Education and person-centred approaches to dementia care.
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Aged↗
Biomedical subjects
M Armstrong
Publications and source records attributed to M Armstrong.
Analysis of the human KCNH2(HERG) gene: identification and characterization of a novel mutation Y667X associated with long QT syndrome and a non-pathological 9 bp insertion.
Long QT (LQT) syndrome is a potentially life-threatening disorder, characterized by a distinct cardiac arrhythmia known as torsades de pointes. Mutations within a number of genes linked to the familial form, including that coding for a cardiac potassium channel called KCNH2 (HERG), have been described based on the characterized genomic organization. A standardized method was developed to screen the entire gene for gene variants. We report a single base pair substitution, introducing a premature STOP codon at codon 667 of the gene in a healthy individual with an extended QTc interval (460 msec). In vitro expression of the codon Y667X variant in Xenopus oocyte suggests that the autosomal dominant variant does not function in a dominant/negative manner and cannot co-assemble to form a channel, resulting in a reduction of the KCNH2 current, and an extension of the QT interval. This indicates that pathogenic LQT gene variants exist in the apparently normal population, the prognosis and clinical consequences of which remain to be determined. The assays described should facilitate future studies into this area.
Animals↗
Geographic variation in blood plasma protein concentrations of young herring gulls (Larus argentatus) and Caspian terns (Sterna caspia) from the Great Lakes and Lake Winnipeg.
Relative and total amounts of plasma protein fractions are affected by infections, inflammation, and nutritional and physiological status, and are therefore important health indicators in free-living animals. Our objectives were: (1) to examine intercolony differences in plasma protein fractions in prefledgling gulls and terns; (2) to investigate relationships between plasma proteins and other physiological measures such as weight loss, growth, and immune function; and (3) to examine potential associations between organochlorine exposure and plasma proteins. During 1992, blood was collected from 3-week-old herring gull (Larus argentatus) chicks from six sites on Lakes Superior, Huron, Michigan, Erie, and Winnipeg and from 3-week-old Caspian tern (Sterna caspia) chicks from five sites on Lakes Huron, Michigan, and Ontario. These sites provided a wide gradient of organochlorine contamination. Plasma proteins were separated by high-resolution agarose gel electrophoresis and stained with Coomassie brilliant blue dye. Six major fractions were quantified: prealbumin, albumin, alpha-globulins, beta(1)-globulins, beta(2)-globulins, and gamma-globulins. Total protein, prealbumin, albumin, and gamma-globulin concentrations and the albumin/globulin ratio did not differ among sites. Total protein, albumin, and the albumin/globulin ratio were not decreased in birds experiencing food stress or weight loss. Intersite differences were found in alpha- and beta-globulins. In gulls, beta(2)-globulins were positively associated with polychlorinated biphenyls (PCBs) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ether (DDE). In terns, PCBs were negatively associated with alpha-globulins and positively associated with beta(1)-globulins. Additional research is needed to identify individual proteins and elucidate causal relationships between the particular protein concentrations and factors such as contaminants, growth, and condition.
Alpha-Globulins↗
Severe sclerokeratitis due to Pseudomonas aeruginosa in noncontact-lens wearers.
PURPOSE: To review the clinical presentation, treatment and outcome in four cases of severe anterior segment infection by Pseudomonas aeruginosa unrelated to contact lens wear. METHODS: Four cases presenting over an 18 month period were reviewed. RESULTS: The cases had variable presenting features and outcomes. Complications such as persistent infection, corneal thinning and phthisis bulbi were noted. Possible factors influencing adherence and tissue disruption are discussed. CONCLUSIONS: Suspicion of infection by P. aeruginosa and prompt isolation of the organism is needed early in the course of disease. Intensive and prolonged treatment with parenteral and topical antibiotics combined with judicious use of topical steroid gives the best chance of a favourable outcome.
Aged↗
Utility of history, examination and laboratory tests in screening those returning to Europe from the tropics for parasitic infection.
