Biomedical subjects
Publications and source records attributed to J Laird.
Anaemia is a common side-effect of malignancy and cancer therapy. Both red cells and erythropoietin will improve anaemia; however, the scarcity and risks of allogeneic blood transfusion need to be carefully considered against the expense and benefits of recombinant human erythropoietin. Both treatment options have significant economic implications and the definitive evaluation from NICE must be awaited with much interest.
We report a case of venous intravasation of barium sulphate occurring during a routine barium enema examination for investigation of rectal bleeding. The patient suffered a cardiopulmonary arrest, but made a full recovery after organ support in intensive care. Review of radiographs from the examination showed intravasated barium in pelvic vessels. We review the literature on this rare, but serious, complication of barium enema examination and suggest measures by which intravasation can be prevented.
Current diagnostic tests to detect disorders of fatty acids metabolism, such as long-chain hydroxyacyl CoA dehydrogenase deficiency (LCHAD), are hampered by insensitivity or a long delay time required for results. Children with LCHAD deficiency are known to excrete 3-hydroxydicarboxylic acids with chain lengths of 10-16 carbons, but a quantitative method to measure excretion of these potentially diagnostically important compounds has not been reported. We report synthetic schemes for synthesis of 3-hydroxydodecanedioic acid and a di-deuterated analog, suitable for use in a stable-isotope dilution mass spectrometric analytical approach. Evaluation of several common derivatization protocols to produce a volatile derivative for gas chromatography determined that trimethylsyl derivatives produced the best efficiency and stability. Positive-ion chemical ionization mass spectrometry provided the greatest yield of characteristic ions. These results indicate the basic reagents needed to develop sensitive and accurate 3-hydroxydodecanedioic acid measurements for diagnosis of LCHAD deficiency and other fatty acid oxidation disorders.
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Two important goals in allied health education are to prepare future allied health professionals to function as members of interdisciplinary teams and to increase their awareness of issues related to the growing older adult population. The responsibility for achieving these goals rests on the faculty and administrators of allied health education programs, who may not themselves be proficient in either of these domains. A multidisciplinary team of health educators and administrators was brought together to produce six problem-based learning (PBL) cases related to older adults. Members of the team represented a variety of disciplines in health care, diverse philosophies of educational development, a variety of roles in allied health education, and differing levels of knowledge of issues related to older adults--parameters similar to those found in the members of an interdisciplinary healthcare team. The methods by which this multidisciplinary group functioned and the dynamics in attaining the goals of the project are presented.
OBJECTIVE: The somatostatin analogue octreotide (Sandostatin, Novartis, Basie) significantly improves the syndromes suffered by most patients with neuroendocrine tumours (NETs). The use of [111In-DTPA-D-Phe1]-octreotide scintigraphy ([111In]-pentetreotide) to predict the response to octreotide treatment has been described. Short-term hormone inhibition by a single injection of octreotide has also been reported. This study aimed to compare the effects of the suppression test with the response to long-term somatostatin analogue treatment, and to seek a correlation between the short-term suppression test, [11In]-pentetreotide observations and long-term somatostatin analogue treatment. DESIGN AND MEASUREMENTS: Short octreotide suppression test and octreotide scintigraphy. Blood samples were collected before (0900, 0930 h), at (1000 h), and after (1030, 1100, 1200, 1300 h) the injection of 50 micrograms octreotide subcutaneously. Plasma hormones relevant to the syndrome were analysed by radioimmunoassay. The short suppression effects, the [111In]-pentetreotide observations and the response to long-term treatment with somatostatin analogue were evaluated and compared. PATIENTS: Twenty-six patients with metastatic NETs were evaluated, including 14 carcinoid tumours, 10 pancreatic endocrine tumours and 2 medullary carcinomas of thyroid (MCTs). Twelve patients had received octreotide treatment before the study, another 4 patients were treated subsequently with somatostatin analogue. RESULTS: During the short suppression test, hormones relevant to the syndromes were suppressed in 24 patients (those with carcinoids and pancreatic endocrine tumours). There was no suppression in the 2 patients with MCT. [111In]-pentetreotide observations closely correlated with the short suppression response to octreotide. Fourteen patients were treated with somatostatin analogue, and responded clinically; they had a positive short inhibition test and positive tumour uptake. Two patients with MCT did not respond to the treatment and had a negative suppression test and a negative [111In]-pentetreotide. CONCLUSION: Our results suggest that a consistent relationship exists between the short suppression test and the response to somatostatin analogue treatment in the majority of the patients with neuroendocrine tumours. The octreotide suppression test and octreotide scintigraphy together will be helpful in selecting appropriate patients for clinical treatment with somatostatin analogues.
