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Biomedical subjects

D Ho

Publications and source records attributed to D Ho.

At least 19 recordsLinked to original sources
PubMed2007

Transport of living cells with magnetically assembled nanowires.

We present a technique of transporting and positioning living cells internalized by nickel (Ni) nanowires guided by magnetic field. Nanoscale magnetic nanowires are internalized by the Rat Neuroblastoma (ATCC number CRL-2754) and the cells are transported and positioned by magnetic fields from the magnetic material-coated electrodes. This technique may enable the interfacing between neurons and electronic devices to empower investigations pertaining to non-invasive neuron probing as well as nanofabricated neural pharmacological technologies.

Animals↗
PubMed2005

Randomized double-blind trial of sotalol versus lignocaine in out-of-hospital refractory cardiac arrest due to ventricular tachyarrhythmia.

AIM: We aimed to compare the efficacy of sotalol versus lignocaine for the treatment of patients with out-of-hospital ventricular fibrillation refractory to > or = 4 defibrillatory shocks. BACKGROUND: The outcome of patients in ventricular fibrillation refractory to > or = 4 defibrillatory shocks is poor. In a previous randomized trial, sotalol was superior to lignocaine for acute termination of ventricular tachycardia not causing loss of consciousness. METHODS: Patients of the Ambulance Service of New South Wales treated by paramedics with continued ventricular fibrillation despite standard resuscitation and > or = 4 defibrillatory monophasic shocks were eligible. Drug doses were sotalol 100 mg or lignocaine 100 mg, given as i.v. boluses. A further 2 min of cardiopulmonary resuscitation was given and then defibrillation was repeated twice. If this failed, half the initial dose of the trial drug was repeated and a further > or = 2 shocks were given. RESULTS: Sixty patients were randomized to sotalol and 69 randomized to lignocaine. There was no significant difference between the two groups in the clinical characteristics of the patients or in the number of shocks received. Outcomes in the sotalol and lignocaine groups were survival to hospital admission in 7 (12%) and 16 (23%), respectively (P = 0.09), and survival to hospital discharge in 2 (3%) and 5 (7%), respectively (P = 0.33). CONCLUSIONS: Sotalol is not superior to lignocaine for treatment of ventricular fibrillation refractory to multiple shocks. The overall outcome of this group of patients is poor regardless of the pharmacological intervention (lignocaine or sotalol).

Aged↗
PubMed2005

Factors influencing the diagnosis and treatment of periodontal disease by dental practitioners in Victoria.

BACKGROUND: Healthy periodontal tissues are essential to overall dental health. Therefore, the detection and management of periodontal disease is an integral part of general dental practice. The aim of this study was to investigate confidence in diagnosis and management of periodontal disease by general dental practitioners (GDPs), assess if the Dental Practice Board guidelines on periodontal record keeping are being addressed, and, if necessary, try to find ways of improving the periodontal knowledge of GDPs. METHODS: A survey assessing practitioner confidence in diagnosing and treating periodontal disease was sent to a random selection of 550 dental care providers registered with the Dental Practice Board of Victoria. RESULTS: Two hundred and eighty five (51.8 per cent) of questionnaires were returned completed. It was found that 79.7 per cent of the sampled population screened all new patients for periodontal disease. The majority of respondents felt confident to diagnose and treat gingivitis and initial periodontitis. However, only 61.9 per cent felt confident to diagnose aggressive/early onset periodontitis, and many were not confident in treating advanced periodontitis (36.3 per cent) or aggressive periodontitis (51.6 per cent). The majority of dentists reported that they provided most of the non surgical periodontal therapy to their patients, while most surgical treatments were referred to specialist periodontists. Factors deemed to be important in influencing the decision to provide periodontal treatment included level of training and ability to motivate patients to improve oral hygiene. Many responents requested periodontic continuing education (CE) courses be run. CONCLUSIONS: Most of the dentists surveyed were confident to diagnose periodontal disease and to treat the more common presentations of periodontal disease. There is some evidence to suggest that some practitioners are not following the minimum requirements set by the Dental Practice Board of Victoria in relation to periodontal record keeping. The results also indicate a need for more periodontic CE courses in Victoria.

