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Biomedical subjects

W Borkowsky

Publications and source records attributed to W Borkowsky.

At least 73 records · Page 4Linked to original sources

Evolution of phenotypic memory T cells in HIV-1 infected infants and children.

Infants are reported to be devoid of memory T cells at birth but acquired them with time. A cross-sectional study of peripheral blood mononuclear cells from HIV-infected and uninfected infants and children that bear the CD4R0 antigen was undertaken to describe the development of memory T cells. Linear regression lines derived from the data revealed increasing percentages of memory CD4 and CD8 cells in the uninfected children. Memory CD4 cells in the infected children were detected at a frequency equal to or greater than that seen in uninfected children until 6 months of age but subsequently declined with age. In contrast, memory CD8 cells were found to be significantly increased in HIV-infected children early in life with a rate of increase similar to that seen in the uninfected population. This increase in memory CD8 cells may facilitate the early diagnosis of HIV infection.

CD4-Positive T-Lymphocytes↗

Cell-mediated and humoral immune responses in children infected with human immunodeficiency virus during the first four years of life.

OBJECTIVES: To determine whether cell-mediated and humoral immune responses to recall antigens develop in children infected with the human immunodeficiency virus (HIV) and, if so, whether these responses are retained. METHODS: Children infected with HIV and uninfected children born to mothers infected with HIV were compared with respect to lymphoproliferative responses to recall antigens and protective levels of antibody to bacterial toxoids during the first 4 years of life. RESULTS: Children infected with HIV who were enrolled in a prospective study of the natural history of the infection were relatively normal (1) in their lymphoproliferative responses to diphtheria toxoid, tetanus toxoid, and Candida, and (2) in their ability to make protective diphtheria and tetanus antitoxins during the first 2 years of life. During the next 2 years, attrition was noted in both lymphoproliferative and humoral responses. Attrition in response was not necessarily correlated with declining numbers of helper T cells. CONCLUSIONS: These results suggest that both cellular and humoral immune responses develop early in life in most children infected with HIV, while they remain relatively well both clinically and immunologically. Previously reported severe immune deficits in these children were probably attributable to advanced clinical disease when they were first studied.

Age Factors↗

Fatal disseminated infection with human herpesvirus-6.

A 13-month-old immunocompetent girl had fever, rash, and multisystem disease, and she eventually died of cardiac failure. Autopsy revealed intracellular viral inclusions of the herpesvirus group, with results of in situ hybridization positive for human herpesvirus-6. This is apparently the first case of fatal disseminated herpesvirus-6 infection.

Exanthema Subitum↗

Early diagnosis of human immunodeficiency virus infection in children less than 6 months of age: comparison of polymerase chain reaction, culture, and plasma antigen capture techniques.

Three techniques were evaluated for their ability to detect human immunodeficiency virus (HIV) in infants from birth to 6 months of age. Polymerase chain reaction (PCR) and HIV cocultivation were of comparable sensitivity, detecting 90% of all positive specimens. Both techniques found positive results in approximately 5% of samples from seroreverting children. Both assays detected HIV in only half of infected newborns, suggesting that this fraction of children was infected during gestation. Plasma p24 antigen was detected in three-fourths of all samples tested but in only half of infected children during the first 2 months of life and 88% of samples from children during the next 4 months. The specificity of p24 antigen detection was 100%.

Cells, Cultured↗

Lack of predictive value of maternal human immunodeficiency virus p24 antigen for transmission of infection to their children.

The association of maternal-to-infant transmission of human immunodeficiency virus type 1 (HIV-1) with maternal p24 antigenemia was assessed in 86 HIV-1-infected mothers. We retrospectively examined serum or plasma samples collected in the peripartum period (delivery +/- 11 days; sd 16.89 days; range, delivery +/- 2 months). Immune complexes of p24 antigen and anti-p24 antibody were dissociated using acid hydrolysis (Method A, glycine-HCl buffer; Method B, HCl) in an attempt to increase the sensitivity of the test. The detection of HIV-1 p24 antigenemia in serum was increased from 23 of 86 (26.7%) to 37 of 82 (45.1%) following acid hydrolysis with Method A (chi square = 5.4, P = 0.02) and to 36 of 78 (46.1%) with Method B (chi square = 5.874, P = 0.015). Mothers of HIV-1-infected children were no more likely to have p24 antigenemia than mothers of seroreverted infants when untreated samples were assayed (7 of 23 vs. 10 of 48; chi square = 0.348, P = 0.55). Although acid hydrolysis increased the ability to detect p24 antigen, it did not enhance any association between p24 antigenemia and maternal-to-infant transmission of HIV infection: Method A, 9 of 23 in mothers of infected children vs. 21 of 45 in mothers of seroreverted children (chi square = 0.112, P = 0.738); and Method B, 9 of 22 in mothers of infected children vs. 18 of 42 in mothers of seroreverted children (chi square = 0.014; P = 0.907), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Varicella does not appear to be a cofactor for human immunodeficiency virus infection in children.

