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Biomedical subjects

M Roddie

Publications and source records attributed to M Roddie.

9 recordsLinked to original sources
PubMed1998

Phase I trial of temozolomide using an extended continuous oral schedule.

Temozolomide, a methylating imidazotetrazinone, has antitumor activity against gliomas, malignant melanoma, and mycosis fungoides and is presently administered as a 5-day oral schedule every 4 weeks. This Phase I study aimed to determine the maximum tolerated dose of temozolomide administered as a single oral daily dose for a continuous 6- or 7-week period, evaluate the plasma pharmacokinetics on this schedule, and compare total plasma exposure over 7 weeks with the conventional 5-day regimen. Twenty-four patients with varying tumor types (17 of 24 gliomas) received temozolomide. All had clinically evaluable, refractory disease; normal renal, hepatic, and bone marrow function; and WHO performance status < or = 2. Temozolomide was administered at 50 mg/m2/day, increasing by 25 mg/m2/day/cohort until at 100 mg/m2/day grade 4 myelotoxicity forced dose reductions to 85 mg/m2/day, then 75 mg/m2/day. At 75 mg/m2/day the regimen was extended to 7 weeks, allowing the future potential combination with irradiation for primary gliomas. Patient responses (standard Union International Contre Cancer criteria; for gliomas objective response) and toxicity were assessed. Temozolomide plasma pharmacokinetics were determined on day 1 and at the beginning of the final week of administration (n = 5). The most frequent toxicities were myelosuppression and grades 1 and 2 nausea and vomiting. Grade 4 leucopenia and thrombocytopenia occurred in one of four patients receiving 100 mg/m2/day temozolomide and in one of seven patients receiving 85 mg/m2/day. These hematological toxicities did not exceed grade 2 in 10 patients receiving 75 mg/m2/day temozolomide. One of 4 malignant melanoma patients and 7 of 17 glioma patients (41%) demonstrated tumor responses. The overall response rate for this prolonged schedule was 33% (objective response, 7 of 24 patients; partial response, 1 of 24 patients); also, 6 of 17 glioma patients maintained SD. Peak plasma temozolomide concentrations were obtained 30-90 min after oral administration. Elimination in plasma was best described by a monoexponential equation with an elimination half-life of 96 +/- 16 min. No plasma accumulation of temozolomide occurred. Toxicity was greatest in higher dose cohorts, with a resultant maximum tolerated dose of 85 mg/m2/day, whereas lower dose cohorts tolerated the schedule well. The area under the temozolomide plasma versus time curve was noncumulative between the first and last week of the schedule. Temozolomide administration of 75 mg/m2/day over a 7-week period permits a 2.1-fold greater drug exposure/4 weeks in comparison with the 5-day schedule of 200 mg/m2/day repeated every 28 days. The overall response rate was 33% (glioma patients, 41% and a further 25% SD). Temozolomide (75 mg/m2/day) for 7 weeks is the recommended starting dose for further assessment of this schedule.

Administration, Oral↗
PubMed1998

Radiology report times: impact of picture archiving and communication systems.

OBJECTIVE: We investigated the impact on radiologist reporting time of the change from conventional film to hard-copy computerized radiography and of the subsequent move to soft-copy images on picture archiving and communication system (PACS) workstations. MATERIALS AND METHODS: A controlled before and after research design was undertaken. Data were collected on four occasions: two relating to conventional film, one relating to hard-copy computerized radiography, and one relating to soft-copy PACS images. Data collection was by direct observation of radiology reporting sessions by independent health service researchers. Data were collected on report times, details of images viewed, characteristics of the radiologist, and details of interruptions. To control for potential biases in the before and after comparisons, ordinary least squares multiple regression analysis was used. The principal comparison was between reports with PACS and reports with computerized radiography hard-copy because no change was noted in the organization of the reporting process between these two data collection rounds other than the introduction of the PACS. RESULTS: Data were collected on a total of 5568 report observations. Report time in the PACS data collection period was not significantly different (p = .32) than that in the computerized radiography hard-copy period. Reporting with the PACS was associated with significantly more (p < .01) historical images (i.e., images of the same patient obtained in previous examinations) being viewed. CONCLUSION: Report time was not lengthened by the introduction of the PACS. The finding that more historical images were viewed when the PACS was in use indicates that the PACS brought about a positive change in reporting practice.

