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Biomedical subjects

G Doyle

Publications and source records attributed to G Doyle.

At least 19 recordsLinked to original sources
PubMed2005

Preliminary study of immunomagnetic quantification of circulating tumor cells in patients with advanced disease.

OBJECTIVES: To enumerate the amount of circulating tumor cells (CTCs) in patients with advanced prostate cancer and to investigate the relationship between these numbers, prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) expression, and clinical parameters. METHODS: Whole blood was collected in proprietary CellSave tubes. Mononuclear cell fractions were isolated using epithelial cell antibody-coated magnetic nanoparticles. On one half of each immunomagnetically enriched cell fraction, automated fluorescent microscopy was used to identify the epithelial tumor cells. From the remainder of each sample, RNA extraction, cDNA synthesis, and polymerase chain reaction amplification of PSA and PSM were performed. RESULTS: Eighty-four patients with advanced prostate cancer submitted 130 samples for analysis. Intact CTCs were identified in 62% of samples; 83.3% of CTC-positive and 0% of CTC-negative samples were reverse transcriptase-polymerase chain reaction positive for PSA and PSM (P = 0.001). A significant positive correlation was found between the CTC number and PSA (r = 0.49), alkaline phosphatase (r = 0.47), and lactate dehydrogenase (r = 0.55) levels, and a significant negative correlation with hemoglobin (r = -0.35). The initial Gleason grade, prior therapy, current therapy, and type of metastasis (bone, soft tissue) did not correlate significantly with the CTC number. CONCLUSIONS: The presence of intact CTCs and the expression of PSA and PSM demonstrated robust agreement. The tumor cell numbers reflected current disease status and correlated significantly with the clinical disease indicators of PSA, hemoglobin, and liver function tests. These findings warrant further investigation of the diagnostic and prognostic value of enumerating intact CTCs.

Adult↗
PubMed2003

Carpal tunnel syndrome - is high-frequency ultrasound a useful diagnostic tool?

This study assessed the clinical use of three ultrasound measurements; median nerve cross-sectional area, median nerve flattening ratio and palmar displacement of the flexor retinaculum, for the diagnosis of carpal tunnel syndrome. The measurements were made in 20 carpal tunnel sufferers and 20 controls. The sensitivity, specificity and predictive values of each were calculated in various clinical settings. Values for each of the three variables were significantly different in the patient and control populations. The differences we recorded were smaller than those found in previous studies. The tests had a sensitivity of 72% and a specificity of 90%. Alterations in the morphology of the carpal tunnel in patients with carpal tunnel syndrome can be measured in the district general hospital setting. The measurements described maybe a useful non-invasive confirmatory test in patients in whom there is a strong clinical suspicion of carpal tunnel syndrome. However, they would be of no benefit in epidemiological surveys of populations with a low incidence of carpal tunnel syndrome.

Adult↗
PubMed2001

Changes in circulating carcinoma cells in patients with metastatic prostate cancer correlate with disease status.

OBJECTIVES: To investigate the diurnal variations in circulating tumor cells (CTCs) in metastatic carcinoma of the prostate (CAP) and to determine whether the change in CTCs correlated with disease progression. METHODS: Samples were prepared by immunomagnetic selection of cells from 7 mL of blood targeting the epithelial cell adhesion molecule and differential fluorescent labeling of the collected cells using a nucleic acid dye, antibodies directed against the common leukocyte (CD45), and cytokeratin antigens. Events that stained with the nucleic acid dye and expressed cytokeratin but lacked CD45 were defined as CTCs by multiparameter flow cytometry. RESULTS: Male controls (n = 22) exhibited 0.8 +/- 1.2 events per 7 mL blood compared with 5.9 +/- 4.7 in 10 samples from patients with localized CAP and 46.6 +/- 65.6 events in 10 samples from patients with metastatic CAP. Diurnal testing of 8 cases demonstrated stable levels of CTCs. Ten patients were serially analyzed during a 6-month period for serum prostate-specific antigen and CTCs. The correlation between the prostate-specific antigen level and CTC number was fair. Slow disease progression was found in 4 patients with low CTC numbers (3.0 +/- 3) but it was significantly higher than the control group (P <0.002). Rapid disease progression occurred in 6 patients who demonstrated high CTC numbers (68.5 +/- 71.9). Two patients received chemotherapy that caused substantial fluctuations in the CTCs with less pronounced changes in the prostate-specific antigen level. CONCLUSIONS: We conclude that the level of CTCs can be quantified in the circulation of patients with metastatic CAP and that the change in CTCs correlates with disease progression with no diurnal variations.

