PubMed Health⌕ Search

Biomedical subjects

John Walker

Publications and source records attributed to John Walker.

51 records · Page 3Linked to original sources
PubMed2003

NS-398, a selective cyclooxygenase-2 blocker, acutely inhibits receptor-mediated contractions of rat aorta: role of endothelium.

NS-398 (N-(2-cyclohexyloxy-4-nitrophenyl)-methane sulfonamide) is a selective inhibitor of the cyclooxygenase-2 isozyme in vitro and in vivo. This study reports on acute inhibition of receptor-mediated contractions of isolated rat aorta by NS-398 and its modulation by endothelium-derived nitric oxide. NS-398 (1-10 microM) blocked norepinephrine, and 5-hydroxytryptamine (5-HT) evoked contractions and suppressed E(max) responses for both agonists. E(max) changes occurred in endothelium-intact vessel rings and in the absence, as well as in the presence of cycloheximide or dexamethasone in the physiological salt solution (PSS) bathing the tissues. NS-398 altered contractions to these receptor agonists in denuded rings only at 10 microM, and did not significantly alter contractions to KCl and sodium fluoride in all situations. NS-398 (3 and 10 microM) reduced aortic contractions initiated by cyclopiazonic acid (CPA), a sarcoplasmic reticulum Ca(2+)-ATPase blocker, in endothelium intact rings bathed with PSS with/without nitro-D-arginine methyl ester (D-NAME; 100 microM), but did not alter contractions to the compound in endothelium-denuded aortic rings and in vessel rings bathed with PSS+L-NAME (100 microM). Western blot analyses reveal significantly denser cyclooxygenase-2 protein expressions in freshly isolated endothelium-intact, compared to, denuded vessel segments. We conclude that: (1) cyclooxygenase-2 is constitutively expressed in rat aortic endothelial and smooth muscle cells, and (2) NS-398 modulates aortic contractions principally through an action on endothelial cyclooxygenase-2. Our data strongly suggest that cyclooxygenase-2 and/or its product(s), in concert with endothelium-derived nitric oxide, regulates the sarcoplasmic reticulum Ca(2+) pump activity in rat aorta.

Animals↗
PubMed2003

Toxocara canis: egg presence in Melbourne parks and disease incidence in Victoria.

PURPOSE: Toxocara canis can cause blinding eye disease. This study assessed the presence of T. canis eggs in soil from parks in Melbourne and also the incidence of presumed ocular toxocariasis in Victoria. METHODS: One hundred and eighty soil samples were collected from nine suburban locations in Melbourne, Australia. These were analyzed for the presence of T. canis eggs. A search of laboratory records of T. canis serology requests from Victorian patients over an 8-year period was performed. RESULTS: Only one soil sample was positive for T. canis eggs. Positive T. canis serology was reported in 13 samples from patients. These patients all had ocular features suggestive of T. canis infection. CONCLUSION: Toxocara canis eggs are rare in public parks in Melbourne and symptomatic ocular toxocariasis is uncommon in the Victorian population. The acquisition of the disease is unlikely to be from public parks.

Adolescent↗
PubMed2003

Cost of glaucoma in Canada: analyses based on visual field and physician's assessment.

