We review here the definition, history, and current findings of quality assessment. Difficulties with quality assessment center principally on methods problems, including using the medical record as a source of information, using process versus outcome criteria, and ignoring decision analysis methods in establishing quality criteria. One overriding issue is placing a value on health and, by extension, on quality assurance and assessment efforts; another is the degree to which improvements in the quality of care can be achieved through changes in physician practices. Several sets of recommendations address these topics. With the assumption that such recommendations could be acted on in a transition period, a hypothetical quality assurance system is described for the 1980s and beyond. This system is based on preservation of the fee-for-service system, adoption of a national health insurance plan, and minimal federal involvement in quality of care decisions at the regional level.

Idiopathic pulmonary fibrosis is a fatal disorder that starts as an alveolitis and progresses to interstitial fibrosis. Correlative morphologic, physiologic, and biochemical studies in 29 patients have shown that the inflammatory process in best followed by serial bronchoalveolar lavage and 67 Ga citrate scanning, and the fibrotic process is best followed by quantitation of the exercise-induced drop in arterial oxygen tension per unit of oxygen consumed. Although biopsies in idiopathic pulmonary fibrosis seem to show increased amounts of fibrotic tissue, biochemical studies suggest that the disease is probably one of collagen rearrangement rather than collagen increase. Perhaps becasue of this, peripheral lymphocytes of these patients recognize collagen as "non-self" and, when exposed to it in vitro, produce lymphokines and cell lysis. The fibrotic process is probably irreversible, but the inflammatory and immune processes that cause it may be amenable to therapy if diagnosed early.

A decade ago an antigen was identified by immunodiffusion and subsequently proved to be closely associated with hepatitis B virus. Further studies showed that hepatitis B virus circulates as a large particle containing a protein coat and a DNA core, and that excess coat particles are produced and circulate freely. Immunization with surface protein produced protective antibodies, and this led to the development of a prototype vaccine. Patients with hepatitis may develop a variety of extrahepatic manifestations, including polyarteritis, vasculitis, and glomerulonephritis. These associated symptoms may be due to immune complexes consisting of hepatitis B surface antigen and its antibody. The role of cellular immunity in hepatitis B is unknown. The relation between type B virus and the liver is both destructive (leading to severe acute hepatic disease and eventually to cirrhosis) and symbiotic (existing among carriers who have neither liver disease nor symptoms). If the factors that cause these divergent courses were delineated and understood, the results may lead to the prevention and cure of hepatitis B and its sequelae.

Minocycline has proved to have a wider spectrum of activity against both aerobic and anaerobic bacteria and has enhanced tissue penetration when compared with its tetracycline congeners. The latter, and possibly the former, can be related to its increased lipophilicity in the physiologic pH range. It appears to be a superior chemoprophylactic agent against sulfonamide-resistant meningococci that do not become minocycline resistant as a result of treatment. The clinical promise of this agent has been dimmed, however, by recent reports of vestibular toxicity manifest in ambulatory patients. Though data on the frequency and severity of these symptoms are in some conflict, minocycline cannot currently be recommended for general clinical use.

Our review focuses on low density lipoprotein (LD lipoprotein) and very low density lipoprotein (VLD lipoprotein) in their roles as transporters of cholesterol and triglyceride and as factors contributing to premature arteriovascular disease. We describe the clinical manifestations of the common, primary hyperlipoproteinemias--that is, hyper-beta-lipoproteinemia, combined hyperlipoproteinemia, hyper-pre-beta-lipoproteinemia, and sporadic hyperlipoproteinemia--and discuss the variations in lipoprotein structure and metabolism that occur in these diseases. Based on an understanding of the physiologic control of lipoprotein metabolism, it is possible for the physician to alter the concentrations of LD lipoprotein and VLD lipoprotein by selecting a course of therapy appropriate to the specific disease. We describe the effects of obesity, diet, insulin, ethanol, estrogens, and the drugs clofibrate, nicotinic acid, and cholestyramine.

The cellular change (phenotypic) leading to leukemia may involve a disorder of leukocyte maturation, but the etiologic molecular change (genotypic) remains unknown. We present evidence here that human leukemic cells contain type-C viral information and consider the possible significance of this observation in the context of a working hypothesis. We reexamine reticuloendothelial neoplasms in the light of newer immunologic, cytochemical, and ultrastructural methods for identifying cells of the T-lymphocytic, B-lymphocytic, and monocyte-macrophage systems. Use of these methods has led to a challenging concept of malignant lymphomas as neoplasms of various anatomic and functional compartments of the immune system. Functional studies, although still in their inception, have already provided provocative clues in the etiology and pathophysiology of these disorders. Advances in laboratory research have been paralled by dramatic changes in clinical oncology, as evidenced by trends in the treatment of acute lymphocytic leukemia, acute myelogenous leukemia, Hodgkin's disease, and diffuse histocyte lymphoma.

