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Biomedical subjects

P Walker

Publications and source records attributed to P Walker.

At least 37 records · Page 2Linked to original sources

Impact of the Edmonton Labeled Visual Information System on physician recall of metastatic cancer patient histories. a randomized controlled trial.

The Edmonton Labeled Visual Information System (ELVIS) is a novel method of documenting clinical information because it is a pictorial method of representing cancer burden and treatment. This randomized, crossover, multiperiod trial involved 16 physicians who each reviewed two ELVIS and two control (text) cancer patient cases (total 32 ELVIS and 32 text cases). Short-answer questionnaires were administered immediately and 18--24 hours following. Mean (+/- SD) recall of basic disease and treatment information was superior immediately following the ELVIS cases (83% +/- 14%) versus text cases (60% +/- 14%, P < 0.0001) and 18--24 hours later (ELVIS cases 65% +/- 21% versus text cases 43% +/- 21%, P < 0.0001). Mean (+/- SD) time required to memorize information was reduced in the ELVIS cases (4 +/- 2 min) versus text cases (13 +/- 6 min, P < 0.0001). Ratings of overall physician preference strongly favored the ELVIS over text. The data indicate that ELVIS aids the process of learning complex cancer patient histories.

Audiovisual Aids↗

Using postoperative cardiac Troponin-I (cTi) levels to detect myocardial ischaemia in patients undergoing vascular surgery.

BACKGROUND: Cardiac complications occur commonly in vascular surgery patients. Diagnosis of cardiac complications is difficult because of the inaccuracies associated with traditional cardiac enzyme measurements. CTi, a highly sensitive and specific marker of myocardial injury, may be able to detect cardiac complications with greater ease and accuracy. METHODS: The study prospectively examined 100 consecutive patients who underwent major vascular surgery between 6/7/98 and 31/12/98 at the Royal Brisbane Hospital. Daily measurements of cTi, creatine kinase (CK), creatine kinase MB (CKMB), CKMB index, renal function and haemoglobin were taken for three postoperative days. One postoperative electrocardiograph (ECG) was taken. An extensive cardiac history was taken. Intraoperative and postoperative events were recorded. FINDINGS: There were 100 patients. 18 patients (18%) had a cTi elevation. On the basis of classical diagnostic criteria, 15 patients (15%) suffered one or more cardiac complication (either myocardial infarction, congestive cardiac failure, unstable angina or atrial fibrillation). One patient (1%) who had a cTi elevation died. CTi elevation occurred in five patients (5%) who were not diagnosed with cardiac complications based on traditional criteria. Despite not meeting specific diagnostic criteria for cardiac complications, all patients showed signs and symptoms that could be attributed to myocardial ischaemia. Every patient who developed congestive cardiac failure or atrial fibrillation had a cTi elevation. A Chi-square analysis revealed a significant association between cTi elevation and postoperative cardiac complications. Four variables contributed small but significant amounts of unique variance to the prediction of peak cTi on linear regression analysis. These were peak CKMB index, postoperative congestive cardiac failure, postoperative chest pain and postoperative cardiac complications. CONCLUSIONS: Routine cTi monitoring of postoperative vascular patients would be an effective and inexpensive way to detect patients with cardiac complications. The relationship between postoperative cTi elevation and significant coronary artery disease remains to be shown.

Adult↗

Pediatric adenoidectomy under vision using suction-diathermy ablation.

OBJECTIVES: To compare adenoidectomy using suction-diathermy ablation with adenoidectomy by way of curettage in a pediatric tertiary care setting. STUDY DESIGN: A prospective series of 68 children undergoing adenoidectomy (without tonsillectomy) under vision using a suction-diathermy ablation technique over 2 years was compared with an historical control group of 58 children undergoing adenoidectomy (without tonsillectomy) by way of curettage over 2 years. METHOD: Intraoperative blood loss was recorded and compared. Efficacy in improving nasal symptomatology was compared between the two groups using an ordinal "nasal symptom score" preoperatively and postoperatively. Complications were recorded and compared. Analysis was performed using two-tailed t tests. RESULTS: The two groups were well matched for age, weight, and adenoid size (P > .4). Follow-up ranged from 4 to 48 months. Adenoidectomy using suction-diathermy resulted in significantly less blood loss (P < .001). The technique was no less efficacious in terms of reducing the nasal symptom score than conventional adenoidectomy by way of curettage (P = .07). Complication rates were no different. No recurrences were identified and no instances of nasopharyngeal stenosis were recognized. CONCLUSIONS: Routine use of suction-diathermy ablation for adenoidectomy converts a difficult, often bloody procedure into a surgically precise operation. It is especially applicable to children. It may have additional advantages in aiding the prevention of the spread of the human form of bovine spongiform encephalopathy (variant Creutzfeldt-Jakob disease [CJD]). Compared with other recently introduced techniques for adenoidectomy, it is considerably less expensive.

