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Biomedical subjects

M Doyle

Publications and source records attributed to M Doyle.

At least 37 records · Page 2Linked to original sources

A comparison of regularly administered sustained release oral morphine with intramuscular morphine for control of postoperative pain.

UNLABELLED: We studied the efficacy and side effect profile of regularly administered, oral sustained-release morphine sulfate tablets (MST) and IM morphine in patients undergoing total hip arthroplasty under lumbar spinal anesthesia. Patients in Group I received MST 20 mg 12 hourly and a placebo IM injection 6 hourly regularly. Group II patients received an oral placebo 12 hourly and morphine sulfate 10 mg IM 6 hourly regularly. Rescue analgesia was provided with regular diclofenac suppositories and patient-controlled analgesia. Pain scores assessed by using visual analog scale and verbal pain scoring at rest and with movement were low in both groups, with no statistical difference between groups. Mean patient-controlled analgesia morphine consumption during the 48-h study was 16.7 mg in the IM group and 25.9 mg in the MST group. The difference between the groups was significant at 36 h postoperatively (0.03). Side effects of sedation and respiratory depression were not problematic in either group, with a maximal sedation score of 2 occurring once in a patient in Group II. Nausea and vomiting occurred more often in Group II, but this was not statistically significant, with a mean nausea/vomiting score for Group II of 1.7. We conclude that oral, sustained-release morphine is an attractive alternative to IM opiates in patients undergoing body surface surgery under regional anesthesia. IMPLICATIONS: Each postoperative analgesic has its own limitations for route of administration, dosage, and potential side effects. Using the oral route for drug administration seems more attractive than other methods but may not be suitable in all postoperative patients. We studied the efficacy and side effect profile of sustained-release, oral morphine compared with standard IM morphine for the treatment of pain after hip replacement surgery. We concluded that use of the oral preparation is a suitable alternative to the IM route in this population undergoing surgery under spinal anesthesia.

Administration, Oral↗

Suprarenal mycotic aneurysm exclusion using a stent with a partial autologous covering.

PURPOSE: To report a combined endovascular and open technique to manage a suprarenal mycotic aortic aneurysm using a stent-graft partially covered with a section of autologous artery. METHODS AND RESULTS: A 50-year-old was hospitalized for staphylococcal septicemia and severe back pain. A previously diagnosed 3-cm abdominal aortic aneurysm was found to have expanded 2 cm in 3 weeks. Aortography documented some periaortic thickening and 2 mycotic aneurysms, one posterior at the level of the superior mesenteric artery and the second at the aortic bifurcation. After intensive antibiotic therapy, an endovascular approach to exclude the suprarenal mycotic aneurysm was undertaken in tandem with surgical excision of the infrarenal aneurysm. The harvested right common iliac artery was used to partially cover a Palmaz stent, which was deployed under direct vision just above the renal artery ostia so that the covered portion of the stent excluded the aneurysm. A right axillofemoral bypass with a femorofemoral bypass completed the revascularization. Postoperatively, the patient developed renal failure, ischemic colitis necessitating a left hemicolectomy, and paraplegia. Although the patient is paralyzed, the aneurysm remains excluded with patent visceral vessels at 12 months following surgery. No organisms were grown from excised aortic tissue, and no signs of recurrent infection have been seen. CONCLUSIONS: Stent-graft repair may be able to lessen the invasiveness and reduce the morbidity associated with treatment of mycotic aortic aneurysms.

Aneurysm, Infected↗

Violence risk prediction. Clinical and actuarial measures and the role of the Psychopathy Checklist.

