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Biomedical subjects

Philip Rosenthal

Publications and source records attributed to Philip Rosenthal.

At least 19 recordsLinked to original sources
PubMed2007

Immunotherapy for severe aplastic anemia following orthotopic liver transplantation in children.

Severe aplastic anemia is a well-recognized complication of fulminant non-A, non-B, and non-C hepatitis requiring orthotopic liver transplantation. The first line of therapy for cure in the treatment of aplastic anemia is a histocompatible bone marrow transplant. Immunosuppressive therapy is also effective if a histocompatible donor is not available. We describe two children who developed severe aplastic anemia following orthotopic liver transplant who achieved bone marrow recovery with a single course of anti-thymocyte globulin, solumedrol, and adjustments to their immunosuppressive therapy for prevention of liver allograft rejection.

Anemia, Aplastic↗
PubMed2006

The comprehensive assessment of physical fitness in children following kidney and liver transplantation.

BACKGROUND: Pediatric organ transplant recipients may have elevated cardiovascular (CV) risk. Low cardiorespiratory fitness (CRF) may contribute to CV risk; however, studies of CRF in children following kidney transplantation (KTx) and liver transplantation (LTx) are limited. METHODS: Laboratory testing included assessment of CRF (VO2peak), muscle strength, and body composition (%fat). Field testing (FITNESSGRAM) included the PACER, curl-up, and sit-and-reach tests. Values obtained were compared to sex- and age-based criterion-referenced standards (Healthy Fitness Zone, HFZ). The Previous Day Physical Activity Recall was used to assess after-school physical activity (PA) participation. Independent t tests were used to compare groups. RESULTS: Twenty-five KTx and 11 LTx recipients were tested. The groups were similar in all measures. Both groups demonstrated below normative values for VO2peak and muscle strength. Only 4% of the KTx and 9% of the LTx recipients achieved the HFZ for the PACER and 24% of the KTx and 45% of the LTx attained the HFZ for the curl-up test. Approximately 44% of both groups had percent fat greater than the upper criterion value of the HFZ. Both groups reported spending only 8% of their after-school time participating in physical activity. CONCLUSIONS: Pediatric KTx and LTx recipients have significantly reduced CRF, muscle strength, and physical activity. Routine counseling and encouragement for increased physical activity is recommended as a part of routine care. A randomized clinical exercise intervention trial after pediatric solid organ transplantation is warranted to determine the impact of such lifestyle intervention on improving physical fitness and cardiovascular health.

Adolescent↗
PubMed2006

A mathematical model of hepatitis a transmission in the United States indicates value of universal childhood immunization.

BACKGROUND: US recommendations issued in 1999 for hepatitis A (HA) childhood immunization varied according to regional HA incidences prior to vaccination. Mathematical models of HA transmission, especially those accounting for herd protection, can be useful in formulating new, highly effective recommendations that could lead to disease elimination. METHODS: A mathematical model of HA transmission was designed to assess the impact of different vaccination strategies on the evolution of HA infection over time in the United States. The model represents HA transmission dynamics and is stratified by age and regions defined in the Advisory Committee for Immunization Practices 1999 recommendations. The model accounts for herd protection and HA importation, using an age-dependent "force of infection" varying over time as a function of the prevalence of subjects with infectious HA. RESULTS: The model predicts a clear benefit of vaccinating all US children at as young an age as possible. Nationwide routine immunization at 1 year of age with 70% coverage would prevent 57% of additional cases during the period 1995-2029, compared with the continuation of the regional strategy of vaccinating children at 2 years of age, as recommended by the Advisory Committee for Immunization Practices in 1999. In contrast, the model also predicts that nationwide routine immunization for children 12 years of age only would result in a 14% increase of HA cases during the period 1995-2029, compared with the number of cases predicted with the regional strategy of the immunization of 2-year-olds. CONCLUSIONS: These findings highlight the importance of accounting for herd protection induced by early childhood HA vaccination. They also support the very recent Advisory Committee for Immunization Practices recommendations for universal HA immunization of 1-year-olds.

Adolescent↗
PubMed2006

Trends over a decade of pediatric liver transplantation in the United States.

