Bio

Clinical Focus


  • Pediatric Allergy/Immun
  • Allergy and Immunology

Academic Appointments


Administrative Appointments


  • Clinical Associate Professor, Stanford University School of Medicine (2004 - Present)
  • Clinical Assistant Professor, Stanford University School of Medicine (2000 - 2004)

Honors & Awards


  • Excellence in Teaching Award, Department of Pediatrics, UCSF (1997)
  • Excellence in Teaching Award, Department of Pediatrics, UCSF (1995)
  • Schering Travel Grant Award, 48th Annual Meeting of the AAAAI (1992)
  • Schering Travel Grant Award, 47th Annual Meeting of the AAAAI (1991)

Professional Education


  • Residency:Univ Of Texas Health Science Ctr at Houston (1990) TX
  • Board Certification: Allergy and Immunology, American Board of Allergy and Immunology (1997)
  • Board Certification, American Board of Pediatrics, Pediatrics (1990)
  • Fellowship:Baylor College of Medicine (1992) TX
  • Internship:Univ Of Texas Health Science Ctr at Houston (1988) TX
  • Medical Education:Universidad Autonoma Metropolitana (1986) Mexico

Community and International Work


  • New Anti-HIV Medications: A Look at Nevirapine

    Partnering Organization(s)

    KEST, 1450 AM, radio station

    Populations Served

    San Francisco Bay Area

    Location

    International

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • National Youth Leadership Forum on Medicine

    Topic

    Why and How I Became a Pediatric Immunologist

    Partnering Organization(s)

    National Youth Leadership Forum

    Populations Served

    Students

    Location

    Bay Area

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • Bring Your Daughter to Work Program, UCSF

    Topic

    What Every Teen Needs to Know about HIV

    Partnering Organization(s)

    UCSF

    Populations Served

    Teens

    Location

    California

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • Pediatric HIV Infection, from Diagnosis to Chronic Care, San Francisco

    Partnering Organization(s)

    Mission Health Center, San Francisco

    Populations Served

    Underserved

    Location

    International

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • Introduction to the Human Immune System, San Francisco

    Partnering Organization(s)

    Saint Ignatius High School

    Populations Served

    Students

    Location

    Bay Area

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • HIV Weekly Update

    Topic

    The Women's and Children's Specialty Clinic at UCSF

    Partnering Organization(s)

    KALW, National Public Radio affiliate

    Location

    Bay Area

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • Is Pediatric HIV Increasing in Our Community?, Temple Beth El, San Francisco

    Partnering Organization(s)

    Bay TV, television broadcast

    Populations Served

    General

    Location

    California

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • Can Infants Clear the HIV Infection from Their Blood?, San Francisco

    Partnering Organization(s)

    Bay TV, television broadcast

    Populations Served

    General

    Location

    California

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • Pediatric Disease Prevention, radio broadcast, San Francisco

    Partnering Organization(s)

    KIQI Radio, Spanish Broadcasting, Inc.

    Populations Served

    Spanish-speaking

    Location

    Bay Area

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • Immunodeficiency in Children, radio broadcast, San Francisco

    Partnering Organization(s)

    KIQI Radio, Spanish Broadcasting, Inc.

    Populations Served

    Spanish-speaking

    Location

    International

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • Hemophilia Camp

    Topic

    Immunodeficiency in hemophilia patients

    Partnering Organization(s)

    UCSF & Hemophilia Foundation of Northern California

    Populations Served

    Hemophilia patients and their families

    Location

    California

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

Teaching

Graduate and Fellowship Programs


Publications

Journal Articles


  • Relative Bioavailability of Sapropterin From Intact and Dissolved Sapropterin Dihydrochloride Tablets and the Effects of Food: A Randomized, Open-Label, Crossover Study in Healthy Adults CLINICAL THERAPEUTICS Musson, D. G., Kramer, W. G., Foehr, E. D., Bieberdorf, F. A., Hornfeldt, C. S., Kim, S. S., Dorenbaum, A. 2010; 32 (2): 338-346

    Abstract

    Phenylketonuria (PKU) is an autosomal recessive metabolic disorder characterized by hyperphenylalaninemia in association with neurocognitive and neuromotor impairment. Sapropterin dihydrochloride (hereafter referred to as sapropterin) administered orally as dissolved tablets is approved by the US Food and Drug Administration for hyperphenylalaninemia in patients with tetrahydrobiopterin responsive PKU.This study compared the relative oral bioavailability of sapropterin when administered as intact and dissolved tablets. It also assessed the effect of food on the oral bioavailability of sapropterin administered as intact tablets.This was a randomized, open-label, 3-treatment, 6-sequence, 3-period crossover study in healthy male and female subjects. Subjects were randomized to receive single oral 10-mg/kg doses of sapropterin administered as dissolved tablets after a fast; as intact tablets after a fast; and as intact tablets with a high-calorie, high-fat meal. The 3 dosing periods were separated by a washout period of at least 7 days. In each dosing period, blood samples were obtained within 40 minutes before and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, and 24 hours after dosing. A follow-up assessment was performed 5 to 7 days after the last dosing period. The relative bioavailability of sapropterin from the 3 dosing regimens was assessed based on C(max), AUC(0-t), and AUC(0-infinity), estimated from calculated plasma tetrahydrobiopterin concentrations using a noncompartmental model. Safety assessments included physical examinations, clinical laboratory tests, and ECGs at the beginning and end of the study. Vital signs were monitored periodically during each treatment period.The study enrolled 32 healthy subjects (16 men, 16 women) with a mean (SD) age of 29.2 (9.0) years, height of 172.7 (10.0) cm, weight of 73.0 (13.9) kg, and body mass index ranging from 18 to 30 kg/m(2). Twenty-three were white, 5 African American, 2 Asian/Pacific Islander, 1 Hispanic, and 1 Native American. The estimated geometric mean ratio of AUC(0-t) for intact compared with dissolved tablets under fasting conditions was 141.24% (90% CI, 122.05-163.43), and the geometric mean ratio of AUC(0-t) for intact tablets under fed compared with fasting conditions was 143.46% (90% CI, 124.22-165.69). Nine subjects (28.1%) reported a total of 20 treatment-emergent adverse events (AEs). The most frequently reported AEs were gastrointestinal disorders (6 subjects [18.8%]) and central nervous system disorders (4 [12.5%]). Eight AEs considered possibly or probably related to sapropterin were reported by 4 subjects (12.5%); these were of mild severity and gastrointestinal in nature. No severe or serious AEs or discontinuations due to AEs occurred during the study.Administration of sapropterin as intact tablets and with a high-calorie, high-fat meal was associated with increased drug exposure. Oral administration of sapropterin 10 mg/kg as intact tablets with or without food was generally well tolerated.

