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D Young

Publications and source records attributed to D Young.

At least 109 records · Page 6Linked to original sources
PubMed2001

Effect of changes in lung volume on acoustic transmission through the human respiratory system.

The variation of acoustic attenuation with lung density was determined in experimental studies on seven healthy human volunteers, using a change of lung volume as a means of varying lung density. White noise between 50 and 680 Hz was introduced into the mouth and the transmitted signals were recorded with four microphones on the posterior chest wall (left/right, top/base) at 24, 40, 60 and 80% of total lung capacity. The change in lung volume had a frequency-dependent effect on acoustic attenuation in all subjects. A frequency between 177 and 243 Hz was identified, where altering the lung volume between 24 and 80% of total lung capacity induced a change in attenuation of only 1.0 (+/-0.5) to 2.7 (+/-1.8) dB, while at a frequency of 364-436 Hz marked variations in attenuation 8.9 (+/-2.0) to 21.5 (+/-4.8) dB occurred with similar lung volume changes.

Acoustics↗
PubMed2001

Automated identification of Fos expression.

The concentration of Fos, a protein encoded by the immediate-early gene c-fos, provides a measure of synaptic activity that may not parallel the electrical activity of neurons. Such a measure is important for the difficult problem of identifying dynamic properties of neuronal circuitries activated by a variety of stimuli and behaviours. We employ two-stage statistical pattern recognition to identify cellular nuclei that express Fos in two-dimensional sections of rat forebrain after administration of antipsychotic drugs. In stage one, we distinguish dark-stained candidate nuclei from image background by a thresholding algorithm and record size and shape measurements of these objects. In stage two, we compare performance of linear and quadratic discriminants, nearest-neighbour and artificial neural network classifiers that employ functions of these measurements to label candidate objects as either Fos nuclei, two touching Fos nuclei or irrelevant background material. New images of neighbouring brain tissue serve as test sets to assess generalizability of the best derived classification rule, as determined by lowest cross-validation misclassification rate. Three experts, two internal and one external, compare manual and automated results for accuracy assessment. Analyses of a subset of images on two separate occasions provide quantitative measures of inter- and intra-expert consistency. We conclude that our automated procedure yields results that compare favourably with those of the experts and thus has potential to remove much of the tedium, subjectivity and irreproducibility of current Fos identification methods in digital microscopy.

Journal Article↗
PubMed2001

Large-dose oral dextromethorphan as an adjunct to patient-controlled analgesia with morphine after knee surgery.

Dextromethorphan is a weak N-methyl-d-aspartate (NMDA) receptor antagonist that inhibits spinal cord sensitization in animal models of pain and also inhibits the development of cutaneous secondary hyperalgesia after tissue trauma. Perhaps coadministration of an NMDA antagonist with an opioid would lead to better pain relief, particularly with movement and an opioid-sparing effect. This has been shown for ketamine, but previous studies with dextromethorphan that have used small doses have shown only a modest reduction in morphine requirements with no or minimal changes in the postoperative pain experience. We sought to determine whether a large dose of this drug, just below the maximum tolerated dose, could potentiate morphine analgesia while simultaneously causing a significant improvement in the management of the postoperative pain experience. Sixty-six patients undergoing knee surgery were enrolled in the study. The study design was a prospective, randomized double-blinded comparison with placebo of 200 mg of dextromethorphan given eight hourly. Postoperative pain experiences were assessed by postoperative morphine usage. Visual analog and verbal rating scales were used to assess pain with movement as well as side effects. Dextromethorphan treatment led to a significant but modest reduction in morphine requirements (29.3% P < 0.05) but no reduction in postoperative pain levels. We conclude that increasing orally administered dextromethorphan to near maximum tolerated doses does not provide greater morphine sparing than 20-40 mg given 6-8 hourly as in previous studies. Furthermore we conclude that dextromethorphan does not improve pain scores in a manner expected of a drug with NMDA antagonist properties.

Administration, Oral↗
PubMed2001

Variables influencing end-of-life care in children and adolescents with cancer.