Aged↗
PubMed2001

Onset of analgesia for liquigel ibuprofen 400 mg, acetaminophen 1000 mg, ketoprofen 25 mg, and placebo in the treatment of postoperative dental pain.

Ibuprofen is a peripherally acting nonsteroidal anti-inflammatory drug indicated fo ranalgesia, antipyresis, and various arthritic conditions. A solubilized 200 mg liquigel formulation of ibuprofen has been shown to have a more rapid rate of absorption compared with ibuprofen 200 mg tablets. Ibuprofen liquigels have a kinetic profile similar to ibuprofen suspension, with both a higher Cmax and an earlier tmax than any solid tablet. The objective of this single-dose, double-blind, triple-dummy, parallel-group study was to assess the time to onset of relief and overall analgesic efficacy of liquigel ibuprofen 400 mg, ketoprofen 25 mg compared with acetaminophen 1000 mg, and placebo in 239 patients with moderate or severe pain following third molar extractions. Treatments were compared over 6 hours using standard scales for pain intensity and relief and stopwatch onset of meaningful relief. All active treatments provided meaningful relief significantly faster compared with placebo. Ibuprofen provided significantly faster relief compared with acetaminophen and ketoprofen. By the end of the study (6 h), onset of meaningful relief was achieved by 36%, 99%, 96%, and 88% of the patients in the placebo, ketoprofen, ibuprofen, and acetaminophen groups, respectively. The median times to onset of relief were > 6 hours for placebo, 25.5 minutes for ketoprofen, 24.2 minutes for ibuprofen, and 29.9 minutes for acetaminophen. In addition, both ibuprofen and ketoprofen showed statistical superiority over acetaminophen at earlier time points on the time-effect curves for pain relief and pain intensity difference. Consistent results were seen with respect to the 6-hour summary efficacy variables: the three active treatments were significantly better than placebo, and ibuprofen was significantly better than both acetaminophen and ketoprofen. Liquigel ibuprofen 400 mg was shown to provide faster relief and superior overall efficacy compared with ketoprofen 25 mg, acetaminophen 1000 mg, and placebo. No serious adverse effects were reported in this single-dose study.

Abdominal Pain↗
PubMed2000

Performance of screening mammography in organized programs in Canada in 1996. The Database Management Subcommittee to the National Committee for the Canadian Breast Cancer Screening Initiative.

BACKGROUND: The results of randomized trials show that breast cancer screening by mammography reduces breast cancer mortality by up to 40% in women aged 50-69 years. Because of these results, by 1998, 22 countries, including Canada, had established population-based organized screening programs. This paper presents the results of screening mammography in 1996 for 7 provincially organized breast cancer screening programs in Canada. METHODS: Analyses of interim performance indicators for screening mammography have been calculated from data submitted to the Canadian Breast Cancer Screening database. The data set consisted of data from 7 provincial programs and was limited to mammographic screens for women aged 50-69 years (n = 203,303). Screening outcomes and performance indicators were calculated for abnormalities detected by screening mammography only. RESULTS: The abnormal recall rate was 9.5% for first screens and 4.6% for subsequent screens, and the cancer detection rate per 1000 women screened was 6.9 for first screens and 3.8 for subsequent screens. The positive predictive value (i.e., the proportion of women who tested positive by mammography who were found to have breast cancer on screen-initiated diagnostic work-up) increased from 7.2% at the first screen to 8.2% at subsequent screens. Estimated participation rates within organized programs varied from 10.6% to 54.2%, depending on the province. INTERPRETATION: For 1996, organized breast cancer screening programs met or exceeded many of the interim measures used in international programs. It is possible to translate the benefits of breast cancer screening by mammography, as demonstrated in randomized trials, into population-based community programs. Screening mammography through organized programs should increase to allow more comprehensive monitoring in Canada.

Aged↗
PubMed2000

Ibuprofen liquigel for oral surgery pain.

