We identified 24 modern studies of childhood exposures to lead in relation to IQ. From this population, 12 that employed multiple regression analysis with IQ as the dependent variable and lead as the main effect and that controlled for nonlead covariates were selected for a quantitative, integrated review or meta-analysis. The studies were grouped according to type of tissue analyzed for lead. There were 7 blood and 5 tooth lead studies. Within each group, we obtained joint P values by two different methods and average effect sizes as measured by the partial correlation coefficients. We also investigated the sensitivity of the results to any single study. The sample sizes ranged from 75 to 724. The sign of the regression coefficient for lead was negative in 11 of 12 studies. The negative partial r's for lead ranged from -.27 to -.003. The power to find an effect was limited, below 0.6 in 7 of 12 studies. The joint P values for the blood lead studies were less than .0001 for both methods of analysis (95% confidence interval for group partial r, -.15 +/- .05), while for the tooth lead studies they were .0005 and .004, respectively (95% confidence interval for group partial r, -.08 +/- .05). The hypothesis that lead impairs children's IQ at low dose is strongly supported by this quantitative review. The effect is robust to the impact of any single study.

Single-photon emission computed tomography has received increasing attention as radiopharmaceuticals that reflect perfusion, metabolism, and receptor and cellular function have become widely available. Perfusion single-photon emission computed tomography of the brain provides functional information useful for the diagnosis and management of stroke, dementia, and epilepsy. Single-photon emission computed tomography has been applied to myocardial, skeletal, hepatic, and tumor scintigraphy, resulting in increased diagnostic accuracy over planar imaging because background activity and overlapping tissues interfere far less with activity from the target structure when tomographic techniques are used. Single-photon emission computed tomography is substantially less expensive and far more accessible than positron emission tomography and will become an increasingly attractive alternative for transferring the positron emission tomography technology to routine clinical use. In addition, single-photon emission computed tomography has unique applications that are increasingly finding their way into the routine practice of clinical nuclear medicine.

Persons with overwhelming damage to the cerebral hemispheres commonly pass into a chronic state of unconsciousness (ie, loss of self-awareness) called the vegetative state. When such cognitive loss lasts for more than a few weeks, the condition has been termed a persistent vegetative state, because the body retains the functions necessary to sustain vegetative functions. Recovery from the vegetative state does occur, but many persons in persistent vegetative states live for months or years if provided with nutritional and other supportive measures. The withdrawal of life support from these persons with loss of higher brain function is a controversial issue, as highlighted by public debates and judicial decisions. This article provides criteria for the diagnosis of permanent unconsciousness and reviews the available data that support the reliability of these criteria. Significant legal decisions have been made with regard to withdrawal of life support to patients in persistent vegetative states, and the trends in this area are discussed.

This is the second of two articles reviewing the recommendations of the US Preventive Services Task Force for interventions by physicians, nurses, and other clinicians to prevent the major oral diseases and conditions. Physicians and other health professionals should be aware of their many opportunities to assist in preventive oral health care and should take appropriate action in collaboration with the patient's dentist.

To evaluate the comparative efficacy and cost-effectiveness of various antihypertensive medications in persons aged 35 through 64 years with diastolic blood pressure of 95 mm Hg or greater and no known coronary heart disease, we used the Coronary Heart Disease Policy Model, which is a computer simulation of overall mortality as well as the mortality, morbidity, and cost of coronary heart disease in the US population. From the pooled literature, we estimated the antihypertensive and total cholesterol effects of various antihypertensive regimens. For 20 years of simulated therapy from 1990 through 2010, the cost per year of life saved was projected to be $10,900 for propranolol hydrochloride; $16,400 for hydrochlorothiazide; $31,600 for nifedipine; $61,900 for prazosin hydrochloride; and $72,100 for captopril. Doubling the cholesterol effects of the agents under study did not significantly change their effectiveness because, in general, lowering diastolic blood pressure by 1 mm Hg was equivalent to lowering the cholesterol level by 6%. Although any projection requires multiple estimates, each of which may be open to debate, propranolol appears to be the preferred initial option under most of a variety of alternative assumptions.