Adenoidectomy↗

Anxiety levels in women attending colposcopy clinics for treatment for cervical intraepithelial neoplasia: a randomised trial of written and video information.

OBJECTIVE: To assess the effectiveness of video information in reducing the level of anxiety in women attending Colposcopy clinics. DESIGN: An observational study followed by a randomised trial. SETTING: Colposcopy Clinic, Royal Free Hospital, London. PARTICIPANTS: Between April and December 1999, all new referrals to the clinic with a cervical smear showing moderate or severe dyskaryosis. MAIN OUTCOME MEASURE: The level of anxiety measured by the Spielberger State Anxiety Inventory. CONCLUSION: Women attending colposcopy clinics for either diagnosis or treatment, experience a high level of anxiety. The highest levels occur in women attending a one-stop see and treat clinic. The introduction of visual information in the form of an explanatory video prior to attendance significantly reduced anxiety.

Anxiety↗

Management of pressure ulcers.

Pressure ulcers are a common problem, with about 1.5 to 3 million individuals in the United Stated affected. Treatment may be costly, requiring lengthy periods of hospitalization. Central to the development of pressure ulcers is the loss of the ability of bedridden patients to move spontaneously. When this ability is impaired by neurologic injury or debility, damage caused by unrelieved pressure against tissue trapped between the support surface and a bony prominence becomes evident. Current recommendations for prevention advise providing optimal skin care to those at risk of tissue breakdown. Once a pressure ulcer is diagnosed, an initial assessment, including staging the ulcer and a comprehensive assessment, is required. A treatment plan can then be devised. Planning should include management of tissue loads, ulcer care, and nutritional support. The dogma that all pressure ulcers are caused by poor care should be recognized as incorrect. Even the most exemplary care may not prevent the development of, or heal existing, pressure ulcers in high-risk patients.

Algorithms↗

Expression of thyrotropin-releasing hormone receptor 2 (TRH-R2) in the central nervous system of rats.

The distribution of the recently discovered thyrotropin-releasing hormone (TRH) receptor subtype TRH-R2 was studied in rat brain, pituitary, and spinal cord by in situ hybridization histochemistry and compared with the distribution patterns of the other elements of TRH signaling, namely TRH, TRH-R1, and the TRH-degrading ectoenzyme (TRH-DE). In contrast to the very restricted mRNA expression of TRH-R1 in the central nervous system, TRH-R2 mRNA was widely distributed with highest transcript levels throughout the thalamus, in the cerebral and cerebellar cortex, medial habenulae, medial geniculate nucleus, pontine nuclei, and throughout the reticular formation. In accordance with the well-known endocrine function of TRH, TRH-R1 is found predominantly expressed in hypothalamic regions. Expression of TRH-R1 in various brainstem nuclei and spinal cord motoneurons seems to be associated with the described effects of TRH on the vegetative and autonomic system as well as on the somatomotor system. Furthermore, the fully complementary expression of both receptor subtypes, even in regions where transcripts for both receptors were found (e.g., medial septum, lateral hypothalamus superior colliculi, substantia nigra, etc.), indicates that in discrete neuroanatomical pathways the two receptors serve highly specific functions for the transmission of TRH signals. Together with TRH-DE, the putative terminator of TRH actions that shows in various, but not all, brain areas, an overlapping mRNA distribution pattern with both receptors, the distribution of TRH-R2 mRNA seems to provide the anatomical basis for the described effects of TRH on higher cognitive functions as well as its effect on arousal, locomotor activity, and pain perception.

Aminopeptidases↗

Newly synthesized human delta opioid receptors retained in the endoplasmic reticulum are retrotranslocated to the cytosol, deglycosylated, ubiquitinated, and degraded by the proteasome.

We have previously shown that only a fraction of the newly synthesized human delta opioid receptors is able to leave the endoplasmic reticulum (ER) and reach the cell surface (Petäjä-Repo, U. E, Hogue, M., Laperrière, A., Walker, P., and Bouvier, M. (2000) J. Biol. Chem. 275, 13727-13736). In the present study, we investigated the fate of those receptors that are retained intracellularly. Pulse-chase experiments revealed that the disappearance of the receptor precursor form (M(r) 45,000) and of two smaller species (M(r) 42,000 and 39,000) is inhibited by the proteasome blocker, lactacystin. The treatment also promoted accumulation of the mature receptor form (M(r) 55,000), indicating that the ER quality control actively routes a significant proportion of rescuable receptors for proteasome degradation. In addition, degradation intermediates that included full-length deglycosylated (M(r) 39,000) and ubiquitinated forms of the receptor were found to accumulate in the cytosol upon inhibition of proteasome function. Finally, coimmunoprecipitation experiments with the beta-subunit of the Sec61 translocon complex revealed that the receptor precursor and its deglycosylated degradation intermediates interact with the translocon. Taken together, these results support a model in which misfolded or incompletely folded receptors are transported to the cytoplasmic side of the ER membrane via the Sec61 translocon, deglycosylated and conjugated with ubiquitin prior to degradation by the cytoplasmic 26 S proteasomes.

