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Biomedical subjects

K Morris

Publications and source records attributed to K Morris.

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

Growing pains of East Timor: health of an infant nation.

In August, 1999, three-quarters of East Timorese adults voted to end more than two decades of an Indonesian administration never recognised by the United Nations. The ensuing spree of violence and destruction by militia backed by the Indonesian military meant the birth of the fledgling nation became a complex humanitarian disaster. 1 year on, progress was heartening: a transitional government, a judiciary, and tax systems were in place, and East Timor was a proud competitor in the Sydney Olympic games. Rebuilding a country from ground level has brought a golden opportunity for fresh approaches. However, reconstruction is also a slow, complex, and sometimes controversial process at the mercy of multiple agendas. The health sector has seen basic care restored, establishment of a much-needed public-health service, and planning for the future health system. An innovative partnership between WHO/Roll Back Malaria and Merlin for post-conflict research has provided data to guide malaria control. The story of progress from humanitarian emergency to national health plan epitomises the triumphs and challenges of this newest nations' first 18 months.

Developing Countries↗
PubMed2001

Modulation of MK-801-induced behaviour by noradrenergic agents in mice.

RATIONALE: Inhibition of glutamatergic N-methyl-D-aspartate (NMDA) receptors following the administration of NMDA receptor antagonists results in psychotic-like behaviour. Whereas it is known that pharmacological manipulation of dopaminergic and serotonergic pathways affect this drug-induced psychosis, a role for noradrenaline has not yet been clearly defined. OBJECTIVES: Thus, in the present study, we assessed a possible role for noradrenaline in the behavioural response to the non-competitive NMDA receptor anatgonist, MK-801, in male CD-I mice. RESULTS: MK-801 (0.02-1.28 mg/kg; ED50 0.2 mg/kg; s.c.) induced a dose-dependent increase in locomotor, stereotypic and ataxic behaviours. Pre-treatment with the noradrenaline re-uptake inhibitors, desipramine (10 mg/kg; i.p.) and reboxetine (20 mg/kg; i.p.), attenuated the locomotor, stereotypic and ataxic response to MK-801 (0.2 mg/kg; s.c.). The noradrenergic system was lesioned with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4, 50 mg/kg; i.p., 7 and 4 days prior to challenge) to reduce noradrenaline concentrations in the cortex by 70%-80%. Whereas DSP-4 lesioning had little effect on the response to MK-801, it completely reversed the attenuating effects of reboxetine. Pre-treatment with the alpha2 adrenoceptor agonist, clonidine (0.2 mg/kg; i.p.), and the antagonist, yohimbine (2 mg/kg; i.p.), attenuated and potentiated the response to MK-801, respectively. Pre-treatment with the alpha1 adrenoceptor antagonist, prazosin (2 mg/kg; i.p.), reduced the MK-801-induced response. CONCLUSIONS: It therefore appears that presynaptic noradrenergic alpha2 and postsynaptic alpha1 adrenoceptor stimulation exert opposing effects on the behavioural expression of MK-801 in mice.

Adrenergic Agents↗
PubMed2001

The relationships between post-prandial lipaemia, endothelial function and oxidative stress in healthy individuals and patients with type 2 diabetes.

Post-prandial lipaemia (PPL) is a factor in atherogenesis and results in reversible endothelial dysfunction in healthy individuals. Oxidative stress and triglyceride (TG)-rich lipoproteins have been implicated. Type 2 diabetes (NIDDM) results in exaggerated PPL. We attempted to delineate the mechanisms of PPL induced, endothelial dysfunction (EF) and oxidative stress in 12 NIDDM and 12 matched healthy subjects. Subjects underwent a fat tolerance test, with endothelial function assessed by flow-mediated vasodilatation and oxidative stress measured by venous lipid-derived free radicals ex vivo and lipid peroxidation products over the postprandial phase. Fasting TG, post-prandial hypertriglyceridaemia and the TG enrichment of all lipoproteins was significantly greater in NIDDM. Post-prandial endothelial function inversely correlated with fasting HDL-C (r=-0.84, P=0.001) in both the control and NIDDM groups. The deterioration in EF in the NIDDM group also correlated with TG enrichment of VLDL and LDL. PPL in both groups also resulted in increased oxidative stress. The increment in free radicals correlated with TG enrichment of VLDL in both groups and was, therefore, greater in NIDDM. Thus, PPL -- with the production of TG-enrichment of VLDL -- results in endothelial dysfunction by an oxidative stress mechanism in both groups. The magnitude is greater in NIDDM. Fasting HDL-C appears to contribute to the protection of the endothelium against this phenomenon. Hence, exaggerated PPL associated with reduced HDL-C may be important in the pathogenesis of vascular disease, particularly in NIDDM.