Over the past decade, numerous impressive advances have been made using nonpharmacologic methods for control of cardiac arrhythmias. These methods include surgical or catheter ablation of abnormal foci. Current techniques involve catheter ablation of the atrioventricular junction to control supraventricular arrhythmias. In addition, surgical techniques have proved to be remarkably safe and effective for treatment of patients with accessory pathways and those with atrioventricular nodal reentrant tachycardia. Patients with drug-refractory ventricular tachycardia may benefit from surgical resection of the ventricular tachycardia focus. The use of these interventional methodologies has radically altered the approach to management of patients with drug-refractory cardiac arrhythmias.

Primary care physicians and nurses have numerous opportunities to assist in the prevention of dental caries, periodontal diseases, malocclusion, trauma to the mouth and teeth, and oral cancer. This is the first of two articles that provide background for the US Preventive Services Task Force recommendations for interventions by physicians, nurses, and other clinicians to prevent these oral diseases and conditions. Physicians and other health professionals are urged to be aware of these opportunities and to take appropriate action in collaboration with the patient's dentist.

Widespread illicit anabolic steroid use has recently been reported. A review of available evidence suggests that elevations of serum levels of steroid hormones, including anabolic steroids, have profound psychological effects. Long-term, high-dose anabolic steroid use may lead to a preoccupation with drug use, difficulty stopping despite psychological side effects, and drug craving. Reductions in serum levels of steroid hormones appear to result in acute hyperadrenergic withdrawal symptoms that respond to steroid replacement or to agents that also ameliorate withdrawal symptoms in alcohol and opioid dependence. A delayed depression syndrome when serum steroid levels drop precipitously has been reported that appears similar to that observed in withdrawing cocaine-dependent individuals. We conclude that a proportion of anabolic steroid abusers may develop a previously unrecognized sex steroid hormone-dependence disorder and that treatment should be based on research into steroid effects on opioid and aminergic neurotransmission systems and relapse prevention.

Many diagnostic studies and procedures are available for the evaluation of jaundice. By judicious selection of those that are most likely to lead to a prompt diagnosis and by weighing their relative risk and efficacy, the physician can better ensure the comfort and safety of the patient and the cost-effectiveness of medical care. A guideline is presented that recommends an approach to the evaluation of jaundice. It is based on a critical review of the literature and its application to clinical practice.

Magnetic resonance imaging provides superior contrast, resolution, and multiplanar imaging capability, allowing excellent definition of soft-tissue and bone marrow abnormalities. For these reasons, magnetic resonance imaging has become a major diagnostic imaging method for the evaluation of many musculoskeletal disorders. The applications of magnetic resonance imaging for musculoskeletal diagnosis are summarized and examples of common clinical situations are given. General guidelines are suggested for the musculoskeletal applications of magnetic resonance imaging.

The black community contends daily with the phenomena of suicide and homicide. However, it is the killing of black males that constitutes the heaviest burden for the group. Black suicide rates, on the other hand, continue to be lower than white suicide rates. Nevertheless, it is the black male group between the ages of 25 and 34 years that bears the brunt of both suicide and homicide. This article reviews the major theories advanced to explain the existence of these serious public health problems in the black community, suggests ways of attacking these problems, and also delineates significant areas for future research.

The addition of Doppler principles to two-dimensional echocardiography has revolutionized the noninvasive evaluation of valvular heart disease. Doppler techniques allow precise measurements of blood flow velocity at different locations in the heart and great vessels, so that many aspects of hemodynamics can now be measured noninvasively. These techniques are particularly useful for the quantitative assessment of valvular stenosis; both valve areas and transvalvular gradients may be determined. Doppler echocardiography (particularly with color flow mapping) is also useful for the qualitative assessment of valvular regurgitation. By understanding the uses and limitations of Doppler echocardiography, physicians may now confidently follow up patients with mild or moderate valvular disease with serial noninvasive studies, avoiding the risks of cardiac catheterization in many patients.