    View details for DOI 10.1016/j.clinthera.2010.02.012

    View details for Web of Science ID 000275495200012

    View details for PubMedID 20206791

  • Efficacy of Sapropterin Dihydrochloride in Increasing Phenylalanine Tolerance in Children with Phenylketonuria: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study JOURNAL OF PEDIATRICS Trefz, F. K., Burton, B. K., Longo, N., Casanova, M. M., Gruskin, D. J., Dorenbaum, A., Kakkis, E. D., Crombez, E. A., Grange, D. K., Harmatz, P., Lipson, M. H., Milanowski, A., Randolph, L. M., Vockley, J., Whitley, C. B., Wolff, J. A., Bebchuk, J., Christ-Schmidt, H., Hennermann, J. B. 2009; 154 (5): 700-707

    Abstract

    To evaluate the ability of sapropterin dihydrochloride (pharmaceutical preparation of tetrahydrobiopterin) to increase phenylalanine (Phe) tolerance while maintaining adequate blood Phe control in 4- to 12-year-old children with phenylketonuria (PKU).This international, double-blind, randomized, placebo-controlled study screened for sapropterin response among 90 enrolled subjects in Part 1. In Part 2, 46 responsive subjects with PKU were randomized (3:1) to sapropterin, 20 mg/kg/d, or placebo for 10 weeks while continuing on a Phe-restricted diet. After 3 weeks, a dietary Phe supplement was added every 2 weeks if Phe control was adequate.The mean (+/-SD) Phe supplement tolerated by the sapropterin group had increased significantly from the pretreatment amount (0 mg/kg/d) to 20.9 (+/-15.4) mg/kg/d (P < .001) at the last visit at which subjects had adequate blood Phe control (<360 micromol/L), up to week 10. Over the 10-week period, the placebo group tolerated only an additional 2.9 (+/-4.0) mg/kg/d Phe supplement; the mean difference from the sapropterin group (+/-SE) was 17.7 +/- 4.5 mg/kg/d (P < .001). No severe or serious related adverse events were observed.Sapropterin is effective in increasing Phe tolerance while maintaining blood Phe control and has an acceptable safety profile in this population of children with PKU.

    View details for DOI 10.1016/j.jpeds.2008.11.040

    View details for Web of Science ID 000265501200016

    View details for PubMedID 19261295

  • Safety and Efficacy of 22 Weeks of Treatment With Sapropterin Dihydrochloride in Patients With Phenylketonuria AMERICAN JOURNAL OF MEDICAL GENETICS PART A Lee, P., Treacy, E. P., Crombez, E., Wasserstein, M., Waber, L., Wolff, J., Wendel, U., Dorenbaum, A., Bebchuk, J., Christ-Schmidt, H., Seashore, M., Giovannini, M., Burton, B. K., Morris, A. A. 2008; 146A (22): 2851-2859

    Abstract

    Phenylketonuria (PKU) is an inherited metabolic disease characterized by phenylalanine (Phe) accumulation, which can lead to neurocognitive and neuromotor impairment. Sapropterin dihydrochloride, an FDA-approved synthetic formulation of tetrahydrobiopterin (6R-BH4, herein referred to as sapropterin) is effective in reducing plasma Phe concentrations in patients with hyperphenylalaninemia due to tetrahydrobiopterin (BH4)-responsive PKU, offering potential for improved metabolic control. Eighty patients, > or =8 years old, who had participated in a 6-week, randomized, placebo-controlled study of sapropterin, were enrolled in this 22-week, multicenter, open-label extension study comprising a 6-week forced dose-titration phase (5, 20, and 10 mg/kg/day of study drug consecutively for 2 weeks each), a 4-week dose-analysis phase (10 mg/kg/day), and a 12-week fixed-dose phase (patients received doses of 5, 10, or 20 mg/kg/day based on their plasma Phe concentrations during the dose titration). Dose-dependent reductions in plasma Phe concentrations were observed in the forced dose-titration phase. Mean (SD) plasma Phe concentration decreased from 844.0 (398.0) micromol/L (week 0) to 645.2 (393.4) micromol/L (week 10); the mean was maintained at this level during the study's final 12 weeks (652.2 [382.5] micromol/L at week 22). Sixty-eight (85%) patients had at least one adverse event (AE). All AEs, except one, were mild or moderate in severity. Neither the severe AE nor any of the three serious AEs was considered related to sapropterin. No AE led to treatment discontinuation. Sapropterin is effective in reducing plasma Phe concentrations in a dose-dependent manner and is well tolerated at doses of 5-20 mg/kg/day over 22 weeks in BH4-responsive patients with PKU.

    View details for DOI 10.1002/ajmg.a.32562

    View details for Web of Science ID 000260846800002

    View details for PubMedID 18932221

  • Pharmacokinetics of Sapropterin in Patients with Phenylketonuria CLINICAL PHARMACOKINETICS Feillet, F., Clarke, L., Meli, C., Lipson, M., Morris, A. A., Harmatz, P., Mould, D. R., Green, B., Dorenbaum, A., Giovannini, M., Foehr, E. 2008; 47 (12): 817-825

    Abstract

    Untreated phenylketonuria is characterized by neurocognitive and neuromotor impairment, which result from elevated blood phenylalanine concentrations. To date, the recommended management of phenylketonuria has been the use of a protein-restricted diet and the inclusion of phenylalanine-free protein supplements; however, this approach is often associated with poor compliance and a suboptimal clinical outcome. Sapropterin dihydrochloride, herein referred to as sapropterin, a synthetic formulation of 6R-tetrahydrobiopterin (6R-BH4), has been shown to be effective in reducing blood phenylalanine concentrations in patients with phenylketonuria. The objective of the current study was to characterize the pharmacokinetics and pharmacokinetic variability of sapropterin and to identify the characteristics that influence this variability.This was a 12-week, fixed-dose phase of an open-label extension study. The study was conducted at 26 centres in North America and Europe.Patients with phenylketonuria were eligible to participate if they were > or =8 years of age and had received > or =80% of the scheduled doses in a previous 6-week, randomized, placebo-controlled study or had been withdrawn from that study after exceeding a plasma phenylalanine concentration of > or =1500 micromol/L to > or =1800 micromol/L, depending on the subject's age and baseline plasma phenylalanine concentration. A total of 78 patients participated. Patients received oral once-daily doses of sapropterin (Kuvan) 5, 10 or 20 mg/kg/day. Blood samples for the pharmacokinetic analysis were obtained during weeks 6, 10 and 12. A D-optimal sparse sampling strategy was used, and data were analysed by population-based, nonlinear, mixed-effects modelling methods.In a prospectively planned analysis, the apparent clearance, apparent volume of distribution, absorption rate constant and associated interindividual variabilities of each parameter were estimated by modelling observed BH4 plasma concentration-time data.The best structural model to describe the pharmacokinetics of sapropterin was a two-compartment model with first-order input, first-order elimination and a baseline endogenous BH4 concentration term. Total bodyweight was the only significant covariate identified, the inclusion of which on both the apparent clearance (mean = 2100 L/h/70 kg) and central volume of distribution (mean = 8350 L/70 kg) substantially improved the model's ability to describe the data. The mean (SD) terminal half-life of sapropterin was 6.69 (2.29) hours and there was little evidence of accumulation, even at the highest dose.These findings, taken together with the observed therapeutic effect, support bodyweight-based, once-daily dosing of sapropterin 5-20 mg/kg/day.

