Immunodeficiency disorders

Patients with cancer, human immunodeficiency virus, and other infectious and immunodeficiency disorders Seizures... 

Immunostimulants are potentially of benefit in immunodeficiency disorders such as acquired immunodeficiency syndrome (AIDS), in chronic infectious diseases, and in some selected malignancies, especially those that involve the lymphatic system. 

Yin EZ, Frush DP, Donnelly LF, and Buckley RH. Primary immunodeficiency disorders in pediatric patients Clinical features and imaging findings. Am J Roentgenol 2001 176 1541-1552. 

Primary immunodeficiency Immune globulin (IV)2 Consult the manufacturer s dosing recommendations for the specific Primary immunodeficiency disorders include specific antibody deficiencies... 

Immunomodulating agents are being investigated for their potential application in immunodeficiency disorders, chronic infections, and neoplasms. 

There are also immunodeficiency states that are primary and can be caused by phagocytic cell defects, deficiencies in the complement system, B- and T-cell deficiency, and other causes. Secondary immunodeficiency disorders can result from malnutrition, cytotoxic drugs, infections with pyrogenic bacteria, and infections with an RNA retrovirus, as in the acquired immunodeficiency syndrome (AIDS). 

Davis, J.J., Heyman, M.B., Ferrell, L., Kerner, J., Kerlan, R.jr., Thaler, M.M. Sclerosing cholangitis associated with chronic cryptosporidiosis in a child with a congenital immunodeficiency disorder. Amer. X Gastroenterol. 1987 2 1196-1202... 

Roder JCJ, Haliotis TT, Klein MM, Korec SS, Jett JRJ, Ortaldo JJ et al (1980) A new immunodeficiency disorder in humans involving NK cells. Nature 284 553-555... 

In this chapter we will review the anatomy and physiology of the thymus gland as currently conceived. We will pay particular attention to the variety of polypeptides that are produced by thymic epithelial cells and that have been well characterized biochemically. Finally, we will discuss the various primary and secondary immunodeficiency disorders that are associated with abnormalities of the endocrine thymus. 

In this section we will summarize the status of the currently available methodologies for determining serum levels of products that reflect the endocrine function of the thymus. It had been hoped that specific abnormalities in blood levels of thymic hormones would provide important information for diagnosing specific immunodeficiency disorders. However, this has not turned out to be the case, and even though the currently available assays can frequently detect abnormalities on the part of the endocrine thymus, there have been no specific serum alterations that are diagnostic of any particular immunodeficiency disorder, and no strong correlations exist between low or high serum thymic hormone levels and the immune status of the patient as defined in T cell functional assays. 

Serum thymic hormone levels, based on either the bioassay of Bach and Dardenne or the method of Twomey and colleagues, have now been determined for a variety of primary and secondary immunodeficiency disorders (summarized in Table 1). 

A great variety of patients with primary immunodeficiency disorders have now been studied with both bioassay procedures (Bach et al., 1972, 1975 Incefy et al, 1977 Lewis et al, 1978 Iwata et al., 1981). Serum thymic hormone levels are lower than age-matched normal levels for all patients studied with DiGeorge s syndrome, and a high proportion of patients with severe combined immunodeficiency. In patients vdth the complete Di-George s syndrome, thymic hormone levels are always undetectable, whereas in the partial form, FTS-like bioactivity is measurable but lower than normal. In some cases in which thymus grafi ing was utilized as a therapeutic modality, serum FTS-like bioactivity became detectable as early as 1 day after transplantation (Incefy et al., 1977) and eventually returned to normal (Lewis et al, 1978). These results have suggested that the increase in serum thymic hormone levels resulted from production by the transplanted thymus. In patients with SCID, regardless of the bioassay employed, thymic hormone levels were found to be either undetectable or much lower than that of age-matched normal donors. In rare cases serum FTS-like bioactivity... 

The initial Taj RIA that employs rabbit hetero mtiserum has been used to evaluate serum levels in children with primary immunodeficiency disorders (D. Wara et al., 1982). With this assay, 11 of 13 children with combined immunodeficiency, 5 to 7 children with ataxia-telangiectasia and all 3 patients with Wiscott-Aldrich syndrome exhibited serum Taj levels below the mean of the normal age-matched donors. Such findings were similar to those reported using the Bach-Dardenne bioassay (Iwata et al., 1981). A major inconsistency, however, was in children with DiGeorge s syndrome. Whereas all such children manifested low serum thymic hormone bioactivity, only 3 of 6 exhibited levels below the mean of normals using the Taj RIA and serum levels were actually quite high in 2. 

An RIA has been reported for thymopoietin that can detect as little as 20 pg of the polypeptide (Goldstein, 1976 Lisi et al., 1980). The assay utilizes an antithymopoietin serum raised in rabbits and I-labeled thymopoietin as tracer. The RIA is specific for thymopoietin and no cross-reactions were observed with FTS or prealbumin. At present no studies have been reported concerning thymopoietin levels in patients with primary or secondary immunodeficiency disorders. 

Effects of Thymus Grafting in Human Primary Immunodeficiency Disorders... 

From the studies described in this section, it is apparent that in selected clinical conditions associated with either primary or secondary immunodeficiency, various thymic preparations are capable of restoring T cell numbers and function. However, clinical trials with thymic hormones are in their infancy and a number of questions still must be resolved before thymic factor therapy can become an accepted form of treatment. Most of the reported studies to date, particularly in primary immunodeficiency disorders, were nonrandomized and involved small patient numbers, and so they need confirmation in large-scale, randomized trials. Both the dosage and schedule dependency of each of the thymic factors have been empirically established, and further emphasis is needed in defining the optimal dosage and frequency of administration. Nevertheless, because they are nontoxic preparations, the thymic factors hold promise as important new drugs for treating a wide variety of disorders associated with abnormalities of thymic-dependent immunity. 

By far the most important clinical application of the thymic hormones is their potential therapeutic use in selected patients with primary immunodeficiency disorders (e.g., DiGeorge s syndrome), infections, cancer, and autoimmune disorders. The overwhelming evidence available to date indicates that thymic hormones exert immunorestorative effects when administered to patients with impaired T cell immunity. However, it remains for future clinical investigations to identify the most active preparations, to firmly establish the optimal dosages and sehedules for their administration, and to determine which clinical conditions will benefit from their use. 

Dapsone is an antibiotic used to treat leprosy and for prophylaxis against malaria and Pneumocystis carinii infections in patients with AIDS and other immunodeficiency disorders. It is also used In rheumatologic and rate dermatologic disorders. 

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