PURPOSE: A longitudinal, retrospective study investigated the cost of primary open angle glaucoma (POAG). METHODS: Patient files from two tertiary care glaucoma practices were reviewed. Patients diagnosed with POAG and >/=2.5 years of follow-up data were included. Data collected included visual field mean deviation, physician's assessment, and resource utilization (physician visits, procedures, and medications). Costs, reported in 2001 Canadian dollars, were compared between groups, based on initial visual field mean deviation, including mild (<5 dB), moderate (5 to <12 dB), and severe (>/=12 dB), and based on physician's assessment, including controlled, uncontrolled, or patients initially uncontrolled for 12 months who become controlled. RESULTS: Of 411 patient charts extracted, 265 were included; 35 were excluded for ocular comorbidities and 111 patients with insufficient follow-up. Mean (standard deviation) yearly costs overall (N = 265) and for mild (n = 90), moderate (n = 91), and severe (n = 84) groups were $508 ($278), $408 ($266), $512 ($288), and $609 ($243), respectively. Differences between mean yearly costs were statistically significant for all three groups (P < 0.05). Costs for controlled (n = 110), uncontrolled (n = 76), and uncontrolled then controlled group (n = 79) were $423 ($243), $594 ($314), and $542 ($256), respectively. The controlled group cost was significantly lower than both of the other groups (P < 0.05). DISCUSSION AND CONCLUSIONS: The cost of treating POAG increases with visual field mean deviation severity and uncontrolled disease. Many patients diagnosed with glaucoma had already progressed to later stages in the disease process. Early disease detection may provide a substantial cost savings to the health care system.

Canada↗
PubMed2003

A preliminary assessment of Internet-based nuclear telecardiology to support the clinical management of cardiac disease in a remote community.

A portable nuclear medicine (NM) processing system was established in Kalgoorlie and an acute myocardial perfusion scintigraphy (MPS) service was provided for the local regional hospital. After scanning the patient, the data were processed on a laptop computer and JPEG images were transmitted to a secure Web server. A secure email message, with the URL link enclosed and a provisional indication of normal or abnormal findings, was sent to the referring clinician from the NM facility. Use of the Internet allowed for a group consultation between the NM technician, the referrer and the cardiologist in Perth. During a three-month study period, 42 patients were referred for exclusion of acute coronary syndrome. Of these, 21 (50%) demonstrated abnormal perfusion studies, two of which were classified as requiring urgent medical intervention. Seventeen studies were normal (41%) and four (10%) were designated equivocal. There was an alteration in the treatment plan for 32 patients (76%), including four for whom admission or further investigation was deemed unwarranted. The results suggest that MPS findings, distributed via the Internet, allow for earlier risk stratification and have a direct affect on clinical decision making.

Adult↗
PubMed2003

Increased fistula risk following palatoplasty in Treacher Collins syndrome.

OBJECTIVE: Patients with Treacher Collins syndrome have abnormal vascular supply to the palate, yet it is unknown whether there are increased postoperative healing problems following palatoplasty. This study investigated the correlation between Treacher Collins syndrome and postoperative palatal fistula formation. DESIGN: Retrospective chart review was performed. PATIENTS: Children undergoing palatoplasty at Children's Hospital Los Angeles from 1987 to 2000 were evaluated. Ten children with Treacher Collins syndrome, 92 children with other syndromes and cleft palate, and 458 nonsyndromic patients with isolated cleft palate were studied. INTERVENTIONS: All children were treated with a one-stage, double-reversing Z-plasty cleft palate repair. MAIN OUTCOME MEASURES: Outcome measures included intraoperative observations of surgical anatomy and postoperative clinic follow-up of fistula formation. Palatal fistula rates between patients with Treacher Collins syndrome, other syndromes, and no syndrome were compared with chi-square analysis. RESULTS: Children with Treacher Collins syndrome had significantly greater palatal fistula rates (50%) than children with other syndromes (8.7%) or no syndrome (4.1%). Treacher Collins patients demonstrated large palatal fistulas and poor flap vascularity. CONCLUSIONS: Children with Treacher Collins syndrome and cleft palate have significantly higher palatal fistula risk than other children with cleft palate when double-reversing Z-plasty palate repair is performed. Our findings suggest that children with Treacher Collins syndrome and cleft palate may have poor vascularity to palatal flaps created during palatoplasty. Furthermore, we recommend that surgeons performing palatoplasty minimize the dissection of mucoperiosteal flaps around the greater palatine arterial pedicle and utilize closure techniques creating the least vascular disruption of palatal tissue.

Chi-Square Distribution↗
PubMed2003

Registered nurse-administered propofol sedation for upper endoscopy and colonoscopy: Why? When? How?