    View details for Web of Science ID 000262692400005

    View details for PubMedID 19026037

  • Pharmacokinetics of oral zidovudine administered during labour: a preliminary study HIV MEDICINE Mirochnick, M., Rodman, J. H., Robbins, B. L., Fridland, A., Gandia, J., Hitti, J., Bardeguez, A., Rathore, M. H., Garcia, A. G., Cababasay, M., Samson, P., Mofenson, L., Bryson, Y. J., Dorenbaum, A. 2007; 8 (7): 451-456

    Abstract

    The aim of this study was to determine whether oral zidovudine (ZDV) given during labour would provide a similar systemic exposure to the established intravenous regimen used to prevent mother-to-child transmission in HIV-infected pregnant women.ZDV pharmacokinetic parameters following oral administration during labour were determined in 10 HIV-infected pregnant women in active labour. All subjects were converted to intravenous ZDV prior to delivery.In cohort 1 (n=6), subjects received 300 mg oral ZDV every 3 h for three doses. Oral therapy was well tolerated but plasma ZDV concentrations were substantially lower than previously reported with continuous intravenous therapy. Based on the pharmacokinetic results from cohort 1, women in cohort 2 (n=4) received an initial 600 mg dose followed by two 400 mg doses every 3 h. ZDV area under the curve and concentrations in cohort 2 increased approximately in proportion to the increase in dose but varied 6-7-fold. In both cohorts, ZDV pharmacokinetic parameters suggested erratic absorption.While ZDV exposure improved with the increased dosing regimen, our sample size was small and larger studies are needed to establish whether oral ZDV administration during labour can consistently provide equivalent exposure to intravenous administration.

    View details for Web of Science ID 000248997100006

    View details for PubMedID 17760737

  • The response of patients with phenylketonuria and elevated serum phenylalanine to treatment with oral sapropterin dihydrochloride (6R-tetrahydrobiopterin): a phase II, multicentre, open-label, screening study JOURNAL OF INHERITED METABOLIC DISEASE Burton, B. K., Grange, D. K., Milanowski, A., Vockley, G., Feillet, F., Crombez, E. A., Abadie, V., Harding, C. O., Cederbaum, S., Dobbelaere, D., Smith, A., Dorenbaum, A. 2007; 30 (5): 700-707

    Abstract

    This study aimed to evaluate the response to and safety of an 8-day course of sapropterin dihydrochloride (6R-tetrahydrobiopterin or 6R-BH4) 10 mg/kg per day in patients with phenylketonuria (PKU), who have elevated blood phenylalanine (Phe) levels, and to identify a suitable cohort of patients who would respond to sapropterin dihydrochloride treatment with a reduction in blood Phe level. Eligible patients were aged > or = 8 years, had blood Phe levels > or = 450 micromol/L and were not adhering to a Phe-restricted diet. Suitable patients were identified by a > or = 30% reduction in blood Phe level from baseline to day 8 following sapropterin dihydrochloride treatment. The proportion of patients who met these criteria was calculated for the overall population and by baseline Phe level (< 600, 600 to < 900, 900 to < 1200 and > or = 1200 micromol/L). In total, 485/490 patients completed the study and 20% (96/485) were identified as patients who would respond to sapropterin dihydrochloride. A reduction in Phe level was observed in all subgroups, although response was greater in patients with lower baseline Phe levels. Wide variability in response was seen across all baseline Phe subgroups. The majority of adverse events were mild and all resolved without complications. Sapropterin dihydrochloride was well tolerated and reduced blood Phe levels across all PKU phenotypes tested. Variability in reduction of Phe indicates that the response to sapropterin dihydrochloride cannot be predicted by baseline Phe level.

    View details for DOI 10.1007/s10545-007-0605-z

    View details for Web of Science ID 000250065300012

    View details for PubMedID 17846916

  • Phenylalanine blood levels and clinical outcomes in phenylketonuria: A systematic literature review and meta-analysis MOLECULAR GENETICS AND METABOLISM Waisbren, S. E., Noel, K., Fahrbach, K., Cella, C., Frame, D., Dorenbaum, A., Levy, H. 2007; 92 (1-2): 63-70

    Abstract

    Blood phenylalanine (Phe) levels provide a practical and reliable method for the diagnosis and monitoring of metabolic status in patients with phenylketonuria (PKU). To assess the reliability of blood Phe levels as a predictive biomarker of clinical outcomes in the development of treatments for PKU, a systematic literature review and meta-analysis of published trials of PKU, which included Phe level and neurological and dietary compliance outcome measures, was conducted. Within-study correlations between Phe level and intelligence quotient (IQ) were extracted from 40 studies. Significant, proportional correlations were found during critical periods (from 0 to 12 years of age) for early-treated patients with PKU (r=-0.35; 95% confidence interval [CI]: -0.44 to -0.27), where each 100 micromol/l increase in Phe predicted a 1.3- to 3.1-point reduction in IQ. Similar significant correlations were observed between IQ and mean lifetime Phe level for early-treated patients (r=0.34; 95% CI: -0.42 to -0.25), where each 100 micromol/l increase in Phe predicted a 1.9- to 4.1-point reduction in IQ. Moderate correlations were found between concurrent Phe level and IQ for early-treated patients. In conclusion, these results confirm a significant correlation between blood Phe level and IQ in patients with PKU, and support the use of Phe as a predictive biomarker for IQ in clinical trials.

