Unilateral adrenal enlargement due to Histoplasma capsulatum.

Human infection with Histoplasma capsulatum runs the gamut from asymptomatic to disseminated disease. CT-directed fine-needle aspiration of bilaterally enlarged adrenal glands has been used in diagnosing serious infections with this ubiquitous organism. Three cases have previously been reported in which H. capsulatum infection caused unilateral adrenal enlargement; this enlargement was diagnosed post-mortem. We describe three patients with unilateral adrenal enlargement due to H. capsulatum whose conditions were diagnosed antemortem. We encourage clinicians to include infection with H. capsulatum as well as other granulomatous diseases and tumors in the differential diagnosis of unilateral adrenal enlargement.

Clinical experience with HIV-infected patients at the University of Oklahoma Health Sciences Center: an update.

We reviewed the course of 545 human immunodeficiency virus (HIV)-infected patients seen between 1983 and March 30, 1991. A majority were Caucasian homosexual or bisexual men, while parenteral drug abusers represented a smaller proportion than seen nationwide. In the 274 patients with the acquired immunodeficiency syndrome (AIDS), the distribution of AIDS-defining conditions was generally consistent with those reported in studies from elsewhere in the United States. However, toxoplasmosis remained relatively uncommon. There was a slightly higher incidence of disseminated histoplasmosis compared to other studies. HIV encephalopathy (AIDS dementia) was likely underdiagnosed. Although data suggested prolongation of the asymptomatic phase of HIV infection, median survival after AIDS diagnosis remained approximately 12 months.

Rocky Mountain spotted fever. A clinical review based on 48 confirmed cases, 1943-1986.

We reviewed 48 cases of Rocky Mountain spotted fever seen between 1943 and 1986. The data provided a view of the diverse presentations and manifestations of this disease. Exposure to a rural environment or to dogs was the rule, and over two-thirds of patients specifically remembered tick exposure. Clinical presentation was highly variable. Although fever, headache, and rash were each common, only 62% had the complete triad. Neurological symptoms and signs were common in this series. Cerebrospinal fluid abnormalities, particularly leukocytosis, were the rule in those patients who underwent lumbar puncture. Neurologic sequelae occurred in several patients. Multiple other organ systems were involved at presentation or during the course of illness--gastrointestinal, cardiovascular, pulmonary, renal, muscular, hematologic. These manifestations could, and often did, confuse physicians seeing these patients initially. They further accounted for the diverse complications seen. Outcome was good in this series. Mortality rate was 2%, and most patients recovered without sequelae. However, morbidity during hospitalization was often severe. Even in an endemic area with high index of suspicion, the diagnosis of RMSF was often delayed, usually because of failure of the physician to consider this possibility at initial presentation. This series emphasizes the importance of considering RMSF in any febrile patient in an endemic area, regardless of "atypical" presentation or apparent lack of tick exposure.

Clinical experience with HIV-infected patients at the University of Oklahoma Health Sciences Center.

Two hundred seventy-two patients infected with human immunodeficiency virus (HIV) have received care from the members of the adult infectious disease section at the University of Oklahoma Health Sciences Center. The majority of these patients met the diagnostic criteria for acquired immunodeficiency syndrome. This group of patients was characterized by relatively few parenteral drug abusers, a high incidence of disseminated histoplasmosis, and an unexpectedly low frequency of toxoplasmosis. The prevalence of risk behaviors and endemic disease may be responsible for these particular case distributions.

Immunoblot analysis of antibody responses to Sporothrix schenckii.

The serologic response to Sporothrix schenckii was investigated in patients with sporotrichosis by solid-phase enzyme-linked immunosorbent assays (ELISAs) and Western immunoblot techniques. A soluble antigen preparation derived from an S. schenckii isolate contained 15 protein staining components ranging in molecular size from 22 to 70 kilodaltons (kDa) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Sera from 40 patients with sporotrichosis demonstrated Sporothrix immunoglobulin G antibody by ELISA with titers between 128 and 65,200. No sera from 300 healthy individuals or 100 patients with various systemic mycoses other than sporotrichosis had ELISA titers greater than 64. By Western immunoblotting of the antigens separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, sera from 10 patients with cutaneous sporotrichosis reacted with 8 to 10 antigen components (range, 40 to 70 kDa), while sera from 15 patients with extracutaneous sporotrichosis reacted with a greater number of antigen components (15 to 20 bands) over a wider range of molecular sizes (22 to 70 kDa). Antibody to 40- and 70-kDa antigen components was detected by immunoblots in all sera tested from patients with sporotrichosis. Antibody to 22- to 36-kDa antigen components was present in sera from 13 of 15 patients with extracutaneous sporotrichosis, but these lower-molecular-weight components were not detected by sera from patients with cutaneous sporotrichosis. Antibody to these components was not detected by Western blotting in sera from 19 of 20 patients with other fungal diseases or from 30 healthy individuals. Purification of these specific antigen fractions could provide the basis of a sensitive and specific serodiagnostic test to indicate the presence and activity of extracutaneous sporotrichosis.