BACKGROUND: Violence risk prediction is a priority issue for clinicians working with mentally disordered offenders. AIMS: To review the current status of violence risk prediction research. METHOD: Literature search (Medline). Key words: violence, risk prediction, mental disorder. RESULTS: Systematic/structured risk assessment approaches may enhance the accuracy of clinical prediction of violent outcomes. Data on the predictive validity of available clinical risk assessment tools are based largely on American and North American studies and further validation is required in British samples. The Psychopathy Checklist appears to be a key predictor of violent recidivism in a variety of settings. CONCLUSIONS: Violence risk prediction is an inexact science and as such will continue to provoke debate. Clinicians clearly need to be able to demonstrate the rationale behind their decisions on violence risk and much can be learned from recent developments in research on violence risk prediction.

Clinical Protocols↗

Hemodynamic evaluation with TURBO BRISK--a rapid phase contrast angiography technique.

Hemodynamic imaging by phase contrast angiography was significantly accelerated by selective interpolation and segmentation in k-space using TURBO BRISK. The method was tested in vitro on three independent flowfields, representative of human blood rheology: a straight tube simulating the descending aorta, a curved tube simulating the aortic arch and a two-chamber orifice flow model simulating valvular regurgitation. The results were compared to data obtained by Laser Doppler Velocimetry (LDV) and showed good agreement. For the straight tube, the flow velocity obtained by five TURBO BRISK methods with increasing segmentation factors and corresponding time savings showed good agreement with LDV. For the curved tube, the velocity showed good general agreement with some differences in the decelerating part of the cycle, and in the low-velocity secondary flow structures. The orifice flow evaluation, the most time consuming case, was performed by the control volume method. It showed good agreement with actual flows through the orifice. Data acquisitions for TURBO-4 BRISK could be performed in 20s for each velocity component. The method shows promise for breath-hold acquisitions in clinical applications, including calculation of blood flow volumes through diseased arteries, measurement of blood backflow volumes through dysfunctional heart valves to time valve replacement operations, and evaluation of arterial wall shear stress, an important factor in the genesis of atherosclerosis.

Aorta, Thoracic↗

Protein kinase C activation inhibits tyrosine phosphorylation of Cbl and its recruitment of Src homology 2 domain-containing proteins.

One of the major proteins that is rapidly tyrosine phosphorylated upon stimulation of the TCR/CD3 complex is the 120-kDa product of the c-cbl protooncogene (Cbl). Upon activation, tyrosine-phosphorylated Cbl interacts with the Src homology 2 (SH2) domains of several signaling proteins, e.g., phosphatidylinositol 3-kinase (PI3-K) and CrkL. In the present study, we report that pretreatment of Jurkat T cells with PMA reduced the anti-CD3-induced tyrosine phosphorylation of Cbl and, consequently, its activation-dependent association with PI3-K and CrkL. A specific protein kinase C (PKC) inhibitor (GF-109203X) reversed the effect of PMA on tyrosine phosphorylation of Cbl and restored the activation-dependent association of Cbl with PI3-K and CrkL. We also provide evidence that PKCalpha and PKCtheta can physically associate with Cbl and are able to phosphorylate it in vitro and in vivo. Furthermore, a serine-rich motif at the C terminus of Cbl, which is critical for PMA-induced 14-3-3 binding, is also phosphorylated by PKCalpha and PKCtheta in vitro. These results suggest that, by regulating tyrosine and serine phosphorylation of Cbl, PKC is able to control the association of Cbl with signaling intermediates, such as SH2 domain-containing proteins and 14-3-3 proteins, which may consequently result in the modulation of its function.

Adaptor Proteins, Signal Transducing↗

Chronic lymphocytic leukemia-associated membranous glomerulopathy: remission with fludarabine.

In some individuals, chronic lymphocytic leukemia (CLL) may be associated with glomerular disease from membranous nephropathy with resultant nephrotic syndrome. CLL is characterized by abnormal immunoregulation with a malignant clonal proliferation of lymphocytes. The association between the abnormal clone and nephrotic syndrome is suggested in some cases by the remission of proteinuria with a reduction in abnormal lymphocyte number after treatment with antineoplastic agents. For the first time, we describe a patient with CLL and associated membranous glomerulopathy whose nephrotic syndrome remitted after treatment with fludarabine, a new purine analogue used in the treatment of refractory CLL.