Clinical Competence↗
PubMed2004

Medical management of deliberate drug overdose: a neglected area for suicide prevention?

OBJECTIVES: Overdoses account for a quarter of all suicides in England. The number of people who survive the immediate effects of their overdose long enough to reach medical attention, but who subsequently die in hospital is unknown. The aim of this study was to determine the proportion of overdose suicides dying in hospital and describe their sociodemographic characteristics. METHOD: Cross sectional analysis of routinely collected Hospital Episode Statistics data for England (1997 to 1999) to identify hospital admissions for overdose among people aged 12+ and the outcome of these admissions. RESULTS: Between 1997 and 1999 there were 233 756 hospital admissions for overdose, 1149 (0.5%) of these ended in the death of the patient such deaths accounted for 28% [corrected] of all overdose suicides and 8% [corrected] of total suicides. The median time between admission and death was three days (interquartile range one to nine days). The most commonly identified drugs taken in fatal overdose were paracetamol compounds, benzodiazepines, and tricyclic/tetracyclic antidepressants. CONCLUSION: Around a quarter of all overdose suicide deaths occur subsequent to hospital admission. Further more detailed research is required to discover if better pre-admission and in-hospital medical management of those taking serious overdoses may prevent some of these deaths.

Acetaminophen↗
PubMed2003

The use of a distal occlusion balloon protection device in acute coronary syndrome.

We report our early experience in using the PercuSurge GuardWire Plus system as a distal protection device in patients with acute coronary syndrome and acute myocardial infarction. Forty-three patients received percutaneous coronary intervention with the GuardWire Plus system. Thirteen had unstable angina, five had non-Q myocardial infarction and 25 had ST segment elevation myocardial infarction. Forty-one target lesions were in native coronary vessels and two were in saphenous vein grafts. Total occlusion occurred in 18 patients. The mean occlusion time by the distal protective balloon was 262.8 +/- 114.1 s. Preoperatively, TIMI 0 flow was present in 18, TIMI II flow in two and TIMI III flow in 23 patients. Post-operatively, TIMI II and TIMI III flow were established in two and 41 patients, respectively. All procedures were successful and the GuardWire Plus system was successfully deployed in all but two patients. There was no procedure-related major adverse clinical event. There was no major adverse clinical event at 30 days. There was no device-related complication. We believe that the GuardWire Plus system is safe and feasible in patients with acute coronary syndrome and acute myocardial infarction.

Angina, Unstable↗
PubMed2002

The Shikani Seeing Stylet for difficult intubation in children: initial experience.

The Shikani Seeing Stylet is a recently introduced reusable intubating stylet, produced in adult and paediatric versions. It combines features of a fibreoptic bronchoscope and a lightwand. Inside a malleable stainless steel sheath, the Shikani Seeing Stylet has a fibreoptic cable leading to a distal light source and high-resolution lens. In use, the stylet is placed in the lumen of the selected endotracheal tube and the light source enables the stylet to be used as a lightwand, while the fibreoptic capability enables visualization of the laryngeal inlet. It is portable, relatively inexpensive and easy to maintain. This report describes the use of the stylet on eight occasions in seven children, all of whom were assessed preoperatively as being potentially difficult to intubate. Three had been difficult to intubate previously. All were anaesthetized using inhalational anaesthesia. Once an adequate depth of anaesthesia had been achieved, conventional direct laryngoscopy was performed and identified as Grade 3 in six of the patients and Grade 1 in one. Tracheal intubation was then attempted using the Shikani Seeing Stylet. On six of the eight occasions the attempt was made by different anaesthetists, none of whom had any prior clinical experience with the stylet. There were seven successful intubations and one failure in a patient who could not be intubated by any method. The Shikani Seeing Stylet seems a useful device for use in children with difficult airway problems, suspected cervical spine instability or limited mouth-opening.

