Annual Review of Medicine - Volume 41, 1990

Two features of human parietal pleura explain its role in the formation and removal of pleural liquid and protein in the normal state: the proximity of the microvessels to the pleural surface and the presence of stomata situated between mesothelial cells. For pleural fluid to accumulate in disease, there must be increased production from increased hydrostatic pressure, decreased oncotic or pleural pressure, increased microvascular permeability, or peritoneal-pleural movement. The rate of formation must overwhelm lymphatic clearance, which may be decreased by hydrostatic forces or blocked by malignant infiltration.

As the cells forming the luminal vascular surface, endothelium regulates both barrier function, and pro- and anticoagulant reactions. Endothelial cells can do this by controlling the expression of cell surface molecules, such as receptors that regulate the hemostatic balance and those that affect permeability across the endothelial monolayer. This regulation occurs in response to environmental stimuli, such as cytokines, which have a central role in inflammation, or glucose-modified proteins, which accumulate in the vasculature in aging and diabetes and are associated with vascular complications. The endothelial cell emerges as a dynamic regulator maintaining homeostasis in the quiescent state and contributing to the pathogenesis of vascular lesions in the stimulated state.

The B19 strain ofparvovirus causes several distinct and important clinical diseases in humans. Aplastic crisis in patients with chronic hemolytic anemia, persistent bone marrow depression in immunocompromised individuals, and hydrops fetalis all result from direct infection of hematopoietic cells by the virus. Erythema infectiosum, arthritis, and purpuric vasculitis are postinfectious manifestations of B19 parvovirus infection.

A parathyroid hormone-like peptide that probably causes hypercalcemia associated with solid tumors was recently characterized. It is a potent hypercalcemic and hypophosphatemic factor whose production is strongly associated with hypercalcemia and whose properties account for most aspects of the clinical syndrome. Diagnostic tests for this peptide have been developed. The parathyroid hormone-like peptide as well as other cytokines, such as tumor necrosis factor-alpha, likely play a role in causing hypercalcemia in multiple myeloma and lymphomas.

The management of patients with congestive heart failure is based upon an understanding of the pathogenetic mechanisms. Therapy aimed at optimizing preload, decreasing afterload, and improving contractility can improve symptoms, and in some instances, improve survival.

Thrombospondin is a large, multifunctional glycoprotein released from activated platelets and secreted by growing cells. It binds to components of the cell surface and extracellular milieu. Thrombospondin probably modulates a number of processes, including aggregation of platelets, formation and lysis of fibrin, adhesion and migration of cells, and progression of cells through the growth cycle. Studies relating thrombospondin to disease processes are just beginning.

The insulin receptor is a large cell surface glycoprotein that concentrates insulin at the site of action and also initiates responses to insulin. The receptor is a disulfide-linked oligomer comprised of two α and two β subunits. Signal transduction through the insulin receptor appears to require the activation of an intrinsic tyrosine-specific protein kinase activity. A variety of disorders, both acquired and genetic, are associated with the development of insulin resistance and are frequently the result of cellular defects in insulin receptor structure, function, and action. The recent cloning of several mutant receptors from patients with genetic forms of extreme insulin resistance has increased our understanding of insulin resistance on the molecular level.

Internists should be aware of the increased frequency of most communicable diseases among parents and child care providers exposed to children attending child day care centers. Episodes of shigellosis and hepatitis A among adults in contact with children in day care centers should be promptly reported to public health authorities, since they may indicate the presence of a day care center outbreak for which effective control measures are available. Although effective treatment or intervention is limited or not available for many other infections acquired by adults from children in day care centers, significant illness may result in a minority of individuals at increased risk for infection with agents such as cytomegalovirus and varicella. Acute infectious diseases of children caused by organisms transmitted from day care center staff are less common and largely preventable by ensuring that staff are appropriately immunized and screened for tuberculosis.

Neurologic consequences of cocaine use frequently present as medical emergencies in the form of stroke, repeated seizures, encephalopathy, acute headache, and unusual transient neurological deficits. The often fatal or disabling neurologic syndromes have only recently been recognized but are now well documented. Cocaine use is a significant cause of stroke in young adults, and the full, long-term ramifications of maternal cocaine use on the fetus will not be known for years to come. Unfortunately, there is not effective treatment other than abstinence, and our understanding of the pathophysiology of cocaine-associated neurologic illness remains limited.

Gut hormones serve as chemical messengers for communication between different cells of the gastrointestinal tract. Several technologic advances have contributed to the rapid evolution of peptide hormone biochemistry and physiology. Peptide hormones are potentially useful as diagnostic and therapeutic modalities in the practice of gastroenterology.