Propofol for sedation during gastrointestinal endoscopic procedures has been associated with improved patient satisfaction relative to combinations of meperidine and midazolam. Delivery of propofol by registered nurses has been shown to be more cost-effective than administration by anesthesiologists or nurse anesthetists. Here, the authors review their experience with nurse-administered propofol sedation (NAPS) at their institutions (a hospital endoscopy unit in a tertiary medical center and an ambulatory surgery center). Endoscopic procedures for which NAPS is (or is not) recommended are listed, and a profile of patients for whom NAPS is contraindicated is given. Steps toward the development of programs and acquisition of training in NAPS are recommended; these include determining what state, local, and institutional laws apply to propofol administration; developing a written protocol; and instituting a training program that proceeds from observation to supervised administration to independent administration of propofol, with appropriate monitoring of safety records. Experience with NAPS using bolus titration (dosage, timing, coadministration with other agents) is detailed, and proper patient monitoring is discussed. NAPS is in its infancy, but this method of sedation shows considerable promise for improving patient satisfaction with, and thereby the reputation of, endoscopic procedures.

Colonoscopy↗
PubMed2003

Mapping the proteome of Leishmania Viannia parasites using two-dimensional polyacrylamide gel electrophoresis and associated technologies.

In this study we have demonstrated the potential of two-dimensional electrophoresis (2DE)-based technologies as tools for characterization of the Leishmania proteome (the expressed protein complement of the genome). Standardized neutral range (pH 5-7) proteome maps of Leishmania (Viannia) guyanensis and Leishmania (Viannia) panamensis promastigotes were reproducibly generated by 2DE of soluble parasite extracts, which were prepared using lysis buffer containing urea and nonidet P-40 detergent. The Coomassie blue and silver nitrate staining systems both yielded good resolution and representation of protein spots, enabling the detection of approximately 800 and 1,500 distinct proteins, respectively. Several reference protein spots common to the proteomes of all parasite species/strains studied were isolated and identified by peptide mass spectrometry (LC-ES-MS/MS), and bioinformatics approaches as members of the heat shock protein family, ribosomal protein S12, kinetoplast membrane protein 11 and a hypothetical Leishmania-specific 13 kDa protein of unknown function. Immunoblotting of Leishmania protein maps using a monoclonal antibody resulted in the specific detection of the 81.4 kDa and 77.5 kDa subunits of paraflagellar rod proteins 1 and 2, respectively. Moreover, differences in protein expression profiles between distinct parasite clones were reproducibly detected through comparative proteome analyses of paired maps using image analysis software. These data illustrate the resolving power of 2DE-based proteome analysis. The production and basic characterization of good quality Leishmania proteome maps provides an essential first step towards comparative protein expression studies aimed at identifying the molecular determinants of parasite drug resistance and virulence, as well as discovering new drug and vaccine targets.

Animals↗
PubMed2002

Biphasic transmittance waveform in the APTT coagulation assay is due to the formation of a Ca(++)-dependent complex of C-reactive protein with very-low-density lipoprotein and is a novel marker of impending disseminated intravascular coagulation.

A decrease in light transmittance before clot formation, manifesting as a biphasic waveform (BPW) pattern in coagulation assays, was previously correlated with the onset of disseminated intravascular coagulation (DIC). In this study of 1187 consecutive admissions to the intensive care unit, the degree of this change on admission predicts DIC better than D-dimer measurements. Additionally, the BPW preceded the time of DIC diagnosis by 18 hours, on average, in 56% (203 of 362) of DIC patients. The BPW is due to the rapid formation of a precipitate and coincident turbidity change on recalcification of plasma. The isolated precipitate contains very-low-density lipoprotein (VLDL) and C-reactive protein (CRP). The addition of CRP and Ca(++) to normal plasma also causes the precipitation of VLDL and IDL, but not LDL or HDL. The K(d) of the CRP/VLDL interaction is 340 nM, and the IC(50) for Ca(++) is 5.0 mM. In 15 plasmas with the BPW, CRP was highly elevated (77-398 microg/mL), and the concentration of isolated VLDL ranged from 0.082 to 1.32 mM (cholesterol). The turbidity change on recalcification correlates well with the calculated level of the CRP-VLDL complex. Clinically, the BPW better predicts for DIC than either CRP or triglyceride alone. The complex may have pathophysiological implications because CRP can be detected in the VLDL fraction from sera of patients with the BPW, and the VLDL fraction has enhanced prothrombinase surface activity. The complex has been designated lipoprotein complexed C-reactive protein.

