PubMed Health⌕ Search

Biomedical subjects

Robert H Squires

Publications and source records attributed to Robert H Squires.

12 recordsLinked to original sources
PubMed2006

Bile acylcarnitine profiles in pediatric liver disease do not interfere with the diagnosis of long-chain fatty acid oxidation defects.

BACKGROUND: Plasma acylcarnitine measurement is an important diagnostic tool for inherited disorders of fatty acid and organic acid metabolism. Biliary excretion has been shown to be the primary route of excretion for acylcarnitines and analysis of bile acylcarnitine profiles may provide greater sensitivity for detecting metabolic disorders. Disorders of fatty acid oxidation frequently present with deranged liver function and the effect of hepatic disease on biliary acylcarnitine excretion are unknown. METHODS: We measured biliary acylcarnitine levels in pediatric patients aged 6 months to 1 year undergoing open liver biopsy with prospectively determined non-metabolic liver disease in order to determine the effect of the liver disease on acylcarnitine excretion. Bile was collected in syringes and was transported immediately and stored at -70 degrees C until the time of testing. The disease patient population consisted of 2 patients with known defects in long- and short-chain fatty acid oxidation (long-chain L-3-hydroxy acyl-CoA dehydrogenase: LCHAD and short-chain L-3-hydroxy acyl-CoA dehydrogenase: SCHAD). The sample from the LCHAD patient was collected at autopsy and the patient with SCHAD deficiency was subsequently diagnosed as part of the prospective study and removed from the unknown etiology group. Acylcarnitine profiles were obtained for each specimen as butylated derivatives using tandem mass spectrometry. RESULTS: The non-metabolic liver disease had no effect on the diagnostic value of bile acylcarnitine levels for detecting LCHAD deficiency. The concentrations of bile long-chain acylcarnitine species analyzed from patients with non-metabolic liver disease were far lower than the levels seen in LCHAD deficiency which also demonstrated a characteristic pattern of 3-hydroxyacylcarnitine excretion. In SCHAD deficiency, for which pathognomonic markers have not yet been established, bile analysis did not improve the diagnostic ability. CONCLUSION: The analysis of bile acylcarnitines for the diagnosis of long-chain fatty acid oxidation defects will provide unbiased information even in the presence of severe non-metabolic liver disease.

Bile↗
PubMed2006

Acute liver failure in children.

Acute liver failure (ALF) is a rare but devastating illness. Specific therapy to promote liver recovery is often not available, and the underlying cause of the liver failure is often unknown. This article examines current knowledge of the epidemiology, pathobiology, and treatment of ALF in children and identifies potential gaps in this knowledge for future study.

Child↗
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

Detection of acetaminophen protein adducts in children with acute liver failure of indeterminate cause.

OBJECTIVE: Acetaminophen cysteine protein adducts are a widely recognized correlate of acetaminophen-mediated hepatic injury in laboratory animals. The objective of this study was to use a new assay for the detection of acetaminophen cysteine protein adducts in children with acute liver failure to determine the role of acetaminophen toxicity in acute liver failure of unknown cause. METHODS: Serum samples from children with acute liver failure were measured for acetaminophen cysteine protein adducts using high-performance liquid chromatography with electrochemical detection. For comparison, samples from children with well-characterized acetaminophen toxicity and children with known other causes of acute liver failure also were measured for acetaminophen cysteine protein adducts. The analytical laboratory was blinded to patient diagnoses. RESULTS: Acetaminophen cysteine protein adduct was detected in 90% of samples from children with acute liver failure that was attributed to acetaminophen toxicity, 12.5% of samples from children with acute liver failure of indeterminate cause, and 9.6% of samples from children with acute liver failure that was attributed to other causes. Adduct-positive patients from the indeterminate cause subgroup had higher levels of serum aspartate aminotransferase and alanine aminotransferase and lower levels of bilirubin. Adduct-positive patients also had lower rates of transplantation and higher rates of spontaneous remission. CONCLUSIONS: A small but significant percentage of children with acute liver failure of indeterminate cause tested positive for acetaminophen cysteine protein adducts, strongly suggesting acetaminophen toxicity as the cause of acute liver failure. An assay for the detection of acetaminophen cysteine protein adducts can aid the diagnosis of acetaminophen-related liver injury in children.