Current status of our understanding of the metabolism of vitamin D and its implications in metabolic bone disease is reviewed. The details of metabolism of vitamin D3 to 25-hydroxyvitamin D3 in the liver and its further conversion in the kidneys to either 1,25-dihydroxyvitamin D3 or 24,25-dihydroxyvitamin D3 are presented. The latter conversions are regulated by the vitamin D status, serum calcium through the parathyroid gland system, and serum inorganic phosphorus concentration. The 1,25-dihydroxyvitamin D3 can now be regarded as a calcium- and a phosphate-mobilizing hormone and must be considered as one of the most important serum calcium-regulating hormones. Disruption of the vitamin D metabolic sequence or the signal system for 1,25-dihydroxyvitamin D3 results in several bone and calcium metabolism disorders such as renal osteodystrophy, hypoparathyroidism, pseudohypoparathyroidism, and vitamin D-dependency rickets. The use of the synthetic analogs of 1,25-dihydroxyvitamin D3 as well as 1,25-dihydroxyvitamin D3 itself in the management of these disease states is discussed.

We describe 14 patients with congenital absence of the vagina associated with a variable abnormality of the uterus and review the literature. Associated developmental anomalies of the urinary tract and skeleton are common. As a result of the analysis of two affected families, we believe that the disorder may represent the variable manifestation of a single underlying genetic defect that can be expressed alone or in any combination of vertebral, renal, and genital abnormalities. Some affected persons may have lethal manifestations such as absence of both kidneys, and some cases may result from multifactoral causes rather than a single gene defect. Whatever the cause, the defect involves mesodermal development and the mesonephric kidney, the latter resulting in abnormalities in the paramesonephros (uterus and vagina) and in the metanephric kidney. Both nonoperative and surgical treatments are generally successful in repairing the vaginal abnormality.

Dopamine-beta-hydroxylase, the enzyme responsible for conversion of dopamine to norepinephrine, is released along with catecholamines from the adrenal medulla and from sympathetic nerve endings. The properties and mechanisms of the enzyme's action are discussed and its distribution described. Dopamine-beta-hydroxylase is a valuable indicator of exocytosis as a mechanism for neurotransmitter release. The enzyme is present in plasma, but its levels vary widely between individuals. This variation seems to be related more to genetic factors than to sympathetic nerve activity. Abnormally high or low plasma levels are associated with several diseases. However, the relation of these levels to disease pathogenesis rather than to genetic determinants is unclear. Levels of the enzyme are elevated in patients with pheochromocytoma and decline after removal of the tumor. Dopamine-beta-hydroxylase levels seem to be normal in hypertensive patients. Inhibition of dopamine-beta-hydroxylase provides a useful pharmacologic approach to evaluating the role of norepinephrine in psychiatric disorders.

Clinical studies involving 5-azacytidine, a ring analogue of cytidine, began in Europe in 1967 and the United States in 1970, and we review available preclinical and clinical studies here. The drug possesses cytotoxic, antimicrobial, antineoplastic, abortive, and mutagenic activity in various biological systems. 5-Azacytidine is thought to exert its antineoplastic effect through interference with nucleic acid metabolism. The dose-limiting toxicities are nausea, vomiting, and leukopenia, while the incidence of thrombocytopenia is low. Hepatic toxicity ranges from abnormal findings in liver function tests to hepatic coma. Clinical results in solid tumors are not encouraging, but 5-azacytidine shows consistent antitumor activity in patients with acute myelogenous leukemia resistant to previous treatment. An overall response rate of 36%, with 20% complete remissions, was achieved in 200 previously treated patients with acute myelogenous leukemia. Further studies must define the role of 5-azacytidine alone and in combination for the first-line treatment of acute myelogenous leukemia.

The premise that measures used to lower the plasma lipids in patients with hyperlipidemia will lead to reductions in new events of coronary heart disease (the Lipid Hypothesis) should be reconsidered today as a result of several recent reports of large-scale double-blind drug trials in the United Kingdom and in the United States. To that end, the published evidence that bears on tests of the hypothesis by dietary and drug interventions is reviewed, and the conclusion reached that the hypothesis has not yet been adequately tested. A phased program is described that will prepare the ground for a fuller and more definitive trial of the premise in the future: the first steps must be to establish that a combined diet/drug regimen in large numbers of adult male hyperlipidemic patients is acceptable and essentially harmless and that during an observation period of several years a high rate of adherence to the regimen can be attained. Any advice to the general public to make large dietary changes now is considered premature.

A single intramuscular injection of 0.2 g of spectinomycin hydrochloride is highly effective for the treatment of uncomplicated anogenital infections with Neisseria gonorrhoeae. Spectinomycin hydrochloride is indicated for uncomplicated anogenital gonococcal infections in men and women who cannot receive penicillin or probenecid, and is the drug of choice for the retreatment of patients with uncomplicated anogenital gonococcal infection who have not responded to other antibiotics. A single dose of spectinomycin does not appear to be reliably effective in the treatment of gonococcal pharyngitis. Preliminary reports indicate that multiple-dose schedules of spectinomycin will prove to be effective in gonococcal pelvic inflammatory disease and disseminated gonococcal infection. In the dosage used for gonococcal infections, spectinomycin has little effect on infection with Treponema pallidum. Evaluation of this antibiotic against other microorganisms suggests little utility for this agent in conditions other than gonococcal infections.

