A comparison of coccidioidin and spherulin skin testing in the diagnosis of coccidioidomycosis.
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Biomedical subjects
Publications and source records attributed to A Catanzaro.
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A patient with recurrent chronic histoplasmosis was diagnosed also as having Hodgkin's disease. Studies of cell-mediated immunity (CMI) demonstrated no reaction to histoplasmin by skin test, lymphocyte transformation (LT), or leukocyte inhibition factor (LIF) assay. Clinical and immunologic studies were performed during treatment with 19 doses of dialyzable transfer factor (TF) prepared from a normal donor with strong CMI against histoplasmin. Transfer of CMI to the patient was demonstrated by all three tests. All tests reverted to nonreactive during the period of observation. Repeated doses of dialyzable TF were followed by reconversion of skin tests. The LIF assay was most reactive. Reactivation of histoplasmosis occurred during antimetabolic therapy for Hodgkin's disease; however, the lesions cleared rapidly when TF was added to amphotericin B. Amphotericin B was administered at a dosage of 25 mg three times each week during the entire study.
The authors present the results of their experiment on the immune response of the guinea pig tympanic membrane. The first step was to develop an antiserum in the rabbit from the guinea pig tympanic membrane (RAGPTM). The lamina propria was used and IgG was identified as the main constituent of this antiserum. In their initial experiment, the RAGPTM IgG seemed to be specific to the acellular connective tissues of the respiratory tract and TM. The experiment presented here is concerned with the immune response of the guinea pig tympanic membrane. The animals were sensitized by intracardiac injection with the antiserum, and within one hour the right TM was traumatized in diverse fashions (bacteriological, chemical, mechanical traumas). The left TM served as a negative control. Animals were sacrificed at 24 hours, 7 days and 21 days. Immunofluorescence staining, complement studies (C23) and immunoperoxidase techniques were used on the TM. It appears that the GPTM can be antigenic in the rabbit. The right TMs of the sensitized guinea pigs reacted differently in the sense that there seems to be homing of the RAGPTM IgG to the site of trauma and that the complement participates in the reaction at least in the first week. The lamina propria of the TM is the site of the immune response. This work will need more elaborate studies but allows us to address different questions concerning the possible role of the combination of trauma and sensitization in conditions clinically involving the TM and middle ear.
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Bone and gallium scans were performed on 79 patients to determine the presence and extent of disseminated coccidioidomycosis. Bone scans appeared to be more sensitive than skeletal radiographs or gallium scans in determining the extent of coccidioidal bone involvement. The gallium scan was useful only in the identification of coccidioidal tissue abscesses. All patients with clinical evidence suggestive of dissemination and all patients with poor prognostic factors who are to receive amphotericin B therapy should be evaluated with a bone scan.
San Diego is located within the geographic distribution of known occurrence of Coccidioides immitis contamination of the soil. Forty-five to fifty-five cases are diagnosed in San Diego hospitals each year. Skin tests were administered to one thousand and twenty-seven ninth grade students in five selected San Diego schools. Coccidioidin 1:100 was administered by Mantoux technique, intradermally. Induration was measured at forty-eight hours. Greater than 5 mm of induration was noted in 9.7% of students tested. Among 378 students who had been lifelong residents of San Diego County, 7% had greater than 5 mm of induration. Coccidioidomycosis is endemic in San Diego but the level of endemicity is rather modest.
Immunocompetence of the middle ear was studied in guinea pigs in two series of experiments. The first, afferent phase, consisted of grafting iso and allografts in the guinea pig's middle ear to sensitize the animals which were later to receive a skin graft on the back. The second, efferent phase, first sensitized the animals with a skin graft on their back and later in the middle ear. The results show a rather low capacity of the middle ear to elicit a second-set rejection of the skin grafts. This lack of sensitization is explained by the authors by the concept of tolerance.
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Five cases of disseminated coccidioidomycosis (DC) are presented, to illustrate the complementary nature of bone scanning and radiography in the assessment of skeletal involvement. As shown in other unflammatory and neoplastic processes, bone scanning is more sensitive than radiography in the detection of early skeletal disease, but correlation with radiographs remains a necessity.