Adolescent↗
PubMed2001

Interactions among ascorbate, dehydroascorbate and glucose transport in cultured hippocampal neurons and glia.

There is an increasing recognition of the damaging role played by oxygen radicals in mediating necrotic neuronal injury. As such, it becomes important to understand the transport mechanisms that help maintain appropriate levels of small molecule antioxidants such as ascorbate in the brain. It has long been known that the transport of dehydroascorbate (DHA) into a variety of cell types is accomplished through the Glut-1 glucose transporter. In this paper, we characterize interactions among the transports of ascorbate, DHA and glucose in hippocampal cultures. We find: (a) sodium-dependent transport of ascorbate in mixed neuronal/glial, pure glial, and neuron-enriched hippocampal cultures; in contrast, we observed no such transport of DHA; (b) such ascorbate transport appeared to be independent of the glucose transporter, in that glucose did not compete for such transport, and overexpression of the Glut-1 glucose transporter did not alter ascorbate uptake; (c) in contrast, ascorbate, at concentrations ranging from 1 to 20 mM inhibited 2-dexogyglucose transport in mixed, glial and enriched neuronal hippocampal cultures; (d) potentially, ascorbate, by acting as an electron donor, could impair the function of molecules involve in the transport or metabolism of glucose. We observed mild inhibition of glucose transport by one unrelated electron donor (glutathione). Moreover, transport was also inhibited by an ascorbate analog which is not an electron donor. Thus, we conclude that ascorbate transport in hippocampal neurons and glia occurs independent of the glucose transporter but that, nevertheless, ascorbate, at concentrations generally thought to be supraphysiological, has the potential for disrupting glucose transport.

Animals↗
PubMed2001

Synthesis of the amino sugar from C-1027.

[reaction: see text] The amino sugar side chain (2) from C-1027Chr was synthesized in 12 steps from mannose. The key reactions are an internal displacement by nitrogen to introduce the cis amino group at C-4 and the methylation of an enolate at C-5.

Amino Sugars↗
PubMed2001

Defective binding of factor XI-N248 to activated human platelets.

Variants of factor XI containing Gln226 to Arg (Q226 to R) and Ser248 to Asn (S248 to N) substitutions were first identified in an African American family with a history of excessive bleeding. The substitutions have recently been identified in unrelated individuals, suggesting they are relatively common. Both amino acids are located in the third apple domain of factor XI, an area implicated in binding interactions with factor IX and activated platelets. Recombinant factor XI-R226 and factor XI-N248 were compared with wild-type factor XI in assays for factor IX activation or platelet binding. Factor XI-R226 activates factor IX with a Michaelis-Menten constant (K(m)) about 5-fold greater than wild-type protein. The catalytic efficiency of factor IX activation is similar to wild-type protein, however, due to an increase in the turnover number (k(cat)) for the reaction. Iodinated factor XI-N248 binds to activated platelets with a dissociation constant (K(d)) more than 5-fold higher than wild-type protein (55 nM and 10 nM, respectively). Activation of factor XI-N248 by thrombin in the presence of activated platelets is slower and does not progress to the same extent as activation of the wild-type protein under similar conditions. Factor XI-N248 activates factor IX normally in a purified protein system and has relatively normal activity in activated partial thromboplastin time (aPTT) assays. Factor XI-N248 is the first factor XI variant described with a clear functional difference compared with wild-type protein. Importantly, the defect in platelet binding would not be detected by routine clinical evaluation with an aPTT assay.

Amino Acid Substitution↗
PubMed2001

Model for a factor IX activation complex on blood platelets: dimeric conformation of factor XIa is essential.