Biomarkers↗
PubMed2002

ATP synthase from Saccharomyces cerevisiae: location of the OSCP subunit in the peripheral stalk region.

A biotinylation signal has been fused to the C terminus of the oligomycin sensitivity conferral protein (OSCP) of the ATP synthase complex from Saccharomyces cerevisiae. The signal is biotinylated in vivo and the biotinylated complex binds avidin in vitro. By electron microscopy of negatively stained particles of the ATP synthase-avidin complex, the bound avidin has been localised close to the F(1) domain. The images were subjected to multi-reference alignment and classification. Because of the presence of a flexible linker between the OSCP and the biotinylation signal, the class-averages differ in the position of the avidin relative to the F(1) domain. These positions lie on an arc, and its centre indicates the position of the C terminus of the OSCP on the surface of the F(1) domain. Since the N-terminal region of the OSCP is known to interact with the N-terminal regions of alpha-subunits, which are on top of the F(1) domain distal from the F(o) membrane domain, the OSCP extends almost 10nm along the surface of F(1) down towards F(o) where it interacts with the C terminus of the b subunit, which extends up from F(o). The labelling technique has also allowed a reliable 2D projection map to be developed for the intact ATP synthase from S.cerevisiae. The map reveals a marked asymmetry in the F(o) part of the complex that can be attributed to subunits in the F(o) domain.

Avidin↗
PubMed2002

Establishing two-dimensional gels for the analysis of Leishmania proteomes.

Several different sample preparation methods for two-dimensional electrophoresis (2-DE) analysis of Leishmania parasites were compared. From this work, we were able to identify a solubilization method using Nonidet P-40 as detergent, which was simple to follow, and which produced 2-DE gels of high resolution and reproducibility.

Animals↗
PubMed2002

Orbital dirofilariasis.

Dirofilariasis is a parasitic disease of domestic and wild animals that occasionally may present as zoonotic infection in humans. The microfilariae are accidentally transmitted to humans by Culex and Aedes mosquitoes. Ophthalmic infections with Dirofilaria are well documented all over the world, including America, Europe and Australia. The infection may be periorbital, subconjunctival or intraocular. In this report a case is described of orbital dirofilariasis that presented as ptosis and lid swelling. Australian ophthalmologists should consider dirofilariasis as part of the differential diagnosis of orbital swelling and inflammation.

Aged↗
PubMed2002

Evaluation of the ICT malaria P.f/P.v and the OptiMal rapid diagnostic tests for malaria in febrile returned travellers.

Rapid diagnostic tests (RDTs) are less reliant on expert microscopy and have the potential to reduce errors in malaria diagnosis but have not been extensively evaluated in nonimmune persons or in countries where infection is not endemic. We evaluated the ICT P.f/P.v (ICT-Amrad, Sydney, Australia) and OptiMal (Flow Inc., Portland, Oreg.) assays prospectively for the diagnosis of malaria in 158 specimens from 144 febrile returned travellers in Australia by using expert microscopy and PCR as reference standards. Malaria was diagnosed in 93 specimens from 87 patients by expert microscopy, with 3 additional specimens from recently treated patients testing positive for Plasmodium falciparum by PCR. For the diagnosis of asexual-stage P. falciparum malaria, the sensitivity and specificity of the ICT P.f/P.v assay were 97 and 90%, respectively, and those of the OptiMal assay were 85 and 96%, respectively. The ICT P.f/P.v assay missed one infection with a density of 45 parasites/ micro l, whereas the OptiMal assay missed infections up to 2,500/ micro l; below 1,000/ micro l, its sensitivity was only 43%. For the diagnosis of P. vivax malaria, the sensitivity and specificity of the ICT P.f/P.v assay were 44 and 100%, respectively, and those of the OptiMal assay were 80 and 97%, respectively. Both assays missed infections with parasite densities over 5,000/ micro l: up to 10,000/ micro l with the former and 5,300/ micro l with the latter. Despite the high sensitivity of the ICT P.f/P.v assay for P. falciparum malaria, caution is warranted before RDTs are widely adopted for the diagnosis of malaria in nonimmune patients or in countries where malaria is not endemic.

