoglobulin. A diagnosis of hereditary persistence foetal haemoglobin (HPFH) was only confirmed by access to flow cytometry making use of both anti-HbF and anti-D labels. The case highlights the importance of a high index of clinical suspicion for HPFH and the importance of access to flow cytometry estimation of minor RhD red cell populations postnatally in RhD-negative mothers.

Adult↗
PubMed2003

Effects of insulin lispro and chronic vitamin C therapy on postprandial lipaemia, oxidative stress and endothelial function in patients with type 2 diabetes mellitus.

BACKGROUND: Insulin therapy may influence cardiovascular disease (CVD) and lipid metabolism in type 2 diabetes (T2D). Exaggerated postprandial lipaemia (PPL) is a feature of diabetic dyslipidaemia affecting CVD via enhanced oxidative stress (OS) and endothelial dysfunction. We assessed endothelial function and OS during PPL following insulin and vitamin C. Twenty (17 M) T2D patients were studied (mean Hba1c 8.4%) at baseline, following 6 weeks of insulin lispro (0.2 Iu kg-1) and vitamin C 1-g daily. Eight-h lipid and glucose profiles were measured following a fatty meal. Endothelial function (flow-mediated vasodilatation: FMD) and OS were measured at fasting, 4 h and 8 h. MATERIALS AND METHODS: Glucose, body mass index, and total and LDL cholesterol remained unchanged. FMD improved. Placebo group: fasting, 1.1 +/- 1.2 to 4.2 +/- 1.1% (P < 0.001); 4-h, 0.3 +/- 1.2 to 3.1 +/- 0.9% (P < 0.01); 8-h, 0.7 +/- 1.1 to 3.76 +/- 1.1% (P < 0.001). Vitamin C group: fasting, 0.9 +/- 1.1 to 6.1 +/- 1.3% (P < 0.001); 4-h, 0.7 +/- 1.5 to 4.9 +/- 2.1% (P < 0.001); 8-h, 0.8 +/- 0.9 to 5.8 +/- 0.6% (P < 0.01). Post-prandial lipaemia was attenuated: TG area-under-curve (mmol L-1 8 h-1), 52.6 +/- 11 to 39.1 +/- 12.5 (placebo group), P < 0.02; and 56.9 +/- 8 to 40.1 +/- 10.3 (vitamin C group), P < 0.02. Oxidative stress was reduced, with greater changes in the vitamin C group. CONCLUSION: Insulin may thus exert vascular benefits in T2D, by modifying fasting and postprandial lipid metabolism resulting in reduced OS and improved EF. Vitamin C therapy may augment the vascular benefits of insulin in T2D through additional effects on OS and EF.

Adult↗
PubMed2003

Amygdala volumetry in "imaging-negative" temporal lobe epilepsy.

OBJECTIVE: Although amygdala abnormalities are sometimes suspected in "imaging-negative" patients with video EEG confirmed unilateral focal epilepsy suggestive of temporal lobe epilepsy (TLE), amygdala asymmetry is difficult to assess visually. This study examined a group of "imaging-negative" TLE patients, estimating amygdala volumes, to determine whether cryptic amygdala lesions might be detected. METHODS: Review of video EEG monitoring data yielded 11 patients with EEG lateralised TLE and normal structural imaging. Amygdala volumes were estimated in this group, in 77 patients with pathologically verified hippocampal sclerosis (HS), and in 77 controls. RESULTS: Seven of 11 "imaging-negative" cases had both significant amygdala asymmetry and amygdala enlargement, concordant with seizure lateralisation. Although significant amygdala asymmetry occurred in 35 of 77 HS patients, it was never attributable to an abnormally large ipsilateral amygdala. Compared with patients with HS, patients with amygdala enlargement were less likely to have suffered secondarily generalised seizures (p<0.05), and had an older age of seizure onset (p<0.01). CONCLUSION: Abnormal amygdala enlargement is reported in seven cases of "imaging-negative" TLE. Such abnormalities are not observed in patients with HS. It is postulated that amygdala enlargement may be attributable to a developmental abnormality or low grade tumour. It is suggested that amygdala volumetry is indicated in the investigation and diagnosis of "imaging-negative" TLE.

Adult↗
PubMed2003

Gas-phase detection of trinitrotoluene utilizing a solid-phase antibody immobilized on a gold film by means of surface plasmon resonance spectroscopy.

A multilayered biosensor was constructed and found to detect trinitrotoluene (TNT) in ppb concentrations in air both prior to and after detonation of TNT without use of a liquid phosphate buffered saline (PBS) superstrate. The biosensor surface was fabricated from a monoclonal antibody for TNT covalently bound to an 11,11'-dithio-bis(succinimidoylundecanoate) (DSU) self-assembled monolayer immobilized on a thin gold film bonded to a BK7 glass slide. The binding between the immobilized antibody and TNT antigen was detected using surface plasmon resonance spectroscopy (SPRS). Biosensor specificity for TNT was demonstrated with chemical homologues as well as against an unrelated explosive, RDX.

Air Pollutants↗
PubMed2002

The influence of the Pro12Ala mutation of the PPAR-gamma receptor gene on metabolic and clinical characteristics in treatment-naïve patients with type 2 diabetes.

Peroxisome proliferator activated receptor-gamma is an important factor in adipocyte differentiation and energy metabolism and is thus a candidate gene for obesity, insulin resistance and dyslipidaemia. We therefore assessed the associations between the most common variant of the PPAR-gamma, the Pro12Ala (P12A) substitution in the PPAR-gamma 2 gene, with BMI, blood pressure, fasting plasma glucose, HbA1c, total cholesterol, LDL and HDL cholesterol and plasma triglyceride in 183 treatment-naïve patients with type 2 diabetes (T2D). The P12A allele associated with lower fasting plasma glucose but had no influence on HbA1c or BMI. In obese patients (BMI > 29 kg/m2), the P12A substitution associated with elevated total and non-HDL cholesterol levels.

Adult↗