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The impact of medical care on the quality and length of life of the population has been poorly documented. The rapid growth of evidence of efficacy of therapy for individual medical conditions now offers the opportunity to create an inventory of benefits. A method for creating such an inventory is described, as is its application to a selection of condition-treatment pairs, chosen for their high incidence of prevalence, their serious outcomes, and the demonstrated efficacy of their treatment. An aggregate effect of medical care on life expectancy is found to be roughly five years during this century, with a further potential of two years. Although there is no overall index of quality of life analogous to life expectancy, our inventory demonstrates the enormous burden of pain, suffering, and dysfunction that afflicts the population for which medical care can provide a large measure of relief.

This introduction and the three essays that follow examine ambulatory cardiac monitoring for specific clinical indications. They also examine the ways in which evidence from the literature may be synthesized through the framework of decision analysis to guide its appropriate use and identify areas in which more research is needed. The essays discuss ambulatory cardiac monitoring for evaluation of syncope in the elderly; detection of silent ischemia after a myocardial infarction; and selection of antiarrhythmic drugs for malignant ventricular arrhythmias.

Given a group of individuals presenting with syncope, the use of the standard diagnostic maneuvers will yield a diagnosis for approximately half. Promising new diagnostic tests offer the prospect of more efficient diagnostic pathways and treatments and demonstrate the need for better clinical trials before they are adopted.

Three postoperative patients with oliguirc renal failure and hypochloremic metabolic alkalosis were treated with hemodialysis using a specailly prepared high-chloride, low-acetate dialysate. This mode of therapy corrected the metabolic abnormalities and was significantly more effective than treatment with commercially available high-acetate dialysate at increasing the serum chloride and hydrogen ion concentration. Furthermore, hemodialysis with high-chloride, low-acetate dialysate corrected the clinical sequelae of hypoventilation, cardiac arrhythmia, and neuromuscular irritability associated with metabolic alkalosis while treating uremia simultaneously.

The driving force for active transport of Na+ in the isolated toad bladder, ENa, was measured as the reciprocal slope of the change in conductance with change in short-circuit current after stimulation with antidiuretic hormone. The base-line short-circuit current was altered by change in ambient Na+ concentration or addition of amiloride, maneuvers which alter availability of Na+ at the site of active transport. In the absence of a chemical gradient for Na+ across the bladder, ENa was found to be inversely related to the rate of Na+ transport, a finding incompatible with the simple electrical analogue that has been proposed for the system. The results provide additional support for the view that ENa measured in this way has both energetic and kinetic components.

Evaluation of the efficacy of a medical intervention requires valid measurements of both its benefits and risks as compared to those of alternative forms of management. The requisite measurements are more difficult to make than this simple description suggests, and the accumulation of information is further inhibited by certain characteristics of our pattern of health care. These features include, for example, discontinuous care by a variety of unrelated providers, inadequate records, the autonomy of physicians as decision-makers, financial disincentives, ambiguities in what we mean by "experimental" and "accepted" forms of therapy, and failure to see continuing evaluation as a necessary component of the cost of providing good medical care. Although no single change will solve all the problems of evaluation, several offer promise of improving our ability to choose from among medical interventions those most likely to be useful.

The mechanism responsible for active sodium transport in the urinary bladder of the toad appears to be located at the serosal boundary of the epithelial cell layer of the bladder. Studies of the potential step observed at the serosal boundary in the open-circuited state were undertaken in an attempt to define the factors responsible for its production. Glass micropipettes were used to measure the serosal potential step in bladders exposed on the serosal side to solutions of high potassium or of high potassium and low chloride concentration. Observed potentials exceed the maximum values which would have been expected if the serosal potential step were a potassium or chloride diffusion potential. Measurements of net cation flux exclude the possibility of a diffusion potential at this border due to the passive movement of any anionic species. The observed independence of transbladder potential and short-circuit current from the pH of the serosal medium over a wide range of pH makes it unlikely that the observed serosal potential step is a hydrogen ion diffusion potential. We conclude that the active sodium transport mechanism in toad bladder is "electrogenic."

