Clinics in Immunology and Allergy最新文献

The lungs are the most frequent site of involvement for the infectious processes that are associated with AIDS. In addition, non-infectious disorders, such as Kaposi’s sarcoma and lymphoid interstitial pneumonia, occur in the lungs and must be considered in the differential diagnosis in patients with respiratory symptoms or findings.

The diagnostic evaluation of a patient with or suspected of having AIDS and pulmonary involvement is founded in a knowledge of the epidemiology and pathophysiology of the process so that the proper risk groups are targeted and the types of problems can be anticipated. The sequence of studies should proceed in an orderly fashion from less to more invasive. Non-invasive studies including chest radiography, pulmonary function testing and gallium lung scanning assist in identifying patients who should have further diagnostic testing. Examination of sputum induced by inhalation of 3% saline can make the diagnosis of P. carinii pneumonia in more than 50% of patients with the disease. Bronchoscopy with bronchoalveolar lavage and transbronchial lung biopsy is a highly accurate means of establishing diagnoses thereby making open lung biopsy rarely necessary.

P. carinii is by far the most frequent pathogen causing pulmonary disease in patients with AIDS. Treatment is successful in 75-80% of initial episodes of P. carinii pneumonia using TMP-SMX or pentamidine. These drugs are equally effective, but both have a high frequency of adverse reactions. The survival rate in patients who require mechanical ventilation because of P. carinii pneumonia is approximately 15%.

Tuberculosis is the other important treatable infection in patients with AIDS. This disease occurs most commonly among groups such as Haitians or intravenous drug abusers, that have increased risks of tuberculosis even without AIDS. Tuberculosis in patients with AIDS responds to conventional antituberculosis drugs.

M. avium complex, an organism isolated frequently from patients with AIDS, is very resistant to treatment. The role of this organism in causing significant disease in AIDS patients is not clear, however.

Intensive care for patients with AIDS is most commonly indicated for respiratory failure caused by P. carinii pneumonia. However, because of the poor short-term and worse long-term prognoses, critical care is used less commonly than in the past. Nevertheless, critical care may be of extreme value in some instances and should not be withheld.

Infection control measures for patients with AIDS are essentially the same as those for hepatitis B. In patients with respiratory disease infection control should also take the possibility of tuberculosis into account until a diagnosis is established.

AIDS occurs worldwide, affecting both adults and children on all major continents. Much progress has been made since the disease was first described in 1981. The causative agent, HIV, has been discovered and isolated. A screening test to protect the blood supply is widely available. Researchers have determined how the virus can be inactivated in vitro.

Most importantly, the modes of transmission of HIV are understood. Effective risk-reduction recommendations have been made; until specific vaccines or therapies are available, education will be the primary public health weapon for combating this epidemic.

Most forms of immunologically mediated human renal disease are associated with deposits of immunoglobulin in granular immune complex form in renal glomeruli. These deposits may develop in a subepithelial, subendothelial, mesangial or mixed distribution. The histological, immunopathological and functional equivalents of these human immune complex nephropathies can be produced experimentally by the production of immune complex deposits in situ, either as a consequence of antibody binding to several cell or basement membrane antigens or through initial localization of an antigen or antibody followed by immune complex formation at the site of tissue injury. Several mechanisms can lead to in situ immune complex formation including electrical interactions between capillary wall anionic sites and oppositely charged antigens or antibodies, glomerular localization of non-immune cationic proteins followed by binding of anionic antigens or antibodies, chemical affinity between certain antigens and structural components of the glomerulus itself and mesangial uptake of circulating antigenic macromolecules. Local immune complex formation appears to be the predominant mechanism which leads to subepithelial immune complex deposits, whereas subendothelial and mesangial deposits may result from either local deposit formation or preformed immune complex trapping.

When antigen and antibody combine to form immune complexes within the glomerulus, complement activation is a major mechanism which leads to immune tissue injury. When complement is activated at an in-tramembranous, subendothelial or mesangial site, neutrophils recruited through immune adherence or chemotactic mechanisms usually participate in causing the injury that results. However, recent studies document an important role for a C5b-9 complement membrane attack (CMA) complex mechanism in producing antibody-mediated glomerular disease, particularly that associated with subepithelial immune complex deposits. The mechanism by which C5b-9 induces glomerular damage has not been defined but may involve a non-lytic effect on glomerular cell metabolism leading ultimately to an altered glomerular permeability to proteins.

The cause or causes of MCD remain unknown. Although recent work has suggested roles for various portions of the glomerular capillary filter and soluble mediators acting on the filter, many findings are inconsistently observed, have not been confirmed, or are not causal, but rather present only as a consequence of the nephrotic state. Some findings are reproducible, however, and may provide the greatest likelihood of providing new insights in the future. The visceral epithelial layer of the glomerular capillary filter is altered morphologically in nephrotic states in humans and in animal models like PAN-induced nephrosis. Such changes are presumably accompanied by changes in the cell surface and/or metabolism, and are reversible as shown in animal studies (Seiler et al, 1977) and temporally related to the onset of proteinuria (Blau and Michael, 1972). The importance of visceral epithelial integrity is further supported by the fact that disruption, elevation and death of visceral epithelial cells is a proximate event in the development of sclerosis of glomerular segments.

The visceral epithelium resides in a locus which is separated from the vascular compartment by the glomerular capillary wall where interaction with other cells is limited. It is highly probable that mechanisms for control of these cells depend in part on factors that traverse that glomerular capillary. The rapid development of recurrences of the nephrotic syndrome in children after the onset of respiratory infection suggests to us that a ’cellular effect’ plays a dominant role in this disease, rather than a change in fixed basement membrane components. The well recognized electron microscopic changes in the visceral epithelium—once thought to be a consequence of proteinuria—may in fact reflect a primary injury induced by a filterable circulating component. The recognition of Iymphohaemopoietic antigens on the visceral epithelium that appear at specific stages of ontogenesis (Platt et al, 1983) suggests to us that communication may exist between these cells and components of Iymphohaemopoietic system. Knowledge of the nature of this factor(s) and its putative derivation from Iymphohaemopoietic or other cells will, we believe, lead to a more complete understanding of this disease.