PURPOSE: To determine the maximum-tolerated doses (MTDs), principal toxicities, and pharmacokinetics of the combination of docetaxel and cisplatin administered every 3 weeks to patients with advanced non-small-cell lung cancer (NSCLC) who have not received prior chemotherapy and to recommend a dose for phase II studies. PATIENTS AND METHODS: Patients with advanced NSCLC and performance status 0 to 2 who had not received prior chemotherapy received docetaxel over 1 hour followed by cisplatin over 1 hour with hydration. Dose levels studied were (docetaxel/cisplatin) 50/75, 75/75, 75/100, and 100/75 mg/m2 repeated every 3 weeks. Colony-stimulating factor (CSF) support was not used. Pharmacokinetics of docetaxel and cisplatin were studied in the first cycle of therapy. Most patients (79%) had metastatic disease or intrathoracic recurrence after prior radiation and/or surgery. RESULTS: Of 24 patients entered, all were assessable for toxicity and 18 for response. The MTD schedules were docetaxel 75 mg/m2 with cisplatin 100 mg/m2 (dose-limiting toxicities [DLTs] in five of six patients), and docetaxel 100 mg/m2 with cisplatin 75 mg/m2 (DLTs in two of two patients, including one fatal toxicity). Limiting toxicities were febrile neutropenia and nonhematologic, principally diarrhea and renal. Two patients had neutropenic enterocolitis. Pharmacokinetics of both drugs were consistent with results from single-agent studies, which suggests no major pharmacokinetic interaction. Neutropenia was related to docetaxel area under the plasma concentration-versus-time curve (AUC). An alternative schedule was investigated, with cisplatin being administered over 3 hours commencing 3 hours after docetaxel, but toxicity did not appear to be less. Independently reviewed responses occurred in eight of 18 patients (44%; 95% confidence interval, 22% to 69%), most following 75 mg/m2 of both drugs. CONCLUSION: Docetaxel 75 mg/m2 over 1 hour followed by cisplatin 75 mg/m2 over 1 hour is recommended for phase II studies. The responses seen in this phase I study suggest a high degree of activity of this combination in previously untreated advanced NSCLC.
Alcohol intake is known to impair memory in animals and humans. However, five studies reported that "medium" (0.05 ml/kg body weight) to "high" (1.0 ml/kg body weight) doses of alcohol improved memory when drunk immediately after initial learning of verbal or visual material. It was proposed that alcohol brought about this retroactive facilitation either through enhanced consolidation of memory traces or by protecting against retroactive interference. The present double blind study compared the performances of an alcohol and a placebo group on a kinesthetic memory task before alcohol or placebo intake and at retest 1 h after consumption. A second experiment was identical to the first except that all subjects carried out two trials on a T maze in the hour between testing and retesting. The alcohol group in the first experiment performed significantly better than the placebo group at retest (p < .05) but this was not the case in the second experiment. Alcohol therefore enhanced performance on the kinesthetic memory task in the first experiment but may not have protected against the moderate interference from the T maze in the second. The low levels of alcohol could have had a stimulant effect on trace consolidation, perhaps via raised blood glucose levels.
The need to control costs must be balanced with consumers' demands for high quality in their health care. An integrated approach that uses a multidisciplinary team, a case manager, and a clinical path to improve the quality of patient care offers one method by which both goals may be achieved. The report details the results of a case study in which these three elements were applied to the care of patients undergoing total hip replacement surgery. Results included a length of patients' stay of 3.92 days, cost reduction of $667 per patient in direct costs, no reported cases of readmission for complications during the 2 year process, reductions in length of stay for patients referred to extended care facilities, and a shortened period in home health services. These results are attributed to extensive use of prior screening for all patients by multiple care disciplines, better patient education processes before admission and surgery, improved communication between team members on patient progress, and coordination of care across the continuum.
A phase I/II study of the intralesional administration of ricin-labelled monoclonal antibodies was conducted in patients with hepatic metastases of gastrointestinal origin. The anti-carcinoembryonic antigen (CEA) antibody I-1 was conjugated to blocked ricin via a disulphide bridge. After a test dose of antibody, patients were injected with ricin-antibody conjugates under computed tomography (CT) guidance on two occasions 1 week apart. Patients with stable or responding disease would receive a third course. The dose of ricin relative to surface area was increased in a predefined manner in cohorts of 3 patients. A total of 27 patients with hepatic metastases were entered into this study. All patients had metastatic colorectal cancer (26 patients) or adenocarcinoma of unknown primary with elevated CEA levels (1 patient). The presence of malignancy was documented cytologically in 9 of 11 patients tested. Minor responses were seen in 7 patients. However, no major objective responses or changes in the growth rate of injected lesions were observed. Toxicity was generally mild, the most common being hepatic capsular pain 24-48 h after each injection. 6 patients experienced rigors. One patient had anaphylaxis. Human anti-mouse and anti-ricin antibody responses were observed. Although substantial amounts of ricin conjugated to monoclonal antibodies were delivered into single lesions, this therapeutic approach was unsuccessful. Future studies of ricin-labelled antibodies should incorporate the systemic administration of immunoconjugates.
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A preliminary, double-blind placebo controlled trial of cisapride in reflux oesophagitis was conducted. Eighteen patients were allocated to treatment with either placebo or cisapride, 10 mg three times daily, orally, before meals. Gastric emptying of a scrambled egg meal, oesophageal transit of a liquid bolus and ambulatory monitoring of oesophageal pH were assessed before and after four weeks' therapy. Overall, gastric emptying rates were not influenced by cisapride, although a small but significant reduction in gastric isotope retention, 20 minutes after meal ingestion was observed in patients on the active drug. Oesophageal transit times were not altered by cisapride. A small but significant reduction in the duration of gastro-oesophageal reflux followed cisapride therapy when compared with placebo.
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