Human coagulation factor XI (FXI) is a plasma serine protease composed of 2 identical 80-kd polypeptides connected by a disulfide bond. This dimeric structure is unique among blood coagulation enzymes. The hypothesis was tested that dimeric conformation is required for normal FXI function by generating a monomeric version of FXI (FXI/PKA4) and comparing it to wild-type FXI in assays requiring factor IX activation by activated FXI (FXIa). FXI/PKA4 was made by replacing the FXI A4 domain with the A4 domain from prekallikrein (PK). A dimeric version of FXI/PKA4 (FXI/PKA4-Gly326) was prepared as a control. Activated FXI/PKA4 and FXI/PKA4-Gly326 activate factor IX with kinetic parameters similar to those of FXIa. In kaolin-triggered plasma clotting assays containing purified phospholipid, FXI/PKA4 and FXI/PKA4-Gly326 have coagulant activity similar to FXI. The surface of activated platelets is likely to be a physiologic site for reactions involving FXI/FXIa. In competition binding assays FXI/PKA4, FXI/PKA4-Gly326, and FXI have similar affinities for activated platelets (K(i) = 12-16 nM). In clotting assays in which phospholipid is replaced by activated platelets, the dimeric proteins FXI and FXI/PKA4-Gly326 promote coagulation similarly; however, monomeric FXI/PKA4 has greatly reduced activity. Western immunoblot analysis confirmed that activated monomeric FXI/PKA4 activates factor IX poorly in the presence of activated platelets. These findings demonstrate the importance of the dimeric state to FXI activity and suggest a novel model for factor IX activation in which FXIa binds to activated platelets by one chain of the dimer, while binding to factor IX through the other.

Blood Coagulation↗
PubMed2001

Open-label phase II trial of amprenavir, abacavir, and fixed-dose zidovudine/lamivudine in newly and chronically HIV-1--infected patients.

A Phase II clinical trial was designed to evaluate the efficacy and tolerability of twice-daily abacavir, amprenavir, and zidovudine (ZDV)/lamivudine (3TC) in HIV-1-infected study subjects naive to protease inhibitors and 3TC. Plasma and cerebrospinal fluid (CSF) HIV-1 RNA levels and T-cell subsets were measured. In all, 27 newly diagnosed and 12 chronically HIV-1-infected study subjects are included in the analysis. Week 48 plasma HIV-1 RNA levels were <500 copies/ml in 100% of study subjects, and <50 copies/ml in 80% of chronically infected and 100% of newly infected study subjects. The mean change in CD4 was (+)150 cells/microl (newly infected, p <.001), and (+)155 cells/microl (chronically infected, p <.001). At Week 48, evidence of cellular activation persisted in both cohorts. A twice-daily regimen of amprenavir, abacavir, and ZDV/3TC affords potent viral suppression and significant increases in total CD4(+) cells in HIV-1--infected study subjects. Patient intolerance may limit the efficacy of this combination.

AIDS Dementia Complex↗
PubMed2001

Design and synthesis of tricyclic derivatives as high density lipoprotein cholesterol enhancers.

A pharmacophore for increasing HDLC was proposed based on common structural features of non-thio-containing compounds with HDLC enhancing properties. A search of the compound database identified various series of these non-thio-containing compounds, including a novel tricyclic imidazoisoquinolone. Preparation of 1-aryl-3-oxo-1,3-dihydro-2-benzofuran-1-carboxamides using a novel and widely applicable one-step process from 2-acyl benzoic acids is reported. Reaction of diamines with 1-aryl-3-oxo-1,3-dihydro-2-benzofuran-1-carboxamides and related aza-analogues proceeded with regio-control to furnish imidazoisoquinolones, pyrimidoisoquinolones, and imidazonaphthyridines. NMR studies and X-ray crystallography confirmed the regiochemistry of the products. Compounds of these series increased concentrations of HDLC in test animals following oral administration.

Administration, Oral↗
PubMed2001

The contribution of chemoreflex drives to resting breathing in man.