BACKGROUND: The purpose of this study was to describe the variables influencing end-of-life care in children and adolescents dying of cancer. MATERIALS AND METHODS: Records of 146 children with cancer who died at Children's Hospital were reviewed for demographics, diagnosis, location of death, withdrawal of life support, use of "do not resuscitate" (DNR) orders, and the length of time that those orders were in effect. RESULTS: Ninety-five patients were evaluated. Fifty-nine died of progressive disease and 36 deaths were therapy-related. Sixty-four percent of disease-related deaths occurred at home with support from home care or hospice. Only 10% of all patients died while receiving maximal aggressive support in the intensive care unit. Age, diagnosis (solid tumor vs. leukemia), cause of death, length of last hospital admission, and the duration of DNR orders had a significant correlation with the place of death and referral to and use of hospice. Thirty-five percent of all patients had hospice support. CONCLUSIONS: Most children who die of cancer die because of progressive disease at home with hospice support. Do not resuscitate orders were written for most patients who died. End-of-life decisions are influenced by patient diagnosis, cause of death, and age.

Adolescent↗
PubMed2001

Letting the genome out of the bottle: prospects for new drug development.

Use of the information gained from sequencing the Mycobacterium tuberculosis genome will enable scientists to accelerate the development of reagents for improved tuberculosis control. Cloning and expressing genes encoding the enzymes involved in cell-wall biosynthesis will provide the tools for screening millions of novel compounds. Cell wall inhibitors will be mainly useful in treating resistant disease, but cost factors are likely to limit the application of novel compounds in the design of new treatment regimens. More effective might be an approach to target metabolic processes that are essential even in nondividing bacteria. A third target for drug action is elimination of latent disease through a drug that acts in synergy with the immune response.

Antitubercular Agents↗
PubMed2001

Role of Mycobacterium tuberculosis copper-zinc superoxide dismutase.

Superoxide dismutases (SODs) play an important role in protection against oxidative stress and have been shown to contribute to the pathogenicity of many bacterial species. To determine the function of the mycobacterial copper and zinc-cofactored SOD (CuZnSOD), we constructed and characterized Mycobacterium tuberculosis and Mycobacterium bovis BCG CuZnSOD null mutants. Both strains were more sensitive to superoxides and hydrogen peroxide than were their respective parental strains. The survival of M. bovis BCG in unstimulated as well as activated mouse bone marrow-derived macrophages was not affected by the loss of CuZnSOD. The survival of CuZnSOD deficient-M. tuberculosis in guinea pig tissues was comparable to that of its parental strain. These results indicate that the mycobacterial CuZnSOD is not essential for intracellular growth within macrophages and does not detectably contribute to the pathogenicity of M. tuberculosis.

Animals↗
PubMed2001

UV-induced binding of ING1 to PCNA regulates the induction of apoptosis.

Previous studies have shown that UV-induced binding of p21(WAF1) to PCNA through the PCNA-interacting protein (PIP) domain in p21(WAF1) promotes a switch from DNA replication to DNA repair by altering the PCNA protein complex. Here we show that the p33(ING1b) isoform of the ING1 candidate tumour suppressor contains a PIP domain. UV rapidly induces p33(ING1b) to bind PCNA competitively through this domain, a motif also found in DNA ligase, the DNA repair-associated FEN1 and XPG exo/endonucleases, and DNA methyltransferase. Interaction of p33(ING1b) with PCNA occurs between a significant proportion of ING1 and PCNA, increases more than tenfold in response to UV and is specifically inhibited by overexpression of p21(WAF1), but not by p16(MTS1), which has no PIP sequence. In contrast to wild-type p33(ING1b), ING1 PIP mutants that do not bind PCNA do not induce apoptosis, but protect cells from UV-induced apoptosis, suggesting a role for this PCNA-p33(ING1b) interaction in eliminating UV-damaged cells through programmed cell death. These data indicate that ING1 competitively binds PCNA through a site used by growth regulatory and DNA damage proteins, and may contribute to regulating the switch from DNA replication to DNA repair by altering the composition of the PCNA protein complex.

Apoptosis↗
PubMed2001

Integration from the Australian GP's perspective.