We performed a retrospective analysis of longitudinal clinical and immunologic data obtained from 22 children in the early stages of infection with human immunodeficiency virus (HIV) when they developed varicella. We studied the course of HIV infection to determine whether clinical deterioration occurred after chickenpox. We examined the following indices: growth and development; neurologic status; helper T lymphocyte counts; blood values of core (p24) antigen of HIV; changes in the stage of HIV infection; and need for administration of zidovudine. We studied children for a mean of 2.8 years and for as long as 9.8 years after onset of varicella. There was little evidence that chickenpox affected HIV infection. Three (14%) children developed clinical zoster, 2 of whom (9%) had evidence of chronic infection with varicella-zoster virus. One additional child (5%) had 2 episodes of chickenpox. These observations suggest that children with early HIV infection could be considered for immunization with live attenuated varicella vaccine, which would be predicted to decrease their morbidity from varicella-zoster virus.

CD4-Positive T-Lymphocytes↗

Delayed recognition of human immunodeficiency virus infection in preadolescent children.

Thirty-two (18%) of 181 children cared for at our institution who were infected with the human immunodeficiency virus type 1 (HIV-1) were first seen, and HIV was diagnosed, when they were 4 years of age and older. Initial complaints or diagnoses for these children included the following: hematologic disorders (5) (3 idiopathic thrombocytopenic purpura, 1 neutropenia, 1 anemia); recurrent bacterial infections (10); Pneumocystis carinii pneumonia (3); developmental delay (1); skin disorders (2) (1 genital wart, 1 chronic zoster); weight loss (3); malignancy (1); and nephropathy (1). Eight children were referred for evaluation because of maternal HIV-1 infection. The risk factors for HIV-1 infection included maternal/perinatal exposure (22), perinatal blood transfusion (6), blood transfusion during infancy (2), and sexual abuse (2). Ten (31%) of the 32 children have subsequently died. The longest survival from perinatal infection was 12 years. HIV-1 infection in children can result in a prolonged clinical latency and can masquerade as other pathologic conditions. The absence of clinical symptoms in older children at risk for HIV-1 infection should not deter HIV testing.

Child↗

Opportunistic infections and tumors in immunocompromised children.

HIV infection is responsible for a major proportion of the immunodeficiency disease seen in the pediatric population. The radiologic findings are varied and generally non-specific. The development of secondary neoplasms may present new diagnostic and therapeutic challenges as therapy for superimposed infections becomes more successful.

Child↗

Perinatal human immunodeficiency virus infection: ruminations on mechanisms of transmission and methods of intervention.

Perinatal human immunodeficiency virus (HIV) infection is undoubtedly a multifactorial process. Neither the quantity of viremia nor the level of neutralizing antibody in the infected mother is alone predictive of HIV transmission to her offspring. Additional cofactors may include the ability of maternal immunity to control the host cell range and rate of viral replication. The placenta probably constitutes an effective barrier to viral transmission unless disrupted by processes such as syphilis. Prevention of such breaks in the trophoblast barrier and efforts to stimulate maternal and newborn HIV-specific immunity may further decrease the perinatal transmission rate.

Female↗

Chronic varicella zoster in a child infected with human immunodeficiency virus: case report and review of the literature.

Chronic zoster represents an infrequent presentation of varicella zoster virus infection. It is observed with increased frequency in patients infected with human immunodeficiency virus, especially when their lymphocyte counts are depressed. We report a child infected with human immunodeficiency virus who showed a long-standing cutaneous zoster lesion and was treated for a prolonged period of time with acyclovir. The occurrence of resistance to acyclovir by varicella zoster virus was suspected based on the clinical picture. The clinical and laboratory features of this case and a review of the literature are presented.

Acyclovir↗

A multicenter trial of oral zidovudine in children with advanced human immunodeficiency virus disease. The Protocol 043 Study Group.

BACKGROUND AND METHODS: Zidovudine has been shown to be an effective antiretroviral treatment in adults with human immunodeficiency virus (HIV) infection. We examined the safety of zidovudine and the tolerance of and therapeutic response to the drug in 88 children with advanced HIV disease. During a 24-week outpatient trial, zidovudine (180 mg per square meter of body-surface area per dose) was given by mouth every six hours and serial measurements were made of clinical, immunologic, and virologic indexes. Children who completed 24 weeks of treatment were permitted to continue receiving zidovudine. RESULTS: Of the 88 children (mean age, 3.9 years; range, 4 months to 11 years), 61 completed the initial 24-week trial, and 49 continued to receive zidovudine for up to 90 weeks (median follow-up, 56 weeks). The patients generally tolerated zidovudine well. One or more episodes of hematologic toxicity occurred in 54 children (61 percent)--anemia (hemoglobin level, less than 75 g per liter) in 23 children (26 percent) and neutropenia (neutrophil count, less than 0.75 x 10(9) per liter) in 42 (48 percent). Many of these abnormalities resolved spontaneously, but 30 children required transfusions or a modification of the dose of zidovudine. Only three children had to stop receiving the drug because of hematologic toxicity. Kaplan-Meier analysis demonstrated that the probability of survival was 0.89 after 24 weeks and 0.79 after 52 weeks. There was marked improvement in weight gain, cognitive function (mainly in children less than 3 years old), serum and cerebrospinal fluid concentrations of p24 antigen, and the proportion of cerebrospinal fluid cultures negative for HIV. CD4+ lymphocyte counts (mean at base line, 0.263 x 10(9) per liter) improved during the first 12 weeks, although the improvement was not sustained through the 24th week. CONCLUSIONS: Zidovudine in a dose of 180 mg per square meter every six hours can be safely administered to children with advanced HIV disease. The resultant clinical, immunologic, and virologic improvements in children are similar to those reported with zidovudine in adults.