During the last 10 to 15 years, medical and surgical innovations have established pediatric liver transplantation as the optimal therapy for children suffering acute and chronic liver disease. We hypothesized that the profile of current pediatric liver transplant recipients would differ significantly from that of an earlier era. We collected and compared data regarding the characteristics of children undergoing liver transplantation alone in 2 eras separated by more than a decade from the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Transplant recipients from March 1, 2002 to December 31, 2004, compared to those from January 1, 1990, to December 31, 1992, tended to be more evenly distributed across age, race/ethnicity, and disease etiology. There was a major shift toward utilization of partial grafts from both deceased and living donors to achieve transplantation for the youngest children (<1 and 1-5 yr) in particular. However, in spite of these innovative transplant strategies and only a modest increase in demand for pediatric liver transplantation, wait list times for both pediatric candidates and recipients have still increased between eras. In conclusion, the sobering reality that mortality on the waiting list remains highest for the youngest pediatric liver candidates frames our challenge for the next decade.

Adolescent↗
PubMed2006

Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group.

OBJECTIVES: To determine short-term outcome for children with acute liver failure (ALF) as it relates to cause, clinical status, and patient demographics and to determine prognostic factors. STUDY DESIGN: A prospective, multicenter case study collecting demographic, clinical, laboratory, and short-term outcome data on children from birth to 18 years with ALF. Patients without encephalopathy were included if the prothrombin time and international normalized ratio remained > or = 20 seconds and/or >2, respectively, despite vitamin K. Primary outcome measures 3 weeks after study entry were death, death after transplantation, alive with native liver, and alive with transplanted organ. RESULTS: The cause of ALF in 348 children included acute acetaminophen toxicity (14%), metabolic disease (10%), autoimmune liver disease (6%), non-acetaminophen drug-related hepatotoxicity (5%), infections (6%), other diagnosed conditions (10%); 49% were indeterminate. Outcome varied between patient sub-groups; 20% with non-acetaminophen ALF died or underwent liver transplantation and never had clinical encephalopathy. CONCLUSIONS: Causes of ALF in children differ from in adults. Clinical encephalopathy may not be present in children. The high percentage of indeterminate cases provides an opportunity for investigation.

Adolescent↗
PubMed2006

A multicenter study of the outcome of biliary atresia in the United States, 1997 to 2000.

OBJECTIVE: To determine the prognostic factors and optimal approaches to the diagnosis and management of biliary atresia, the leading indication for liver transplantation in children. STUDY DESIGN: A retrospective study was performed of all children who underwent hepatoportoenterostomy (HPE) for biliary atresia between 1997 and 2000 at 9 centers in the United States. Outcome at age 24 months was correlated with demographic and clinical parameters. RESULTS: A total of 104 children underwent HPE; 25% had congenital anomalies, and outcome was worse in those with biliary atresia splenic malformation syndrome. Diagnostic and clinical approaches varied, although specific approaches did not appear to correlate with outcome. The average age at referral was 53 days, and the average age at HPE was 61 days. At age 24 months, 58 children were alive with their native liver, 42 had undergone liver transplantation (37 alive, 5 dead), and 4 had died without undergoing transplantation. Kaplan-Meier analysis of survival without liver transplantation revealed markedly improved survival in children with total bilirubin level<2 mg/dL at 3 months after HPE (84% vs 16%; P<.0001). CONCLUSIONS: Outcome in the study centers was equivalent to that reported in other countries. Total bilirubin in early follow-up after HPE was highly predictive of outcome. Efforts to improve bile flow after HPE may lead to improved outcome in children with biliary atresia.

Abnormalities, Multiple↗
PubMed2006

Propylthiouracil-associated liver failure presenting as probable autoimmune hepatitis in a child with Graves' disease.

This case describes a young girl with Graves' disease, who presented with fulminant hepatic failure 9 months into propylthiouracil (PTU) therapy. Her clinical presentation was consistent with 'probable autoimmune hepatitis,' as defined by the International Autoimmune Hepatitis Group scoring system. Despite discontinuation of PTU and high-dose steroid therapy, she required liver transplantation. Subsequent pathology could not definitively rule out autoimmune hepatitis. PTU is an important cause of drug-related liver failure in children, and clinicians should be mindful that it is frequently used in patients who already have an underlying risk of autoimmune liver disease.

Antithyroid Agents↗
PubMed2005

Underdiagnosis of pediatric obesity and underscreening for fatty liver disease and metabolic syndrome by pediatricians and pediatric subspecialists.