Bias↗
PubMed1995

Explaining variation in radiologists' reporting times.

This paper describes an investigation into the reasons for variation in the time taken by senior radiologists to complete radiological reports. An observational study of the reporting process at one UK hospital was undertaken for a 25 day period. An independent health service researcher observed the radiology reporting process and collected data on a variety of factors including the time taken to produce the report, the number and nature of all images viewed, the experience of the radiologist, and the number of disturbances that occurred. The nature of the variation in reporting time was explored using both simple comparative statistics and more sophisticated multiple regression techniques. Data were collected on 2345 report observations and the median report time was 117 s. This research provides the first empirical evidence for systematic variation in reporting time. The results confirm the importance of certain factors that were expected to explain report time variation. For example, the results indicate that report time tended to be significantly shorter in reporting sessions that were busy, and significantly longer when the radiologist was disturbed during the reporting process or was training juniors during a reporting session. More surprising were the results indicating that there was no significant difference in report time for reports categorized as urgent or "hot" and those categorized as less urgent or "cold", and that report time appeared to vary systematically depending on the day of the week and on the time of day.

Humans↗
PubMed1992

Langerhans' cell histiocytosis and the nervous system.

We report two cases of Langerhans' cell histiocytosis with unusual central nervous system (CNS) involvement. The first patient had behavioural disturbances, memory loss and diabetes insipidus. His response to a range of treatments was poor. The second patient presented with seizures and headaches suggestive of raised intracranial pressure. Etoposide (VP16) chemotherapy led to a dramatic clinical and radiological improvement. The various CNS manifestations of Langerhans' cell histiocytosis and their management are discussed.

Adult↗
PubMed1991

Ureteric obstruction in renal transplants: the role of percutaneous balloon dilatation.

With widespread use of balloon dilatation catheters outside the vascular system, percutaneous balloon dilatation has become an accepted alternative to surgery. Seventeen patients who developed ureteric stenosis following renal transplantation underwent 21 transrenal angioplastic balloon dilatations. Fifteen patients had lower ureteric strictures (2-22 mm long), and two had multiple strictures. The time interval between transplantation and obstruction ranged from 11 to 1370 days (median 71, mean 228.9 days). Nine patients were treated successfully (53%) with no stricture recurrence during the follow-up period, which ranged from 3 to 44 months (median 16, mean 17.8 months). In eight of nine patients in this group, the stricture impression on the inflation balloon was eliminated, and this appears to correlate best with a successful outcome. The eight patients who failed balloon dilatation and restenosed, did so within 7-42 days in seven patients; one patient had late stricturing at 238 days. Serious complications occurred in only one patient, who developed an A-V fistula not amenable to correction and necessitating transplant nephrectomy.

Adult↗
PubMed1991

Self-expandable stainless steel endoprostheses for treatment of malignant bile duct obstruction.

The Wallstent biliary endoprosthesis is a mesh of stainless steel that is delivered percutaneously over a 7-French catheter but expands to achieve a 1-cm lumen when released across a bile-duct stricture. The small transhepatic track required makes insertion easier, less painful, and probably safer when compared with plastic stents, and the large internal lumen reduces the rate of occlusion by encrusted bile. Wallstent endoprostheses were inserted under local anesthesia in 41 consecutive patients with malignant obstructive jaundice. Biliary drainage was considered the treatment of choice in all of these patients. The diagnosis was based on biopsy results in 32 patients and on radiologic appearances in nine. The patients were followed up in outpatient clinics for 16 months and had repeated radiologic examinations only if they had symptoms suggesting stent occlusion. No cases of hemobilia due to damaged hepatic vessels occurred. Two patients had septicemia treated with antibiotics. Three patients had recurrent jaundice due to growth of tumor below or above the stents. Endoprosthesis migration was not seen. No cases of stent occlusion due to encrustation of bile occurred. The median survival of patients was 105 days (range, 10-545 days). Our experience shows that Wallstent endoprostheses can be inserted with little discomfort for the patient and with relatively few complications. They provide good palliation in patients with malignant obstructive jaundice.

Adult↗