Studies have been made on the isolated urinary bladder of the toad, Bufo marinus, in an attempt to evaluate gradients of chemical activity across the mucosal surfaces of the epithelial cells which would serve to maintain a net movement of sodium from the mucosal medium into the cells. The likelihood of such chemical gradients has been established by the demonstration of lower contents of sodium within the tissue, expressed as microequivalents per gram of tissue water, than of concentrations of sodium in the mucosal medium at all levels of the latter examined. The transepithelial transport of sodium and the sodium content of the tissue were found to increase rapidly with rise in concentration of sodium in the mucosal medium up to values of 30 to 60 meq per liter. Further increase in concentration of the medium above this value failed to induce further stimulation of sodium transport or increase in the sodium content of the tissue. Vasopressin increased the rate of transport of sodium at every concentration of sodium in the mucosal medium without altering this relationship. Although entry of sodium across the mucosal surface of the epithelial cells may be passive it is not by free diffusion but involves some considerable interaction with the mucosal surface of the bladder and constitutes the major determinant of the rate of transepithelial transport of sodium. Vasopressin acts to enhance this initial step in the transport of sodium.

Vasopressin increases the net transport of sodium across the isolated urinary bladder of the toad by increasing the mobility of sodium ion within the tissue. This change is reflected in a decreased DC resistance of the bladder; identification of the permeability barrier which is affected localizes the site of action of vasopressin on sodium transport. Cells of the epithelial layer were impaled from the mucosal side with glass micropipettes while current pulses were passed through the bladder. The resulting voltage deflections across the bladder and between the micropipette and mucosal reference solution were proportional to the resistance across the entire bladder and across the mucosal or apical permeability barrier, respectively. The position of the exploring micropipette was not changed and vasopressin was added to the serosal medium. In 10 successful impalements, the apical permeability barrier contributed 54% of the initial total transbladder resistance, but 98% of the total resistance change following vasopressin occurred at this site. This finding provides direct evidence that vasopressin acts to increase ionic mobility selectively across the apical permeability barrier of the transporting cells of the toad bladder.

The relationship between hydrogen ion secretion and the transport of other electrloytes was examined in the isolated urinary bladder of the water turtle. Symmetrical solutions which were free from exogenous carbon dioxide and bicarbonate bathed the two surfaces of the preparation, and the spontaneous electrical potential of the bladder was nullified by a voltage clamp. Active transport of sodium from mucosal to serosal medium was confirmed by simultaneous bidirectional flux measurements and found to be slightly, but not significantly, greater than the short-circuit current. In the absence of sodium in the bathing solutions, the normal potential difference across the bladder reversed and the current required to nullify this reversed potential difference had the same magnitude as the simultaneously measured rate of hydrogen ion secretion. The results indicate that, under these experimental conditions, the bladder transports sodium and hydrogen ion actively, but that chloride movement does not contribute to the short-circuit current. The rate of secretion of hydrogen ion was not affected by replacement of the sodium in the bathing media by cesium, or by inhibition of sodium transport by dinitrophenol. Acidification continued when chloride in the solutions was replaced by sulfate, or when potassium or calcium was removed from the solution bathing the mucosal surface. Secretion of hydrogen ion by the turtle bladder is not dependent on the simultaneous transport of other electrolytes across the bladder.

The electrical potential profile of the isolated toad bladder was examined in the spontaneously active, chronically short-circuited, and intermittently short-circuited states by means of glass micropipettes. The position of the micropipette tip within the bladder was evaluated by measuring the D.C. resistance between the micropipette tip and the reference electrode on the serosal side of the bladder. In the spontaneously active state, with concentrations of sodium in the mucosal solution ranging from less than 1 to 114 meq per liter, the potential profile consisted in the majority of impalements of two steps, each positive to the mucosal solution. A minority of impalements showed more than two potential steps, each positive to the mucosal solution. In the short-circuited state, the interior of the bladder was found to be negative to the bathing solution by approximately 5 mv. The results are interpreted as showing a potential step at the two surfaces of the epithelial cell layer of the toad bladder. In the spontaneously active state the potential change at the mucosal boundary is of the wrong polarity to bring about net sodium entry; the small electrical driving force across the mucosal surface which is present in the short-circuited state may contribute to the net entry of sodium from mucosal solutions with low sodium concentration.

The inward transport of potassium by separated dog erythrocytes has been studied at concentrations of potassium in the medium from 2.9 to 25.0 m.eq./liter and at 38.0 and 33.0 degrees C. At the physiological concentration of external potassium (4.06 m.eq./liter medium), the inward potassium flux is 0.11 m.eq./liter cells hour and the glucose consumption is 2.0 mM/liter cells hour. The dependence of potassium influx on extracellular potassium concentration is given by the following equation, K influx (m.eq./liter cells hour) = 0.028 [K](amb.) - 0.003 in which [K](amb.) refers to the potassium concentration in the medium. In a single 93 hour experiment, 94 per cent of the intracellular potassium was exchanged at an apparently uniform rate. The average apparent activation energy for the process is 7,750 calories +/- 2,000 calories/mol and there is some indication that the apparent activation energy of inward K transport decreases with increasing external K concentration.