The contribution of automatic drives to breathing at rest, relative to behavioural drives such as "wakefulness", has been a subject of debate. We measured the combined central and peripheral chemoreflex contribution to resting ventilation using a modified rebreathing method that included a prior hyperventilation and addition of oxygen to maintain isoxia at a P(ET,O2) (end-tidal partial pressure of oxygen) of 100 mmHg. During rebreathing, ventilation was unrelated to P(ET,CO2) (end-tidal partial pressure of carbon dioxide) in the hypocapnic range, but after a threshold P(ET,CO2) was exceeded, ventilation increased linearly with P(ET,CO2). We considered the sub-threshold ventilation to be an estimate of the behavioural drives to breathe (mean +/- S.E.M. = 3.1 +/- 0.5 l min(-1)), and compared it to ventilation at rest (mean +/- S.E.M. = 9.1 +/- 0.7 l min(-1)). The difference was significant (Student's paired t test, P < 0.001). We also considered the threshold P(CO2) observed during rebreathing to be an estimate of the chemoreflex threshold at rest (mean +/- S.E.M. = 42.0 +/- 0.5 mmHg). However, P(ET,CO2) during rebreathing estimates mixed venous or tissue P(CO2), whereas the resting P(ET,CO2) during resting breathing estimates P(a,CO2) (arterial partial pressure of carbon dioxide). The chemoreflex threshold measured during rebreathing was therefore reduced by the difference in P(ET,CO2) at rest and at the start of rebreathing (the plateau estimates the mixed venous P(CO2) at rest) in order to make comparisons. The corrected chemoreflex thresholds (mean +/- S.E.M. = 26.0 +/- 0.9 mmHg) were significantly less (paired Student's t test, P < 0.001) than the resting P(ET,CO2) values (mean +/- S.E.M. = 34.3 +/- 0.5 mmHg). We conclude that both the behavioural and chemoreflex drives contribute to resting ventilation. Experimental Physiology (2001) 86.1, 109-116.

Adult↗
PubMed2000

Sparing of neuronal function postseizure with gene therapy.

Numerous studies have demonstrated that gene therapy interventions can protect neurons from death after neurological insults. In nearly all such studies, however, "protection" consists of reduced neurotoxicity, with no demonstrated preservation of neuronal function. We used a herpes simplex virus-1 system to overexpress either the Glut-1 glucose transporter (GT) (to buffer energetics), or the apoptosis inhibitor Bcl-2. Both decreased hippocampal neuron loss to similar extents during excitotoxic insults in vitro and in vivo. However, the mediating mechanisms and consequences of the two interventions differed. GT overexpression attenuated early, energy-dependent facets of cell death, blocking oxygen radical accumulation. Bcl-2 expression, in contrast, blocked components of death downstream from the energetic and oxidative facets. Most importantly, GT- but not Bcl-2-mediated protection preserved hippocampal function as assessed spatial maze performance. Thus, gene therapeutic sparing of neurons from insult-induced death does not necessarily translate into sparing of function.

Animals↗
PubMed2000

Quantification of cell turnover kinetics using 5-bromo-2'-deoxyuridine.

5-Bromo-2'-deoxyuridine (BrdU) is frequently used to measure the turnover of cell populations in vivo. However, due to a lack of detailed mathematical models that describe the uptake and loss of BrdU in dividing cell populations, assessments of cell turnover kinetics have been largely qualitative rather than quantitative. In this study, we develop a mathematical framework for the analysis of BrdU-labeling experiments. We derive analytical expressions for the fraction of labeled cells within cell populations that are growing, declining, or at equilibrium. Fitting the analytical functions to data allows us to quantify the rates of cell proliferation and cell loss, as well as the rate of cell input from a source. We illustrate this for the BrdU labeling of T lymphocytes of uninfected and SIV-infected rhesus macaques.

Animals↗