Use of modern materials and methods has given bone scintiscanning a larger role in clinical medicine, The safety and ready availability of newer agents have led to its greater use in investigating both benign and malignant disease of bone and joint. Present evidence suggests that abnormal accumulation of 99mTc-polyphosphate and its analogues results from ionic deposition at crystal surfaces in immature bone, this process being facilitated by an increase in bone vascularity. There is, also, a component of matrix localization. These factors are in keeping with the concept that abnormal scintiscan sites represent areas of increased osteoblastic activity, although this may be an oversimplification. Increasing evidence shows that the bone scintiscan is more sensitive than conventional radiography in detecting focal disease of bone, and its ability to reflect the immediate status of bone further complements radiographic findings. The main limitation of this method relates to nonspecificity of the results obtained.

Left ventricular pressure and volume during diastole reflect the interaction of ventricular elastic, viscous, and inertial properties, and the completeness of myocardial relazation. Myocardial relaxation may be impaired in the acutely ischemic ventricle, partly accounting for the abnormal diastolic pressure-volume relation in this condition. Altered elasticity of its wall can cause increased stiffness of the ventricular chamber, as in aortic stenosis, coronary heart disease, and infiltrative cardiomyopathies. In aortic stenosis, increased left ventricular stiffness results in an increase in pressure increment associated with left atrial contraction. Generation of such a high filling pressure is critical in maintaining adequate end diastolic sarcomere stretch in the left ventricle and probably accounts for the frequent deterioration of patients with aortic stenosis after development of atrial fibrillation or nodal rhythm. Many signs and symptoms of cardiac failure, previously attributed to impaired systolic performance, may be due to partly to altered diastolic properties of the ventricular chambers.

The administration of glucocorticosteroids results in a wide range of effects on inflammatory and immunologically mediated disease processes. Glucocorticosteroids cause neutrophilic leukocytosis together with eosinopenia, monocytopenia, and lymphocytopenia. A principal mechanism whereby corticosteroids suppress inflammation is their impeding the access of neutrophils and monocytes to an inflammatory site. Granulocyte function is relatively refractory, whereas monocyte-macrophage function seems to be particularly sensitive to corticosteroids. Corticosteroid administration causes a transient lymphocytopenia of all detectable lymphocyte subpopulations, particularly the recirculating thymus-derived lymphocyte. The mechanism of this lymphocytopenia is probably a redistribution of circulating cells to other body compartments. There is considerable disagreement about the direct effects of corticosteroid administration on human lymphocyte function. The corticosteroid regimen should be adjusted to attain maximal therapeutic benefit with minimal adverse side effects. Often, alternate-day dosage regimens effectively maintain disease remission with minimization or lack of Cushingoid and infectious complications.

In 81 cases of toxoplasmosis in patients with neoplasia, collagen-vascular disorders, and organ allografts, the clinical manifestations were highly variable but neurologic syndromes consistent with diffuse encephalopathy, meningoencephalitis, or cerebral mass lesions predominated. Many concomitant infections with DNA viruses were seen. The diagnosis of toxoplasmosis was not made until postmortem examination in most cases. Biopsy of lymph nodes or brain and serologic tests needed for definitive diagnosis were done infrequently. Twenty patients received antitoxoplasma chemotherapy (pyrimethamine and sulfonamide), 16 (80%) showing marked clinical improvement or complete remission. In immunosuppressed hosts disseminated toxoplasmosis appears to result from defects in cellular immunity that permit recrudescence of latent infection. Because cell-mediated immunity to Toxoplasma gondii can be enhanced in animals by administration of adjuvants, immunotherapy may become a useful adjunct to chemotherapy in immunoincompetent humans suffering potentially lethal infection.

The clinical spectrum of isoniazid-induced liver injury seems to be clinically, biochemically, and histologically indistinguishable from viral hepatitis, except that the injury occurs primarily in persons older than 35 years. A possible relation between susceptibility of patients to isoniazid liver injury and rapid metabolism (acetylation) of the drug has been found. Examination of isoniazid metabolites showed that patients with rapid acetylator phenotype hydrolyze much more isoniazid to isonicotinic acid and the free hydrazine moiety than do slow acetylators. The hydrazine moiety liberated from isoniazid is primarily acetylhydrazine, and studies in animals show this metabolite to be converted to a potent acylating agent that produces liver necrosis. It seems likely that formation of chemically reactive metabolites is also the biochemical event initiating isoniazid liver injury in man. Recognition of the seriousness of isoniazid hepatic injury, not readily accepted at first, has led to revisions in the uses of isoniazid prophylaxis.