OBJECTIVE: To report on what general practitioners' perceptions are about their role in relation to activities that support integration and what they are doing. METHOD: General practitioner perceived integrative behaviour was measured using a survey containing 114 statements about, 'what constitutes a well integrated GP'. Four hundred and forty-eight GPs were randomly sampled from the Health Insurance Commission (HIC) Medicare billing database in 1996. A response rate of 47% was obtained, yielding 208 surveys for analysis. RESULTS: General practitioners reported integrative activities such as being accessible to patients and working within a multidisciplinary team as currently occurring optimally. Not occurring optimally were: hospital and community involvement; participation in local projects; student education; and payment for working with others. Rural practitioners reported significantly more hospital and community involvement compared with metropolitan practitioners. Less than one-third of GPs reported that they were linked to other services by computer and used a computer for storage/communication of patient information. DISCUSSION: There are many obstacles preventing integrative activities in daily general practice. Policy and attitudinal changes as well as financial incentives are required to enable GPs to practise in an integrated manner. Infrastructure support to encourage GP education, training and information technology are essential to improve GP integration. Many such initiatives are currently in progress, and will require future evaluation. Findings from this 1996 survey will provide some useful baseline information assisting with future evaluation studies.

Australia↗
PubMed2001

Two-year composite/dentin bond stability.

PURPOSE: To examine the composite-to-dentin shear bond strengths over 2 yrs of three chemically different single bottle dentin adhesives: water-based Syntac Single Component (SSC); acetone-based Prime & Bond 2.1 (PB), and; ethanol-based and filled OptiBond Solo (OS). MATERIALS AND METHODS: Extracted human molars stored in 0.2% sodium azide were randomly assigned to each of three dentin bond groups for testing at 5 time periods (n=15). The crowns of the teeth were sectioned to expose occlusal dentin and the roots embedded in acrylic. The dentin was etched with 37% H3PO4 for 20 s, rinsed and dentin adhesives applied per manufacturers' instructions. A column of Z-100 composite was bonded to the treated dentin surface and light cured. Teeth were stored in distilled water at 37 degrees C and thermocycled for 1,000 cycles between 5 degrees C and 55 degrees C and tested in shear at 24 hrs (baseline), 6, 12, 18 and 24 months. Mean +/- SD shear bond strengths (SBS) were determined. RESULTS: ANOVA at a significance level of P< 0.05 revealed OS had significantly higher SBS at 6 and 12 months compared to baseline. PB had significantly higher SBS at 12 months compared to baseline. SSC had significantly higher SBV at 18 months compared to baseline. However, at 24 months the SBV for OS and SSC were significantly lower than at baseline. During all time periods, OS and PB had significantly higher SBS than SSC. CLINICAL SIGNIFICANCE: The long-term stability of resin-based composite to dentin bond strengths from single bond adhesives is questionable because after 2 yrs, bond strengths for two of the three tested dentin adhesives, OptiBond Solo and Syntac Single Component, were significantly lower than initial strengths.

Acid Etching, Dental↗
PubMed2001

Tracheal-innominate artery fistula caused by the endotracheal tube tip: case report and investigation of a fatal complication of prolonged intubation.

CASE REPORT: A patient with extensive burns was intubated with an 8.0 mm internal diameter endotracheal tube (ETT) equipped with a subglottic suction port (Mallinckrodt HiLo Evac). The ETT was secured to a left upper molar with wire sutures throughout the hospitalization course to ensure airway stability. On the 40th day of intubation, the patient exsanguinated and died from a tracheo-innominate artery fistula. Postmortem examination revealed a 1 cm lesion of the left anterior tracheal wall at the position of the ETT tip. The prolonged stationary position of the ETT was considered the primary factor responsible for the fistula. Yet tracheo-innominate artery fistula normally is associated with high cuff pressures rather than with the tube tip. The special ETT construction required for the subglottic suction feature was suspected to have increased tube rigidity and may have played a contributory role. METHODS: The rigidity of the Mallinckrodt HiLo Evac was measured with a mechanical model and compared to 5 other commercially-available ETTs. Rigidity was expressed as the force generated by the ETT tip when the tube curvature was altered by 5 cm and 10 cm of flexion from its resting position. RESULTS: The mean force exerted by the Mallinckrodt HiLo Evac was 10.1 +/- 2.8 g at 5 cm of flexion and 17.7 +/- 5.1 g at 10 cm of flexion. This was significantly greater than all other ETT brands tested (by one-way analysis of variance and Student-Newman-Kuels test, p < 0.05). CONCLUSION: This case of fatal tracheo-innominate artery fistula formation associated with an ETT tip was unusual because of the extended duration of endotracheal intubation and the complexity of the patient's airway management problems. Our data suggest that the higher rigidity of the HiLo Evac ETT may have contributed to fistula development at the tube tip. However, we do not believe that the higher rigidity of the HiLo Evac ETT necessarily poses any greater risk than other ETTs under normal circumstances, in which the tube tip is not fixed in a stationary position for an extended period.

