Tamara Rakusan

Basic fibroblast growth factor in HIV-associated hemolytic uremic syndrome

Abstract Endothelial injury is the primary pathogenic event leading to the renal thrombotic microangiopathic lesions typical of the hemolytic uremic syndrome (HUS). Basic fibroblast growth factor (bFGF) is an angiogenic growth factor released by injured endothelial cells. In a previous study we have found a significant accumulation of bFGF in human immunodeficiency virus (HIV)-transgenic mice with renal disease. Here we investigated whether bFGF was accumulated in the circulation and kidneys of two children with HIV-associated HUS (HIV-HUS), and studied the mechanisms involved in this process. The plasma levels of bFGF in children with HIV-HUS (124±20 pg/ml) were increased compared with five children with HIV nephropathy (49±6 pg/ml) and twenty HIV-infected children without renal disease (26±4 pg/ml, P<0.001). Immunohistochemistry and receptor binding studies showed that bFGF was accumulated bound to heparan sulfate proteoglycans in renal glomeruli and interstitium surrounding renal tubules in HIV-HUS kidneys. Basic FGF stimulated the proliferation of mesangial and urinary renal tubular epithelial cells isolated from both patients. These findings support the hypothesis that bFGF and its low-affinity binding sites may play a relevant role in modulating the process of glomerular and renal tubular regeneration during the acute stages of HIV-HUS. A follow-up study in a larger sample population is required to confirm these results.

Human immunodeficiency virus-infected adolescents: a descriptive study of older children in New York City, Los Angeles County, Massachusetts and Washington, DC.

Background. Children infected with HIV are entering adolescence with challenging and changing medical and social needs. Through chart review we describe certain medical and social characteristics of adolescents who acquired HIV as children. Methods. HIV‐infected children 12 years of age and older in 1995 were monitored through the Pediatric Spectrum of HIV Disease study from four US sites. In addition to standard 6‐month medical chart reviews, a special chart abstraction in 1997 collected available psychosocial and sexual history information. Results. A total of 131 adolescents HIV‐infected as children were studied: 52 infected perinatally; 44 infected through a contaminated blood transfusion; 30 through receipt of contaminated blood products for hemophilia; and 5 with unknown transmission mode. Mean age at last medical contact was 15.5 years, 67% were Hispanic or African‐American, 12% were employed, 66% attended regular school, 66% knew their HIV status and 48% (8% for the perinatally infected) lived with their biologic mother. Information on sexual activity showed that 18% had sexual relations, 28% did not and for 53% sexual activity was not recorded in the medical chart. Four percent used illicit drugs, which along with sexual activity showed a positive association with age. Forty‐two percent had an AIDS‐defining opportunistic infection, and 56% had a recent CD4+ lymphocyte count <200 cells/&mgr;l. Conclusions. Adolescents in this study represent a heterogeneous group of surviving HIV‐infected children some of whom are sexually active and potential sources of HIV transmission. Clinicians who treat HIV‐infected and high risk adolescents face the challenges of providing care and prevention services appropriate to adolescent development.

Lack of Definitive Severe Mitochondrial Signs and Symptoms among Deceased HIV-Uninfected and HIV-Indeterminate Children ≤ 5 Years of Age, Pediatric Spectrum of HIV Disease Project (PSD), USA

Abstract: Background: In response to recent reports of mitochondrial dysfunction in HIV‐uninfected infants exposed to antiretroviral (ARV) prophylaxis, the Perinatal Safety Review Working Group reviewed deaths in five large HIV‐exposed perinatal cohorts in the United States to determine if similar cases of severe mitochondrial toxicity could be detected. We describe the results of this review for the PSD cohort.

Increasing trend of Cesarean deliveries in HIV-infected women in the United States from 1994 to 2000.

