Biomedical subjects
D F Moore
Publications and source records attributed to D F Moore.
The effect of thalidomide on the developing rat foetus.
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Organ preservation using ultrabaric oxygen.
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Evaluation of Tomudex in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a Southwest Oncology Group study.
A phase II trial of Tomudex (raltitrexed, ZD 1694), a new thymidylate synthase inhibitor, was performed in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. This trial demonstrated that Tomudex was well tolerated in this patient population. Nausea and vomiting were minimal, and hematologic toxicities were relatively infrequent. Only one patient was withdrawn from the study due to toxicity (grade 4 diarrhea). One patient exsanguinated from a rent in the carotid artery in an area of tumor involvement, and was categorized as a grade 5 toxicity. Thus 25/27 patients were able to complete at least 2 cycles of treatment. Tomudex demonstrated a 3.7% response rate (95% CI 0.1-19%), with a median survival of 6 months in this highly resistant disease population. Tomudex is not considered active enough as monotherapy for further evaluation in this disease population.
Phase II trial of 9-aminocamptothecin (NSC 603071) administered as a 120-hr continuous infusion weekly for three weeks in metastatic colorectal carcinoma.
9-Aminocamptothecin (9-AC) is a camptothecin derivative with broad antitumor activity in preclinical studies. Prior investigations suggested that prolonged maintenance of 9-AC lactone plasma concentrations above 10 nmol/l and frequent administration of the drug are important determinants of antitumor activity. Our phase II study, therefore, examined a 5-day continuous infusion of 9-AC weekly for 3 weeks in patients with advanced colorectal cancer. Eighteen patients previously untreated for metastatic disease received 480 microg/m2/day of 9-AC. No responses were observed in 17 evaluable patients. Severe toxicities included granulocytopenia, nausea, vomiting and diarrhea. The median absolute granulocyte count (AGC) nadir was 2,300/microl (range 0-9,000/microl) and occurred on day 10. Eight patients received an escalated dose of 600 microg/m2/day. The median AGC nadir at the escalated dose was 1,500/microl (range: 300-2,700/microl) and occurred on day 22. The median number of courses given was 2 (range: 1-8); and the median time to disease progression was 8 weeks (range: 1-40 weeks). 9-AC administered by this schedule lacked antitumor activity in patients with advanced colorectal carcinomas.
Stiripentol in acute/chronic efficacy tests in monkey model.
Acute and chronic efficacy tests of stiripentol (4,4-dimethyl-1-[3,4-(methylenedioxy)-phenyl]-1-penten-3-ol) were conducted in alumina-gel rhesus monkeys. In the acute study (n = 6), discrete serial seizures precipitated by 150 mg/kg of 4-deoxypyridoxine hydrochloride were challenged by intravenous administration of stiripentol and the data compared with those obtained with valproate similarly tested in other monkeys (reported here) and with those from four other standard anticonvulsants (phenytoin, carbamazepine, phenobarbital, and diazepam--data published previously). In the acute challenge (Study 1), stiripentol performed comparably to valproate by delaying the onset of seizures but not eliminating them as did the other four drugs. In two separate chronic studies (at different doses, n = 6 each), stiripentol was given every 4 h by gastric catheter for 4 weeks, preceded and followed by 4 weeks of baseline. In these studies, stiripentol significantly reduced EEG interictal spike rates at mean plasma concentrations from 20 to 27 micrograms/ml in Study 2 and 11 to 14 micrograms/ml in Study 3. From these results, and those evinced in other studies, it appears that stiripentol should be evaluated for absence epilepsy and possible synergistic effects in polytherapy.
Follow-up of University of Virginia experience with the modified Lothrop procedure.
Current surgical treatment of the frontal sinus disease include external approaches to obliterate or ablate the sinus and both external and transnasal methods to restore drainage into the nasal cavity. The original Lothrop procedure resects the medial frontal sinus floor, superior nasal septum, and intersinus septum, creating a large frontonasal communication. However, as described, the external approach used in this procedure often allowed medial collapse of soft tissue and the stenosis of the nasofrontal communication. This report further relates our experience with the modified transnasal endoscopic Lothrop procedure using suction drills for cases in which frontal recess exploration had failed to relieve obstruction of the frontal sinus. We present an update of the University of Virginia experience in performing the modified Lothrop procedure in 20 patients from 10/93 to 4/95. Our findings over the follow-up period (average 12 months) have verified that this procedure is effective, with a 95% patency rate for the surgically enlarged frontal sinus ostium. When compared to osteoplastic flap with fat obliteration, the modified transnasal Lothrop procedure offers the advantages of a less invasive procedure with a shorter and usually no hospitalization, less morbidity, and the increased ability to evaluate post-operatively for recurrent disease. A patient charge analysis was also performed comparing patients undergoing frontal sinus obliteration during the same time period, revealing an additional benefit of decreased patient costs for the modified transnasal Lothrop procedure. None of our patients experienced complications, and all showed significant improvement, if not complete resolution of their symptoms. Although this procedure has produced favorable results, it should be noted that this procedure is technically demanding and will require further long term follow-up to verify its efficacy and proper role in the spectrum of surgical approaches for the treatment of chronic sinusitis.
Evaluation of docetaxel in previously untreated extensive-stage small cell lung cancer: a Southwest Oncology Group phase II trial.
PURPOSE: This phase II multi-institutional trial of the Southwest Oncology Group was designed to evaluate the efficacy and toxicity of docetaxel in chemotherapy-naive patients with extensive-stage small cell lung cancer. PATIENTS AND METHODS: Forty-seven patients with extensive-stage small cell lung cancer were entered onto the study. Treatment consisted of docetaxel, 100 mg/m2, as a 1-hour intravenous infusion repeated every 21 days, with protocol-specified dose reductions for toxicity. RESULTS: Forty-three patients were eligible. A total of 158 cycles of docetaxel were administered (median, three cycles; range, one to nine). Ten patients (23%) (95% confidence interval, 12% to 39%) achieved partial responses. The median progression-free and overall survivals were 3 and 9 months, respectively. Therapy was generally well tolerated. Grade 4 neutropenia occurred in 58% of patients. Febrile neutropenia developed in five patients (12%), and infection was documented in 14% of patients. There was one treatment-related death caused by pneumonia in a patient who had developed bilateral pneumothoraces. Other toxicities (grade 3/4) included malaise, fatigue, and lethargy (21%); nausea (19%); stomatitis (14%); edema (9%); and sensory neuropathy (9%). DISCUSSION: Docetaxel, at a dose of 100 mg/m2, is an active agent in the treatment of small cell lung cancer. Reversible neutropenia is the most common toxicity associated with this treatment. The overall survival (9 months) with this agent is comparable to that reported with other new chemotherapeutic agents in small cell lung cancer and warrants additional evaluation of docetaxel in combination therapy.
Clinical use of diffusion-tensor imaging for diseases causing neuronal and axonal damage.
Diffusion-tensor imaging is an emerging technique that can supply microscopic structural information about tissue in vivo. With this technique it is possible to measure the amount of anisotropy of water diffusion within tissues and to assess the degree to which directionally ordered tissues have lost their normal integrity. This study was performed in four patients to evaluate the feasibility of applying this technique in clinical situations in which there is known or suspected damage to white matter tracts.