    View details for DOI 10.1016/j.ymgme.2007.05.006

    View details for Web of Science ID 000249992300009

    View details for PubMedID 17591452

  • Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised placebo-controlled study LANCET Levy, H. L., Milanowski, A., Chakrapani, A., Cleary, M., Lee, P., Trefz, F. K., Whitley, C. B., Feillet, F., Feigenbaum, A. S., Bebchuk, J. D., Christ-Schmidt, H., Dorenbaum, A. 2007; 370 (9586): 504-510

    Abstract

    Early and strict dietary management of phenylketonuria is the only option to prevent mental retardation. We aimed to test the efficacy of sapropterin, a synthetic form of tetrahydrobiopterin (BH4), for reduction of blood phenylalanine concentration.We enrolled 89 patients with phenylketonuria in a Phase III, multicentre, randomised, double-blind, placebo-controlled trial. We randomly assigned 42 patients to receive oral doses of sapropterin (10 mg/kg) and 47 patients to receive placebo, once daily for 6 weeks. The primary endpoint was mean change from baseline in concentration of phenylalanine in blood after 6 weeks. Analysis was on an intention-to-treat basis. The study is registered with ClinicalTrials.gov, number NCT00104247.88 of 89 enrolled patients received at least one dose of study drug, and 87 attended the week 6 visit. Mean age was 20 (SD 9.7) years. At baseline, mean concentration of phenylalanine in blood was 843 (300) micromol/L in patients assigned to receive sapropterin, and 888 (323) micromol/L in controls. After 6 weeks of treatment, patients given sapropterin had a decrease in mean blood phenylalanine of 236 (257) micromol/L, compared with a 3 (240) micromol/L increase in the placebo group (p<0.0001). After 6 weeks, 18/41 (44%) patients (95% CI 28-60) in the sapropterin group and 4/47 (9%) controls (95% CI 2-20) had a reduction in blood phenylalanine concentration of 30% or greater from baseline. Blood phenylalanine concentrations fell by about 200 micromol/L after 1 week in the sapropterin group and this reduction persisted for the remaining 5 weeks of the study (p<0.0001). 11/47 (23%) patients in the sapropterin group and 8/41 (20%) in the placebo group experienced adverse events that might have been drug-related (p=0.80). Upper respiratory tract infections were the most common disorder.In some patients with phenylketonuria who are responsive to BH4, sapropterin treatment to reduce blood phenylalanine could be used as an adjunct to a restrictive low-phenylalanine diet, and might even replace the diet in some instances.

    View details for Web of Science ID 000248717800029

    View details for PubMedID 17693179

  • Efficacy and safety of heparinase I versus protamine in patients undergoing coronary artery bypass grafting withl and without cardiopulmonary bypass ANESTHESIOLOGY Stafford-Smith, M., Lefrak, E. A., Qazi, A. G., Welsby, I. J., Barber, L., Hoeft, A., Dorenbaum, A., Mathias, J., Rochon, J. J., Newman, M. F. 2005; 103 (2): 229-240

    Abstract

    Hemodynamic protamine reactions with heparin reversal during cardiac surgery are common and associated with adverse outcomes. As an alternative to protamine, the authors examined heparinase I reversal of heparin after aortocoronary bypass graft surgery.In a randomized, double-blind, double-dummy trial, 167 on- and off-pump aortocoronary bypass graft surgery patients received either heparinase I (maximum 35 microg/kg) or protamine (maximum 650 mg) for heparin reversal, monitored by activated clotting time values and clinical assessment. Hemodynamic parameters were recorded electronically; safety evaluation was to 30 days postoperatively. Noninferiority was predefined as 400 ml or less median 12-h chest tube drainage from intensive care unit arrival for heparinase I patients, after risk adjustment. Hemodynamic instability was defined as systemic hypotension (> or = 30 mmHg decrease) and/or pulmonary hypertension (> or = 40 mmHg with an increase > or = 10 mmHg) within 30 min of heparin reversal initiation.Patient enrollment was terminated on advisement of the Data Safety Monitoring Board. Although heparinase I was noninferior for 12-h chest tube drainage, protamine had a superior safety profile. Overall, heparinase I subjects had longer hospital stays (P = 0.04), were more likely to experience a serious adverse event (P = 0.01), and were less likely to avoid transfusion (P = 0.006). A composite morbidity score was not different (P = 0.24), and similar rates of hemodynamic instability were observed between groups. Findings were consistent in analyses stratified by on- and off-pump surgery.Heparinase I reverses heparin anticoagulation after aortocoronary bypass graft surgery but is not equivalent to protamine because of its inferior safety profile.

    View details for Web of Science ID 000230983800004

    View details for PubMedID 16052104

  • The impact of race/ethnicity on mother-to-child HIV transmission in the united states in pediatric AIDS clinical trials group protocol 316 JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES Cunningham, C. K., Balasubramanian, R., Delke, I., Maupin, R., Mofenson, L., Dorenbaum, A., Sullivan, J. L., Gonzalez-Garcia, A., Thorpe, E., Rathore, M., Gelber, R. D. 2004; 36 (3): 800-807

    Abstract

    The present analysis was designed to determine whether race/ethnicity was independently associated with mother-to-child HIV-1 transmission risk in subjects enrolled in a trial of 2-dose intra-partum nevirapine in combination with standard antiretroviral therapy and to determine what factors, including race/ethnicity, predicted maternal viral suppression at the time of delivery. Women enrolled in Pediatric AIDS Clinical Trials Group (PACTG) 316 from sites in the United States and Puerto Rico were included. Distribution of selected maternal disease and treatment characteristics was assessed by race/ethnicity category. Logistic regression models were fit to evaluate possible association of factors with HIV transmission and with viral load at delivery. Variables associated with the outcome at P < 0.05 level were retained in the final models. Of 1052 women randomized at PACTG sites, 891 were included in the present analysis: 572 (64%) were black; 206 (23%) were Hispanic; and 113 (13%) were white. All women who had infected infants were black or Hispanic (11/572 and 3/206, respectively), whereas none of the women identified as white had an infected infant (0/113). This difference was not statistically significant (P = 0.54). White women had higher entry CD4 cell counts and lower HIV-1 RNA at delivery than women of other races/ethnicities. Black and Hispanic women were more likely than white women to start therapy during their current pregnancy but did not initiate prenatal care later. In bivariate models that included antiretroviral type and variables that had values of P < or = 0.25 in univariate analysis, time of antiretroviral initiation, time of prenatal care initiation, and race/ethnicity each retained significance in predicting viral suppression at delivery. Race/ethnicity remained predictive of viral suppression at delivery in a multivariate model incorporating all of these variables (P = 0.01). Higher HIV-1 RNA and lower CD4 cell counts in women identified as black or Hispanic have significant implications for the health of these women and their newborns. Race/ethnicity is significant in predicting viral suppression at the time of delivery.