OBJECTIVES: To examine the utility of the different elements of screening expatriates and travellers returned from the tropics for parasitic disease (exposure history, symptoms, examination and laboratory tests). METHODS: In phase 1 (conducted prospectively 1990-91), 1029 asymptomatic returnees had a detailed questionnaire and interview on risk-behaviour, physical examination and laboratory tests. In phase 2 (1997-98), 510 consecutive patients referred for routine screening (276 symptomatic and 234 asymptomatic) were screened with laboratory tests. RESULTS: Exposure history did not correlate reliably with parasite burden. In phase 1 physical examination revealed 387 abnormalities, only three of which indicated parasitic disease. Schistosomal serology was positive in 11% (CI 9-13) of these asymptomatic cases including patients with light or no reported freshwater exposure. Stool microscopy was positive in 19% (CI 16-22) of cases not correlated with reported eating habits, and eosinophilia was present in 8% (CI 6-10). In phase 2 reported symptoms did not correlate with parasitic disease. Schistosomiasis was present in 15% (CI 13-24) of asymptomatic and 18% (CI 13-22) of symptomatic individuals (OR 1.2 P = 0.46); stool microscopy was positive in 14% of both symptomatic and asymptomatic patients, and eosinophilia in 9% of symptomatic and 6% of asymptomatic individuals. CONCLUSION: Potentially serious asymptomatic infection is common in travellers. Detailed exposure history, symptom history and physical examination added little to detecting cases. Stool microscopy, schistosomal serology and eosinophil count all had good yield. Filarial serology had low yield in patients without eosinophilia.
Adolescent↗
Two linked mutations in transcriptional regulatory elements of the CYP3A5 gene constitute the major genetic determinant of polymorphic activity in humans.
Cytochrome P450 3A subfamily members (CYP3A) are the most abundant liver cytochrome P450 forms, responsible for the biotransformation of over 50% of all drugs. The expression and activity of isoforms CYP3A4 and CYP3A5 show wide inter-individual variation, influencing both drug response and disease susceptibility. The molecular basis for this variation has never been defined. In this study, we used midazolam to characterize CYP3A5 phenotype in a panel of liver samples. A clear bimodality in metabolism was observed. Analysis of the 5' flanking region of the CYP3A5 gene identified two linked polymorphisms, T-369G and A-45G, located in transcriptional regulatory elements which are associated with increased expression and activity of the gene. A polymerase chain reaction based detection assay is described facilitating future studies into both the metabolic consequences of this variation and disease association studies relating to CYP3A5.
5' Untranslated Regions↗
Randomized, placebo-controlled, double-blind, multicenter trial of efficacy and safety of granulocyte colony-stimulating factor in liver transplant recipients.
BACKGROUND: Infection and rejection are two common complications after liver transplants. In a preliminary study, administration of granulocyte colony-stimulating factor (G-CSF) to liver transplant recipients was associated with a decrease in sepsis episodes, sepsis-related deaths, and rejection compared with a historical control group of patients. The purpose of this study was to evaluate further the efficacy of G-CSF in liver transplant patients in a randomized, placebo-controlled, double-blind, multicenter trial. METHODS: Adult patients with a United Network Organ Sharing classification of 1 or 2 were randomized to receive a placebo, 100 microg/day of G-CSF or 300 microg/day of G-CSF. The study drug was started preoperatively and then continued after the transplant for a maximum of 21 days. Patients were evaluated for microbiologically-documented infection, biopsy-proven rejection, number of treatments for rejection, length of stay in the intensive care unit and hospital, graft survival, death, and adverse events. RESULTS: During the first 30 days after the transplant, the median peak white blood cell count was 16.5x10(9)/L, 34.6x10(9)L, and 54.8x10(9)/L for the placebo, low-dose G-CSF, and high-dose G-CSF patients, respectively. The incidence of infection was 30% in G-CSF patients (34 of 114 patients) and 34% in placebo patients (20 of 58 patients). Except for more nosocomial pneumonias in the G-CSF patients (7 in 114 patients vs. 0 in 58 patients, P=0.056), the types of infections and causative organisms were also similar in both treatment groups. Although the number of treatments for clinically suspected or proven rejection was similar in the G-CSF and placebo patients, biopsy-proven rejection occurred more often in G-CSF patients (34 of 114 patients or 30%) than placebo patients (11 of 58 patients or 19%) (P=0.093). There were no cases of graft loss caused by rejection. G-CSF had no effect on length of stay in the intensive-care unit or hospital. There were 22 G-CSF patients (18%) and 10 placebo patients (15%) who died within 120 days after the transplant. No serious adverse events were attributed to G-CSF. CONCLUSION: Despite producing substantial increases in the white blood cell count after the transplant, G-CSF had no beneficial effects on infection, rejection, or survival in this study. Biopsy-proven rejection and nosocomial pneumonias were more common in patients treated with G-CSF compared with those taking the placebo. No serious adverse events were attributed to G-CSF.
