Magnetic resonance imaging (MRI) has many bona fide applications in the head and neck region. The major strengths of its current conventional use include excellent soft-tissue contrast, multiplanar capabilities, noninvasiveness, and lack of ionizing radiation. Newer advances, including gradient-echo techniques, three-dimensional fourier transformation, paramagnetic contrast, and more efficient receiver coils, will improve images and expand indications for MRI. The technology, however, remains relatively expensive, and the additional information compared with that of other techniques might not always justify the difference in cost. Moreover, MRI's insensitivity to calcifications, lack of depiction of fine bone detail, and, in some areas, degradation caused by motion and other artifacts make computed tomography and other noninvasive studies more appropriate as a primary imaging tool in many circumstances. Continued careful clinical research should clarify the relative role of MRI and other imaging tools during the next several years.

The splicing of long transcripts of RNA (copied from DNA in the cell nucleus) into smaller, specific mRNA (ready for export to the protein-producing machinery in the cytoplasm) is an important event in the regulation of gene expression in eukaryotic cells. The splicing reaction occurs as a late step in the nuclear pathway for synthesis of mRNAs. This pathway commences with initiation of transcription by RNA polymerase II and probably involves an integrated series of steps each dependent on previous events. Splicing of precursors to mRNAs involves the formation of a spliceosome complex containing the 5' and 3' splice sites. This complex contains the evolutionarily highly conserved small nuclear RNAs (snRNAs) U2, U4, U5, and U6. The most abundant snRNA, U1, is required to form the spliceosome and may be a part of the spliceosome. Analogues of these snRNAs have been identified in yeast. Assembly of the spliceosome probably involves the binding of a multi-snRNA complex containing U4, U5, and U6 snRNAs. Several observations suggest that the association of snRNAs in such complexes is quite dynamic. It is argued that the snRNAs in the spliceosome form a catalytic RNA structure that is responsible for the cleavage and ligation steps during splicing.

Clinical success in rehabilitation of heroin addicts with maintenance treatment requires stability of the blood level in a pharmacologically effective range (optimally, 150 to 600 ng/mL)-a phenomenon that emphasizes the central importance of narcotic receptor occupation. It is postulated that the high rate of relapse of addicts after detoxification from heroin use is due to persistent derangement of the endogenous ligand-narcotic receptor system and that methadone in an adequate daily dose compensates for this defect. Some patients with long histories of heroin use and subsequent rehabilitation on a maintenance program do well when the treatment is terminated. The majority, unfortunately, experience a return of symptoms after maintenance is stopped. The treatment, therefore, is corrective but not curative for severely addicted persons. A major challenge for future research is to identify the specific defect in receptor function and to repair it. Meanwhile, methadone maintenance provides a safe and effective way to normalize the function of otherwise intractable narcotic addicts.

Certain RNA molecules can mediate their own cleavage or splicing or act as enzymes to promote reactions on substrate RNA molecules. Thus, RNA is not restricted to being a passive carrier of genetic information but can have an active role in directing cellular biochemistry. These findings suggest the possibility that other cellular RNAs, including the RNA components of small nuclear ribonucleoproteins, of the ribosome, and of various ribonucleoprotein enzymes, are catalysts. RNA enzymes (ribozymes) can be used as sequence-specific RNA cleavage agents in vitro, providing useful tools for biochemical studies of RNA. On a more speculative note, ribozymes directed against viral RNAs have the potential of serving as therapeutic agents. Finally, some infectious agents, including hepatitis delta virus and perhaps poliovirus and rhinoviruses, are themselves ribozymes, providing potential targets for pharmaceuticals.

Mitral regurgitation is a valvular heart lesion that is difficult to diagnose accurately; thus, it is difficult to determine the appropriate timing for surgical correction. With increasing use of reparative techniques, including local resection of valve pathology and placement of an annuloplasty ring, and the realization that chronic atrial fibrillation leads to decreased long-term survival, the timing of surgery has changed. In addition, serial noninvasive studies have indicated that despite the absence of symptoms, patients may progress to a myopathic condition if the regurgitation progresses over a long period and surgery is not performed when signs of left ventricular dysfunction are evident. Preservation of the papillary muscle is also extremely important for late postoperative function in patients with mitral regurgitation, and reparative surgery that preserves both anterior and posterior papillary muscle complexes and continuity with the anulus appears to satisfy this assumption. Worldwide experience is reviewed and I present conclusions related to the appropriate indications for mitral valve repair or replacement in patients with mitral regurgitation.

