Synthesis and Properties of Haptens for the Development of Radioimmunoassays for Thioridazine,Mesoridazine, and Sulforidazine

For the separate development of radioimmunoassay procedures for thioridazine and its two major active metabolites, mesoridazine and sulforidazine, three haptens, respectively, 2-methylthio-, 2-methylsulfinyl-, and 2-methylsulfonyl-substituted 10-[2-[l-(2-carboxyethyl)-2-piperidinyl]ethyl]-10H-phenothiazine, were synthesized and characterized. Thioridazine hapten was coupled to bovine serum albumin, whereas the haptens for mesoridazine and sulforidazine were coupled to porcine thyroglobulin. The number of hapten residues per mole of carrier protein was determined in each case by an ultraviolet spectrophotometric method. Polyclonal antibodies to each hapten–protein conjugate were obtained in rabbits, and titers of the antisera were checked by evaluating their binding characteristics to the appropriate tritiated analyte. A hapten for the ring sulfoxide metabolite of thioridazine was also synthesized.     

Treatment of mandibular condylar process fractures: biological considerations.

The topic of condylar injury in adults has generated more discussion and controversy than any other in the field of maxillofacial trauma. It is an important subject because such injuries are common and complications of trauma to the temporomandibular joint (TMJ) are far-reaching in their effects. Why are there so many different methods to treat this injury? How can seemingly disparate treatment options all produce satisfactory outcomes in the majority of patients? The reason lies with the biological adaptations that occur within the masticatory system that are poorly understood, not readily quantifiable, and variable from one person to the next. This discussion presents our current understanding of the adaptations that must occur to provide the patient with a satisfactory outcome. The adaptations for patients treated open are different than for those treated closed. However, it is when these adaptations fail to occur that unsatisfactory outcomes occur, regardless of how they were treated.     

Phase III study of interferon alfa-NL as adjuvant treatment for resectable renal cell carcinoma: an Eastern Cooperative Oncology Group/Intergroup trial.

PURPOSE: To evaluate the role of adjuvant interferon alfa after complete resection of locally extensive renal cell carcinoma. PATIENTS AND METHODS: A total of 283 eligible patients with pT3-4a and/or node-positive disease were randomly assigned after radical nephrectomy and lymphadenectomy to observation or to interferon alfa-NL (Wellferon, Burroughs-Wellcome, Research Park, NC) given daily for 5 days every 3 weeks for up to 12 cycles. Patients were stratified on the basis of pathologic stage. Patients remained on treatment until documented recurrence, excessive toxicity, or patient/physician preference deemed removal appropriate. RESULTS: At median follow-up of 10.4 years, median survival was 7.4 years in the observation arm and 5.1 year in the treatment arm (log-rank P =.09). Median recurrence-free survival was 3.0 years in the observation arm and 2.2 years in the interferon arm (P =.33). Performance status (P =.003), nodal status (N2 v N0, P <.0001), and tumor stage (P =.0002) were significant prognostic factors in multivariate analysis. A proportional hazards model examining the effects of treatment arm and time to recurrence on survival after recurrence among patients who recurred found that random assignment to interferon treatment (P =.009) and shorter time to recurrence (P <.0001) were independent predictors of shorter survival after recurrence. Although no lethal toxicities were observed, severe (grade 4) toxicities including neutropenia, myalgia, fatigue, depression, and other neurologic toxicities occurred in 11.4% of those randomly assigned to interferon treatment. CONCLUSION: Adjuvant treatment with interferon did not contribute to survival or relapse-free survival in this group of patients.     

Significant efficiency findings while controlling for the frequent confounders of CAI research in the PlanAlyzer project's computer-based,self-paced,case-based programs in anemia and chest pain diagnosis

Richard E. Clark in his widely published comprehensive studies and meta-analyses of the literature on computer assisted instruction (CAI) has decried the lack of carefully controlled research, challenging almost every study which shows the computer-based intervention to result in significant post-test proficiency gains over a non-computer-based intervention. We report on a randomized study in a medical school setting where the usual confounders found by Clark to plague most research, were carefully controlled. PlanAlyzer is a microcomputer-based, self-paced, case-based, event-driven system for medical education which was developed and used in carefully controlled trials in a second year medical school curriculum to test the hypothesis that students with access to the interactive programs could integrate their didactic knowledge more effectively and/or efficiently than with access only to traditional textual “nonintelligent” materials. PlanAlyzer presents cases, elicits and critiques a student's approach to the diagnosis of two common medical disorders: anemias and chest pain. PlanAlyzer uses text, hypertext, images and critiquing theory. Students were randomized, one half becoming the experimental group who received the interactive PlanAlyzer cases in anemia, the other half becoming the controls who received the exact same content material in a text format. Later in each year there was a crossover, the controls becoming the experimentals for a similar intervention with the cardiology PlanAlyzer cases. Preliminary results at the end of the first two full trials shows that the programs have achieved most of the proposed instructional objectives, plus some significant efficiency and economy gains. 96 faculty hours of classroom time were saved by using PlanAlyzer in their place, while maintaining high student achievement. In terms of student proficiency and efficiency, the 328 students in the trials over two years were able to accomplish the project's instructional objectives, and the experimentals accomplished this in 43% less time than the controls, achieving the same level of mastery. However, in spite of these significant efficiency findings, there have been no significant proficiency differences (as measured by current factual and higher order multiple choice post-tests) between the experimental and control groups. Very careful controls were used to avoid what Clark has found to be the most common confounders of CAI research. Accordingly, this research proved Clark's rival hypothesis, that the computer, in itself, does not appear to contribute to proficiency gains, at least as measured by our limited post-testing. Clark's position is that the computer is primarily a vehicle—as is either a pill or a hypodermic needle for delivering a drug. The hypodermic needle can deliver the drug more efficiently than can the pill, (as can the computer deliver the subject matter content more efficiently, as our research indicates), but the same content is delivered. At the same time, we proved our own hypothesis, as far as efficiency gains resulting from the computer are concerned. However, going beyond Clark's research, we may be teaching processes both more effectively and efficiently with the computer (experience in problem-solving or clinical reasoning and pattern recognition) which our current post-tests do not adequately measure. Our on-going research suggests additional inquiry in several areas: better evaluation instruments to measure the clinical reasoning skills PlanAlyzer was designed to teach; the addition of more advanced cases to determine if this might transform efficiency gains of the computer group into proficiency gains; the addition of enhanced graphic decision support tools and other pedagogical enhancements including cognitive feedback to strengthen PlanAlyzer's power to teach complex concepts of medical decision-making.