Serologic studies in the diagnosis and management of meningitis due to Sporothrix schenckii.

Eight patients have previously been reported to have central nervous system infections caused by Sporothrix schenckii. In those patients the fungus proved quite difficult to culture, delaying correct diagnosis and treatment. We describe seven additional patients with sporotrichosis meningitis, all of whom had antibody to this fungus in cerebrospinal fluid and serum. The antibody in the cerebrospinal fluid was most likely produced locally, as evidenced by its oligoclonality and the relatively high ratio of immunoglobulin to albumin in the cerebrospinal fluid as compared with the serum. Only one of these seven patients, who had active sporotrichosis of the knee joint, had obvious extrameningeal infection. None of 130 patients with meningitis known to be caused by other agents and none of 170 patients with other neurologic disorders had antibody to S. schenckii in their cerebrospinal fluid. We suggest that cerebrospinal fluid should be tested for S. schenckii antibody (in addition to other fungal agents) in any patient with chronic meningitis for which no cause is discovered by the usual diagnostic tests.

Sonography of the adrenal glands in chronic disseminated histoplasmosis.

In this retrospective study, the findings on abdominal sonograms in six patients newly diagnosed as having chronic disseminated histoplasmosis are reported. Five of six patients showed bilateral adrenal gland enlargement that was similar in degree from side to side. The most characteristic feature was the maintenance of a triangular shape in five glands and a cylindrical shape in two glands. Four glands had a nonspecific round or oval shape. All sonographic findings correlated well with the computed tomographic (CT) findings on each patient except that CT detected the one enlarged right adrenal gland not demonstrated sonographically. Abdominal sonography may provide the initial important clue to the diagnosis of chronic disseminated histoplasmosis.

Activation of the alternative complement pathway by Sporothrix schenckii.

We studied the activation of complement by Sporothrix schenckii yeast cells. Total complement activity, and the effect of various activators on this activity, were assayed on aliquots of fresh nonimmune human serum with and without prior treatment with chelators. Both total hemolytic complement and C3 were consumed (activated) in serum chelated with magnesium ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, which blocks the classical pathway but leaves the alternative pathway intact. Further, C3 was consumed, but C4 (exclusively a component of the classical pathway) was preserved, in nonchelated serum after challenge by S. schenckii yeast cells. Absorption of serum with S. schenckii yeast cells to deplete antibodies did not alter these results. Furthermore, immunofluorescence studies demonstrated that C3, but not immunoglobulin G, was deposited on yeast cells during incubation with nonimmune serum. These data indicate that S. schenckii yeast cells activate the alternative complement pathway in vitro independently of antibody. These data do not define a role for the alternative pathway in in vivo host defenses against infection with this organism but provide a foundation for studies to evaluate such a role.

Histoplasmosis of the adrenal glands studied by CT.

Computed tomography (CT) of the adrenal glands was performed on seven patients who had histologically proved disseminated histoplasmosis. All seven patients showed some degree of adrenal gland abnormality. The range of CT findings included minimal enlargement with faint flecks of calcium, moderate enlargement with focal low attenuation nodules, and massive enlargement with large areas of necrosis or dense calcification. The changes in each patient were bilateral and symmetrical. Adrenal gland shape was usually preserved. Findings of percutaneous adrenal biopsy, which was performed under CT guidance, made the diagnosis in one patient. Five of seven patients had adrenal insufficiency. We conclude that the diagnosis of disseminated histoplasmosis should be considered in any patient who has bilateral adrenal gland enlargement and who resides in an endemic area, especially if there is evidence of adrenal insufficiency, and that CT is superb for the assessment of adrenal gland morphology in this disease, and CT-directed biopsy is the recommended method of confirming the diagnosis in difficult cases.

Survival of human parainfluenza viruses in the South Polar environment.

