Harold W. Lischner

Detection of Human Immunodeficiency Virus Type 1 Provirus in Mononuclear Cells by in Situ Polymerase Chain Reaction

BACKGROUND Studies of human immunodeficiency virus type 1 (HIV-1) infection have attempted to quantitate the viral load correlate it with the degree of immune deficiency. In one study, only about 1 in 10,000 peripheral-blood mononuclear cells (PBMC) expressed HIV-1, but in other studies, at least 1 in 100 CD4-positive cells was infected and harbored the HIV-1 provirus. METHODS We developed a new, highly sensitive in situ polymerase-chain-reaction (PCR) method that amplifies selected genetic regions within intact single cells. We used this technique to determine the proportion of PBMC carrying HIV-1 provirus in infected patients in different stages of disease. RESULTS None of the PBMC from 11 HIV-1--seronegative patients were found to be positive for HIV-1 provirus by the in situ PCR method. In 56 patients infected with HIV-1, the percentage of PBMC with HIV-1 ranged from 0.1 percent to 13.5 percent. The mean percentage of infected mononuclear cells was greater in 13 patients with persistent generalized adenopathy (mean, 6.6 percent) and 19 with the acquired immunodeficiency syndrome (Stages IV-A to IV-C) (4.6 percent) than in 19 patients with asymptomatic HIV-1 infection (0.9 percent) (P less than 0.001). However, in five patients with Kaposis sarcoma (Stage IV-D), an average of only 1.6 percent of mononuclear cells were infected. CONCLUSIONS In HIV-1 infection, the proportion of PBMC that are infected appears to be at least 10 times higher than previously described. It is likely that most infected cells contain HIV-1 provirus in a latent or defective form that was not detected in some earlier studies.

COMBINATION THERAPY WITH EFAVIRENZ, NELFINAVIR, AND NUCLEOSIDE REVERSE-TRANSCRIPTASE INHIBITORS IN CHILDREN INFECTED WITH HUMAN IMMUNODEFICIENCY VIRUS TYPE 1

BACKGROUND Consistent long-term viral suppression has been difficult to achieve in children with human immunodeficiency virus type 1 (HIV-1) infection. We tested the safety and antiviral efficacy of a novel combination consisting of efavirenz, nelfinavir, and one or more nucleoside reverse-transcriptase inhibitors in 57 children previously treated with only nucleoside reverse-transcriptase inhibitors. METHODS The children were monitored for 48 weeks after the initiation of therapy. We assessed plasma concentrations of efavirenz and nelfinavir, plasma HIV-1 RNA levels, and lymphocyte subpopulations. RESULTS At base line, the 57 HIV-1-infected children (age range, 3.8 to 16.8 years) had a median of 699 CD4 cells per cubic millimeter and 10,000 copies of HIV-1 RNA per milliliter of plasma. The most common treatment-related effects of at least moderate severity were rash (in 30 percent of children), diarrhea (in 18 percent), neutropenia (in 12 percent), and biochemical abnormalities (in 12 percent). Serious side effects were uncommon. The mean values for the area under the curve for efavirenz and nelfinavir corresponded to expected values. In an intention-to-treat analysis, 76 percent of children had plasma HIV-1 RNA levels of less than 400 copies per milliliter after 48 weeks of therapy and 63 percent had levels of less than 50 copies per milliliter. A high plasma HIV-1 RNA level at base line significantly decreased the likelihood that plasma levels of HIV-1 RNA would become undetectable during treatment. CONCLUSIONS In HIV-1-infected children who were previously treated with nucleoside reverse-transcriptase inhibitors, the combination of efavirenz, nelfinavir, and nucleoside reverse-transcriptase inhibitors was generally well tolerated and had a potent and sustained antiviral effect.

Bone marrow transplantation in chronic granulomatous disease

A 5-month-old Amish infant boy with chronic granulomatous disease underwent bone marrow transplantation from his 5-year-old, histocompatible brother after a preconditioning regimen of busulfan 2 mg/kg/day for 4 days, followed by cyclophosphamide 50 mg/kg/day for 4 days. At the time of bone marrow transplantation, he was free of infection, and remained so throughout the course of the transplant. He was engrafted promptly, with complete reversal of the neutrophil function defect and no sign of graft-versus-host disease. This was followed by loss of the erythroid graft and deterioration in neutrophil function over a period of 9 months. Sixteen months after transplantation, he is free of infection and growing normally, with essentially no evidence for neutrophil engraftment.

