Marxist studies of medical care emphasize political power and economic dominance in capitalist society. Although historically the Marxist paradigm went into eclipse during the early twentieth century, the field has developed rapidly during recent years. The health system mirrors the society's class structure through control over health institutions, stratification of health workers, and limited occupational mobility into health professions. Monopoly capital is manifest in the growth of medical centers, financial penetration by large corporations, and the "medical-industrial complex." Health policy recommendations reflect different interest groups' political and economic goals. The state's intervention in health care generally protects the capitalist economic system and the private sector. Medical ideology helps maintain class structure and patterns of domination. Comparative international research analyzes the effects of imperialism, changes under socialism, and contradictions of health reform in capitalist societies. Historical materialist epidemiology focuses on economic cycles, social stress, illness-generating conditions of work, and sexism. Health praxis, the disciplined uniting of study and action, involves advocacy of "nonreformist reforms" and concrete types of political struggle.

Cromolyn is a prototype of a new series of drugs, the pharmacologic activities of which may offer an entirely new approach in the treatment of asthma. Whereas bronchodilator drugs and steroids act primarily at tissue sites to counteract the effects of various toxic mediators released from tissue mast cells, cromolyn prevents the release of such mediators from mast cell membranes. The advent of cromolyn sodium therapy has been recognized as a significant advance by the pharmaceutical industry, which is rapidly developing a series of cromolyn-like drugs with similar properties. Many of these compounds are active orally, and some preliminary investigations suggest that they also could be clinically effective. Cromolyn has therapeutic value in immunologic and nonimmunologically induced bronchospasm, being particularly suited for conditions amenable to long-term prophylactic therapy. The risk-to-benefit ratio of cromolyn sodium therapy is excellent. Cromolyn sodium is an important adjunct in the treatment of asthma. By topical administration the drug has been effective in seasonal and perennial rhinoconjunctivitis and in selected cases of gastrointestinal allergy to foods.

We undertook a literature review to document whether certain therapeutic measures could be considered safe during pregnancy in the allergic patient. With the possible exception of brompheniramine, the commonly used antihistamine drugs appear to be safe during pregnancy. The bronchodilators ephedrine and theophylline also appear to be safe, as does cromolyn. Corticosteroids do not appear to have adverse effects in pregnancy beyond those well recognized in nonpregnant patients. Because side effects are reduced when steroids are administered as aerosols in the nose or lung, these preparations seem well suited for use in pregnancy. The safety of allergic immunotherapy has been confirmed. For asthma, annual influenza vaccination is indicated.

Disseminated candidiasis has become an important infection, particularly in immunocompromised and postoperative patients. Although serologic tests may, in some settings, facilitate a premortem diagnosis, the disease is usually diagnosed by comprehensive clinical evaluation. Detection of the relatively newly recognized peripheral manifestations of candidemia may be vital to early diagnosis: endophthalmitis, osteomyelitis, arthritis, myocarditis, meningitis, and macronodular skin lesions. Studies in patients with chronic mucocutaneous candidiasis and in-vitro manipulations have begun to elucidate normal immune defense mechanisms against Candida, including serum factors, phagocytosis, intracellular killing mechanisms, and lymphocyte function (particularly T cell). The primary drugs for the treatment of disseminated candidiasis are still amphotericin B or amphotericin B plus 5-fluorocytosine; the mainstay of therapy for chronic mucocutaneous candidiasis is amphotericin B. Other antifungals and immune system-stimulating modalities (transfer factor, thymosin, thymus epithelial cell transplantation, and levamisol) may be useful for chronic mucocutaneous candidiasis in some settings and deserve further evaluation.