Inositol lipids play a major role in cell signaling by functioning as precursors of second messengers. Of the three common inositol-containing lipids found in the plasma membrane, phosphatidylinositol (4,5)-bisphosphate is hydrolyzed to give diacylglycerol, which stimulates protein kinase C, and inositol 1,4,5-trisphosphate, which diffuses into the cell to release intracellular calcium. Inositol 1,4,5-trisphosphate is metabolized to give free inositol by two separate pathways. Lithium inhibits the final dephosphorylation step of both pathways, thus reducing the supply of the free inositol required to maintain the lipid precursors used for signaling. An inositol-depletion hypothesis may explain both the teratogenic effects of lithium and its therapeutic action in controlling manic-depressive illness. One of the metabolic pathways generates inositol tetrakisphosphate, which may also play a messenger role by expanding the size of the inositol 1,4,5-trisphosphate-sensitive pool of calcium. Calcium imaging of single cells has begun to reveal that this inositol 1,4,5-trisphosphate/calcium signaling system is organized in complex patterns, which include localization of calcium signals to discrete regions of cells and the generation of both calcium waves and calcium oscillations.

Protein kinase C, an enzyme that is activated by diacylglycerol resulting from the receptor-mediated hydrolysis of inositol phospholipids, relays information of a variety of extracellular signals across the cell membrane to regulate many intracellular processes. Since this enzyme also serves as a major receptor for phorbol esters, a class of tumor promoters, it has attracted great attention from biologists interested in the mechanism of signal transduction and carcinogenesis. Recent analysis has revealed that protein kinase C is a large family of proteins, with the multiple subspecies that possess subtle individual enzymological characteristics. Biochemical and immunohistochemical studies indicate that the protein kinase C subspecies may be differently distributed in particular cell types and with limited intracellular locations. Presumably, each member of the family plays discrete roles in the processing of various physiological and pathological responses to external signals, such as in the modulation of membrane functions and the activation of gene transcription.

The steroid RU-486 (mifepristone) is an antiprogesterone that works at the receptor level. It can interrupt pregnancy very early on (contragestion), mostly by interfering with the process of implantation and decidua function. It also may facilitate surgical evacuation of the uterus and certain difficult deliveries. It impedes ovulation when taken during the follicular phase. Also, RU-486 is the first antiglucocorticosteroid available for clinical use. It deserves further studies to assess its wide range of therapeutic potential.

The first example of an enzyme that undergoes phosphorylation and dephosphorylation was phosphorylase, which catalyzes the initial step in the breakdown of tissue glycogen, a process that occurs when cells are stimulated by certain hormones. The phosphorylation reaction that activates phosphorylase is catalyzed by an enzyme designated "phosphorylase kinase," whereas the dephosphorylation reaction is catalyzed by an enzyme called "phosphorylase phosphatase." Phosphorylase kinase, like phosphorylase itself, is regulated by phosphorylation-dephosphorylation. In this instance the enzyme is phosphorylated and activated by a protein kinase that is the intracellular target of adenosine 3',5'-cyclic phosphate, the second messenger of hormone action that was discovered by the late Earl Sutherland. Knowledge of these steps led to the establishment of the glycogenolytic cascade in which adenosine 3',5'-cyclic phosphate, formed as a result of hormone action, first activates the adenosine 3',5'-cyclic phosphate-dependent protein kinase, which in turn activates phosphorylase kinase, which then converts inactive phosphorylase to its active form. This is followed by the breakdown of glycogen.

The cellular plasma membrane contains highly specialized systems for integration, amplification, and transduction of information that presents itself in the form of extracellular hormones, neurotransmitters, other regulatory molecules, and physical stimuli. A major mechanism for processing this information involves the sequential interactions of three membrane-bound proteins. Receptors for many extracellular regulators bind these molecules and interact with one or more of a family of guanine nucleotide-binding regulatory proteins (G proteins). Conformational alteration of the G protein permits exchange of tightly bound guanosine diphosphate (an inactive ligand) for guanosine triphosphate (the activating ligand). The guanosine triphosphate-bound G protein in turn interacts with intracellular effector molecules, such as adenylyl cyclase, and controls their functions.