Antineoplastic Agents↗

Dobutamine stress echocardiography in women with chest pain. Pilot phase data from the National Heart, Lung and Blood Institute Women's Ischemia Syndrome Evaluation (WISE).

OBJECTIVES: The aim of this project was to assess the utility of dobutamine stress echocardiography (DSE) for evaluation of women with suspected ischemic heart disease. BACKGROUND: Most investigations addressing efficacy of diagnosis and treatment of coronary artery disease (CAD) have been performed in predominantly male populations. As part of the Women's Ischemia Syndrome Evaluation (WISE) study, DSE was assessed in women participating at the University of Florida clinical site. METHODS: Women with chest pain or other symptoms suggestive of myocardial ischemia and clinically indicated coronary angiography were eligible for the WISE study. Enrolled subjects underwent DSE using a modified protocol. Coronary stenosis was assessed by core laboratory quantitative coronary angiography (QCA). RESULTS: The 92 women studied ranged in age from 34 to 82 years (mean 57.5). All women had > or = 1 major risk for CAD, and most (89, 97%) had > or = 2 risk factors. In 78 women (85%), left ventricular wall motion was normal at baseline and during peak infusion. The remaining 14 women had wall motion abnormalities during DSE. By QCA, 25 women (27%) had > or = 50% coronary stenosis, including 10 with single-vessel obstruction. Dobutamine stress echocardiography was abnormal in 10 of these 25 women, yielding overall sensitivity of 40%, and 60% for multivessel stenosis. Exclusion of women with inadequate heart rate response yielded overall sensitivity of 50%, and 81.8% for multivessel stenosis. Dobutamine stress echocardiography was normal in 54 of the 67 women with < 50% coronary narrowing, specificity 80.6%. CONCLUSIONS: Dobutamine stress echocardiography reliably detects multivessel stenosis in women with suspected CAD. However, DSE is usually negative in women with single-vessel stenosis, and in the larger subset without coronary stenosis. Ongoing protocols of the WISE study are expected to improve diagnostic accuracy in women with single-vessel disease, as well as provide important data in the substantial number of women with chest pain but without epicardial coronary artery stenosis.

Adult↗

Subjective and external assessments of quality of life in schizophrenia: relationship to insight.

OBJECTIVE: This study assessed the manner in which insight influenced schizophrenic patients' evaluation of their objective life conditions and the concurrent validity between patients' and clinicians' assessments of patients' global quality of life. METHOD: Forty out-patients who fulfilled DSM-III-R criteria for schizophrenia were independently interviewed using the Lancashire Quality of Life Profile and the Standard of Living Interview. Insight was assessed using a self-report questionnaire, the Insight Scale. RESULTS: For insightful patients there was a significant but modest correlation between objective and subjective indicators of quality of life. Likewise, a significant correlation between subjective and external evaluations of global quality of life was limited to those individuals who had good insight. CONCLUSION: Diminished insight may limit the usefulness of the self-report methodology for assessing quality of life for some individuals with schizophrenia.

Adolescent↗

Genetic analysis of the thermolabile variant of 5, 10-methylenetetrahydrofolate reductase as a risk factor for ischemic stroke.