Adolescent↗
Chisel tip suction cautery device for tonsillectomy.
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Adolescent↗
Falls: a coordinated strategy.
Falls are a common and serious health problem. Responses to the problem should address the individual, the individual's environment, the system of health or residential care used by the individual, and the local community. This article describes a response to the issue of falls in Ryde Hospital and its surrounding community. This response has multiple components which include patient and staff education and interventions with people who have fallen. These initiatives have been developed without additional resources and incorporated into existing systems of care provision.
Accidental Falls↗
Inhibition of hypervigilance in the treatment of traumatic simple phobias: three case examples.
OBJECTIVE: In traumatic simple phobia (TSP) fear of retraumatisation tends to be enduring and may show little reduction with time despite frequent and prolonged exposure. This paper describes how hypervigilant behaviour may account for this enduring response by interfering with exposure. METHOD: Three case histories illustrating the clinical features of TSP and its treatment using in vivo exposure coupled with direct inhibition of hypervigilance are presented. RESULT: In all three cases, reduction of anxiety occurred with spontaneous generalisation of improvement. CONCLUSIONS: The efficacy of in vivo therapeutic exposure for fear of retraumatisation may be enhanced by the use of strategies to inhibit hypervigilant behaviour.
Accidents, Traffic↗
Enhanced growth of surface-attached Acanthamoeba polyphaga.
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Acanthamoeba↗
Genetic dissection of cell growth arrest functions mediated by the Epstein-Barr virus lytic gene product, Zta.
Expression of the Epstein-Barr virus (EBV) latency-associated genes activates cell cycle progression and drives immortalization of the infected cell. In contrast, progression of the EBV replication program occurs most efficiently in growth-arrested cells. Previous studies showed that the EBV-encoded immediate-early transcription factor, Zta, can induce expression of the cyclin-dependent kinase inhibitors, p21 and p27, the tumor suppressor, p53, and cell growth arrest. Moreover, Zta-mediated induction of growth arrest occurs independently of its transcriptional transactivation function. Here we show that substitution of Zta's basic DNA binding domain with the analogous region of the Zta homologue, c-Fos, abrogates Zta's ability to induce growth arrest and to induce p21, p27, or p53 expression, suggesting that protein-protein interactions between this region of Zta and key cell cycle control proteins are involved in signaling cell cycle arrest. We also show that despite the crucial role for Zta's basic domain in eliciting cell growth arrest, its amino terminus is required for efficient induction of p27 and it modulates the level of p53 induction. Last, we provide evidence that Zta-mediated inductions of p21, p27, and p53 occur, at least in part, through distinct pathways. Therefore, Zta interacts with multiple growth arrest pathways, a property which may have evolved partly as a means to ensure that lytic replication occurs in a growth-arrested setting in multiple different tissues in various states of differentiation.
Amino Acid Sequence↗
Distinct cellular factors regulate the c-myb promoter through its E2F element.