    View details for Web of Science ID 000222481700005

    View details for PubMedID 15213563

  • Maternal toxicity and pregnancy complications in human immunodeficiency virus-infected women receiving antiretroviral therapy: PACTG 316 AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Watts, D. H., Balasubramanian, R., Maupin, R. T., Delke, I., Dorenbaum, A., Fiore, S., Newell, M. L., Delfraissy, J. F., Gelber, R. D., Mofenson, L. M., Culnane, M., Cunningham, C. K. 2004; 190 (2): 506-516

    Abstract

    The purpose of this study was to evaluate rates of maternal toxicity, pregnancy complications, and peripartum morbidity by type and duration of antiretroviral therapy (ART) during pregnancy.The Pediatric AIDS Clinical Trials Group (PACTG) Protocol 316 (PACTG 316) study evaluated the addition of intrapartum/neonatal nevirapine to background ART to reduce perinatal transmission of human immunodeficiency virus-1 (HIV-1). For this secondary analysis, women were categorized into one of six groups on the basis of ART during pregnancy (monotherapy [monoRx], combination without protease inhibitor [PI], combination with PI), and start time (early: before or during first trimester; late: second or third trimester).One thousand four hundred seven women were included: 288 monoRx late, 34 monoRx early, 327 combo, no PI late, 175 combo, no PI early, 320 combo, PI late, and 263 combo, PI early. Symptoms and laboratory abnormalities of moderate grade or more occurred in less than 5% of women. Only gestational diabetes (highest in combo PI early) varied significantly by therapy group.In HIV-infected women receiving prenatal care and ART, adverse events were uncommon.

    View details for DOI 10.1016/j.ajog.2003.07.018

    View details for Web of Science ID 000189250500035

    View details for PubMedID 14981398

  • Predose infant nevirapine concentration with the two-dose intrapartum neonatal nevirapine regimen: Association with timing of maternal intrapartum nevirapine dose JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES Mirochnick, M., Dorenbaum, A., Blanchard, S., Cunningham, C. K., Gelber, R. D., Mofenson, L., Culnane, M., Sullivan, J. L. 2003; 33 (2): 153-156

    Abstract

    To evaluate cord blood and predose nevirapine concentrations in infants exposed to the two-dose intrapartum neonatal nevirapine regimen.The authors obtained plasma samples for nevirapine assay from cord blood and just prior to the 48-hours to 72-hours after birth neonatal nevirapine dose from a subset of infants participating in PACTG 316, a randomized, placebo-controlled trial of the two-dose intrapartum neonatal nevirapine regimen added to standard antiretroviral therapy.Nevirapine concentrations were measured in 109 cord blood samples and 149 predose samples. Cord blood nevirapine concentrations were below the target concentration of 100 ng/mL (10-times the in vitro IC(50) of nevirapine against wild-type HIV) in eight (7%) of 109 infants (95% confidence interval [CI], 3%-14%); the concentrations in six of these infants were below the assay limit of quantitation. Predose infant nevirapine concentrations were below 100 ng/mL in 23 (15%) of 149 infants (95% CI, 10%-22%); the concentrations in 13 of these infants were below the assay limit of quantitation. Lower predose nevirapine concentrations were associated with lower cord blood concentrations and a shorter interval between maternal dosing and delivery. All but one of the infants with predose nevirapine concentrations below the assay limit of quantitation were born less than 2 hours after maternal dosing.Infants born less than 2 hours after maternal nevirapine dosing during labor should receive a dose of nevirapine immediately after birth in addition to the standard infant dose at 48 to 72 hours.

    View details for Web of Science ID 000183815400006

    View details for PubMedID 12794547

  • When the time comes to talk about HIV: Factors associated with diagnostic disclosure and emotional distress in HIV-infected children JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES Lester, P., Chesney, M., Cooke, M., Weiss, R., Whalley, P., Perez, B., Glidden, D., Petru, A., Dorenbaum, A., Wara, D. 2002; 31 (3): 309-317

    Abstract

    To determine factors related to the timing and probability of nondisclosure of HIV status to perinatally HIV-infected children, and to explore factors associated with emotional distress in HIV-infected children.This is a cross-sectional study of 51 HIV-infected children based on medical records, parent interviews, and child assessments.1) Probability of earlier age of disclosure is associated with higher child IQ (p =.04) and more family expressiveness (p =.01); 2) controlling for child age, disclosure status at time of study is associated with major life events, but not with medical status; and 3) factors associated with increased parent-rated anxiety in HIV-infected children in univariate analyses are: HIV disclosure (p =.04), other major life events (p =.001), higher medication dose frequency ( p=.01), and child age (p =.01). Increased depression is associated only with more medication doses (p =.02).These data indicate that higher child IQ and greater family expressiveness increase the probability of earlier diagnostic disclosure to HIV-infected children. Factors associated with emotional distress highlight important areas of clinical attention. These data suggest that diagnostic disclosure may not necessarily minimize emotional distress, indicating the need for further evaluation of the appropriate timing and type of disclosure for pediatric HIV.

    View details for Web of Science ID 000179082800006

    View details for PubMedID 12439206

  • Concentrations of protease inhibitors in cord blood after in utero exposure PEDIATRIC INFECTIOUS DISEASE JOURNAL Mirochnick, M., Dorenbaum, A., Holland, D., Cunningham-Schrader, B., Cunningham, C., Gelber, R., Mofenson, L., Culnane, M., Connor, J., Sullivan, J. L. 2002; 21 (9): 835-838

    Abstract

    To determine the concentrations of protease inhibitors in cord blood after prenatal protease inhibitor use by pregnant women.Retrospective analysis of samples collected in a clinical trial.Protease inhibitor concentrations were measured in cord blood samples collected from women enrolling in the PACTG 316 study who were receiving prenatal protease inhibitor antiretroviral therapy.In cord blood samples from 68 women treated with protease inhibitors during pregnancy, the concentration of these drugs was below the assay lower limit of detection in most samples, including all samples from women receiving indinavir (n = 21) and saquinavir (n = 8), 5 of 6 samples (83%) from women receiving ritonavir and 24 of 38 samples (63%) from women receiving nelfinavir.Low protease inhibitor concentrations in the fetus decrease the likelihood of teratogenic and toxic effects of these drugs but could fail to provide protection from transplacental or intrapartum transmission of HIV-1.