Mild hyperhomocysteinemia is a risk factor for atherosclerotic vascular disease. Homozygosity for the C677T mutation in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR) is frequently associated with hyperhomocysteinemia, particularly in individuals with low levels of serum folate, and has been directly associated with cardiovascular disease in certain populations. The purpose of this study was to establish whether the C677T mutation, which causes thermolabile MTHFR, is a risk factor for ischemic stroke in the Irish population. The homozygous C677T genotype has previously been associated with coronary heart disease in Ireland. We collected blood from 174 individuals (minimum age 60 years) who had suffered an ischemic stroke that was confirmed by computed tomography brain scan. Control subjects (n=183) aged >/=60 years, who had never suffered a stroke or transient ischemic attack, were recruited from hospitals and active retirement groups in the same geographical area. MTHFR genotypes were determined and other known risk factors for stroke were documented. In the control group, the frequency of subjects with the homozygous C677T genotype was 10.4%. In patients who had suffered ischemic stroke, the frequency was 15.5%. This difference was not statistically significant. The odds ratio of stroke for C677T homozygotes, with other genotypes as a reference group, was 1.59, 95% CI=0.85, 2.97. The data indicate that the homozygous C677T MTHFR genotype is at most a moderate risk factor for ischemic stroke.

Aged↗

Aorto-left renal vein fistula: is there a place for endovascular management?

PURPOSE: To describe the endovascular treatment of an aorto-left renal vein fistula. METHODS AND RESULTS: A 77-year-old man with multiple comorbidities presented with low back pain, hematuria, cyanosis, and a pulsatile abdominal mass. Imaging confirmed a 7-cm abdominal aortic aneurysm with a contained rupture into the left renal vein. Owing to the patient's high surgical risk, a Talent Endoluminal Stent-Graft was implanted to satisfactorily exclude the aneurysm. Hemodynamic stability and normal renal function were restored; however, continued perfusion of the sac prompted an attempt to percutaneously repair the renal vein defect. This effort failed, so open laparotomy was necessary. CONCLUSIONS: Although total endovascular management was not successful in this case, the initial use of a minimally invasive approach allowed the patient's clinical status to improve and lower the risk of subsequent surgery.

Aged↗

Rapid velocity-encoded cine imaging with turbo-BRISK.

Velocity-encoded cine (VEC) imaging is potentially an important clinical diagnostic technique for cardiovascular diseases. Advances in gradient technology combined with segmentation approaches have made possible breathhold VEC imaging, allowing data to be obtained free of respiratory artifacts. However, when using conventional segmentation approaches, spatial and temporal resolutions are typically compromised to accommodate short breathhold times. Here we apply a sparse sampling technique, turbo-BRISK (i.e., segmented block regional interpolation scheme for k-space) to VEC imaging, allowing increased spatial and temporal resolution to be obtained in a short breathhold period. BRISK is a sparse sampling technique with interpolation used to generate unsampled data. BRISK was implemented to reduce the scan time by 70% compared with a conventional scan. Further, turbo-BRISK scans, using segmentation factors up to 5, reduce the scan time by up to 94%. Phantom and in vivo results are presented that demonstrate the accuracy of turbo-BRISK VEC imaging. In vitro validation is performed using conventional magnetic resonance VEC. Pulsatile centerline flow velocity measurements obtained with turbo-BRISK acquisitions were correlated with conventional magnetic resonance imaging measurements and achieved r values of 0.99 +/- 0.004 (mean +/- SD) with stroke volumes agreeing to within 4%. A potential limitation of BRISK is reduced accuracy for rapidly varying velocity profiles. We present low- and high-resolution data sets to illustrate the resolution dependence of this phenomenon and demonstrate that at conventional resolutions, turbo-BRISK can accurately represent rapid velocity changes. In vivo results indicate that centerline velocity waveforms in the descending aorta correlate well with conventional measurements with an average r value of 0.98 +/- 0.01.

Blood Flow Velocity↗

Templates for design of inhibitors for serine proteases: application of the program DOCK to the discovery of novel inhibitors for thrombin.

The program DOCK was used to search for novel inhibitors for alpha-thrombin. Four among the top twelve best scoring compounds from the Cambridge Structural Data Base inhibited this enzyme, and three of them inhibited alpha-thrombin in a competitive mode. These molecules are expected to serve as general templates for structural elaboration in targeting diverse serine proteases for selective inhibition.

Binding Sites↗

Can the number of cigarettes smoked predict high-grade cervical intraepithelial neoplasia among women with mildly abnormal cervical smears?

