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Biomedical subjects

B R Dannemann

Publications and source records attributed to B R Dannemann.

8 recordsLinked to original sources

Treatment of acute toxoplasmosis with intravenous clindamycin. The California Collaborative Treatment Group.

The interim results are presented of an ongoing large-scale, prospective, randomized study to determine the potential role of clindamycin in the treatment of toxoplasmic encephalitis. Patients were seropositive for Toxoplasma gondii antibodies and had clinical signs compatible with toxoplasmic encephalitis. Data was available on 33 patients, 15 of whom received pyrimethamine p.o./clindamycin i.v. and then p.o., and 18 of whom received pyrimethamine p.o./sulfadiazine p.o. The interim evaluation did not reveal a remarkable difference between the two regimens in the clinical or radiologic response. Adverse reactions to both regimens were common and frequently multiple, there being more adverse gastrointestinal reactions in patients on pyrimethamine/clindamycin and more adverse hematological reactions in those on pyrimethamine/sulfadiazine.

Acquired Immunodeficiency Syndrome↗

Toxoplasma serology, parasitemia and antigenemia in patients at risk for toxoplasmic encephalitis.

In order to further characterize the pathogenesis of Toxoplasma gondii infection in patients with AIDS and AIDS-related complex (ARC), a cohort of HIV- and Toxoplasma-infected individuals were identified and prospectively followed. Four hundred and 10 HIV-infected individuals followed in the San Francisco General Hospital AIDS Clinic were screened for antibodies to Toxoplasma between November 1986 and November 1988. Of the 67 (16%) individuals seropositive for Toxoplasma antibodies, 33 (49%) were followed monthly for a mean duration of 7.5 months. One hundred and 11 follow-up blood samples were obtained in order to determine Toxoplasma serology and the incidence of parasitemia. In general, Toxoplasma immunoglobulin (Ig) G antibodies remained stable over time. Detection of Toxoplasma antigenemia and parasitemia was uniformly negative, including those specimens obtained from two individuals within 45 days of their developing toxoplasmic encephalitis.

Animals↗

Differential agglutination test for diagnosis of recently acquired infection with Toxoplasma gondii.

We evaluated the recently described differential agglutination test (HS/AC test) to differentiate recently acquired toxoplasma infections from those acquired in the more distant past in sera obtained from 38 patients with carefully defined symptomatic and asymptomatic infections. AC antigens detect acute-phase-specific immunoglobulin G (IgG) antibodies against Toxoplasma gondii tachyzoites that are formed only during the acute stage of infection in humans. The HS/AC test correctly identified recently acquired infections in patients with toxoplasmic lymphadenopathy or asymptomatic infections (including infections in 7 women who seroconverted during gestation) in 31 of 33 patients. We also studied 15 individuals who had been infected for at least 2 years. In that group, only 13% had an acute pattern in the HS/AC test. However, the wide range in times from infection (from 2 to 14 years) did not allow for an estimate of when the pattern in the HS/AC test changed from acute to not acute. These results reveal that in the appropriate clinical situation, when both IgG and IgM tests are positive and a question still remains about the acuteness of infection, the HS/AC test may be useful for differentiating between toxoplasma infections acquired recently and those acquired in the more distant past.

Agglutination Tests↗

Assessment of human natural killer and lymphokine-activated killer cell cytotoxicity against Toxoplasma gondii trophozoites and brain cysts.

Because previous work has suggested that NK cells may be important in host resistance against the intracellular parasite Toxoplasma gondii we examined whether human NK cells and lymphokine-activated killer (LAK) cells have activity against trophozoites and cysts of this organism in vitro. A method to radiolabel Toxoplasma trophozoites with 51Cr was developed and direct cytotoxic activity was determined by using modifications of the standard 51Cr release assay. Viability of 51Cr-labeled trophozoites assessed by both methylene blue staining and trypan blue exclusion was greater than 90%. Significantly more 51Cr was released by anti-Toxoplasma antibody and C than by antibody in the absence of C. Incubation of trophozoites with freshly isolated human NK cells or NK cells activated with either rIL-2 or rIFN-alpha did not result in significant release of 51Cr (specific lysis was 0 to 2.3%). In contrast, the average specific lysis of radiolabeled trophozoites by LAK cells was significant (specific lysis was 7.8% +/- 1.1, p less than 0.01). In a series of separate experiments, preincubation of radiolabeled trophozoites with heat-inactivated normal or Toxoplasma antibody-positive human serum increased the cytotoxicity of LAK cells from a mean specific lysis of 15% +/- 4.5 to 39% +/- 8.5, respectively (p less than 0.05), as assessed by 51Cr release. Because previous work has shown that radioisotope release from parasites may be nonspecific, separate experiments were performed to determine the cytotoxicity of LAK cells against antibody-coated trophozoites by using ethidium bromide-acridine orange staining to assess effector cell damage. LAK cells had a mean specific lysis of 51% against antibody-coated trophozoites by ethidium bromide-acridine orange staining. Preincubation with heat-inactivated Toxoplasma-antibody positive human serum did not increase activity of rIL-2-activated NK cells against 51CR-labeled trophozoites. Neither human NK cells (freshly isolated or activated by rIL-2 or rIFN-alpha) nor LAK cells were cytotoxic for purified preparations of cysts of Toxoplasma isolated from the brains of chronically infected mice.

Acridine Orange↗

Diagnosis of toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome by using a new serologic method.

The present study was performed to develop a serological method for diagnosing toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome (AIDS). The trophozoite form of Toxoplasma gondii, fixed with either Formalin or acetone, was used in a modification of an agglutination method previously shown to differentiate between the acute and the chronic (latent) stages of infection with toxoplasma in immunologically normal persons. By using these antigens in separate tests and evaluating the data for statistical significance, 70% of patients with AIDS with biopsy-proven toxoplasmic encephalitis were distinguished from control, ambulatory patients with AIDS with toxoplasma antibodies but without signs or symptoms of central nervous system involvement. In a separate study, the agglutination tests identified from controls 84% of patients with AIDS with two or more brain lesions detected by computed-tomographic or magnetic-resonance-imaging scans and suspected of having toxoplasmic encephalitis. Thus, these agglutination tests should prove valuable for the noninvasive diagnosis of toxoplasmic encephalitis in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

Treatment of toxoplasmic encephalitis with intravenous clindamycin.

At present, therapy for toxoplasmic encephalitis (TE) is the combination of pyrimethamine with sulfadiazine or trisulfapyrimidines. Unfortunately, due to adverse reactions to sulfonamides, many patients with acquired immunodeficiency syndrome (AIDS) are unable to receive a complete course of therapy. The promising results with clindamycin phosphate therapy in a mouse model of TE prompted us to seek further information about patients with AIDS with TE who had been treated with clindamycin. Fifteen such patients were identified in whom clindamycin was used to treat 18 episodes of TE. Eleven patients showed clinical or radiologic improvement after receiving clindamycin therapy, either alone or in combination with pyrimethamine. Twelve received oral clindamycin as suppressive therapy after discharge from the hospital. Adverse reactions possibly related to clindamycin therapy included diarrhea, reversible granulocytopenia, and skin reactions. The results of this retrospective study suggest that clindamycin, either alone or in combination with pyrimethamine, may represent an effective alternative therapy for TE in patients with AIDS. Whether this supposition can be substantiated by appropriately designed studies is presently being determined.

Acquired Immunodeficiency Syndrome↗