Background: Meta‐analysis and randomized clinical trial results reported in June 1998 indicated a significant reduction in perinatal HIV transmission rates among mothers undergoing a cesarean section (C‐section). Objective: The objective of this study was to examine recent trends in and factors associated with C‐section deliveries among HIV‐infected women in the United States. Design: A multisite pediatric medical record review of a cohort of HIV‐exposed and HIV‐infected infants in the Pediatric Spectrum of HIV Disease (PSD) Cohort study (n = 6467) and the national Pediatric HIV/AIDS Reporting System (HARS) (n = 8,306) was conducted. Setting/Patients: All infants born between 1994 and 2000 to HIV‐positive mothers referred to the PSD study or to a Pediatric HARS hospital or clinic site were enrolled. Results: The proportion of deliveries by C‐section was steady at about 20% from 1994 through June 1998. From July 1998 through December 2000, this proportion increased to 44% in the PSD study and to nearly 50% in the Pediatric HARS. On analysis by multiple logistic regression, delivery of infants by C‐section was associated with the release of study results (OR = 2.83), delivery in four PSD sites in reference to Texas (OR: 2.02‐1.43), having private medical care reimbursement (OR = 1.62), and having maternal prenatal care (OR = 1.43). Conclusions: The PSD and Pediatric HARS data demonstrate a sharp increase in C‐section rates mainly among HIV‐infected women in the United States after the release of the meta‐analysis and randomized clinical trial results in 1998. This finding highlights the rapid impact of study results on obstetric practice. It underscores the critical role of prenatal care in offering perinatal interventions such as scheduled C‐section when indicated to reduce the likelihood of HIV transmission.

Atypical hemolytic uremic syndrome in human immunodeficiency virus-1-infected children

Abstract. We describe the clinical and pathological findings of the hemolytic uremic syndrome (HUS) in two children with human immunodeficiency virus (HIV) infection. Both patients presented with microangiopathic hemolytic anemia, thrombocytopenia, and subsequently developed renal failure. The diagnosis of HUS was confirmed by renal histopathology in both patients. None of these children presented with bloody diarrhea, evidence of circulating antibody response to Escherichia coli O157 lipopolysaccharide, or other known risk factors for HUS, except for the presence of HIV infection. Each patient was treated with intravenous plasma infusion and renal replacement therapy. Their clinical course was characterized by non-oliguria and lack of significant hypertension throughout the acute phase of the disease. Despite these favorable clinical parameters, both patients developed end-stage renal failure. The etiology of this atypical HUS characterized by poor renal survival remains unknown and the role of HIV infection in its pathogenesis, although possible, is unclear.

Spectrum of chest radiographic abnormalities in children with AIDS and Pneumocystis carinii pneumonia

This report aims to provide a description of the spectrum of radiographic findings in children with AIDS andPneumocystis carinii pneumonia (PCP). The chest radiographs of all children with perinatally transmitted HIV infection who had PCP were reviewed. Thirtyeight episodes of PCP were noted in 32 children. The age range was 2–17 months. The radiographic findings were characterized as to pattern, severity, presence of pulmonary air cyst, thoracic air leak, thoracic lymphadenopathy, and pleural effusion. The initial distribution of disease was as follows: diffuse (n=20), patchy (n=12), focal (n=4), normal (n=2). In nearly one-third of children parenchymal abnormalities were mild enough that most normal lung markings were visible. During the course of the illness pneumothorax was noted in eight cases, pulmonary air cyst in five, and pneumomediastinum in one. Pleural effusions were noted in three (5%) cases. Thoracic lymphadenopathy was not observed in any case. The authors concluded that the initial chest radiographic appearance of PCP in children with AIDS is variable. The initial chest radiograph may be normal. The distribution was patchy or focal in nearly one-half of all cases with parenchymal abnormalities. Pulmonary air cysts or thoracic air leaks were noted during the course of the illness in approximately one-third of all cases.

AMEBIC OSTEOMYELITIS IN a CHILD WITH ACQUIRED IMMUNODEFICIENCY SYNDROME: A Case Report

Disseminated Acanthamoeba infection has been described in immunocompromised or debilitated patients. The usual sites of involvement are skin, sinus, and brain. Sporadic reports of Acanthamoeba infection in patients infected with the human immunodeficiency virus are present in recent literature, predominantly in adults, and one case involving an 8-year-old child. We describe a case of amebic osteomyelitis, seen in a 6-year-old child with vertically acquired human immunodeficiency virus and a 6-month history of cutaneous Acanthamoeba infection.