Cell Line↗

Relationship of infarct artery patency and left ventricular ejection fraction to health-related quality of life after myocardial infarction: the GUSTO-I Angiographic Study experience.

BACKGROUND: Post-myocardial infarction global ejection fraction and infarct-related artery patency might be expected to be associated with health-related quality-of-life (HRQOL) outcomes, but this association has not been previously shown. The GUSTO-I Angiographic Study cohort 2-year follow-up afforded an examination of such potential relationships. METHODS AND RESULTS: A total of 1848 patients (87.7% response rate) who were enrolled in the GUSTO-I Angiographic Study were contacted for a telephone interview regarding their current HRQOL (physical function, psychological well-being, perceived health status, and social function) 2 years after MI. In multivariable models, left ventricular ejection fraction (EF) was significantly related to physical (P:=0.021) and social (P:=0.014) function, psychological well-being (P:=0.042), and perceived health status (P:=0.024). Infarct-related artery patency was not directly related to any HRQOL outcome. A decreasing EF was predictive of poorer outcomes in each HRQOL dimension. Men consistently had better outcomes in all HRQOL dimension with the exception of perceived health status. Increasing age was predictive of poorer outcomes in all dimensions of HRQOL except for psychological well-being where the inverse occurred; younger patients experienced greater depression, anxiety and worry than their older counterparts. The presence of comorbidities increased the likelihood of worse outcomes in all dimensions. CONCLUSIONS: This is the first study to demonstrate a significant relationship between EF and long-term HRQOL outcomes. This advantage in left ventricular function preservation should be added to the mortality advantage when considering the impact of treatment strategies for myocardial infarction.

Aged↗

Export from the endoplasmic reticulum represents the limiting step in the maturation and cell surface expression of the human delta opioid receptor.

Synthesis and maturation of G protein-coupled receptors are complex events that require an intricate combination of processes that include protein folding, post-translational modifications, and transport through distinct cellular compartments. Relatively little is known about the nature and kinetics of specific steps involved in these processes. Here, the human delta opioid receptor expressed in human embryonic kidney 293S cells is used as a model to delineate these steps and to establish the kinetics of receptor synthesis, glycosylation, and transport. We found that the receptor is synthesized as a core-glycosylated M(r) 45,000 precursor that is converted to the fully mature M(r) 55,000 receptor with a half-time of about 120 min. In addition to trimming and processing of two N-linked oligosaccharides, maturation involves addition of O-glycans containing N-acetylgalactosamine, galactose, and sialic acid. In contrast to N-glycosylation, which is initiated co-translationally and is completed when the protein reaches the trans-Golgi network, O-glycosylation was found to occur only after the receptor exits from the endoplasmic reticulum (ER) and was terminated as early as the trans-Golgi cisternae. Once the carbohydrates are fully processed and the receptor reaches the trans-Golgi network, it is transported to the cell surface in about 10 min. The exit from the ER was found to be the limiting step in overall processing of the receptor. This indicates that early events in the folding of the receptor are probably rate-limiting and that receptor folding intermediates are retained in the ER until they can adopt the correct conformation. The overall low efficiency of receptor maturation, less than 50% of the precursor being processed to the fully glycosylated protein, further suggests that only a fraction of the synthesized receptors attain properly folded conformation that allows exit from the ER. This indicates that folding and ER export are key events in control of receptor cell surface expression. Whether or not the low efficiency of the ER export is a general feature among G protein-coupled receptors remains to be investigated.

Biological Transport↗

Involvement of cytosolic phospholipase A2 and secretory phospholipase A2 in arachidonic acid release from human neutrophils.