Most E2F-driven promoters are transiently activated around the G(1)/S transition. Although the promoter for the c-myb proto-oncogene harbors an E2F element, it is induced early in G(1) following entry into the cell cycle. Furthermore, this promoter remains active throughout subsequent cell cycles. Since E2F sites function as repressor elements during G(1) (due to the association of pRb with E2F factors), we investigated whether the E2F element in the c-myb promoter is regulated differently than E2F elements in promoters that are repressed during G(1). By gel shift analysis, the E2F element from the c-myb promoter was found to form a unique complex, referred to as E2Fmyb-sp, which was not observed with E2F elements from several other promoters. Antibodies to DP-1, E2F1 to -5, p107, or pRb failed to either supershift or block E2Fmyb-sp complex formation. Methylation interference experiments indicate that the DNA contact residues for the E2Fmyb-sp complex are distinct from but overlapping with residues required for the binding of E2F proteins. In addition to the identification of E2Fmyb-sp, we have found that SP-1 binds to the c-myb E2F element. Functional studies revealed that E2Fmyb-sp and/or SP-1 are required to achieve full activation of the c-myb promoter in different cell types and to maintain elevated expression of the c-myb promoter during G(1) in NIH 3T3 cells. These studies demonstrate that E2F elements can be regulated differently through the binding of unique sets of proteins.
3T3 Cells↗
When the art is on a body part.
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Adolescent↗
Blood compartmental metabolism of docosahexaenoic acid (DHA) in humans after ingestion of a single dose of [(13)C]DHA in phosphatidylcholine.
The amount and distribution of [(13)C]docosahexaenoic acid (DHA) in plasma, platelet, and erythrocyte lipid classes were followed as a function of time (1 to 72 h) in young adults after ingestion of a single dose of [(13)C]DHA esterified in a phosphatidylcholine (PC), in using gas chromatography combustion;-isotope ratio mass spectrometry. [(13)C]DHA first appeared in plasma non-esterified fatty acids (NEFA) and triglycerides (TG), with a maximal appearance at 6 h and a further decline, then being delayed 3-fold compared to [(13)C]DHA ingested in triglycerides. Lysophosphatidylcholine (LPC) was also enriched in [(13)C]DHA, due mainly to earlier hepatic secretion, and plateaued at 6 h, whereas phosphatidylethanolamine (PE) and phosphatidylcholine (PC) containing [(13)C]DHA plateaued at 9 h. The labeling of erythrocyte and platelet phospholipids exhibited different kinetics, probably involving different metabolic pathways for [(13)C]DHA incorporation in cell membranes. Computation of the relative contribution of LPC and NEFA for delivery of [(13)C]DHA to blood cells showed that the supply to platelets occurred through NEFA. In contrast, [(13)C]DHA was carried by both LPC and NEFA to erythrocytes, which differs from what was previously been observed after intake of triglycerides labeled with [(13)C]DHA where LPC was the only source of [(13)C]DHA for erythrocytes. We conclude that the lipid form of ingested DHA affects markedly its kinetics and partly its metabolic fate.
Adult↗
Obligation to the least well off in setting mental health service priorities: a consensus statement.
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Consensus↗
Obesity as an intrinsic factor affecting wound healing.
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Adult↗
Audiologic presentation of vestibular schwannomas in neurofibromatosis type 2.
OBJECTIVE: The audiologic presentation of vestibular schwannoma (VS) associated with neurofibromatosis type 2 (NF2) has not been well characterized. The goal of this study was to investigate the audiologic features of NF2-associated VS and to determine their relationship to the size of the tumor. STUDY DESIGN: A retrospective case review. SETTING: Quaternary governmental medical research institute evaluating patients fitting specific criteria for ongoing clinical studies. PATIENTS: Audiologic and magnetic resonance imaging data were available for 40 patients (25 males, 15 females), with an average age of 32 years, who had been recruited for ongoing clinical and genetic studies of NF2. MAIN OUTCOME MEASURES: The audiologic profile and magnetic resonance imaging characteristic of tumor were retrospectively reviewed. RESULTS: The average size of the tumor at presentation was 7.26 +/- 16.58 cm3 and measured 1.2, 1.6, and 1.1 cm in the anterior/posterior, lateral/medial, and superior/inferior dimensions, respectively. An increase in lateral/medial size of the tumor most significantly correlated with deterioration in mid- (1,000-2,000 Hz) and high- (4,000-8,000 Hz) frequency hearing levels, elevated speech reception threshold, and prolonged auditory brain stem response waves III and V latency. CONCLUSIONS: Patients with NF2 demonstrate a more predictable audiologic profile for a given size tumor than has been previously described with spontaneous or sporadic VS.
Adult↗