Evaluating contrast-enhancing brain lesions in patients with AIDS by using positron emission tomography.

OBJECTIVE: To determine whether a noninvasive method for evaluating contrast-enhancing brain lesions in patients with the acquired immunodeficiency syndrome (AIDS) can accurately differentiate between lymphoma and nonlymphoma diagnoses. This method is based on Toxoplasma serologic testing and positron emission tomography. DESIGN: Prospective, nonrandomized, criterion-standard clinical study. SETTING: An academic center in the mid-southeastern United States. PATIENTS: 20 patients with AIDS and contrast-enhancing brain lesions. INTERVENTIONS: Positron emission tomographic scanning and Toxoplasma serologic testing. MAIN OUTCOME MEASURE: Diagnoses were confirmed by clinical response, autopsy, or brain biopsy. RESULTS: Eight patients had a confirmed diagnosis of toxoplasmosis, six had lymphoma, four had other diagnoses, and two were not evaluable. Seven of eight patients with toxoplasmosis had positron emission tomographic scans; all of these scans showed hypometabolic lesions consistent with a nonlymphoma diagnosis. The six patients with lymphoma all had hypermetabolic lesions on positron emission tomographic scans. The difference between these two sets of results was statistically significant (P < 0.001, Fisher exact test, two-tailed). The anti-Toxoplasma titer was greater than or equal to 1:4 in all patients with confirmed toxoplasmosis who had serologic testing and in three of six patients with lymphoma. CONCLUSIONS: Evaluating contrast-enhancing brain lesions in patients with AIDS by using Toxoplasma serologic testing and positron emission tomography can accurately guide therapy and obviate the need for most brain biopsies in these patients. A larger, national, multicenter study is needed to confirm our findings and to determine the effect of earlier diagnosis and treatment on morbidity and mortality in patients with AIDS and primary central nervous system lymphoma.

Isolation of human immunodeficiency virus from peritoneal dialysate.

Human immunodeficiency virus (HIV)-seropositive individuals represent a growing population of peritoneal dialysis (PD) patients. An important health care issue in these patients is the potential for their PD fluid to transmit virus. Some body fluids, such as urine, have been demonstrated to be negative for HIV and therefore presumably to be of low risk for virus transmission. To determine whether HIV could be recovered from PD fluid, we cultured the PD fluid from two asymptomatic HIV-seropositive patients and one patient with the acquired immunodeficiency syndrome (AIDS). HIV was isolated from both the PD fluid and the blood of two of the three patients tested, one being only HIV-seropositive and one with AIDS. These findings indicate that such fluid could potentially be a source of viral transmission and emphasize the need for conscientious application of universal precautions both in and out of the hospital.

Effect of the calcium channel blocker verapamil on human immunodeficiency virus type 1 replication in lymphoid cells.

Cell signaling events are known to affect human immunodeficiency virus type 1 (HIV-1) replication. Treatment of lymphoid CEM cells with the calcium channel blocker verapamil (25-75 microM) enhanced HIV-1 expression in acute, whole virus infection experiments, despite lowering intracellular calcium levels, ablating the acute rise in intracellular calcium normally seen with infection, and lengthening the doubling time of cell replication. Verapamil had no effect on cell surface CD4 expression. Transfection of CEM cells with plasmids containing the HIV-1 long terminal repeat linked to the chloramphenicol acetyltransferase reporter gene showed that verapamil enhanced expression of the HIV-1 long terminal repeat in a dose-dependent fashion. This effect was abolished by mutations in the binding sites for nuclear factor kappa-B. Electrophoretic mobility shift assays confirmed that verapamil induced nuclear factor kappa-B activity in CEM cells. Thus, verapamil, in high concentrations, can potentiate HIV-1 replication in lymphoid cells, and this effect may be mediated by induction of nuclear factor kappa-B.

Infiltration of the lower respiratory tract by helper/inducer T lymphocytes in HTLV-1-associated adult T-cell leukemia/lymphoma.

The human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATLL), a disorder in which peripheral blood and multiple organs are infiltrated by malignantly transformed T lymphocytes. We investigated the nature of pulmonary disease in a patient with serologic evidence of HTLV-1 infection. In this case, endobronchial biopsy specimens showed infiltration of the bronchial mucosa by pleomorphic cells exhibiting a high degree of nuclear irregularity. These cells were morphologically identical in appearance to malignant cells found in peripheral blood and infiltrating the dermis, expressed the OKT4/Leu3 phenotype and the receptor for interleukin 2, and, by analogy to gene rearrangement studies on leukemic blood cells, were monoclonal in origin. However, in situ hybridization of endobronchial biopsy specimens with full-length HTLV-1 probes failed to detect retroviral RNA or proviral DNA. These studies indicate that T lymphocytic involvement of the lower respiratory tract in HTLV-1-associated ATLL is characterized by expression of a malignant phenotype despite the inability to document actual cellular infection with this retrovirus by a molecular hybridization technique.

Effects of recombinant soluble CD4 (rCD4) on HIV-1 infection of monocyte/macrophages.