Acetaminophen↗
PubMed2005

Chronic Abdominal Pain In Children: a Technical Report of the American Academy of Pediatrics and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

Chronic abdominal pain, defined as long-lasting intermittent or constant abdominal pain, is a common pediatric problem encountered by primary care physicians, medical subspecialists and surgical specialists. Chronic abdominal pain in children is usually functional-that is, without objective evidence of an underlying organic disorder. The Subcommittee on Chronic Abdominal Pain of the American Academy of Pediatrics and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition has prepared this report based on a comprehensive, systematic review and rating of the medical literature. This report accompanies a clinical report based on the literature review and expert opinion. The subcommittee examined the diagnostic and therapeutic value of a medical and psychologic history, diagnostic tests, and pharmacological and behavioral therapy. The presence of alarm symptoms or signs (such as weight loss, gastrointestinal bleeding, persistent fever, chronic severe diarrhea and significant vomiting) is associated with a higher prevalence of organic disease. There was insufficient evidence to state that the nature of the abdominal pain or the presence of associated symptoms (such as anorexia, nausea, headache and joint pain) can discriminate between functional and organic disorders. Although children with chronic abdominal pain and their parents are more often anxious or depressed, the presence of anxiety, depression, behavior problems or recent negative life events does not distinguish between functional and organic abdominal pain. Most children who are brought to the primary care physician's office for chronic abdominal pain are unlikely to require diagnostic testing. Pediatric studies of therapeutic interventions were examined and found to be limited or inconclusive.

Abdominal Pain↗
PubMed2005

Chronic abdominal pain in children: a clinical report of the American Academy of Pediatrics and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

Children and adolescents with chronic abdominal pain pose unique challenges to their caregivers. Affected children and their families experience distress and anxiety that can interfere with their ability to perform regular daily activities. Although chronic abdominal pain in children is usually attributable to a functional disorder rather than to organic disease, numerous misconceptions, insufficient knowledge among health care professionals and inadequate application of knowledge may contribute to a lack of effective management. This clinical report accompanies a technical report on childhood chronic abdominal pain and provides guidance for the clinician in the evaluation and treatment of children with chronic abdominal pain. The conclusions are based on the evidence reviewed in the technical report and on consensus achieved among subcommittee members.

Abdominal Pain↗
PubMed2004

Autoimmune hepatitis in children.

Autoimmune hepatitis (AIH) remains an enigmatic condition that affects children of all ages. Although much knowledge has emerged over the past four decades regarding autoimmune diseases, the lack of a spontaneous animal model has hindered a more complete understanding of the pathophysiology of AIH. Serum autoimmune markers, combined with biochemical and histologic evidence of hepatocellular injury and absent other diagnostic considerations, are necessary to diagnose AIH. The clinical spectrum ranges from asymptomatic elevation of aminotransferase levels to acute liver failure. Patients with AIH type 1 are more likely to be older and have cirrhosis at the time of diagnosis, whereas those with AIH type 2 may have a more fulminant course and require life-long immunosuppressant medications. Overlap syndromes occur in children but are rare. Treatment with prednisone and azathioprine, alone or in combination, reverses the clinical course and improves biochemical abnormalities. Should liver transplantation be necessary, autoimmune injury may recur in the allograft.

Alkaline Phosphatase↗
PubMed2003

Liver transplantation for cholestasis associated with cystic fibrosis in the pediatric population.

The most common hepatic complications of cystic fibrosis (CF) are steatosis, fibrosis, biliary cirrhosis, atretic gallbladder, cholelithiasis, and sclerosing cholangitis. Cholestatic liver disease is a slow progressive disorder, but will stabilize for many patients. CF patients may suffer from the consequences of their liver disease and without liver transplantation, variceal hemorrhage, malnutrition, or end-stage liver disease can lead to death. Prospective data were collected and reviewed on 311 liver transplants performed in 283 patients at the Children's Medical Center of Dallas between October 1984 and November 2000. Ten children received an orthotopic liver transplant (OTLX) for end-stage liver disease associated with cystic fibrosis. Pulmonary function tests were obtained preoperatively in all cases. There were nine boys and one girl. Six are currently alive, and four are dead. Both patient and graft survival was 5.75 yr. Among those currently alive, mean patient and graft survival is 7.71 yr (range 0.10-12.62 yr). Mean patient and graft survival of those who died was 2.35 yr (range 0.78-5.33 yr). No survivor required re-transplantation and currently, all have normal serum aminotransferase values. Chronic sinusitis was not a significant pre- or post-transplant morbidity, although systematic radiographic evaluation of the sinuses did not occur. Pulmonary deaths occurred in three patients from pulmonary hemorrhage, pulmonary infection with Aspergillus and Candida glabrata, and acute bronchopneumonia associated with polymicrobial sepsis because of Pseudomonas, Klebsiella, and Candida albicans 1.44, 0.78, and 1.83 yr, respectively, after transplantation. The fourth death was associated with chronic rejection, and occurred 5.33 yr after transplantation. All non-survivors were below the 5th percentile for height and weight at the time of liver transplantation. Mean age at transplantation was 9.72 yr (range 1.23-19.09, median 9.61). Survivors were transplanted at a younger age than non-survivors (mean of 9.21 yr vs. 10.66 yr), and had shorter waiting times from diagnosis of end-stage liver disease to transplantation (6.87 months vs. 13.83 months). Eighty percentage (n = 8) of patients had pretransplant variceal bleeds (83% of survivors, 75% of non-survivors). While all non-survivors had a history of meconium ileus and preoperative need of pancreatic enzymes, only 67% of those alive experienced these complications. Preoperative forced vital capacity FVC was 103% for survivors and 95% for non-survivors. The corresponding numbers for forced expiratory flow (FEF) 25-75 were 74-84% respectively. Preoperative Aspergillus was identified in 30% of patients (n = 3). Two of these patients are alive. Cystic fibrosis constitutes an indication for 3.5% of pediatric liver transplants. Evaluation and transplantation for end-stage liver disease associated with cystic fibrosis should be undertaken at an early age. Most deaths were associated with pulmonary/septic events, and occurred less than 2 yr after OLTX. Those children who did not survive had poor growth and nutrition, prolonged waiting times prior to transplantation, were transplanted at an older age, and had a higher incidence of pancreatic insufficiency and meconium ileus. The presence of Aspergillus in the sputum does not constitute a contraindication for OLTX.