    View details for DOI 10.1097/01.inf.0000027591.04920.c7

    View details for Web of Science ID 000178091400007

    View details for PubMedID 12352805

  • Envelope-based HIV vaccines SCIENCE Donnelly, J. J., Barnett, S. W., Dorenbaum, A., Stamatatos, L. 2002; 297 (5585): 1277-1277

    View details for Web of Science ID 000177573900020

    View details for PubMedID 12194177

  • Development of resistance mutations in women receiving standard antiretroviral therapy who received intrapartum nevirapine to prevent perinatal human immunodeficiency virus type 1 transmission: A substudy of Pediatric AIDS Clinical Trials Group protocol 316 JOURNAL OF INFECTIOUS DISEASES Cunningham, C. K., Chaix, M. L., Rekacewicz, C., Britto, P., Rouzioux, C., Gelber, R. D., Dorenbaum, A., Delfraissy, J. F., Bazin, B., Mofenson, L., Sullivan, J. L. 2002; 186 (2): 181-188

    Abstract

    Pediatric AIDS Clinical Trials Group protocol 316 was an international, multicenter, placebo-controlled trial comparing single-dose oral nevirapine (200 mg to mother and 2 mg/kg to infant) with placebo in human immunodeficiency virus (HIV)-infected pregnant women receiving standard antiretroviral therapy. This substudy evaluated the emergence of nevirapine-resistance mutations at 6 weeks postpartum in a subgroup of participants. Maternal risk factors for the emergence of nevirapine-resistance mutations were evaluated. Mutations associated with nevirapine resistance were detectable at delivery, prior to receipt of study drug, in 5 (2.3%) of 217 women. Fourteen (15%; 95% confidence interval, 8%-23%) of 95 women who received intrapartum nevirapine developed a nevirapine-resistance mutation 6 weeks postpartum. The most common mutation was K103N, which was present in 10 women. The risk for development of a new nevirapine-resistance mutation did not correlate with CD4 cell count or HIV-1 RNA load at delivery or with type of antepartum antiretroviral therapy. The risk of nevirapine resistance should be considered when determining the risks or benefits of intrapartum nevirapine in women receiving antepartum antiretroviral therapy.

    View details for Web of Science ID 000176668500005

    View details for PubMedID 12134253

  • Two-dose intrapartum/newborn nevirapine and standard antiretroviral therapy to reduce perinatal HIV transmission - A randomized trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Dorenbaum, A., Cunningham, C. K., Gelber, R. D., Culnane, M., Mofenson, L., Britto, P., Rekacewicz, C., Newell, M. L., Delfraissy, J. F., Cunningham-Schrader, B., Mirochnick, M., Sullivan, J. L. 2002; 288 (2): 189-198

    Abstract

    A 2-dose intrapartum/newborn nevirapine regimen reduced perinatal human immunodeficiency virus (HIV) transmission in Ugandan women not receiving antenatal antiretroviral therapy (ART). However, it is unknown whether the addition of the 2-dose nevirapine regimen to standard ART would further reduce perinatal HIV transmission.To determine whether a 2-dose nevirapine regimen can decrease perinatal transmission of HIV in nonbreastfeeding women receiving standard ART.International, blinded, placebo-controlled, phase 3 trial enrolling women between May 1997 and June 2000 at clinical sites providing care for HIV infection throughout the United States, Europe, Brazil, and the Bahamas.A total of 1270 women received nevirapine (n = 642) or placebo (n = 628). Infants were followed up for 6 months to determine HIV-infection status, which was available for 1248 deliveries.A 200-mg dose of oral nevirapine to women after onset of labor and a 2-mg/kg dose of oral nevirapine to newborns between 48 and 72 hours after birth.Detection of HIV infection in infants and grade 3 and 4 toxic effects in women and newborns.After review by the data and safety monitoring board, the trial was stopped early because the overall transmission rates were significantly lower than assumed for the study design. Antenatal ART included zidovudine alone in 23%; combinations without protease inhibitors in 36%; and combinations with protease inhibitors in 41%. Thirty-four percent of women had elective cesarean delivery. No significant safety concerns were identified for women or infants. Detection of HIV infection occurred in 9 (1.4%; 95% confidence interval [CI], 0.6%-2.7%) of 631 nevirapine group deliveries and 10 (1.6%; 95% CI, 0.8%-2.9%) of 617 placebo group deliveries. The 95% CI for the difference in transmission rate (-0.2) between the 2 study arms ranged from -1.5% in favor of nevirapine to 1.2% in favor of placebo (P =.82, Fisher exact test). The transmission rate was higher in women with lower baseline CD4 cell counts and higher delivery HIV RNA levels, but there was no significant difference between treatment arms in any subgroup.Risk of perinatal HIV transmission was low and no benefit from additional intrapartum/newborn nevirapine was demonstrated when women received prenatal care and antenatal ART, and elective cesarean section was made available.

    View details for Web of Science ID 000176711100019

    View details for PubMedID 12095383

  • When parents reject interventions to reduce postnatal human immunodeficiency virus transmission ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE Wolf, L. E., Lo, B., Beckerman, K. P., Dorenbaum, A., Kilpatrick, S., Weintrub, P. S. 2001; 155 (8): 927-933

    Abstract

    In a recent Oregon case, the state successfully sued for custody of an infant to prevent his human immunodeficiency virus (HIV)-infected mother from breastfeeding him and to require antiretroviral prophylaxis. As more HIV-infected women give birth, pediatricians may increasingly face dilemmas when parents reject medical recommendations to forego breastfeeding and to administer antiretroviral prophylaxis to the infant. Such disagreements create ethical dilemmas because pediatricians have an obligation to both protect the infant and respect parental decision making. Pediatricians need to balance these obligations in deciding whether to ask the courts to intervene on the infant's behalf. To that end, we analyze the legal and ethical issues that arise when an HIV-infected mother refuses interventions to reduce neonatal transmission of HIV to her infant, provide an approach for addressing these disagreements, and present illustrative scenarios in which pediatricians should, may, and should not seek a court order to intervene.

