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Biomedical subjects

J M Hofflin

Publications and source records attributed to J M Hofflin.

10 recordsLinked to original sources

Laboratory-acquired Chagas disease.

A laboratory technician developed fever, malaise, headache and non-tender erythematous swelling proximal to the site of accidental inoculation of his thumb, 24 days earlier, with a needle contaminated with Trypanosoma cruzi. Findings included a characteristic rash, remarkable fever, relative bradycardia and leukopaenia--T lymphopaenia with maintenance of a normal helper/suppressor ratio. Trypanosomes were not detected in blood concentrates or in biopsies of an enlarged lymph node and a skin lesion. T. cruzi antibody was first detected 33 days after the laboratory accident, when parasites were first isolated. Therapy with nifurtimox was well tolerated and the patient's serology became negative 9 months after the accident.

Adult↗

Murine model of intracerebral toxoplasmosis.

We established a murine model of toxoplasmic encephalitis by using intracerebral inoculation with Toxoplasma gondii tachyzoites. Normal mice survived, but immunosuppressed mice died from progressive disease. In normal mice, necrosis developed at the site of inoculation, surrounded by areas with intense mononuclear inflammation and cyst formation; tachyzoites were not detectable after two weeks. Immunosuppressed mice had even-larger areas of tissue destruction, and tachyzoites were always detectable. Brains from cortisone-treated mice had numerous tachyzoites, but scant inflammation. Brains from cyclophosphamide-treated mice revealed cysts and a variable degree of inflammation. Compared with brains from controls, brains from cyclosporine-treated mice revealed attenuated inflammation; however, there were fewer tachyzoites and less tissue destruction than in the brains from cortisone-treated mice. The spectrum of histological findings observed in the model is similar to that observed in brains from humans with toxoplasmic encephalitis.

Animals↗

In vivo synergism of roxithromycin (RU 965) and interferon against Toxoplasma gondii.

We investigated the activity of roxithromycin (RU 965) and gamma interferon alone and in combination in a murine model of toxoplasmic encephalitis. Roxithromycin at a dosage of 35 or 50 mg per mouse per day decreased mortality. Gamma interferon alone significantly prolonged time to death. When combined, the two agents were remarkably synergistic.

Animal Feed↗

Clindamycin in a murine model of toxoplasmic encephalitis.

We investigated the efficacy of clindamycin in a murine model of toxoplasmic encephalitis using direct intracerebral inoculation. Clindamycin reduced mortality from 40% in normal mice and 100% in cortisone-treated mice to 0% in both groups. Although we were unable to document appreciable levels of clindamycin in the brains of infected mice, the histological features of cerebral infection were markedly altered. The formation of large numbers of cysts and the intense inflammatory response seen in the brains of normal mice and the unchecked infection and tissue necrosis in the brains of cortisone-treated mice were absent in the brains of clindamycin-treated mice. Enumeration of cysts in the brains of mice 10 weeks after infection revealed a significantly lower number in the clindamycin-treated mice. Spread of infection to other organs was also decreased during clindamycin administration. These observations suggest that clindamycin may have a role in the therapy of toxoplasmic encephalitis.

Animals↗

Infectious complications in heart transplant recipients receiving cyclosporine and corticosteroids.

The rate of infectious complications differed significantly in two groups of heart transplant recipients who received different immunosuppressive regimens. Compared with patients who received conventional immunosuppression, patients treated with cyclosporine had a lower rate of infectious complications, and the contribution of infection to observed mortality was lower. Herpes simplex virus caused less morbidity and there were fewer active cytomegalovirus infections in seropositive recipients treated with cyclosporine. The incidence of bacterial pulmonary infections and associated bacteremia also decreased impressively. A decrease in nocardial infections was offset by a rise in those due to Legionella species. The frequency of aspergillosis was decreased by 54% in the cyclosporine-treated group, but half of these infections disseminated beyond the lung and such dissemination was always fatal. Infections with Pneumocystis carinii were significantly less common with cyclosporine-based immunosuppression. Screening serologic tests for toxoplasma should be done routinely and consideration given to prophylaxis in heart transplant recipients at high risk.

Adolescent↗

Infectious complications in heart-lung transplant recipients.

Infectious complications were studied in 14 patients who received heart-lung transplants at Stanford University Medical Center from March 1981 to November 1983. Twenty-nine infections occurred in 12 patients: 18 bacterial, nine viral, and two fungal. Sixteen (89 percent) of the bacterial infections occurred in the lung. Because of frequent colonization of the lower respiratory tract, the specificity of transtracheal aspiration and bronchoscopy was low. Empiric broad-spectrum antibiotic therapy was usually successful, and no patient died of bacterial infection. Cytomegalovirus infection occurred in six and herpes simplex virus infection in three patients. Two patients had invasive candidiasis at postmortem examination. This series emphasizes the importance of infection, particularly of the lung, in causing morbidity and mortality in heart-lung transplant recipients.

Adult↗

In vivo recombinant interleukin 2 administration enhances survival against a lethal challenge with Toxoplasma gondii.

Administration of recombinant interleukin 2 (rIL 2) resulted in a significant (p less than 0.01) decrease in mortality in mice infected with a dose of Toxoplasma gondii that killed 100% of untreated mice. Mice treated with rIL 2 had a significantly (less than 0.005) lower numbers of cysts in the brains. The protection afforded by rIL 2 could not be correlated with increased antibody synthesis or be explained by increased macrophage killing in the treated mice. Mice treated with rIL 2 after Toxoplasma infection demonstrated increased natural killer (NK) cell activity compared with either Toxoplasma-infected or rIL 2-treated mice. rIL 2 failed to reverse the suppressed proliferative response of lymphocytes to concanavalin A and lipopolysaccharide in mice acutely infected with a virulent strain of T. gondii. These results reveal that rIL 2 may have a remarkably protective effect against intracellular parasites.

Animals↗

Tissue culture isolation of Toxoplasma from blood of a patient with AIDS.

A man with acquired immunodeficiency syndrome and multiple opportunistic infections developed central nervous system signs, and results of computed tomography suggested brain abscess. Histologic study and culture of material obtained from the brain biopsy specimen revealed Aspergillus. The clot from a peripheral venous blood sample obtained at the time of biopsy was processed and cultured on a monolayer of L cells. Five days later, Toxoplasma tachyzoites were identified in the cell culture. We bring this case to the attention of the medical community to point out that inoculation of tissue cell cultures as for viral isolation may aid in the diagnosis of Toxoplasma infection in these and other immunocompromised patients.

Acquired Immunodeficiency Syndrome↗