Child↗
PubMed2003

Liver disease caused by failure to racemize trihydroxycholestanoic acid: gene mutation and effect of bile acid therapy.

BACKGROUND & AIMS: Inborn errors of bile acid metabolism may present as neonatal cholestasis and fat-soluble vitamin malabsorption or as late onset chronic liver disease. Our aim was to fully characterize a defect in bile acid synthesis in a 2-week-old African-American girl presenting with coagulopathy, vitamin D and E deficiencies, and mild cholestasis and in her sibling, whose liver had been used for orthotopic liver transplantation (OLT). METHODS: Bile acids were measured by mass spectrometry in urine, bile, serum, and feces of the patient and in urine from the unrelated recipient. RESULTS: Liver biopsy specimens showed neonatal hepatitis with giant cell transformation and hepatocyte necrosis; peroxisomes were reduced in number. High concentrations of (25R)3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoic acid in the urine, bile, and serum established a pattern similar to that of Zellweger syndrome and identical to the Alligator mississippiensis. Serum phytanic acid was normal, whereas pristanic acid was markedly elevated. Biochemical, MRI, and neurologic findings were inconsistent with a generalized defect of peroxisomal function and were unique. Analysis of the urine from the recipient of the deceased sibling's liver confirmed the same bile acid synthetic defect. A deficiency in 2-methylacyl-CoA racemase, which is essential for conversion of (25R)THCA to its 25S-isomer, the substrate to initiate peroxisomal beta-oxidation to primary bile acids, was confirmed by DNA analysis revealing a missense mutation (S52P) in the gene encoding this enzyme. Long-term treatment with cholic acid normalized liver enzymes and prevented progression of symptoms. CONCLUSIONS: This genetic defect further highlights bile acid synthetic defects as a cause of neonatal cholestasis.

Bile↗
PubMed2002

Treatment of unresectable hepatoblastoma with liver transplantation in the pediatric population.

The purpose of our study was to evaluate the outcome of children who underwent liver transplantation as treatment for unresectable hepatoblastoma. We prospectively collected data on 311 consecutive liver transplants performed at Children's Medical Center of Dallas between October 1984 and November 2000. There were nine recipients (five boys, four girls) with a diagnosis of unresectable hepatoblastoma. Postoperative survival of those currently alive ranged from 6 months to 16 years (mean 6.4 years, median 7.7 years). All recipients received preoperative chemotherapy: 67% received postoperative chemotherapy. Mean AFP level prior to transplantation was 1 448000 ng/mL. Mean age at diagnosis was 0.81 years. Mean age at transplantation was 1.87 years. Only two patients experienced acute cellular rejection in the postoperative period. There was a total of three deaths and one recurrence. The only instance in which AFP levels did not decrease to low or undetectable levels post-transplantation was in the patient with recurrent tumor. Liver transplantation has an established role in the treatment of hepatoblastoma. It accounted for 3% of pediatric liver transplants, and provided the only opportunity for survival in otherwise incurable patients. Early diagnosis and treatment were found to be associated with better results. Response to chemotherapy may be an important factor influencing survival. Rising AFP levels after transplantation are associated with recurrence.

Female↗