The survival of human parainfluenza virus types 1, 2, and 3 was measured in both indoor and outdoor environments at South Pole Station, Antarctica, in an effort to determine the long-term survival of these viruses in this environment and to identify the possible source of respiratory tract illnesses which occurred in this isolated population in 1978 after 10 and 27 weeks of total social isolation. Viruses were applied to plastic petri plate surfaces which were then stored in indoor (21.4 degrees C; water vapor density, 1.50 g of water per m3) and outdoor environments (-22.4 to -33.2 degrees C; water vapor density, 0.706 and 0.247 g of water per m3). Parainfluenza virus type 1 at an initial titer of 3.75 log10 50% tissue culture infective doses per ml was inactivated after 4 days at room temperature and after 7 days outside. Parainfluenza virus type 2 and 3 at initial titers of 5.58 and 5.38 log10 50% tissue culture infective doses per ml were inactivated after 7 and 12 days, respectively, at room temperature and after 17 days of storage outside. Results indicate that the long-term survival of parainfluenza virus in either environment for up to 10 weeks is unlikely and probably did not provide the source of infectious virus responsible for the midisolation outbreaks of parainfluenza virus-related respiratory tract illnesses observed in this population during the 1978 winter season.

Rapid preparation and purification of alkaline phosphatase and 125I-labeled antibody by minicolumn gel centrifugation chromatography.

Gel centrifugation chromatography was used for the preparation, purification and concentration of enzyme and 125I-labeled antibody. Low-molecular-weight reactants were rapidly and efficiently removed from either 125I-labeled antibody or enzyme-antibody conjugates by centrifugation of the reaction mixture through a minicolumn of Sephadex. Further purification of both radiolabeled and enzyme labeled antibodies were possible by the application and elution of each labeled antibody through a minicolumn of Protein A Sepharose. Minicolumns were constructed from readily available inexpensive components and allowed the rapid preparation and purification of antibody of high specific enzyme, and radioactivity. No difference between the 125I, or enzyme labeled antibody detection limit could be detected by a direct solid-phase immunoassay.

Rapid micromethod for preparation of enzyme-antibody conjugates.

A rapid method is described for labeling antibody with alkaline phosphatase by one-step glutaraldehyde linkage. The method involves the centrifugation of a small volume of an enzyme and antibody mixture through a minicolumn packed with hydrated Sephadex. This procedure rapidly removes ammonium sulfate and glutaraldehyde from the enzyme-antibody mixture and results in the efficient recovery of conjugated antibody without significant dilution.

Cryptococcal capsular polysaccharide clearance in nonimmune mice.

Clearance of cryptococcal polysaccharide (CP) from tissues and body fluids of nonimmune mice was studied. Mice were injected intravenously only with one mg of purified CP, and serum, urine and tissues were obtained from each animal at various intervals for a period of 84 days. Tissue extracts, serum and urine were tested for CP content by enzyme-linked immunosorbent assay (ELISA) and latex agglutination. High concentrations of CP were detected by both assays one-half hour after injection in blood (serum), liver, spleen, kidney and lung (extracts). The duration of ELISA detectable CP was longest (70 days) in liver and spleen and shortest (14 days) in lung extract. By 14 days after injection, concentration of CP in the blood fell below that found in the liver and spleen. CP remained detectable (titers 32-64) after all other extracts became negative. These results indicate that CP is stored in tissues (binding mechanism and site unknown), and that the liver and spleen possess greater storage capacity than other tissues. Antibody (IgM) to CP appeared in low titer on the 14th day and thereafter.

Identification of parainfluenza virus serotypes by indirect solid-phase enzyme immunoassay.

An indirect enzyme immunoassay was used to detect and identify parainfluenza virus serotypes 1 and 3 in cell culture residuals from which infectious virus could no longer be recovered.

Enzyme-linked immunosorbent assays in murine cryptococcosis.

In this investigation, enzyme-linked immunosorbent assay (ElISA) procedures were used to study the time of appearance and the duration of demonstrable antigen and antibody in body fluids of mice with disseminated cryptococcosis. The ELISA antigen procedure detected cryptococcal capsular polysaccharide (CCP) in the serum and urine of infected mice 3 days after infection--4 days before it could be demonstrated by the latex agglutination procedure. ELISA-reactive antibody was present throughout the course of infection (mean death time, 32 days), whereas antibody was not detected by whole cell agglutination after day 20. High serum concentrations of CCP (titers to 64,000) persisted throughout the course of infection, while antibody declined to low levels with progression of disease. ELISA provides a sensitive system for quantitation and monitoring of antigen (CCP) processing and clearance (or storage), and for cryptococcal antibody formation in progressive cryptococcosis.