Acquired Immunodeficiency Syndrome↗

Laboratory diagnosis of HIV infection.

Laboratory diagnosis of human immunodeficiency virus (HIV) infection is complicated by absence of data on sensitivity, specificity and predictive value of the various tests as they apply to children. The presence of maternal anti-HIV passively transmitted across the placenta also confounds diagnosis. The authors review currently available data on the detection of HIV, HIV genome, and HIV gene products, as well as the diagnostic value of detecting serologic and cellular responses to HIV in infants and children.

AIDS Serodiagnosis↗

Pathology and human immunodeficiency virus expression in placentas of seropositive women.

The pathology of term placentas from seropositive human immunodeficiency virus (HIV)-infected and seronegative women was investigated by routine histologic, immunocytochemical, and in situ hybridization techniques. Placentas were evaluated for evidence of villitis, chorioamnionitis, and funisitis. Membranes, trophoblast, and decidua were also examined by immunohistochemistry using monoclonal HIV p24 antibody. Twenty placentas were evaluated by combined immunochemical and in situ hybridization techniques, using a 35S-labeled RNA probe complementary to the 3' long terminal repeat and envelope region of HIV-1. HIV-seropositive placentas did not show significant villitis; however, the incidence of chorioamnionitis increased (P less than .01). HIV antigens and nucleic acids were identified in the trophoblast of 10% of the placentas that also showed chorionitis. Term HIV-positive placentas may show histologic changes that may or may not be directly related to the virus. Analysis of tissues from earlier gestational placentas may prove more informative in clarifying the mechanism of maternal-fetal HIV transmission.

Chorion↗

Lymphocyte proliferative responses to HIV-1 envelope and core antigens by infected and uninfected adults and children.

Lymphocytes derived from children and adults infected with the human immunodeficiency virus (HIV-1), as well as from seronegative children and adults, were tested for their ability to proliferate in response to recombinant HIV envelope (env) and core (cor) peptides. Proliferative responses to env were seen in 9% of control children compared with 27% of infected children (p less than 0.02). There was no difference in the response rates of seropositive and seronegative adults (17% and 16%, respectively). Proliferative responses to cor were seen more frequently in children and adults (22% and 28%, respectively) than their seronegative cohorts (11% and 12%, respectively). Also, the proliferative response to env and cor was seen in 27% and 37%, respectively, of seronegative children who were born to seropositive mothers and then subsequently seroreverted. These results suggest that sensitization to HIV recombinant antigens has resulted in a cell-mediated immune response in some HIV-infected individuals. Furthermore, the significant cell-mediated immune response to these antigens in seroreverting children raises the possibility that they may have been sensitized to this antigen by previous HIV infection.

Acquired Immunodeficiency Syndrome↗

A controlled trial of bovine dialyzable leukocyte extract for cryptosporidiosis in patients with AIDS.

Cryptosporidial infection causes severe diarrheal disease in patients with AIDS. Fourteen patients with AIDS and symptomatic cryptosporidiosis were treated with a specific bovine dialyzable leukocyte extract (immune DLE) prepared from lymph node lymphocytes of calves immunized with cryptosporidia or a nonspecific (nonimmune) DLE prepared from nonimmunized calves. Six of 7 patients given immune DLE gained weight and had a decrease in bowel movement frequency, with eradication of oocysts from stool in 5 patients. Six of 7 patients given nonimmune DLE showed no decrease in bowel movement and 4, no clearing of oocytes from stool; 5 continued to lose weight. Subsequently, 5 of these 7 were treated with immune DLE; 4 had a decrease in bowel movement frequency and significant weight gain, with eradication of oocytes from stool in 2 patients. Immune DLE produces sustained symptomatic improvement in patients with AIDS and active cryptosporidiosis, but lack of an appropriate cryptosporidial antigen allows only postulation that an augmentation of cellular immunity to Cryptosporidium parvum induced by immune DLE resulted in the microbiologic and clinical improvement observed.

Acquired Immunodeficiency Syndrome↗