OBJECTIVE: We investigated whether the number of cigarettes smoked by women who had mildly abnormal cytologic study results could identify those at risk for high-grade dysplasia. STUDY DESIGN: This was a prospective study of all women who were referred for colposcopy with a mildly abnormal cervical smear over a 4-year period. A detailed questionnaire was completed that evaluated sociodemographic characteristics including smoking history. Colposcopy then determined the degree of disease. RESULTS: One hundred seventy-three women were referred with a mildly abnormal cervical smear. There was a significant relationship between the numbers of cigarettes smoked and the risk of high grade disease (P = .007). Once the number of cigarettes smoked daily exceeded 20, the risk of high grade cervical intraepithelial neoplasia was increased fivefold (odds ratio 5.85 [95% confidence interval 1.92 to 17.80]). CONCLUSION: Cigarette smoking is associated with a dose-dependent increased risk of cervical intraepithelial neoplasia grade 2 or 3 among women who have mildly abnormal cervical smears.

Adult↗

The efficiency of acute care bed utilization in Newfoundland and Labrador.

Hospital efficiency is closely related to utilization levels and length of stay. This study determined whether inappropriate bed utilization in Newfoundland was related to inefficiency or inadequate access to alternative services. It also compared Canadian Institute for Health information (CIHI) data to our survey to determine whether they provide comparable information for monitoring efficiency. Inappropriate acute care days were identified using a modified Appropriateness Evaluation Protocol. Average length of stay (ALOS) by service for each of the province's acute care institutions was also reviewed from 1993-94 to 1995-96 using the CIHI database. Hospital admissions were Inappropriate in 14.2 percent of 2,007 cases. Of the 14,194 days of care, 22.8 percent were inappropriate, with most (16.4 percent) being avoidable with better use of existing resources. Of the inappropriate days, 49.2 percent related to physicians' functions. The provincial ALOS fell from 5.70 days in 1993-94 to 5.39 days in 1995-96, but remains 10.5 percent above the national average.

Data Collection↗

YAC transgenic analysis reveals Wilms' tumour 1 gene activity in the proliferating coelomic epithelium, developing diaphragm and limb.

Wilms' Tumour 1 gene (WT1) is required for the correct development of the urogenital system. To examine its regulation and expression, we created several transgenic mouse lines containing a beta-galactosidase reporter driven by the human WT1 promoter. A 5 kb promoter weakly recapitulated a subset of the endogenous Wt1 expression pattern. In contrast, 470 and 280 kb YAC transgenes reproduced the correct pattern with high activity and highlighted new expression sites. Wt1 is expressed in the septum transversum revealing how its mutation causes diaphragmatic defects. Wt1 expression in the limb demarcates a zone between chondrogenic and apoptotic domains. Finally, Wt1 is expressed in mesenchymal cells derived from the coelomic epithelium. Based upon these and further data we discuss a Wt1 role in epithelial<-->mesenchymal transitions.

Animals↗

A prospective study comparing intravenous tenoxicam with rectal diclofenac for pain relief in day case surgery.

In a prospective, randomized, double-blind study, we compared intravenous tenoxicam with rectal diclofenac for post-operative pain relief after day case arthroscopy or laparoscopic sterilization. Intravenous tenoxicam (40 mg) was administered as a single bolus at induction, or rectal diclofenac (100 mg) was administered immediately after induction. Both groups were similar with respect to age, weight, sex of the patients, the operation performed and the operative time. There were no significant differences observed between the groups for pain scores at 30 min, 60 min and 24 h post-operatively. The time to first analgesic requirement, the dose of pethidine administered and total analgesic requirements in the first 24 h post-operatively were equivalent in both groups. In view of the similar efficacy of both of these drugs, patient preference and ease of administration, the use of tenoxicam is appropriate in many patients undergoing day case surgery.

Administration, Rectal↗