BACKGROUND: Ibuprofen liquigel is a solubilized potassium ibuprofen 200-mg gelatin capsule formulation that was approved for over-the-counter use in 1995. OBJECTIVE: This study compared the analgesic efficacy and tolerability of ibuprofen liquigel 200 mg, ibuprofen liquigel 400 mg, acetaminophen caplets 1000 mg, and placebo in patients experiencing moderate or severe pain after surgical removal of impacted third molars. METHODS: This randomized, double-blind, parallel-group, 6-hour study was conducted in 210 patients experiencing moderate or severe postoperative pain. Ratings of pain intensity and pain relief were recorded every 15 minutes for the first hour, at 90 and 120 minutes, and then hourly through hour 6. The onsets of first perceptible relief and meaningful relief were recorded using 2 stopwatches. An analysis of variance model was employed to test for significant differences (P < or = 0.05) between treatment groups with respect to pain relief, pain intensity difference, total pain relief (TOTPAR), and summed pain intensity difference (SPID). Stopwatch measures were analyzed using the Cox proportional hazards model. Drug tolerability was assessed by monitoring the occurrence of adverse events. RESULTS: During the first 2 hours of the study (TOTPAR 2 and SPID 2), all active treatments were significantly more efficacious than placebo (P < 0.001), with ibuprofen liquigel 200 and 400 mg significantly more efficacious than acetaminophen 1000 mg (P < 0.05 and P < 0.01, respectively). For the entire duration of the study (TOTPAR 6 and SPID 6), only the 2 doses of ibuprofen liquigel were significantly more efficacious than placebo (P < 0.001). Ibuprofen liquigel 200 and 400 mg were also significantly more efficacious than acetaminophen 1000 mg on the summary measures TOTPAR 6 and SPID 6 (P < 0.01 and P < 0.001, respectively). Analysis of the stopwatch data revealed that all active treatments displayed significantly more rapid onsets to confirmed first perceptible relief (P < 0.001 to < 0.05) and meaningful relief (P < 0.001 to < 0.01) than did placebo, with ibuprofen liquigel 400 mg displaying a significantly more rapid onset to meaningful relief than acetaminophen 1000 mg (P < 0.05) and a significantly more rapid onset to confirmed first perceptible relief than acetaminophen 1000 mg (P < 0.001) and ibuprofen liquigel 200 mg (P < 0.01). All adverse events were considered mild or moderate, with an overall incidence of 11.5% in the ibuprofen liquigel 200-mg group, 6.8% in the ibuprofen liquigel 400-mg group, 19.0% in the acetaminophen 1000-mg group, and 25.9% in the placebo group. CONCLUSIONS: Ibuprofen liquigel provided greater peak and overall analgesic effects and a more rapid onset to analgesia than did acetaminophen 1000 mg.

Acetaminophen↗
PubMed2000

Effects of composite thickness on the shear bond strength to dentin.

The manufacturers of some condensable posterior composites claim that their products can be placed in bulk and light-cured in 5-mm-thick increments. This study compared the shear bond strengths of three composite resins when bonded to dentin in 2- and 5-mm-thick increments. Overall the bond strengths were adversely affected by the composite thickness (p < 0.0001). The shear bond strength of each composite tested was much lower when polymerized in a 5-mm increment than in a 2-mm increment of composite (p < or = 0.0005). The two condensable composites tested had a lower bond strength than the conventional composite when polymerized in a 5-mm bulk increment (p < or = 0.01).

Analysis of Variance↗
PubMed1999

Predicting infection in localized intraabdominal fluid collections: value of pH and pO2 measurements.

PURPOSE: To evaluate the use of pH, pO2, and the subjective opinion of the radiologist compared with bacterial culture in accurate diagnoses of bacterial infection in intraabdominal fluid collections. MATERIALS AND METHODS: Prospectively, 79 patients who were suspected of having an intraabdominal fluid collection underwent diagnostic fluid aspiration. The aspirate was cultured and measured for pH and pO2. A pH < or = 7.1 and a PO2 < or = 49 mm Hg were threshold values used to separate infected from sterile fluid collections. RESULTS: pH alone had a 92% sensitivity and 79% specificity, whereas PO2 alone had a 51% sensitivity and 79% specificity. pH or pO2 combined yielded a 92% sensitivity and 60% specificity. The radiologist's opinion produced a 83% sensitivity and 92% specificity. pH and the radiologist's opinion combined produced a 78% sensitivity and 96% specificity. pH or the radiologist's opinion combined had a 95% sensitivity and a 63% specificity. CONCLUSION: pH is the most sensitive indicator of infection and the radiologist's opinion is the most specific. We recommend proceeding to drainage if the radiologist believes the collection to be infected and performing pH analysis if not. If the pH < or = 7.04, proceed to drainage. If neither of the above criteria are met, drainage could be delayed, pending the results of culture.