OBJECTIVES: To evaluate how often general pediatricians, pediatric endocrinologists, and gastroenterologists diagnose children as overweight and how often interventions are provided, including nutritional counseling and screening for nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. STUDY DESIGN: The study was a retrospective chart review of outpatient visits at 2 academic hospitals. RESULTS: A total of 2256 patient visits were analyzed, including 715 visits by overweight children. Of those 715 visits, 31% resulted in a diagnosis of overweight. Diagnosis of overweight and nutritional counseling were least likely to occur during gastroenterology visits (22% and 13%, respectively, P < .01). Screening for metabolic syndrome was most likely to occur during endocrinology visits (34%; P < .01). Screening for NAFLD was most likely to occur during gastroenterology visits (23%; P < .01). Children age < 5 years and those with a body mass index percentile (BMI%) of 85% to 94% were least likely to receive diagnosis and intervention for overweight. CONCLUSIONS: The majority of overweight children were not diagnosed and did not receive relevant and recommended evaluations and interventions. Specific attention should be focused on providing diagnosis and interventions for overweight children, especially those age < 5 years and with a BMI% of 85% to 94%.

Adolescent↗
PubMed2004

Identification of novel parasitic cysteine protease inhibitors using virtual screening. 1. The ChemBridge database.

Trypanosomiasis, leishmaniasis, and malaria are major parasitic diseases in developing countries. The existing chemotherapy of these diseases suffers from lack of safe and effective drugs and/or the presence of widespread drug resistance. Cysteine proteases are exciting novel targets for antiparasitic drug design. Virtual screening was performed in an attempt to identify novel druglike nonpeptide inhibitors of parasitic cysteine proteases. The ChemBridge database consisting of approximately 241 000 compounds was screened against homology models of falcipain-2 and falcipain-3 in three consecutive stages of docking. A total of 24 diverse inhibitors were identified from an initial group of 84, of which 12 compounds appeared to be dual inhibitors of falcipain-2 and falcipain-3. Four compounds showed inhibition of both the malarial cysteine proteases as well as Leishmania donovani cysteine protease.

Animals↗
PubMed2004

Maternal microchimerism in the livers of patients with biliary atresia.

BACKGROUND: Biliary atresia (BA) is a neonatal cholestatic disease of unknown etiology. It is the leading cause of liver transplantation in children. Many similarities exist between BA and graft versus host disease suggesting engraftment of maternal cells during gestation could result in immune responses that lead to BA. The aim of this study was to determine the presence and extent of maternal microchimerism (MM) in the livers of infants with BA. METHODS: Using fluorescent in situ hybridization (FISH), 11 male BA & 4 male neonatal hepatitis (NH) livers, which served as controls, were analyzed for X and Y-chromosomes. To further investigate MM in BA, 3 patients with BA, and their mothers, were HLA typed. Using immunohistochemical stains, the BA livers were examined for MM. Four additional BA livers underwent analysis by polymerase chain reaction (PCR) for evidence of MM. RESULTS: By FISH, 8 BA and 2 NH livers were interpretable. Seven of eight BA specimens showed evidence of MM. The number of maternal cells ranged from 2-4 maternal cells per biopsy slide. Neither NH specimen showed evidence of MM. In addition, immunohistochemical stains confirmed evidence of MM. Using PCR, a range of 1-142 copies of maternal DNA per 25,000 copies of patients DNA was found. CONCLUSIONS: Maternal microchimerism is present in the livers of patients with BA and may contribute to the pathogenesis of BA.

Biliary Atresia↗
PubMed2004

Cost effectiveness of hepatitis A/B versus hepatitis B vaccination for US prison inmates.

Hepatitis B immunization is provided in many US prison systems. We examined the cost effectiveness of substituting bivalent hepatitis A/B vaccine in this setting, considering regional variation in hepatitis A risks and the potential for disease transmission by former prisoners. Where hepatitis A rates are >200, 100-200, and <100% the national average, declines in hepatitis A treatment costs would offset 137, 88, and 40% of the bivalent vaccine's added cost. In the three regions considered, cost effectiveness would be US$ <0, 2131, and 22,819 per life-year saved, respectively. Prison-based hepatitis A/B immunization would meet accepted standards of cost effectiveness throughout the US.

Adult↗
PubMed2004

The influence of portoenterostomy on transplantation for biliary atresia.

After portoenterostomy (PE) for biliary atresia (BA), many patients suffer progressive deterioration of liver function and ultimately require liver transplantation. We retrospectively reviewed a single center's experience with pediatric liver transplantation for BA from 1988 to 2002. Sixty-six patients underwent 69 liver transplants for BA. Forty-two (63%) patients had previously undergone Kasai PE, 11 (17%) biliary appendicoduodenostomy (BAD), and 13 (20%) had no prior biliary drainage (NBD). The BAD procedure offered only short-term biliary drainage--the mean interval between PE and transplant was more than twice that for Kasai patients than for BAD patients (132 versus 49 weeks). The transplants included 11 cadaveric partial, 27 cadaveric whole, and 31 living related transplants. Three patients required retransplant. Prior PE did not increase the incidence of major perioperative complications or unplanned reexploration. After transplant, the 1-, 5-, and 10-year actuarial graft survival rates were 87%, 86%, and 80%, respectively. The 1-, 5-, and 10-year actuarial patient survival rates were 91%, 89%, and 83%. PE remains an important bridge to transplant. In conclusion, transplantation for BA offers excellent long-term graft and patient survival.