Adult↗
PubMed2000

Induction paclitaxel in previously untreated, resectable, advanced squamous cell carcinomas of head and neck.

BACKGROUND: Previous Phase II trials evaluating paclitaxel as a single agent have produced objective response rates of 38-40%. However, in these studies patients had recurrent disease and had received previous treatment with chemotherapy, radiation, surgery, or some combination of the same. To the authors' knowledge, the study reported here is the first to examine the role of paclitaxel in affecting objective antitumor response, as a single agent, in a previously untreated patient population. METHODS: Patients with untreated, resectable, advanced squamous cell carcinoma of the head and neck were eligible for this Phase II trial. The treatment plan included paclitaxel 250 mg/m(2) administered by 24-hour intravenous infusion every 21 days for a total of 3 courses and primary prophylaxis with colony stimulating factor during each course of chemotherapy. Surgical resection was performed after recovery from the final course of chemotherapy. After adequate wound healing, patients received external beam radiotherapy (median dose to primary site, 55.8 Gray [Gy]; median dose to neck sites, 50.4 Gy). RESULTS: Forty-five patients were registered. Thirty-eight patients completed the planned chemotherapy, 41 patients underwent surgical resection, and 37 patients completed the intended radiotherapy. The objective response rate was 50% (10% complete response; 40% partial response). Severe or life-threatening (Grade 3 or higher) granulocytopenia or thrombocytopenia occurred in 78% and 27% of patients, respectively. Two patients died of sepsis. Seventy-one percent, 67%, and 91% of patients were free of local, lymph node, and distant recurrence, respectively, with a median follow-up of 37 months. The 4-year overall survival and disease-related survival rates were 44.4% and 52.9%, respectively. CONCLUSION: The authors conclude that paclitaxel is an active agent in patients with advanced head and neck carcinoma. However, the overall disease control, achieved by using paclitaxel as induction therapy, did not appear to be better than that achieved with standard treatment methods. Combined modality regimens with concurrent chemotherapy and radiotherapy have demonstrated more promise.

Adult↗
PubMed2000

Early voiding dysfunction associated with prostate brachytherapy.

Introduction: Transperineal prostate brachytherapy is gaining popularity as a treatment for clinically localized carcinoma of the prostate. Very little prospective data exists addressing the issue of complications associated with this procedure. We present an analysis of the early voiding dysfunction associated with prostate brachytherapy. Materials and Methods: Forty-six consecutive patients who underwent Palladium-103 (Pd-103) seed placement for clinically localized prostate carcinoma were evaluated prospectively for any morbidity associated with the procedure. Twenty-three patients completed an International Prostate Symptom Score (IPSS) questionnaire preoperatively, at their first postoperative visit, and at their second postoperative visit. The total IPSS, each of the seven individual components, and the "bother" score were evaluated separately for each visit, and statistical significance was determined. Results: Urinary retention occurred in 7/46 patients (15%). Of these, 5 were able to void spontaneously after catheter removal. One patient is maintained with a suprapubic tube, and one patient is currently on continuous intermittent catheterization. Baseline IPSS was 7.1 and this went to 20.0 at the first postoperative visit (p<0.001). By the second postoperative visit, the IPSS was 8.0. Conclusions: In our experience, prostate brachytherapy for localized carcinoma of the prostate is associated with a 15% catheterization rate and a significant increase in the IPSS (7.1 to 20.0). This increase in the IPSS seems to be self-limited. Patients need to be educated on these issues prior to prostate brachytherapy.