Animals↗
PubMed2002

Lipoprotein-complexed C-reactive protein and the biphasic transmittance waveform in critically ill patients.

The 'biphasic transmittance waveform' (BTW) refers to a decrease in light transmittance that often occurs prior to clotting in coagulation assays of critically ill patient plasmas. It correlates with disseminated intravascular coagulation and mortality. The present work shows that the BTW is due to the rapid formation of a precipitate and a coincident change in turbidity in re-calcified plasma. The precipitate was isolated from patient plasma and contained lipids typical of very low density lipoprotein (VLDL), plus the proteins apolipoprotein B-100 and C-reactive protein (CRP). Precipitation also occurred in normal plasma supplemented with CRP. In addition, CRP precipitated with VLDL and intermediate density lipoprotein, but not low density lipoprotein or high density lipoprotein. The Kd value for the CRP/VLDL interaction is 340 nM. The IC50 value of Ca2+ for complex formation is 5.0 mM, and epsilon-aminocaproic acid inhibits the process. In 15 plasmas with the BTW from critically ill patients, CRP was highly elevated (77-398 microg/mL) and VLDL cholesterol ranged from 0.082 to 1.32 mM. The magnitude of the turbidity change on re-calcification correlated well with the calculated level of the CRP/VLDL complex. Thus, the Ca2+-dependent formation of a complex between CRP and VLDL accounts for the BTW.

C-Reactive Protein↗
PubMedDate not supplied

Cost-effectiveness of treprostinil versus epoprostenol in patients with pulmonary arterial hypertension: a Canadian analysis.

BACKGROUND: Pulmonary arterial hypertension (PAH) is associated with substantial morbidity and mortality, exerting a tremendous health and economic impact on patients. In the present study, an economic evaluation of patients with PAH treated with either treprostinil or epoprostenol was performed. METHODS: A cost-minimization analysis (a cost-effectiveness subtype) was performed under the assumption that treprostinil and epoprostenol were clinically equivalent. Two cohorts of 60 patients, treated with treprostinil or epoprostenol, were evaluated over three years by using a dynamic spreadsheet model. The evaluation included both the provincial ministries of health and societal perspectives. Resource valuation data for drugs, medical supplies, consultations, and surgical and diagnostic procedures were obtained from standard lists. Costs of hospitalizations and adverse events were derived from published sources. Additional outpatient costs were considered equivalent and, therefore, were excluded from the analysis. Costs are presented in 2003 Canadian dollars discounted at 3%. Sensitivity analyses were performed testing all uncertainties in the model. RESULTS: In the base-case analysis (over three years), treatment with treprostinil resulted in an expected savings of 2,610,642 US dollars and 2,781,438 US dollars from the ministries of health and societal perspectives, respectively. On a per-patient level, treatment with treprostinil resulted in an average annual savings of 14,504 US dollars and 15,452 US dollars, respectively. The greatest savings with treprostinil came from reduced hospitalizations. Multivariate sensitivity analyses estimated cost savings in greater than 99% of scenarios. CONCLUSIONS: By initiating and continuing treprostinil treatment over a three-year period, the economic burden associated with PAH may be reduced compared with epoprostenol treatment.

Administration, Oral↗