Recombinant soluble CD4 (rCD4) was tested for its ability to block acute human immunodeficiency virus (HIV) infection in the U937 monocytic cell line and in human pulmonary alveolar macrophages (PAM) and for its ability to prevent transfer of virus from chronically infected PAM to target peripheral blood mononuclear leukocytes (PMNL). With an initial virus inoculum of 10(3)-10(4) TCID50/ml, rCD4 completely prevented acute HIV infection of U937 cells at concentrations greater than or equal to 1 microgram/ml and provided substantial but incomplete protection at 0.1 microgram/ml. With an initial virus inoculum of 10(2) TCID50/ml, rCD4 completely prevented acute infection of PAM at concentrations greater than or equal to 0.1 microgram/ml. The transmission of HIV-1 infection to PMNL cocultured with chronically infected PAM was completely inhibited at concentrations greater than or equal to 1 microgram/ml if cell-to-cell contact was prevented. With direct PAM-PMNL contact, substantial inhibition was obtained at an rCD4 concentration of 10 micrograms/ml, and higher concentrations (200 micrograms/ml) could completely block transfer. These results demonstrated that rCD4 can be effective in preventing de novo infection of cells of the monocyte/macrophage lineage, but microenvironments where cell-to-cell contact predominates are likely to pose a formidable challenge to this therapeutic strategy.

Inactivation of human immunodeficiency virus by Betadine products and chlorhexidine.

Eleven povidone-iodine-containing products (Betadine) and chlorhexidine gluconate solution were tested for their ability to inactivate human immunodeficiency virus (HIV) in a cell culture system. All Betadine products completely inactivated the virus at povidone-iodine concentrations of greater than or equal to 0.5% (10- to 20-fold dilutions of stock) except for Betadine Lubricating Antiseptic Gel, which required 2.5% for efficacy (1:2 dilution). Chlorhexidine gluconate completely inactivated HIV at concentrations of greater than or equal to 0.2% (1:100 dilution of laboratory stock; 1:20 dilution of commercial stock). Betadine douche and medicated douche did not inactivate HIV at the concentrations recommended for clinical use (0.33% and 0.25%, respectively) but were effective at povidone-iodine concentrations of 0.5%. Inactivation appeared to be immediate since no difference in efficacy based on length of exposure to the microbicide was detected. Thus, both microbicides are highly effective at killing HIV in vitro.

Ganciclovir therapy of severe cytomegalovirus infections in solid-organ transplant recipients.

The clinical and virologic efficacy of ganciclovir (9-[1,3-dihydroxy-2-propoxymethyl]guanine) in the treatment of severe CMV infections in solid organ transplant recipients was investigated. Twelve patients (9 liver and 3 kidney transplant recipients) with CMV retinitis, esophagitis, hepatitis, or pneumonia received ganciclovir at a dose of 0.75-7.5 mg/kg/day for 10-30 days (mean duration 17 days). Clinical stabilization or improvement occurred in 8 patients (67%). Serial liver biopsies in 6 liver allograft recipients with CMV hepatitis demonstrated substantial histologic improvement on treatment. Of 6 patients with CMV pneumonia, 4 (67%) recovered and survived. Cultures of blood and other sites became negative in 9 patients (75%). Three patients (25%) had recurrent viral shedding after treatment, but none of these relapsed with invasive infections. Mild neutropenia was the only side effect encountered but was frequent (67%). The overall survival rate was 50%. Ganciclovir is effective in reducing CMV shedding in solid organ transplant recipients and is well tolerated. Our experience suggests a clinical benefit as well in patients with severe, invasive CMV disease. Relapse, in contrast to patients with the acquired immunodeficiency syndrome, is infrequent.

Acyclovir-associated fever: a case report.

Drug-induced fever has been associated with many agents. We treated a patient who developed high, spiking fevers while receiving intravenous acyclovir. Rechallenge with the drug was not attempted. Clinicians should be aware of the possibility of drug-induced fever in patients who receive systemic acyclovir.

Effects of oral digoxin on ventricular ectopy and its relation to left ventricular function.

The ventricular antiarrhythmic properties of oral digoxin were examined in 13 patients with chronic ventricular ectopy using serial 24-hour electrocardiographic monitoring. Mean premature ventricular complex frequency (per 1,000 normal beats) decreased from 56 +/- 47 during the placebo period to 40 +/- 27 (p = not significant [NS]) and 25 +/- 17 (p less than 0.05) during daily administration of digoxin, 0.25 and 0.375 mg. Digoxin had no significant effect on the qualitative occurrence of complex ventricular arrhythmia patterns (multiformity, bigeminy, couplets, ventricular tachycardia). Radionuclide left ventricular (LV) ejection fraction was measured during the placebo period. Seven patients had normal (ejection fraction greater than 50%) and 6 abnormal global LV performance. In the normal group, the mean premature ventricular complex frequency decreased from 69 +/- 58 to 20 +/- 18 (p less than 0.05) and the mean couplet frequency decreased from 0.59 +/- 0.85 to 0.07 +/- 0.06 (p less than 0.04) during the placebo and 0.375 mg digoxin dosing periods, respectively. In contrast, no significant changes in either variable occurred after digoxin in subjects with depressed LV function. This study indicates that oral digoxin is moderately effective in suppressing premature ventricular complexes, and that its effects are greatest in patients with normal overall LV performance.