Fluoxetine was developed as an antidepressant drug. It is more effective than placebo, but a dose-effect relation has not been established. Fluoxetine is almost as effective as tricyclic antidepressant drugs, but the available studies do not allow accurate comparisons. Fluoxetine may be less effective than tricyclic antidepressant drugs for the treatment of inpatients with severe melancholic depression, and it should not be the first choice of a drug for them. Fluoxetine may be most appropriate for patients with moderate depression who can be treated as outpatients. If there is little improvement after treatment for four to six weeks, an alternative treatment should be offered. Fluoxetine does not have the anticholinergic, hypotensive, and sedative effects of tricyclic antidepressant drugs and has no particular cardiovascular effects; overdoses do not cause serious toxic effects. Nausea, anorexia, insomnia, and nervousness--the most common side effects--may be controlled with a careful adjustment to the dose. Clinically important drug interactions may occur with monoamine oxidase inhibitors, tricyclic antidepressant drugs, and other drugs. The published data on the antidepressant effect of fluoxetine do not fully explain its popularity. One may speculate that fluoxetine has psychobiologic effects not strictly related to the biology of depression and that it acts primarily as a mood- or affect-modulating agent.

Progress has been made in understanding the molecular basis of a number of clinical manifestations of thyroid disease, yet many questions remain. Why are there two thyroid hormone-receptor genes? Is the function of each of the two receptors indeed unique? How T3 receptors interact with other nuclear proteins and DNA-binding sites and how these interactions are influenced by T3 is incompletely understood. The developmental regulatory role of T3 receptor alpha 1 and its non-T3-binding alpha 2 variant needs to be defined. Most T3-regulated processes, especially those related to metabolism, muscle contraction, and brain development, function in concert with a number of other regulatory factors. The therapeutic applications of knowledge gained about the basic mechanisms of thyroid hormone action should ultimately extend beyond thyroid disease to processes regulated or influenced by T3; these include cardiac function, lipid metabolism, pituitary hormone secretion, and neural development.

Limb- or life-threatening complications in patients with diabetes can be prevented with an integrated, multidisciplinary approach. Most patients seen in clinical practice are in the early stages of the disease process. Glycemic control retards the progression of neuropathy, which is the most important risk factor for ulceration. Early detection of the loss of protective sensation and implementation of strategies to prevent ulceration will reduce the rates of limb-threatening complications. Clinicians should routinely examine the feet of diabetic patients. Education in foot care, proper footwear, and close follow-up are required to prevent or promptly detect neuropathic injury. If ulceration occurs, removal of pressure from the site of the ulcer and careful management of the wound will allow healing in most cases. The failure to heal despite these measures should prompt a search for associated arterial insufficiency. If infection is present, appropriate antimicrobial therapy combined with immediate surgical intervention, including revascularization when necessary, will increase the chances of saving the limb. With this comprehensive approach, it is possible to achieve the goal of a 40 percent decrease in amputation rates among diabetic patients by the year 2000.