The purpose of this study was to define the role of secretory phospholipase A2 (sPLA2), calcium-independent PLA2, and cytosolic PLA2 (cPLA2) in arachidonic acid (AA) release from fMLP-stimulated human neutrophils. While fMLP induced the release of extracellular sPLA2 activity and AA, 70% of sPLA2 activity remained associated with the cell. Treatment with the cell-impermeable sPLA2 inhibitors DTT or LY311-727, or the anti-sPLA2 Ab 3F10 all inactivated extracellular sPLA2 activity, but had minimal effect on neutrophil AA mass release. In contrast, coincubation of streptolysin-O toxin-permeabilized neutrophils with DTT, LY311-727, or 3F10 all decreased [3H8]AA release from [3H8]AA-labeled, fMLP-stimulated cells. Exposure to fMLP resulted in a decrease in the electrophoretic mobility of cPLA2, a finding consistent with cPLA2 phosphorylation, and stimulated the translocation of cPLA2 from cytosolic to microsomal and nuclear compartments. The role of cPLA2 was further evaluated with the cPLA2 inhibitor methyl arachidonyl fluorophosphonate, which attenuated cPLA2 activity in vitro and decreased fMLP-stimulated AA mass release by intact neutrophils, but had no effect on neutrophil sPLA2 activity. Inhibition of calcium-independent PLA2 with haloenol lactone suicide substrate had no effect on neutrophil cPLA2 activity or AA mass release. These results indicate a role for cPLA2 and an intracellular or cell-associated sPLA2 in the release of AA from fMLP-stimulated human neutrophils.

Arachidonic Acid↗

Multi-variate analysis predicts clinical outcome 30 days after middle cerebral artery infarction.

BACKGROUND AND PURPOSE: To evaluate the functional prognostic value of proton magnetic resonance spectroscopy performed within the 5 days of an infarction of the middle cerebral artery territory, compared with previously demonstrated prognostic factors. METHODS: Proton magnetic resonance spectroscopy was performed on 77 consecutive non-comatosed patients during the acute stage of middle cerebral artery infarction. The functional status was determined for each patient via the Orgogozo score. Proton magnetic resonance spectroscopic data were acquired in the infarction and in contra-lateral normal tissue and the results were expressed as metabolite ratios. Correlations were evaluated between the Orgogozo score at day 1 and day 30, the age, the sex, the volume of the infarction, and the metabolic ratios. RESULTS: In a monovariate analysis, the decrease of the NAA/choline ratio was correlated with a low Orgogozo score at days 1 and 30 (P<0.05) and with a large infarction (P<0.05). A stepwise analysis showed a significant relationship between the Orgogozo score at day 30 and the Orgogozo score at day 1, the sex, the volume of infarction, and the NAA/Cho ratio within the infarction. CONCLUSIONS: Our work demonstrates that a good clinical outcome at day 30 depends on a good initial clinical score at day 1, a small volume of infarction, a small decrease of NAA/Cho, and being of the female gender.

Adult↗

Phase II study of doxorubicin and paclitaxel as second-line chemotherapy of small-cell lung cancer: a Hoosier Oncology Group Trial.

Forty-six evaluable patients with recurrent small-cell lung cancer were entered on a phase II Hoosier Oncology Group (HOG) protocol evaluating bolus doxorubicin 40 mg/m2 followed by paclitaxel 175 mg/m2 over 3 hours. Courses were repeated every 3 weeks for a maximum of 6 courses. Therapy was well-tolerated with grade III neurotoxicity in 5 patients (11%), grade III/IV emesis in 5 (11%), and grade III mucositis in 2 patients. One patient had grade IV myalgias and one patient had grade III cardiotoxicity. The main toxicity was myelosuppression. Twenty-nine patients (63%) had grade IV and 8 (17%) grade III granulocytopenia. Nine patients (20%) were hospitalized for granulocytopenic fever. There was no treatment-related mortality. Nineteen of 46 patients (41%) had an objective response, including 3 complete remissions. Two of 14 patients with refractory disease (progression less than 3 months after initial therapy) responded, compared to 17 of 32 (52%) with sensitive disease (progression beyond 3 months of initial chemotherapy regimen).

Adult↗

Adult respiratory distress syndrome after extensive cytoreductive surgery. A case report.

BACKGROUND: Adult respiratory distress syndrome (ARDS) is characterized by progressive hypoxemia, diffuse bilateral pulmonary infiltrates and normal left ventricular function. CASE: A 58-year-old woman developed ARDS following extensive cytoreductive surgery for a widely disseminated intraperitoneal leiomyosarcoma. The patient had a favorable outcome after 10 days of ventilatory support, sedation, analgesia, parenteral and enteral nutrition, and fluid restriction. The ARDS might have been caused by multiple transfusions or the massive cytoreductive surgery and was probably mediated by cytokines and tumor necrosis factors. CONCLUSION: Gynecologic oncologists should be alert to postoperative ARDS in patients undergoing massive cytoreduction with excessive blood loss and multiple transfusions.

Blood Transfusion↗