    View details for Web of Science ID 000170237100011

    View details for PubMedID 11483121

  • HIV medical advances explored at retrovirus conference AIDS Policy Law Dorenbaum A, Miserez AR 2001; 16 (10): 4
  • Nevirapine - Pharmacokinetic considerations in children and pregnant women CLINICAL PHARMACOKINETICS Mirochnick, M., Clarke, D. F., Dorenbaum, A. 2000; 39 (4): 281-293

    Abstract

    Nevirapine is a potent non-nucleoside inhibitor of HIV-1 reverse transcriptase. It is effective when used as part of combination therapy to treat HIV-1-infected individuals and as monotherapy for prevention of mother-to-child HIV-1 transmission. Nevirapine pharmacokinetics are characterised by rapid absorption and distribution, followed by prolonged elimination. Nevirapine is generally well tolerated. The most common toxicity is rash, which is usually mild and self-limiting. The primary route of nevirapine elimination is through metabolism by the cytochrome P450 enzyme system. Nevirapine elimination accelerates during long term administration because of autoinduction of the enzymes involved in its elimination pathway. The recommended regimen for adults is nevirapine 200mg once daily for 2 weeks, followed by 200mg twice daily. Nevirapine elimination is prolonged in pregnant women during labour and in newborns. A regimen of a single 200mg oral dose administered to the mother during labour and a single 2 mg/kg dose administered to the newborn at 48 to 72 hours after birth maintains serum nevirapine concentrations above 100 microg/L (10 times the in vitro 50% inhibitory concentration against wild-type HIV-1) throughout the first week of life. This limited regimen has been shown to be extremely well tolerated and to reduce mother-to-child transmission by nearly 50% in mothers and infants receiving no other antiretrovirals. There are few data describing the safety and pharmacokinetics of nevirapine during long term use in pregnancy. In children, nevirapine elimination accelerates during the first years of life, reaching a maximum at around 2 years of age, followed by a gradual decline during the rest of childhood. Children should receive 4 mg/kg once daily for the first 2 weeks of therapy, followed by 7 mg/kg doses twice daily if below the age of 8 years or 4 mg/kg twice daily if older than 8 years. Alternatively, children may receive 150 mg/m2 across all ages, once daily for the first 2 weeks of therapy followed by the same dose twice daily.

    View details for Web of Science ID 000090117300004

    View details for PubMedID 11069214

  • Cytokine profile of a long-term pediatric HIV survivor with hyper-IgE syndrome and a normal CD4(+) T-cell count JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Seroogy, C. M., Wara, D. W., Bluth, M. H., Dorenbaum, A., White, C., Durkin, H. G., Elder, M. E. 1999; 104 (5): 1045-1051

    Abstract

    An elevated IgE level and increased production of T(H2) cytokines are factors associated with poor prognosis in HIV infection. We report a pediatric long-term survivor of vertically acquired HIV infection with a normal CD4 count and a low viral burden despite the lack of antiretroviral therapy and a phenotype resembling hyper-IgE syndrome.We sought to characterize the patient's T(H1) versus T(H2) cytokine profile and anti-HIV-specific immune responses.Supernatants collected from cultures of peripheral blood T cells stimulated with phorbol myristate acetate plus ionomycin were assayed for T(H1) and T(H2) cytokines by means of ELISA. Specific IgE antibodies were determined by immunoblot. HIV-specific cytotoxic T-lymphocyte responses were measured from cell lysis by fresh T cells of autologous B-lymphoblastoid cells expressing recombinant HIV proteins.Patient CD4(+) T cells secreted significantly more T(H2) cytokines, IL-4 (P <.003) and IL-5 (P <.03), than HIV-infected and seronegative control cells. No difference was noted in T(H1) cytokine production. IgE specific for HIV gp160, p24, p17, and p66 proteins and Aspergillus fumigatus was detected in patient sera. Despite predominance of T(H2) cytokines, HIV-specific cytotoxic T-lymphocyte activity was vigorous.The patient demonstrated predominantly T(H2) cytokine production in vitro. Unlike other patients with HIV who have hyper-IgE and increased T(H2) cytokine production, our patient has maintained HIV-specific immune responses, a low viral load, and a normal CD4 count without antiretroviral therapy. These findings support a diagnosis of primary hyper-IgE syndrome. Presence of anti-HIV-specific IgE may represent a protective mechanism against HIV replication in our patient.

    View details for Web of Science ID 000083778400029

    View details for PubMedID 10550751

  • Sleep disturbances in children with human immunodeficiency virus infection PEDIATRICS Franck, L. S., Johnson, L. M., Lee, K., Hepner, C., Lambert, L., Passeri, M., Manio, E., Dorenbaum, A., Wara, D. 1999; 104 (5)

    Abstract

    To describe the sleep patterns and level of fatigue in children and adolescents (6-18 years of age) with HIV infection, compared with ethnic-, gender-, and age-matched healthy children in the home setting.Descriptive, comparative.Conducted in each child's home environment.Eighteen HIV-infected and 15 noninfected children completed the study. The Centers for Disease Control and Prevention HIV classifications for the 18 HIV-infected children were: A (n = 7), B (n = 6), and C (n = 5).A symptom diary was developed using a previously validated fatigue assessment scale, modified for use with children. Content validity of the diary was established with a panel of 5 experts in child development and pediatric HIV disease. Children were asked to complete the diary each morning and evening for 3 days. Each child wore a wrist actigraph during the same period.The HIV-infected children had significantly more wake time after sleep onset, compared with noninfected children (13.55% vs 7. 47%). The HIV-infected children had more awakenings (25.33 vs 16.71) and were awake for longer periods (3.01 vs 1.01 minutes), compared with noninfected children. By parent report, 7 HIV-infected children napped and 2 noninfected children napped, indicating greater daytime fatigue in the HIV-infected children. HIV-infected children also reported a greater level of evening tiredness (2.47 vs 1.8).The findings from this study suggest that sleep disturbances occur in HIV-infected children, similar to findings previously described in HIV-infected adults. Additional research is necessary to characterize the nature and patterns of sleep disturbance and fatigue related to pediatric HIV-infection, to assess the impact these may have on daily activities, and to develop strategies to improve sleep for these children.

    View details for Web of Science ID 000083448000042

    View details for PubMedID 10545588

  • Current applications for the use of nevirapine in HIV 1-infected pregnant women, infants and children Journal of HIV Therapy Dorenbaum A, Mirochnick M 1999; 4 (3)
  • Phase I safety and pharmacokinetics study of micronized atovaquone in human immunodeficiency virus-infected infants and children ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Hughes, W., Dorenbaum, A., YOGEV, R., Beauchamp, B., Xu, J., McNamara, J., Moye, J., Purdue, L., Van Dyke, R., Rogers, M., Sadler, B. 1998; 42 (6): 1315-1318

    Abstract

    A phase I dose-escalating safety and pharmacokinetic study evaluated an oral suspension of micronized atovaquone (m-atovaquone) in infants and children stratified into age groups from 1 month to 12 years of age. Dosages of 10, 30, and 45 mg/kg of body weight/day were evaluated as single daily doses over a period of 12 days. Steady-state concentrations in plasma were determined on day 12, and single postdose concentrations were measured on days 1, 3, 5, 7, 9, 13, 15, 18, 21, and 24. Prior studies with adults suggest that the average plasma atovaquone concentration of 15 micrograms/ml is associated with therapeutic success in more than 95% of patients with Pneumocystis carinii pneumonitis. The results showed m-atovaquone to be safe and well tolerated. Dosages of 30 mg/kg/day were adequate to achieve an average steady-state concentration of greater than 15 micrograms/ml in children ages 1 to 3 months and 2 to 12 years, but a dosage of 45 mg/kg/day was needed to reach this concentration in infants 3 to 24 months of age. The oral suspension of atovaquone is safe and well tolerated in children. A single daily dose of 30 mg/kg provides bioavailability considered adequate for therapy of P. carinii pneumonia, but infants between 3 and 24 months of age may require a dosage of 45 mg/kg/day.