Abdominal Abscess↗
PubMed1999

Gastrointestinal safety and tolerance of ibuprofen at maximum over-the-counter dose.

BACKGROUND: Delineation of non-steroidal anti-inflammatory drug (NSAID) gastrointestinal toxicity has largely depended on retrospective epidemiologic studies which demonstrate that lower doses of NSAIDs pose a lower risk of gastrointestinal toxicity. Ibuprofen, a propionic acid NSAID, has, in most such studies, exhibited a favourable profile in terms of gastrointestinal bleeding. Since 1984, ibuprofen has been available as a non-prescription analgesic/antipyretic with a limit of 1200 mg/day for 10 days of continuous use. Trials and spontaneously reported adverse experiences suggest that gastrointestinal symptoms and bleeding are rare. METHODS: This study prospectively evaluated the gastrointestinal tolerability, as compared to placebo, of the maximum non-prescription dose and duration of ibuprofen use in healthy subjects representative of a non-prescription analgesic user population. RESULTS: Gastrointestinal adverse experiences were similar in the placebo and ibuprofen groups (67 out of 413, 16% with placebo vs. 161 out of 833, 19% with ibuprofen). There was no difference between the two groups in the proportion discontinuing due to a gastrointestinal event. Gastrointestinal adverse experiences reported by >/= 1% of subjects were: dyspepsia, abdominal pain, nausea, diarrhoea, flatulence, and constipation. Seventeen (1.4%) subjects had positive occult blood tests: their frequency was comparable between treatments. CONCLUSIONS: When used as directed to treat episodic pain, non-prescription ibuprofen at the maximum dose of 1200 mg/day for 10 days, is well-tolerated.

Adolescent↗
PubMed1996

Clinical evaluation in prosthodontics: practical methods to improve validity and reliability at the undergraduate level.

The potential causes of reliability and validity problems with traditional methods of evaluating a student's clinical prosthodontic skills are reviewed. Practical methods of evaluating critical skills in a reliable and valid way are presented. These methods include clinical tests using written criteria and anonymous examiners, skills assessment by faculty members, patient-based written examinations, and bell ringer examinations.

Clinical Competence↗
PubMed1995

Glomerulonephritis after ventriculo-atrial shunt.

We describe five patients with glomerulonephritis (GN) associated with cerebrospinal fluid shunt insertion to relieve hydrocephalus. A ventriculo-atrial (V-A) shunt had been placed on average 12.5 years prior to the diagnosis of nephritis (range 0.5-21 years). Four patients developed membranoproliferative glomerulonephritis (MPGN) with associated hypocomplementaemia. A single patient developed focal proliferative glomerulonephritis. Coagulase-negative staphylococci were cultured in four patients, either from blood or from the shunt. Four patients had their shunts removed, two of whom also received antibiotics. The other patient received antibiotics alone for infective endocarditis due to staphylococcal bacteraemia which originated in the shunt. All patients had substantial renal impairment at the time of diagnosis (GFR, glomerular filtration rate, 20-45 ml/min). There was significant improvement in renal function after appropriate treatment; four of the five patients doubled their GFRs and two patients regained normal function.

Adolescent↗
PubMed1991

Pharmacokinetics of the anti-inflammatory drug ximoprofen in healthy subjects and in disease states.