Actuarial Analysis↗
PubMed2004

Chronic viral hepatitis.

Although less common in childhood, hepatitis B virus (HBV) and hepatitis C virus (HCV) remain the most common causes of chronic hepatitis in the United States and worldwide. Children with chronic HBV or HCV are often asymptomatic, with normal or mildly elevated serum transaminases. Although chronic HBV and HCV are indolent diseases in childhood, they cause significant morbidity and mortality later in life. Because the dreaded complications of chronic HBV and HCV--cirrhosis with liver failure and hepatocellular carcinoma--can be seen in childhood, routine follow-up with a pediatric gastroenterologist or hepatologist is recommended. The most important role of the primary care physician and pediatric gastroenterologist or hepatologist is prevention of chronic viral hepatitis through education and screening programs.

Adolescent↗
PubMed2004

Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure.

OBJECTIVE: The HepatAssist liver support system is an extracorporeal porcine hepatocyte-based bioartificial liver (BAL). The safety and efficacy of the BAL were evaluated in a prospective, randomized, controlled, multicenter trial in patients with severe acute liver failure. SUMMARY BACKGROUND DATA: In experimental animals with acute liver failure, we demonstrated beneficial effects of the BAL. Similarly, Phase I trials of the BAL in acute liver failure patients yielded promising results. METHODS: A total of 171 patients (86 control and 85 BAL) were enrolled. Patients with fulminant/subfulminant hepatic failure and primary nonfunction following liver transplantation were included. Data were analyzed with and without accounting for the following confounding factors: liver transplantation, time to transplant, disease etiology, disease severity, and treatment site. RESULTS: For the entire patient population, survival at 30 days was 71% for BAL versus 62% for control (P = 0.26). After exclusion of primary nonfunction patients, survival was 73% for BAL versus 59% for control (n = 147; P = 0.12). When survival was analyzed accounting for confounding factors, in the entire patient population, there was no difference between the 2 groups (risk ratio = 0.67; P = 0.13). However, survival in fulminant/subfulminant hepatic failure patients was significantly higher in the BAL compared with the control group (risk ratio = 0.56; P = 0.048). CONCLUSIONS: This is the first prospective, randomized, controlled trial of an extracorporeal liver support system, demonstrating safety and improved survival in patients with fulminant/subfulminant hepatic failure.

Adolescent↗
PubMed2003

Comparison of drainage techniques for biliary atresia.

PURPOSE: Traditional Kasai portoenterostomy and porto-appendiceal duodenostomy have been utilized for biliary atresia. Differences in outcome between patients who underwent either Kasai portoenterostomy or porto-appendiceal duodenostomy were compared. METHODS: A review of all children who underwent a drainage procedure for biliary atresia from 1986 to 2000 (n = 30) was performed. Age at drainage procedure, subsequent liver transplantation, and outcomes were evaluated. Outcome variables included success rates (total bilirubin < 2.0 mg/dL) and survival rate. Statistical analysis was done with chi2 and Student's t test. RESULTS: Long-term follow-up was available on 28 of 30 patients. Age at biliary drainage was insignificant. Success rates between porto-appendiceal duodenostomy (31%) and Kasai portoenterostomy (82%) were statistically significant. Survival rate for patients who underwent a Kasai portoenterostomy was 10 of 11 patients. Survival rate for patients who underwent porto-appendiceal duodenostomy was 14 of 16 patients. Overall survival rate was comparable between porto-appendiceal duodenostomy (88%) and Kasai portoenterostomy (91%). CONCLUSIONS: Although overall survival rate was comparable, patients who underwent porto-appendiceal duodenostomy were less successful in alleviating hyperbilirubinemia compared with Kasai portoenterostomy. This is shown further by the greater incidence of subsequent liver transplantation in infants with prior porto-appendiceal duodenostomy. Although the appendix may serve as an alternative biliary conduit, traditional Kasai portoenterostomy appears to achieve better biliary drainage.

Adolescent↗