An outbreak of neonatal deaths among term infants associated with administration of chloramphenicol

Summary The evidence presented strongly suggests that administration of chloramphenicol in previously recommended doses was responsible for an outbreak of early neonatal deaths in a newborn nursery. A death rate of 67 per cent is reported for 12 term infants who received over 110 mg. per kilogram per day and a cumulative dose over several days of 400 mg. per kilogram or more. Death occurred at 2 to 5 days of age after the sudden appearance of vascular collapse. Similar deaths have been reported in connection with chloramphenicol administration, particularly of premature infants, but possibly of certain older children and adults. The striking similarity between this outbreak of deaths, thought to be due to drug administration, and any outbreak of infectious disease emphasizes the need for broad epidemiologic investigation of any unusual occurrence in a newborn nursery.

Inflammatory demyelinating polyneuropathy in a child with symptomatic human immunodeficiency virus infection.

Children and adults infected with the human immunodeficiency virus may have involvement of the gray and white matter of the brain and spinal cord. l Peripheral nerve involvement is also common in adults with HIV infection2; acute or chronic inflammatory demyelinating polyneuropathy 3 and a predominantly secondary neuropathy with little histopathologic evidence of inflammation may occur. 4 The latter is the most common peripheral neuropathy in HIV-infected patients and usually occurs during the symptomatic period of disease, whereas IDP is usually noted during asymptomatic phases of the illness. Symptomatic peripheral neuropathy of any type has not been described in HIV-infected children. We describe a case of IDP in a child with symptomatic HIV infection.

Multicentric reticulohistiocytosis in a child

1. Hereditary spherocytosis and other hemolytic anemias associated with abnormalities of the red cell membrane. In: Wintrobe MM, Lee GR, Boggs DR, et al., eds. Clinical hematology. Philadelphia: Lea & Febiger, 1981:747-8. 2. Fukagawa N, Friedman S, Gill FM, et al, Hereditary spherocytosis with normal fragility after incubation. JAMA 1979;242:63-4. 3. Dacie JV, Mollison PL, Richardson N, et al. Atypical congenital haemolytic anemia. QJ Med 1953;22:79-99. 4. Zail SS, Krawitz P, Viljoen E, et al. Atypical hereditary spherocytosis: biochemical studies and sites of erythrocyte destruction. Br Med J 1967;13:323-34. 5. Lefrere J J, Courouce AM, Girot R, et al. Six cases of hereditary spherocytosis revealed by human parvovirus infection. Br J Haematol 1986;62:653-7. 6. Dameshek W, Bloom ML. The events in the hemolytic crisis of hereditary spherocytosis, with particular reference to the reticulocytopenia, pancytopenia and abnormal splenic mechanism. Blood 1948;3:1381-409. 7. Paolino W. Variations of the mean diameter in the ripening of the erythrocyte. Acta Med Scand 1949;136:141-7. 8. Griggs RC, Weisman R, Harris JW. Alterations in osmotic fragility related to in vivo erythrocyte aging and splenic sequestration in hereditary spherocytosis. J Clin Invest 1960;39:89-101. 9. Crosby WH, Conrad ME. Hereditary spherocytosis: observations on hemolytic mechanisms and iron metabolism. Blood 1960;15:662-74. 10. Lux SE. Disorders of the red cell membrane. In: Nathan D, Oski F, eds. Hematology of infancy and childhood. Philadelphia: WB Saunders, 1987:488-9.

BONE MARROW TRANSPLANTATION |[lpar]|BMT|[rpar]| IN CHRONIC GRANULOMATOUS DISEASE |[lpar]|CGD|[rpar]|

A 5 month-old Amish male infant with CGD underwent BMT from his 5 year-old, histocompatible brother after a preconditioning regimen of busulfan 8 mg/kg and cyclophosphamide 200 mg/kg. At the time of BMT, he was free of infection and remained so through the course of his transplant. He engrafted promptly with complete reversal of the neutrophil function defect (Table), and no sign of graft vs. host disease. This was followed by loss of the erythroid graft and gradual deterioration in neutrophil function (Table). Now, 16 months after BMT, he is free of infection, growing normally with essentially no evidence for neutrophil engraftment.

Somatosensory Evoked Potential Abnormalities in HIV-Infected Children are More Frequent Than in HIV-Exposed Children, Reflecting the Degree of HIV-Related Neurological Disease

Somatosensory Evoked Potential Abnormalities in HIV-Infected Children are More Frequent Than in HIV-Exposed Children, Reflecting the Degree of HIV-Related Neurological Disease

Lymphoproliferative Responses to HIV-Specific Antigens in the HIV-Infected Pediatric Patient

Lymphoproliferative Responses to HIV-Specific Antigens in the HIV-Infected Pediatric Patient

Assessment of Psychiatric Comorbidity in Children Infected with Human Immunodeficiency Virus, Type 1

Assessment of Psychiatric Comorbidity in Children Infected with Human Immunodeficiency Virus, Type 1