Journal Article↗
PubMed2000

c-Jun promotes neurite outgrowth and survival in PC12 cells.

We investigated the function of c-Jun in PC12 cells by transfecting them with a plasmid containing a c-Jun cDNA transcription cassette. Transfected cells expressed high levels of c-Jun mRNA and protein and demonstrated an increase in both AP-1 DNA binding and gene activation. The c-Jun over-expressing cells showed marked neurite outgrowth but no evidence of spontaneous cell death. In fact, c-Jun over-expressing cells were more resistant to okadaic acid-induced apoptosis. The process outgrowth was not indicative of a full neuronal differentiation response as the transfected PC12 cells did not display action potentials when examined with whole-cell patch-clamping. The phosphorylation of c-Jun on serine 73 appears to be important for this neurite sprouting effect as mutagenesis at this site reduced sprouting whereas a serine 63 mutant tended to increase sprouting. Thus, in PC12 cells c-Jun expression does not induce apoptosis, but rather functions as a neurite outgrowth and neuronal survival signal.

Action Potentials↗
PubMed2000

Drug-excipient interactions and their affect on absorption.

Excipient(s) are traditionally thought of as inert but they can have a tremendous impact on the ultimate pharmacological availability of a drug substance when added to a formulation. The magnitude of this effect will depend on the characteristics of the drug and on the quantity and properties of the excipients. The aim of this article is to identify the various physicochemical and physiological processes that can be altered by drug-excipient interactions and to explore mechanisms by which they might occur. The regulatory implications of drug-excipient interactions will also be discussed.

Journal Article↗
PubMed2000

Antioxidant-rich diets improve cerebellar physiology and motor learning in aged rats.

The free radical theory of aging predicts that reactive oxygen species are involved in the decline in function associated with aging. The present paper reports that diets supplemented with either spinach, strawberries or blueberries, nutritional sources of antioxidants, reverse age-induced declines in beta-adrenergic receptor function in cerebellar Purkinje neurons measured using electrophysiological techniques. In addition the spinach diet improved learning on a runway motor task, previously shown to be modulated by cerebellar norepinephrine. Motor learning is important for adaptation to changes in the environment and is thus critical for rehabilitation following stroke, spinal cord injury, and the onset of some neurodegenerative diseases. These data are the first to indicate that age-related deficits in motor learning and memory can be reversed with nutritional interventions.

Aging↗
PubMed2000

Analysis of post-translational modification of mycobacterial proteins using a cassette expression system.

A recombinant expression system was developed to analyse sequence determinants involved in O-glycosylation of proteins in mycobacteria. By expressing peptide sequences corresponding to known glycosylation sites within a chimeric lipoprotein construct, amino acids flanking modified threonine residues were found to have an important influence on glycosylation. The expression system was used to screen mycobacterial sequences selected using a neural network (NetOglyc) trained on eukaryotic O-glycoproteins. Evidence of glycosylation was obtained for eight of 11 proteins tested. The results suggest that sites involved in O-glycosylation of mycobacterial and eukaryotic proteins share similar structural features.

Alkaline Phosphatase↗
PubMed2000

An oral vaccine against NMDAR1 with efficacy in experimental stroke and epilepsy.

The brain is generally considered immunoprivileged, although increasing examples of immunological responses to brain antigens, neuronal expression of major histocompatibility class I genes, and neurological autoimmunity have been recognized. An adeno-associated virus (AAV) vaccine generated autoantibodies that targeted a specific brain protein, the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor. After peroral administration of the AAV vaccine, transgene expression persisted for at least 5 months and was associated with a robust humoral response in the absence of a significant cell-mediated response. This single-dose vaccine was associated with strong anti-epileptic and neuroprotective activity in rats for both a kainate-induced seizure model and also a middle cerebral artery occlusion stroke model at 1 to 5 months following vaccination. Thus, a vaccination strategy targeting brain proteins is feasible and may have therapeutic potential for neurological disorders.

Administration, Oral↗