Superoxide radicals (O2-) are commonplace products of the biological reduction of oxygen. Their intrinsic reactivity and ability to generate other more reactive entities constitute a threat to cellular integrity. Superoxide dismutases, enzymes that catalytically scavenge these radicals, have evolved to meet this threat. These metalloenzymes are essential for respiring organisms to survive. Several compounds, such as the antibiotic streptonigrin and the herbicide paraquat, augment the production rate of O2- inside cells. This accounts for the oxygen-enhancement of their lethality. Some bacteria respond to this artificially increased rate of O2- production by synthesizing additional superoxide dismutase. Ionizing radiation generates O2- in its passage through oxygenated aqueous media, and superoxide dismutase added to the suspending medium, decreases the oxygen-enhancement of the lethality of such irradiation of the bacterium Escherichia coli. Production of O2- by activated neutrophils is clinically significant, since it is an important component of the bactericidal actions of these cells and the inflammatory process. Superoxide dismutases exert an anti-inflammatory action that may be useful in managing inflammations.

Erosion of joint surfaces in arthritic conditions is always associated with the degradation of the two principal matrix macromolecules of cartilage, proteoglycan and collagen. The major enzymes thought to be involved in articular catabolism have not been isolated, purified, and their properties studied, but precise spatial and temporal activities are still imperfectly understood. We are beginning to understand some aspects of cellular function in the control of catabolic enzyme function. Recent studies on molecular, cellular, and tissue mechanisms in this process are discussed here. Of particular interest is a possible natural control mechanism involving a recently discovered inhibitor of collagenase. A newly developed pharmacologic method of inflammation control utilizes the properties of liposomes in the closed environment of the joint cavity. Very low doses of modified steroids encapsulated within liposomes are capable of substantially reducing inflammation in experimentally arthritic animals and may be applicable to man.

Vancomycin, virtually discarded after development of antistaphylococcal penicillins, has recently been receiving renewed attention. There are several clinical situations in which it appears to offer advantages over other available antimicrobial agents: infections due to methicillin-resistant staphylococci; bacterial endocarditis in patients allergic to penicillin; staphylococcal enterocolitis; staphylococcal infection in patients undergoing hemodialysis; infections caused by penicillin-resistant diphtheroids; and prophylaxis of bacterial endocarditis in patients with prosthetic valves or penicillin allergy. Its penetration into the cerebrospinal fluid suggests that vancomycin may be useful in treating certain infections of the central nervous system. Although its ototoxic and nephrotoxic potential cannot be ignored, these problems can be minimized by keeping the serum concentration at the proper level.

New concepts concerning the pathogenesis and therapy of diabetic ketoacidosis are reviewed. The regulation of ketogenesis by intrahepatic enzymic processes and the roles of insulin deficiency or glucagon or other counterregulatory hormone excess are summarized. Major emphasis is placed on an analysis of the use of low-dose insulin regimens for the treatment of ketoacidosis. Most patients with diabetic ketoacidosis will respond to low-dose, hourly, intravenous or intramuscular regular insulin. Low doses of insulin are as effective as high doses and have fewer associated complications of hypoglycemia and hypokalemia. Phosphorus deficiency is common in diabetic ketoacidosis and hypophosphatemia usually becomes manifest within 4 to 12 h of institution of therapy. Phosphorus supplementation is now generally recommended to replete erythrocyte 2,3-diphosphoglycerate and improve oxygen delivery to tissues. Coexistent and biochemically significant lactic acidosis is a relatively infrequent complication of diabetic ketoacidosis and when present is usually due to underlying disorders associated with poor tissue perfusion.

The apparent paradox of heightened adrenal corticosteroid levels associated with reduction in the competence of the body's defensive apparatus to cope with exposure to new microbial antigens is considered. The question is asked how this lowered defensive capability, which occurs in the face of a threat to body integrity, is consistent with Cannon's principals of the "wisdom of the body." The suggestion is offered that the immunologic response to self-antigens exposed by disease or trauma may be suppressed by corticosteroid to offset the likelihood of autoimmune attack.

Although bronchogenic carcinoma generally remains a tumor resistant to treatment, marked progress in the therapy of the small-cell undifferentiated subtype has occurred in the past 5 years. Many aspects of its growth and metastatic spread are such that it is not satisfactorily treated surgically. However, it is sensitive to both radiation and a variety of chemotherapeutic agents. Use of these agents in combination seems to produce a greater antitumor effect than single drugs. The combination of radiation and chemotherapy results in marked tumor regressions. Untreated, this carcinoma has a very short median survival (2 months). Administration of current "aggressive" combination therapy regimens has resulted in median survivals of nearly 1 year with some patients still living 3 years after therapy.

