Biomedical subjects
Publications and source records attributed to R Gregory.
New histamine H3 receptor antagonists were developed using an acetylene moiety as a replacement for the amide-oxime functionality of verongamine 5. Optimization of receptor binding was performed by following aliphatic Topliss tree guidelines. These new H3 ligands demonstrate excellent blood-brain barrier penetration.
BACKGROUND: High grade astrocytomas remain uniformly fatal despite aggressive surgery and radiotherapy. As existing chemotherapeutic agents are of limited benefit, clinical trials are underway to screen new drugs, such as 9-aminocamptothecin (9-AC), for activity in high grade astrocytomas. PURPOSE: This study was designed to estimate the efficacy of 9-AC in patients with newly diagnosed glioblastoma multiforme and recurrent high grade astrocytomas. The planned dose of 9-AC for this trial was 850 microg/m2 per 24 h as a 72-h continuous intravenous infusion every 2 weeks. This was the maximum tolerated dose (MTD) on this schedule in multiple phase I studies in patients with systemic malignancies. However, we found this dose subtherapeutic in our patient population. As a result, the purpose of the study was altered to determine the MTD. METHODS: A group of 32 patients were studied using 850 microg/m2 per 24 h with a provision to escalate to 1000 microg/m2 per 24 h if the first three cycles of 9-AC were without significant hematologic toxicity. Once it was determined that myelosuppression did not occur in patients on anticonvulsants, dose escalations were initiated using the continual reassessment method. Dose escalations were conducted independently in newly diagnosed and recurrent patients and in those taking and not taking hepatic enzyme-inducing anticonvulsants. Pharmacologic studies were conducted during the first cycle of 9-AC. Toxicity was determined using the NCI common toxicity criteria and efficacy was assessed using serial volumetric brain scans. RESULTS: 9-AC was administered to 59 patients, 31 with newly diagnosed glioblastoma multiforme and 28 with recurrent high grade astrocytomas. No grade III-IV myelosuppression was noted in the 29 patients (128 cycles) on phenytoin, carbamazepine, phenobarbital, and/ or valproic acid who received 850 microg/m2 per 24 h. In contrast, two of three patients (five cycles) who were not taking anticonvulsants developed grade IV myelosuppression. Steady-state total 9-AC plasma levels were lower in patients on anticonvulsants (median 25.3 nM) than in patients who were not taking anticonvulsants (median 76.5 nM). Dose escalations performed in 27 additional patients determined the MTD in patients taking anticonvulsants to be 1776 microg/m2 per 24 h for patients with newly diagnosed tumors and 1611 microg/m2 per 24 h for patients with recurrent disease. CONCLUSIONS: We describe a new and unexpected drug interaction between 9-AC and anticonvulsants. This is similar to recent findings with paclitaxel, and suggests that higher than "usual" doses of some chemotherapeutic agents are required in patients on anticonvulsants. Prospectively defined dose escalations and pharmacologic studies are essential for the careful evaluation of new chemotherapeutic agents in patients with brain tumors.
OBJECTIVES: Assess the acceptance and ease of use of Nutrition Practice Guidelines for Type 1 Diabetes Mellitus by dietitians in a variety of settings; determine if nutrition care activities of dietitians change when practice guidelines are available; measure changes in patient control of blood glucose level, measured as glycated hemoglobin (HbA1c); compare patient satisfaction with care and perceptions about quality of life. DESIGN: Using the approach of outcomes research, volunteer dietitians were recruited and assigned randomly to a usual care group or a practice guidelines group. Patients with type 1 diabetes were enrolled by dietitians and followed up for a 3-month period. Outcome measures included dietitian care activities, changes in patient HbA1c levels, and patient satisfaction and perceptions about quality of life. SUBJECTS/SETTINGS: Dietitians from across the United States who responded to a recruitment notice participated. Their work settings included diabetes referral centers, endocrinology clinics, primary care and community health clinics, hospitals, and a worksite clinic. They recruited patients from their setting for the study. Outcome data were available from dietitians providing care to 24 patients using the new practice guidelines and dietitians providing care to 30 patients using more traditional methods. STATISTICAL ANALYSIS: chi 2 Test, t test, and analysis of covariance. RESULTS: Dietitians in the practice guidelines group spent 63% more time with patients and were more likely to do an assessment and discuss results with patients than dietitians in the usual care group. Practice guidelines dietitians paid greater attention to glycemic control goals. Levels of HbA1c improved at 3 months in 21 (88%) of practice guidelines patients compared with 16 (53%) of usual care patients. Practice guidelines patients achieved greater reductions in HbA1c level than usual care patients (-1.00 vs -0.33). This difference was statistically significant and clinically meaningful. CONCLUSIONS/APPLICATIONS: Dietitians responded positively to practice guidelines for type 1 diabetes. Use of guidelines resulted in changes in dietitian practices and produced greater improvements in patient blood glucose outcomes at 3 months compared with usual care. Practice guidelines did not significantly influence patient satisfaction with care of perceived quality of life.
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Intellectual, psychological and functional outcomes were evaluated in a consecutive series of 20 Parkinsonian patients who had unilateral (UPVP) or simultaneous bilateral posteroventral pallidotomy (BPVP) using Image Fusion and Stereoplan (Radionics Inc., Boston, Mass., USA) with stimulation for lesion localization. Comprehensive baseline and 3-month postoperative neuropsychological and neurological assessment protocols were administered together with questionnaire measures of functional disability, quality of life and psychological symptomatology. Changes in patients' clinical presentation and scores on psychometric tests, questionnaires and observational rating scales were then examined. We observed no new neuropsychiatric sequelae directly related to pallidotomy. Cognitive sequelae were restricted to selective reductions in categorical verbal fluency following UPVP (P < 0.001) and BPVP (P < 0.01) and a reduction in phonemic verbal fluency following BPVP (P < 0.01); these changes were not reported subjectively. A fall in diadochokinetic rates (P < 0.01) and some subjective reports of a worsening in pre-existing dysarthria, hypophonia and hypersalivation/drooling following BPVP also suggested changes in speech motor apparatus; however, these changes did not have significant functional consequences. There was one case of more generalized cognitive impairment following BPVP. We also observed significant symptomatic improvement on neurological rating scales; following UPVP, Total Unified Parkinson's Disease Rating Scale (UPDRS) scores improved by 27% (P < 0.01) and following BPVP the improvement was 53% (P < 0.05). Patients' perceptions of reduced postoperative functional disability and improvements in 'quality of life' also achieved statistical significance on a number of both physical and psychosocial questionnaire subscales.
Laser blepharoplasty was introduced in 1984 by Sterling Baker and although there are few disadvantages, several advantages as compared to traditional blepharoplasty have been assessed. These advantages include an improved scar, a shorter operating time, and a more rapid recovery time in most patients. Methods include laser resurfacing of the periorbital area or full face with excision of the upper eyelid skin and fat, as well as excision of the lower eyelid fat through a transconjunctival incision alleviating the need for a lower eyelid scar. In some cases, an upper eyelid excision may not be necessary following resurfacing of this area. Excellent results have been achieved in over 150 cases with comparisons of scarring in scalpel versus laser incisions.
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