Hospitalization trends among children and youths with perinatal human immunodeficiency virus infection, 1990-2002.

Background: Major improvements in disease progression among HIV-infected children have followed the adoption of combination antiretroviral therapy. Methods: We examined trends in hospitalization rates between 1990–2002 among 3927 children/youths with perinatal HIV infection, ranging in age from newborn to 21 years. We used Poisson regression to test for trends in hospitalization rates by age and year; binomial regression to test for trends in intensive care unit (ICU) admissions and hospitalization at least once and more than once, by age and year; and multivariate logistic regression to examine factors associated with hospitalization, ICU admission, and hospitalization longer than 10 days. Results: Statistically significant downward trends in hospitalization rates and multiple hospitalizations were observed in all age groups from 1990–2002. The proportion of HIV-infected children/youths who were hospitalized at least once declined from 30.4% in 1990 to 12.9% in 2002, with a steady decline occurring after 1996, when the U.S. Public Health Service issued guidelines recommending triple-drug antiretroviral therapy (triple therapy) for HIV-infected children. ICU admissions declined significantly in all age groups except among children younger than 2 years. Logistic regression results indicated that black and Hispanic children/youths were significantly more likely to be hospitalized than white children/youths and that children/youths receiving triple therapy were significantly more likely to be hospitalized than therapy-naive children; the latter association was not observed among children monitored from 1997–2002. Conclusions: Substantial reductions in rates of hospitalization, multiple hospitalizations, and ICU admission have occurred among HIV-infected children/youths from 1990–2002, particularly after 1996, with increased use of triple therapy.

Thrombopoietin levels in HIV-associated thrombocytopenia in children.

OBJECTIVES To determine the mechanism of human immunodeficiency virus (HIV)-associated thrombocytopenia by using thrombopoietin (TPO) levels. STUDY DESIGN TPO levels were measured in 14 HIV+ children with thrombocytopenia (TCP+), 28 HIV+ children without thrombocytopenia (TCP-), and 15 matched control subjects. RESULTS For the patients with moderate symptoms, TPO levels were similar for the TCP+ and TCP- groups (251 pg/mL vs 263 pg/mL; P =.98) and similar to those of control subjects. For the patients with severe symptoms, TPO levels were significantly higher for the TCP+ group versus the TCP- group (1172 pg/mL vs 222 pg/mL; P =.03). Patients with severe symptoms and thrombocytopenia had significantly higher TPO levels than those with moderate symptoms and thrombocytopenia (P <.005), were more likely to require growth factors, and did not respond to treatment with intravenous immunoglobulin. CONCLUSIONS TPO levels can distinguish 2 groups of patients with HIV-associated thrombocytopenia. Patients with severe disease had elevated TPO levels, did not respond to treatment with intravenous immunoglobulin, and were more likely to be growth factor-dependent, suggesting marrow failure.

Epstein-Barr virus DNA in the blood of infants, young children, and adults by age and HIV status.

Polymerase chain reaction (PCR) methodology was used to detect Epstein-Barr virus (EBV) DNA in peripheral blood mononuclear cells (PBMCs) from children and adults whose HIV status (i.e., infected or uninfected) is known. Initial EBV infections especially occurred in children between the ages of 7 and 24 months. EBV-positive children with vertically acquired HIV infection tended to have a detectable blood level of EBV DNA for a period of years, and their EBV DNA blood levels often exceeded 10,000 copies/0.1 ml of blood--hundreds of times higher than levels typically found in EBV-positive, HIV-uninfected children of the same age. EBV DNA was found in PBMCs in 26% of 49 HIV-infected mothers who were sampled during their pregnancy, but the median EBV DNA level in their EBV-positive samples was low--only 50 copies/0.1 ml blood. In limited tests with specimens from children infected with both HIV and EBV, high blood levels of EBV DNA unexpectedly appeared to be associated with decreased blood levels of HIV DNA (p = .063).