Acute coccidioidal pleural effusions were studied in 28 patients. Coccidioidal pleural effusion appeared to be secondary to direct spread of contigous parenchymal infection, rather than to hematogenous dissemination, in more than 90 per cent of these patients. Only 2 of 28 patients had the concomitant development of disseminated infection, and both patients possessed factors known to predispose to dissemination. Because of the excellent prognosis in most patients, therapy in patients with coccidioidal pleural effusion should be expectant. This is true even when substantial increases occur in complement fixation titers; such elevations were frequent in this series. Cultures of pleural biopsy specimens were the most rewarding cultural source in this series, being positive in all 8 patients in whom such biopsy specimens were cultured. Dermal hypersensitivity, including erythema nodosum and erythema multiforme, was commin in patients whose clinical course was uncomplicated.
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Transfer factor (TF) derived from donors with strong delayed hypersensitivity to coccidioidin (CDN) was administered to four patients with active disseminated or progressive pulmonary coccidioidomycosis. The clinical and immunologic response to TF was studied. Before the administration of TF, all four patients had defective thymus-derived lymphocyte (T-cell) function. In no case were lymphocytes in culture stimulated to incorporate [(3)H]thymidine when exposed to CDN. Cases 1 and 2 had no skin test response to CDN or other antigen, nor was antigen-induced migration inhibition factor (MIF) release detected. Cases 3 and 4 had skin reactivity to CDN as well as MIF release. Lymphocyte reactivity to phytohemagglutinin (PHA), as measured by the incorporation of [(3)H]thymidine, was low or absent in all. After the administration of TF, patients with negative skin tests became reactive to CDN, MIF release was present in all but case 1, and lymphocyte stimulation was present in response to CDN in all. Lymphocyte reactivity to PHA was also increased after the administration of TF in all cases. All responses to single doses of TF were transient, lasting no more than 10 days. Subsequent doses were less effective at restoring lymphocyte stimulation once it had waned. Multiple doses of TF administered at frequent intervals appear to be the most effective way to maintain lymphocyte reactivity. Clinical response to the administration of TF correlated closely with specific transfer as measured by response to CDN in skin test, lymphocyte stimulation, and MIF release. After TF administration, all patients mounted a more effective host response against the infecting fungus. In each patient, smears and cultures became negative. Fistulas, when present, diminished in extent or closed; and pulmonary infiltrates cleared. Nonspecific signs of infection such as fever, weight loss, and anorexia also improved. Clinical improvement paralleled immunologic improvement. When immunologic improvement was transient so was clinical improvement. Multiple doses of TF at frequent intervals may maintain transferred T-cell reactivity. TF may prove to be a useful adjunct in the management of patients with coccidioidomycosis. Whether TF from CDN-negative donors may have similar effects is not known and requires exploration.
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Serum levels of specific IgG and the sensitization of peripheral blood T-lymphocytes were measured in guinea pigs after single-dose antigenic sensitization by two routes: intratympanic and intradermal injection. Keyhole limpet hemocyanin (KLH) served as the antigen. Intratympanic injection of antigen resulted in much lower levels of circulating anti-KLH IgG than intradermal injection. When KLH was conjugated with alum to produce nonspecific inflammation and serve as adjuvant, the intratympanic route was considerably enhanced, but remained much less effective than the intradermal route. Development of an IgG response was also somewhat less rapid following intratympanic than following intradermal administration. Marked sensitization of circulating T-lymphocytes was seen after intradermal injection of alum-precipitated KLH. A much weaker, though still positive, response was seen after intradermal injection of KLH alone and with the intratympanic injection of alum-precipitated KLH. No T-lymphocyte sensitization could be detected after intratympanic injection of KLH alone. It was concluded that the afferent limb of both humoral (IgG) and cell-mediated immunity was operative in the middle ear. Therefore, the middle ear does not represent an immunologically "privileged" site. On the other hand, the afferent limb from the middle ear appears to operate less effectively and rapidly than that from the dermis. This observation is consistent with observations in other mucosal systems.