The pharmacokinetics of ximoprofen, a potent new non-steroidal anti-inflammatory agent, has been investigated in normal healthy subjects and in patients with hepatic or renal disease. After intravenous infusion of 22.8 mg to healthy subjects, plasma ximoprofen concentrations declined in a polyexponential manner with a terminal phase half-life of 1.9 h. The systemic clearance of ximoprofen was 115 ml.min-1 and the volumes of distribution were 18.01 Vz and 13.81 Vss. Ximoprofen was 80-90% bound to plasma proteins. The systemic availabilities (f) of orally and rectally administered doses of 30 mg of ximoprofen were 98% and 56% respectively and, in the case of the rectal dose, absorption appeared to be prolonged leading to "flip-flop" kinetics. After single oral doses of 30 mg of ximoprofen to patients with hepatic disease, half-life (2.2 h), peak plasma concentrations (1.55 micrograms.ml-1 cf 1.04 micrograms.ml-1 in healthy subjects) and areas under the curve (6.12 micrograms.h.ml-1 cf 3.54 micrograms.h.ml-1 in healthy subjects) were significantly different from those in healthy subjects. After single oral doses of 30 mg of ximoprofen to patients with renal disease, pharmacokinetic parameters of half-life (4.0 h), mean residence time (6.0 h) and area under the curve (9.2 micrograms.h.ml-1) were significantly different from those in healthy subjects. There were no significant differences in pharmacokinetic parameters between patients having differing degrees of renal disease. These data nevertheless suggest that accumulation of ximoprofen in hepatic or renal disease would be of slight or negligible clinical relevance and that no alteration of the dose regimen (up to 15 mg twice daily) may be required when ximoprofen is administered in these disease states.

Adult↗
PubMed1990

The use of cyclosporin A in adult nephrotic syndrome: nine cases and literature review.

Nine adult patients with resistant nephrotic syndrome were treated with cyclosporin A (CyA). All had failed to respond to high dose corticosteroids with or without cyclophosphamide. Three patients had minimal change disease, 3 had focal sclerosing glomerulosclerosis (FSGS), 2 had mesangiocapillary GN, and one had membranous nephropathy. The mean age of the patients was 26.4 years (range 16 to 39 years). CyA was given orally twice daily at a mean dose of 6.7 mg/kg/24 hours (range 6-10 mg/kg/24 hours). Four patients achieved full remission, two patients went into partial remission and three failed to respond. Two patients developed clinical nephrotoxicity, which reversed on dose reduction or cessation of CyA. All 3 patients with minimal change disease who responded subsequently relapsed after stopping CyA, but remitted rapidly on reintroduction of the drug. We suggest that the mode of action of CyA in nephrotic syndrome may be related to intra-renal vasoconstriction in addition to its direct immunosuppressive effect. In this limited series, we found that CyA can be an effective therapy for otherwise refractory nephrotic syndrome, although relapse on withdrawal of CyA may well be a significant clinical problem.

Adult↗
PubMed1990

Clinical and histopathologic findings in adults with the nephrotic syndrome.

The clinical and histopathologic findings in 225 Irish adults with nephrotic syndrome were reviewed. Membranous nephropathy was the most common lesion found (28%), followed by proliferative glomerulonephritis (17%), and focal sclerosing glomerulonephritis (16%). Minimal change disease was the least frequent cause for idiopathic nephrotic syndrome (12%). The major secondary cause of nephrotic syndrome was amyloidosis (13%). The patients were analysed for the predictive value of the level of renal function, presence or absence of hypertension, and the degree of proteinuria. It was not possible to determine the nature of the underlying lesion giving rise to the nephrotic syndrome using any of these variables. There was also no significant difference between primary and secondary glomerular disease with regard to these factors. It is concluded that renal biopsy remains the only definitive method of establishing the underlying lesion causing idiopathic nephrotic syndrome.

Adolescent↗
PubMed1989

Systemic vasculitis with renal involvement--a review.

Twenty five patients with renal vasculitis presenting over an eight year period were reviewed. Ten had microscopic polyarteritis, 6 classic polyarteritis, 5 overlap syndrome, 2 Churg-Strauss syndrome and 2 Wegener's granulomatosis. Clinical features included hypertension, pulmonary involvement, neurological involvement and arthralgia. Serum creatinine was over 500 umol/l in 13 patients, 10 of whom required dialysis. Visceral angiography was positive in 80% of those studied, Focal and segmental necrotising glomerulonephritis was the commonest renal lesion. Treatment consisted of corticosteroids and cytotoxic agents in most cases. Plasmapheresis was used for rapidly progressive renal failure, severe pulmonary haemorrhage or cerebral vasculitis. Improvement or stabilisation of renal function was seen in 68% of patients treated. There were 4 early deaths and one late death. The diagnosis, histology, treatment and outcome of renal vasculitis is discussed. The importance of early diagnosis and treatment is emphasised in this potentially reversible cause of acute renal failure.

Acute Kidney Injury↗