    View details for Web of Science ID 000073952400002

    View details for PubMedID 9624466

  • Transmission of HIV-1 in infants born to seropositive mothers: PCR-amplified proviral DNA detected by flow cytometric analysis of immunoreactive beads JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY Dorenbaum, A., Venkateswaran, K. S., Yang, G., Comeau, A. M., Wara, D., Vyas, G. N. 1997; 15 (1): 35-42

    Abstract

    The diagnosis of HIV infection in newborns is established by amplification of proviral DNA using the polymerase chain reaction (PCR). We developed a nonisotopic method for heminested PCR using a biotinylated primer among sets of three oligonucleotides, each selected from the HIV long terminal repeat (LTR) and gag sequences. An internal probe incorporating digoxigenin-dUTP was also synthesized by PCR. The PCR products, hybridized with LTR region or gag region probes, were captured with streptavidin-coated magnetic beads and detected by fluorescein isothiocyanate-labeled antidigoxigenin in flow cytometric analysis. This immunoreactive bead assay (PCR-IRB) detected about three copies of HIV proviral DNA. A panel of 50 coded DNA specimens of infants previously assayed by conventional PCR and with known clinical results revealed that the PCR-IRB findings using LTR, but not gag, were in agreement. A double-blind prospective study of blood samples from 14 mother-infant pairs using the PCR-IRB amplification of LTR gave results similar to the commercial Amplicor HIV-1 PCR test and were consistent with the clinical outcomes. PCR-IRB results were positive for 11 mothers and three infants, one at birth, one at 2 weeks after birth, and one at 8 weeks after birth. PCR-IRB is a simple, reliable, specific, and automatable assay useful in the early diagnosis of perinatal HIV infection in clinical practice and regional screening programs.

    View details for Web of Science ID A1997XH94600006

    View details for PubMedID 9215652

  • RECURRENT STAPHYLOCOCCUS-AUREUS RENAL ABSCESS IN A CHILD POSITIVE FOR THE HUMAN-IMMUNODEFICIENCY-VIRUS UROLOGY Brandeis, J. M., Baskin, L. S., Kogan, B. A., Wara, D., Dorenbaum, A. 1995; 46 (2): 246-248

    Abstract

    A 10-year-old girl with the human immunodeficiency virus was found to have a Staphylococcus aureus renal abscess with perinephric extension. The abscess was drained first percutaneously and then surgically, and the patient received a 6-week course of intravenous antibiotics. Three months later, the abscess recurred, necessitating a nephrectomy. The extended morbidity and difficulty of eradicating S aureus suggest that, in immunocompromised patients, early aggressive surgical management is indicated.

    View details for Web of Science ID A1995RM64100021

    View details for PubMedID 7624995

  • RECOVERY OF MALASSEZIA-PACHYDERMATIS FROM 8 INFANTS IN A NEONATAL INTENSIVE-CARE NURSERY - CLINICAL AND LABORATORY FEATURES PEDIATRIC INFECTIOUS DISEASE JOURNAL LaRocco, M., Dorenbaum, A., Robinson, A., Pickering, L. K. 1988; 7 (6): 398-401

    Abstract

    A 15-month retrospective survey of 507 admissions to a neonatal intensive care unit revealed 8 patients from whom Malassezia pachydermatis was isolated from one or more clinical specimens. The fungus was cultured from blood (four patients), central venous catheter tips (three patients), urine (four patients), cerebrospinal fluid (one patient), eye discharge (one patient), ear discharge (one patient) and tracheal aspirate (one patient). Seven of the eight infants displayed an episode of one or more of the following symptoms: apnea, bradycardia, temperature instability and hepatosplenomegaly. These episodes were temporally related to recovery of M. pachydermatis from clinical specimens. The seven symptomatic infants had received multiple antibiotics as well as long term hyperalimentation, including lipids, by infusion through deep vein catheters; the single asymptomatic infant did not. These data suggest an association between M. pachydermatis and the febrile systemic syndrome of neonates recently described for extracutaneous infections due to Malassezia furfur.

    View details for Web of Science ID A1988N815200006

    View details for PubMedID 3134645

  • Case Report Infectious Disease Newsletter Dorenbaum A, Shearer WT, Abramson SL 1987; 6 (5): 38

Conference Proceedings


  • Classification, diagnostic criteria, and treatment recommendations for orofacial manifestations in HIV-infected pediatric patients. Collaborative Workgroup on Oral Manifestations of Pediatric HIV Infection. Ramos-Gomez, F. J., Flaitz, C., Catapano, P., Murray, P., Milnes, A. R., Dorenbaum, A. 1999: 85-96

    Abstract

    The criteria for diagnosis of HIV-related oral lesions in adults are well established, but corresponding criteria in the pediatric population are not as well defined. The Collaborative Workgroup on the Oral Manifestations of Pediatric HIV infection reached a consensus, based upon available data, as to the presumptive and definitive criteria to diagnose the oral manifestations of HIV infection in children. Presumptive criteria refer to the clinical features of the lesions, including signs and symptoms, whereas definitive criteria require specific laboratory tests. In general, it is recommended that definitive criteria be established whenever possible. Orofacial manifestations have been divided into three groups: 1) those commonly associated with pediatric HIV infection; 2) those less commonly associated with pediatric HIV infection; and 3) those strongly associated with HIV infection but rare in children. Orofacial lesions commonly associated with pediatric HIV infection include candidiasis, herpes simplex infection, linear gingival erythema, parotid enlargement, and recurrent aphthous stomatitis. In contrast, orofacial lesions strongly associated with HIV infection but rare in children include Kaposi's sarcoma, non-Hodgkin's lymphoma, and oral hairy leukoplakia. Treatment recommendations, specific for this age group, have been included for some of the more common HIV-related orofacial manifestations.

    View details for PubMedID 10204447

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