Adult↗
PubMed2001

Functional genomic studies of aldo-keto reductases.

Aldose reductase (AR) is considered a potential mediator of diabetic complications and is a drug target for inhibitors of diabetic retinopathy and neuropathy in clinical trials. However, the physiological role of this enzyme still has not been established. Since effective inhibition of diabetic complications will require early intervention, it is important to delineate whether AR fulfills a physiological role that cannot be compensated by an alternate aldo-keto reductase. Functional genomics provides a variety of powerful new tools to probe the physiological roles of individual genes, especially those comprising gene families. Several eucaryotic genomes have been sequenced and annotated, including yeast, nematode and fly. To probe the function of AR, we have chosen to utilize the budding yeast Saccharomyces cerevisiae as a potential model system. Unlike Caenorhabditis elegans and D. melanogaster, yeast provides a more desirable system for our studies because its genome is manipulated more readily and is able to sustain multiple gene deletions in the presence of either drug or auxotrophic selectable markers. Using BLAST searches against the human AR gene sequence, we identified six genes in the complete S. cerevisiae genome with strong homology to AR. In all cases, amino acids thought to play important catalytic roles in human AR are conserved in the yeast AR-like genes. All six yeast AR-like open reading frames (ORFs) have been cloned into plasmid expression vectors. Substrate and AR inhibitor specificities have been surveyed on four of the enzyme forms to identify, which are the most functionally similar to human AR. Our data reveal that two of the enzymes (YDR368Wp and YHR104Wp) are notable for their similarity to human AR in terms of activity with aldoses and substituted aromatic aldehydes. Ongoing studies are aimed at characterizing the phenotypes of yeast strains containing single and multiple knockouts of the AR-like genes.

Alcohol Oxidoreductases↗
PubMed2001

Plutonium solubility in sediment pore waters.

Using in situ porous cup samplers, dissolved Pu concentrations have been measured over a year in the pore waters from two contrasting sites in the valley of the River Esk, North West England. In saltmarsh sediments, dissolved Pu represents approximately 1 part in 10(6) of the total inventory. The Pu concentration in solution is in the range 1.1-3.5 mBq l-1, varying by a factor of 3 in the course of the year. Most of the changes in dissolved Pu coincide with changes in dissolved Fe and Mn concentrations, with Pu being low in the summer months when Fe and Mn are high. Nevertheless, there are a number of factors which make it unclear as to whether these patterns might be related to seasonal redox changes in the saltmarsh. At the highly organic, reducing reedbed site, the proportion of Pu in solution is typically around 1 part in 10(3), proportionately much higher than in the saltmarsh, giving concentrations ranging between 9.0 and 28.5 mBq l-1, and are apparently maintained by complexation to dissolved organic matter. There is no obvious seasonal pattern at the reedbed site nor is there any relation to any of the dissolved species measured (Fe, Mn, Na, DOC).

Ecosystem↗
PubMed2001

Familial deletion of (8)(q24.13q24.22) associated with a normal phenotype.

We report a familial deletion of (8q) detected in amniocytes of a fetus with a normal ultrasound and in the phenotypically normal mother, who has now had three pregnancy losses. Chromosome analysis of amniocytes and maternal peripheral blood cells showed an interstitial deletion of (8)(q24.13q24.22), which is distal to the region associated with Langer-Giedion syndrome (LGS) or trichorhinophalangeal (TRP) syndrome. This deletion was confirmed by fluorescence in situ hybridization with a c-myc cosmid clone and chromosome 8 painting library.

Adult↗
PubMed2001

Multimodality image-guided epilepsy surgery.

Co-registration of imaging modalities in the diagnosis of epilepsy is now commonly used in major epilepsy centres. However, the incorporation of these registrations into an image-guided system has only recently been developed. Using techniques of segmentation, surface matching and/or voxel-based matching, we have been able to co-register FLAIR MRI, SPECT, PET, and subdural grids into the 3-D space of the volumetric MRI and use these images on the StealthStation Image-Guided System to resect these foci. This greatly aids the surgeon in performing a more precise tailoring of the cortical resection so as to maximize the excision of the epileptogenic zone while minimizing the impact on eloquent cortex and epileptogenic foci.

Adult↗
PubMed2001

Integrative noetic therapies as adjuncts to percutaneous intervention during unstable coronary syndromes: Monitoring and Actualization of Noetic Training (MANTRA) feasibility pilot.