Pleural effusion from metastatic malignancy can cause major impairment of respiratory function and eventual death. Although cure is not possible, successful palliative treatment allows months to years of productive life, obviating the need for continuous hospitalization and repeated thoracenteses. Successful palliative treatment requires obliteration of the pleural space. Literature survey indicates that a wide variety of medical agents and surgical methods have been used with variable success. Medical methods include instillation of antineoplastic agents, antimicrobial agents, or colloidal radioisotopes into the pleural space; quinacrine and tetracycline are moderately to highly effective agents, but the toxicity of the former is substantial. Bedside talc poudrage with thoracostomy-tube drainage is a safe and highly effective alternative. Pleurectomy is the definitive method of preventing reaccumulation of pleural fluid that results from metastatic malignancy, even when other methods have failed, but thehigh morbidity and mortality of the procedures mandate careful patient selection.

Indirect evidence, mostly pharmacologic, has suggested a role for brain neurotransmitter amines such as norepinephrine in the production of depression or mania. Clinical investigations have supported this concept but also indicate that depression is probably a biochemically heterogeneous group of illnesses. There may be a clinically, biochemically, and pharmacologically definable subtype of depression in which there is a disorder of norepinephrine metabolism or disposition in brain. I review here the experimental data from which this hypothesis is derived.

Antihemophilic factor (Factor VIII) is an agent in normal plasma that corrects the coagulative defect of classic hemophillia. The plasma of hemophiliacs contains normal amounts of a variant of antihemophilic factor deficient in clot-promoting properties. In contrast, von Willebrand's disease is usually associated with a true deficiency of this protein. In this disorder, the platelets are poorly aggregated by ristocetin, a defect ascribed to deficiency of antihemophilic factor. Structural studies of antihemophilic factor suggest that it is composed of two dissociable subcomponents, one of high molecular weight that contains the bulk of protein and sustains ristocetin-induced platelet aggregation, and another of lower molecular weight with procoagulant activity. Both subcomponents have been identified in hemophilic plasma, as if the smaller subcomponent were qualitatively abnormal. Carriers of hemophilia can often be detected because their plasmas contain a disproportionately high concentration of antihemophilic factor, measured immunologically, compared with the titer of procoagulant antihemophilic factor.

Clinical manifestations of odontogenic orofacial infections are protean and are largely dictated by complex microbiota and anatomic routes of spread. Complications such as suppurative mediastinal or intracranial extension, retropharyngeal spread and airway obstruction, pleuropulmonary involvement, and hematogenous dissemination indicate the potentially serious nature of these infections. In this review we emphasize the pathogenetic mechanisms of infection, the principles of antimicrobial therapy, and the need for early surgical intervention.

Thyroid-related autoimmune diseases (Graves' thyroid disease, Graves' ophthalmopathy, and Hashimoto's thyroiditis) may occur alone or in any association. The diagnosis of Hashimoto's thyroiditis requires multiple criteria; pathologic changes in the thyroid are not due to antibodies but may result from cytotoxic lymphocytes or a deficiency of suppressive T cells. In Graves' and Hashimoto's diseases the increased prevalence of HLA-B8 may not be significant, but that of HLA-AW30 in Hashimoto's disease is. In 48 first-degree relatives of patients with Graves' disease, thyroid abnormalities were frequent but not correlated with HLA type. Elevated serum thyroglobulin levels in all patients with hyperthyroidism fell to normal after surgical resection or radioiodine therapy. Patients whose illness recurred after antithyroid drug treatment was stopped had higher pretreatment thyroglobulin levels and no fall during treatment; those whose illness remitted had lower initial levels and a significant fall during treatment. Sodium ipodate lowered serum triiodothyronine and thyroxine levels in hyperthyroid patients and may be useful in the treatment of hyperthyroidism.

