The increasing resistance of S. pneumoniae to antimicrobial agents is a cause for concern. Although a number of therapeutic strategies are possible, local patterns of resistance must be considered. It is essential to determine the susceptibility of individual strains to penicillin and other antimicrobial agents that could be used for therapy. Communication between the clinician and the laboratory is vital to determine the best therapeutic options. The recent recognition of cephalosporin-resistant strains emphasizes the need to determine susceptibility to cephalosporins. Clinical laboratories should be aware of the recently proposed changes in the definition of cephalosporin resistance, and clinicians need to be aware of how these changes affect the choice of antibiotic therapy. Until pneumococcal disease can be effectively prevented, we can expect resistant pneumococcal infections to continue to pose therapeutic difficulties.

The availability of sensitive thyrotropin assays allows effective biochemical monitoring of both replacement and suppressive therapy with thyroxine. Whatever target organ is examined, there is tissue thyrotoxicosis if the serum thyrotropin concentration is low, even if the serum triiodothyronine and thyroxine concentrations are normal. Although suppression of thyrotropin secretion is recommended in the treatment of patients with thyroid carcinoma, the aim of thyroxine-replacement therapy in patients with primary hypothyroidism should be to maintain the serum thyrotropin concentration in the normal range. The most convincing argument for the treatment of subclinical hypothyroidism is progression to overt hypothyroidism at a rate of 5 to 20 percent per year.

Sotalol is a novel antiarrhythmic agent combining beta-adrenergic-antagonist actions with the ability to increase cardiac repolarization and refractoriness. The drug's electrophysiologic and clinical profile is different from that of conventional beta-receptor antagonists. As compared with other antiarrhythmic agents, sotalol prevents recurrences of arrhythmia in a higher proportion of patients, particularly among those presenting with ventricular tachycardia and aborted sudden cardiac death. The net hemodynamic effect of sotalol is the result of a balance between the depressant effects due to beta-receptor blockade and an action that tends to increase contractility. Although initially marketed in the United States for treatment of life-threatening ventricular arrhythmias, sotalol also has demonstrated efficacy in many patients with supraventricular arrhythmias. As with all drugs that prolong the QT interval, the syndrome of torsade de pointes is a serious potential adverse effect.

It is uncertain whether patients with proximal deep-vein thrombosis should be treated with streptokinase followed by intravenous heparin or with intravenous heparin alone. Published reports indicate that streptokinase plus heparin increases the risk of bleeding, including central nervous system bleeding and death, but decreases the risk of postphlebitic syndrome. Previous recommendations regarding these treatments have not considered patients' preferences or the values they attach to the possible outcomes of therapy.

Although effective treatments for hyperthyroidism are available, none is perfect. Particularly with respect to Graves' disease, what is needed is a therapy directed at modulating the disease process itself rather than merely reducing the synthesis and secretion of thyroid hormones in the hope that the underlying Graves' disease will remit. Greater understanding of the pathogenesis of Graves' disease, resulting from cloning of the thyrotropin receptor and better knowledge of the interactions between these receptors or other thyroid antigens and the immune system, may lead to such treatment. Broad-spectrum immunosuppression, with all its side effects, is not the answer; more focused therapies to inhibit the immune response to specific thyroid antigens may represent the treatment of the future. Meanwhile, radioiodine therapy is the most effective and convenient method of achieving long-term control of hyperthyroidism, although at the cost of hypothyroidism in many patients.

The second-generation H1-antagonist drugs are supplanting their predecessors in the treatment of allergic rhinoconjunctivitis and chronic urticaria. Their use can be justified mainly on the basis of a more favorable risk-benefit ratio, because they are less toxic to the central nervous system. Future research into H1 antagonists should include additional dose-response studies in patients with allergic disorders, especially children and the elderly; objective studies of adverse effects; studies of topical mucosal application of H1 antagonists; and studies of H1-antagonist enantiomers and active metabolites. With the cloning of the gene encoding the H1 receptor and increased understanding of the precise structural requirements for H1-receptor activity, H1 antagonists with an even more favorable therapeutic index may be developed.

The establishment and maintenance of epithelial-cell polarity are prerequisites for normal epithelial-cell and organ function. Knowledge of the processes involved in cell polarity has provided insight into the mechanisms of cell dysfunction and the pathogenesis of several diseases. These insights should lead to the development of specific strategies aimed at preventing or minimizing the progression of these diseases.