BACKGROUND: Patients undergoing percutaneous coronary intervention (PCI) for unstable coronary syndromes have substantial emotional and spiritual distress that may promote procedural complications. Noetic (nonpharmacologic) therapies may reduce anxiety, pain and distress, enhance the efficacy of pharmacologic agents, or affect short- and long-term procedural outcomes. METHODS: The Monitoring and Actualization of Noetic Training (MANTRA) pilot study examined the feasibility of applying 4 noetic therapies-stress relaxation, imagery, touch therapy, and prayer-to patients in the setting of acute coronary interventions. Eligible patients had acute coronary syndromes and invasive angiography or PCI. Patients were randomized across 5 treatment groups: the 4 noetic and standard therapies. Questionnaires completed before PCI reflected patients' religious beliefs and anxiety. Index hospitalization end points included post-PCI ischemia, death, myocardial infarction, heart failure, and urgent revascularization. Mortality was followed up for 6 months after hospitalization. RESULTS: Of eligible patients, 88% gave informed consent. Of 150 patients enrolled, 120 were assigned to noetic therapy; 118 (98%) completed their therapeutic assignments. All clinical end points were available for 100% of patients. Results were not statistically significant for any outcomes comparisons. There was a 25% to 30% absolute reduction in adverse periprocedural outcomes in patients treated with any noetic therapy compared with standard therapy. The lowest absolute complication rates were observed in patients assigned to off-site prayer. All mortality by 6-month follow-up was in the noetic therapies group. In patients with questionnaire scores indicating a high level of spiritual belief, a high level of personal spiritual activity, a low level of community-based religious involvement, or a high level of anxiety, noetic therapies appeared to show greater reduction in absolute in-hospital complication rates compared with standard therapy. CONCLUSIONS: Acceptance of noetic adjuncts to invasive therapy for acute coronary syndromes was excellent, and logistics were feasible. No outcomes differences were significant; however, index hospitalization data consistently suggested a therapeutic benefit with noetic therapy. Of all noetic therapies, off-site intercessory prayer had the lowest short- and long-term absolute complication rates. Definitive demonstration of treatment effects of this magnitude would be feasible in a patient population about 4 times that of this pilot study. Absolute mortality differences make safety considerations a mandatory feature of future clinical trials in this area.

Angioplasty, Balloon, Coronary↗
PubMed2001

Modeling of powder blending using on-line near-infrared measurements.

A model to quantify the degree of mixing in pharmaceutical powder mixing operations was developed. The additive volume mixing model is based on the determination of the characteristic volume of agitation for a given blender, which is dependent on process parameters such as the formulation ingredients, the geometry of the mixer, and the batch load. The calculation of this characteristic volume of agitation is based on the determination of the fitted fraction of formulation mixed after the first blender rotation. A variation of this model, denominated the iterative mixing model, was also developed. On-line near-infrared (NIR) measurements were taken throughout the runs to obtain the mixing profile and the dynamics of the powder bed as a function of blender rotations. Studies were conducted at two scales using two different formulations to study and compare the calculated characteristic volume of agitation for each blender-formulation system. This approach elucidates the existing relationship between the characteristic mixing parameters and critical rotations (required rotations to achieve content uniformity) for a given system and represents a step toward scale-up of solids mixing operations.

Algorithms↗
PubMed2001

Three-year survey of bacteremia and fungemia in a pediatric intensive care unit.

BACKGROUND: Knowledge of the pattern of blood stream infection (BSI) in patients in intensive care units (ICUs) can help determine antibiotic prescribing policy and infection control procedures. However, there have been few pediatric-based studies. METHODS: Surveillance of BSI in a pediatric ICU for 3 years, amounting to 131 episodes of significant bacteremia and fungemia. RESULTS: The incidence of BSI was 39.0 per 1,000 admissions (10.6 per 1,000 bed days). Eighty-four (64.1%) episodes were ICU-acquired, and 27 (20.6%) were community-acquired. Gram-positive, Gram-negative and anaerobic bacteria accounted for 62.2, 30.8 and 1.4%, respectively, of the 143 microorganisms isolated, 5.6% were yeasts. Neisseria meningitidis was the most common species in community-acquired infections, and staphylococci predominated in hospital-acquired episodes. Eighty-seven percent of patients had significant underlying disease, including 60.3% with congenitally acquired conditions. Intravascular devices were the most common source of infection, accounting for 41.2% of all episodes. The crude mortality in children with BSI was 26.5%, compared with 8.1% in those without BSI. CONCLUSIONS: The pattern of BSI in ICUs is partly determined by the type of patient treated. However, some observations are generally applicable, notably the increasing importance of antibiotic-resistant bacteria that are often of low virulence and device-associated. Our experience suggests that universal use of broad spectrum empiric antibiotics to cover these pathogens (which risks further promoting antibiotic resistance) may not improve patient outcome. Our study provides a basis for other pediatric ICUs to evaluate their rates and outcomes of BSI.

Adolescent↗