Menopause is merely a clinically discernible clue symbolic of the multitude of changes preceding or following the cessation of menses by many years. Because of the time span involved, separating changes observed in the menopausal transition from other age-related maturational events presents serious methodologic problems. Of the host of psychologic and psychosomatic symptoms, only hot flushes and associated sweats occur more frequently in this epoch, while an interplay between hormonal and age-related maturational events presents serious methodologic problems. Of the host of psychologic and psychosomatic symptoms, only hot flushes and associated sweats occur more frequently in this epoch, while an interplay between hormonal and age-related effects is assumed in atrophic changes involving the genitourinary organs. The relation between menopause and osteoporosis is suggestive but by no means proven, as is the risk for cardiovascular disease. Empiric evidence points to the usefullness of estrogen for the management of vasomotor instability, the symptoms associated with atrophy of the genitourinary tract, and in the prophylaxis of osteoporosis, but not in the treatment of anxiety, depression, and other psychiatric disorders.

Recent findings have emphasized the importance of the bronchiole to the function of the lung. The surface of the bronchiole differs from that of the alveolus. Rather than being covered by a thin coat of phospholipid, the surface is covered with cilia that are surrounded by a low-viscosity fluid. This permits the removal of foreign particles. Surface forces are important to the function of the bronchiole. The diameter of the bronchiole is a function of the volume of the lung. When the lung is partially collapsed, the bronchiole acts as a capillary tube and is readily obstructed by fluid. In chronic bronchitis, obstruction is related to narrowing by fibrosis and inflammation, alteration in the secretion, and loss of traction on the walls. Obstruction of the bronchiole by fluid in edema of the lung contributes to hypoxemia. Positive end expiratory pressure may prevent obstruction by increasing the bronchiolar diameter.

The mononuclear phagocyte complex is a widespread system of cells originating in the bone marrow monoblast and promonocyte, passing through the intermediate monocyte stage in the blood, and culminating in the tissue macrophages of the lung, liver, spleen, and pleural and peritoneal spaces. The cells are prominently phagocytic and have a well-developed lysosomal system. They function in host defense reactions against micro-organisms, in interactions with lymphoid cells in immunity, in disposal of cell debris, and possible in the regulation of granulopoiesis. Monocytes and the alveolar macrophage are the most accessible cells of this system for study. Several diseases of mononuclear phagocytes have been identified and characterized. These include microbicidal defects associated with increased susceptibility to infection, enzyme defects leading to storage diseases, and neoplastic diseases in which both cell proliferation and biologically active cell products contribute to the clinical disorder.

The most useful new hormonal therapy against estrogen receptor-containing metastatic breast cancer is the development of antiestrogenic agents such as nafoxidine and tamoxifen. Both of these drugs possess antitumor activity comparable to that of other additive hormonal agents, and they are better tolerated for lack of any serious toxicity. The clinical usefulness of antiprolactin drugs in breast cancer is at present limited. Adrenal suppression using aminoglutethimide has been shown to induce useful remissions. We discuss the implications of new treatment modalities for the future management of disseminated breast cancer.

Pancuronium bromide is a nondepolarizing muscle relaxant approved to induce skeletal muscle relaxation during anesthesia and to facilitate the management of patients undergoing mechanical ventilation. The use of pancuronium bromide during surgery led to the appreciation that it has advantages over drugs previously used for muscle relaxation. Patients in whom pancuronium bromide is of value are (1) hypoxemic patients resisting mechanical ventilation and so cardiovascularly unstable that use of sedatives is precluded, (2) patients with bronchospasm unresponsive to conventional therapy, (3) patients with severe tetanus or poisoning where muscle spasm prohibits adequate ventilation, (4) patients with status epilepticus unable to maintain their own ventilation, (5) shivering patients in whom metabolic demands for oxygen should be reduced, and (6) patients requiring tracheal intubation in whom succinylcholine administration is contraindicated. Without concomitant sedation, use of pancuronium bromide is associated with psychological risks. Other risks are undetected ventilator disconnection, tachyarrythmias, prolonged paralysis and drug interactions.