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Predicting clinically significant drug interactions during drug development is a challenge for the pharmaceutical industry and regulatory agencies. Since the publication of the US Food and Drug Administration's (FDA's) first in vitro and in vivo drug interaction guidance documents in 1997 and 1999, researchers and clinicians have gained a better understanding of drug interactions. This knowledge has enabled the FDA and the industry to progress and begin to overcome these challenges. The FDA has continued its efforts to evaluate methodologies to study drug interactions and communicate recommendations regarding the conduct of drug interaction studies, particularly for CYP-based and transporter-based drug interactions, to the pharmaceutical industry. A drug interaction Web site was established to document the FDA's current understanding of drug interactions (http://www.fda.gov/cder/drug/drugInteractions/default.htm). This report provides an overview of the evolution of the drug interaction guidances, includes a synopsis of the steps taken by the FDA to revise the original drug interaction guidance documents, and summarizes and highlights updated sections in the current guidance document, Drug Interaction Studies-Study Design, Data Analysis, and Implications for Dosing and Labeling.

We who work with people with chronic and/or terminal illnesses are often confounded about what we ought to do and what we can do for those who suffer. This paper presents a case study of my work with Marion who began therapy after her presymptomatic testing for HD to address her depression and anxiety. The approach we took is a narrative one. The impact of illness on existing family stories is described followed by an examination of the premises of a narrative model. The case description demonstrates the collaborative nature of the therapy. Some thoughts on the role of the therapist in this model are offered.

The needs of families to reconstruct their relationships in response to the DNA testing for Huntington disease of one or more of their asymptomatic members are presented. Data were collected from family interviews with 18 families, and from their responses on a post interview questionnaire. Findings are that families need to (a) address "unfinished business" associated with the decision for testing; (b) bring family members, peripheral in the decision for testing, into the loop; (c) reorganize patterns of communication and roles altered by the testing and heal ruptures in family membership; and (d) revise family stories about illness to provide a meaning for HD and explain the test results in a way that leaves them with a sense of mastery. Findings suggest that families should be more involved in the initial decision for testing of a member and that protocols should be established to provide help for their ongoing adjustment.

Treatment of rectal carcinomas with endocavitary irradiation is now an established method in the United States and is an important advance in the curative management of patients with selected cancers of the rectum that should be available to all such patients. Excellent palliation can also be achieved in many cases with advanced local disease. The total experience at Highland Hospital, Rochester, New York, is over 70 cases. Now that there are more centers using this method of treatment, an awareness of some of the problems and pitfalls encountered at Highland Hospital becomes relevant.

Direct contact irradiation may be used in the curative treatment of patients with carefully selected early rectal lesions. With earlier diagnosis, a large number of patients may present with suitable lesions. The treatments last three minutes and are administered every two weeks to a total dose of 9,000 rad to 12,500 rad. The patients require no general anesthesia or hospitalization and may continue working during this treatment. There appears to be no risk of morbidity or mortality. The rectum is preserved. Most beneficial of all to the patient, a colostomy is avoided, although later surgery is not precluded for local failures. It has been found that recurrence, should it occur, appears within the 18 months immediately following treatment. Good palliation can be achieved in some cases for patients with metastatic disease, for their local symptoms. We believe that the endocavity method of irradiation contributes an important advance in the management of patients with cancer of the rectum and feel it should be available universally.