Positron emission tomography permits examination of the chemistry of the brain in living human beings. Until recently, positron emission tomography had been considered a research tool, but it is rapidly moving into clinical practice. This report describes the uses and applications of positron emission tomography in examinations of patients with strokes, epilepsy, malignancies, dementias, and schizophrenia and in basic studies of synaptic neurotransmission.

Concern with weight control should begin sufficiently early in life to reduce the risk of developing obesity. The complex etiology of obesity is, in part, responsible for the difficulty physicians encounter in treating this condition. Prevention is the "treatment" of choice. Early identification of individuals genetically at risk can be helpful in targeting those most likely to gain excess weight. Numerous dietary regimens have been devised in an attempt to achieve progressive weight loss in obese individuals. Since the ultimate goal of a weight-reduction program is to lose weight and maintain the loss, a nutritionally balanced, low-energy diet that is applicable to the patient's life-style is most appropriate. Increasing energy expenditure through physical activity, in addition to decreasing energy intake, generally improves results in the management of obesity. Major changes in eating and exercise behaviors are necessary to ensure long-term weight control. Diet, exercise, and behavior modification are interdependent and mutually supportive. A comprehensive weight-reduction program that incorporates all three components is more likely to lead to long-term weight control.

The effects of prophylactic lidocaine hydrochloride on early ventricular fibrillation and death in patients with suspected acute myocardial infarction were investigated in an overview of 14 randomized trials. During follow-up intervals of one to four hours in the trials of intramuscular lidocaine infusion (6961 patients) and 24 to 48 hours in the trials of intravenous lidocaine injection (2194 patients), a total of 103 cases of ventricular fibrillation and 137 deaths were recorded. Overall, allocation to lidocaine was associated with a reduction in the odds of ventricular fibrillation of about one third, with a 95% confidence interval that ranged from a 3% to a 56% reduction. There was no evidence of any beneficial effect on early mortality; indeed, the odds of early death were about one third greater among patients allocated lidocaine, though this difference was not statistically significant (95% confidence interval, 2% reduction to 95% increase). Because of the small numbers of reported events, the short follow-up periods, and the unavailability of data for some specific causes of death, even an overview of all the trial results does not provide good evidence as to whether prophylactic lidocaine is likely to be helpful or harmful. To answer this question reliably, future trials will need to involve large numbers of patients and prolonged follow-up.

Before assessment can begin we must decide how quality is to be defined and that depends on whether one assesses only the performance of practitioners or also the contributions of patients and of the health care system; on how broadly health and responsibility for health are defined; on whether the maximally effective or optimally effective care is sought; and on whether individual or social preferences define the optimum. We also need detailed information about the causal linkages among the structural attributes of the settings in which care occurs, the processes of care, and the outcomes of care. Specifying the components or outcomes of care to be sampled, formulating the appropriate criteria and standards, and obtaining the necessary information are the steps that follow. Though we know much about assessing quality, much remains to be known.

This case study of the public policy implications of introducing a new technology in radiology, namely, low-osmolar contrast media (LOCM), raises the issues of whether and how to place appropriate limits on new technologies. Although these contrast media represent small episodic costs, they may add up to an aggregate expenditure of nearly $1 billion per year if used for all contrast injections. As a result, this technology raises a number of important medical, economic, legal, and public policy questions. Our cost-effectiveness analysis and an analysis of the medical evidence suggest that LOCM should be limited to high-risk patients. We discuss in this article how the legal system might respond to such limitations, and we consider various public policy options for adopting restrictions on use. We conclude that the medical profession should take the lead in developing protocols for appropriate assessment, reimbursement, and use of LOCM.