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Biomedical subjects

R Wyllie

Publications and source records attributed to R Wyllie.

At least 55 records · Page 3Linked to original sources
PubMed1996

Antioxidants in hereditary pancreatitis.

OBJECTIVE: The cause of hereditary pancreatitis (HP) remains unknown. This study evaluated the hypothesis that patients with HP have genetically determined low concentrations of antioxidants that may predispose them to repetitive pancreatic injury. METHODS: This cross-sectional analysis compared antioxidant levels in four groups of patients. Group 1 included 14 related people with chronic pancreatitis. Group 2 (11 individuals) belonged to the same kindred but did not have pancreatitis. Group 3 was a group of 65 unrelated control subjects, and Group 4 consisted of seven unrelated children with chronic pancreatitis from other causes. The antioxidant levels analyzed included glutathione peroxidase, superoxide dismutase, glutathione reductase, glutathione transferase, selenium, and vitamin E. Amylase levels were measured in all patients in groups 1, 2, and 4. RESULTS: People with chronic pancreatitis or relatives of people with hereditary pancreatitis (groups 1, 2, and 4) had significantly lower mean glutathione peroxidase values than controls (group 3, p < 0.001). Group 1 also had significantly lower selenium levels than groups 2 and 3 (p < 0.001) but greater levels than group 4 (p = 0.029). Vitamin E levels were lower in group 1 than in groups 2 and 4. The superoxide dismutase levels were significantly different between each group (p < 0.001), and group 1 had the highest level. The glutathione reductase, glutathione transferase, and amylase levels did not differ significantly between groups. However, group 1 had a significantly higher glutathione transferase level than group 4. CONCLUSION: We identified antioxidant deficiencies in a group of patients with hereditary pancreatitis. Higher selenium and vitamin E levels may have prevented their relatives in group 2 from having pancreatitis secondary to oxidant injury, despite low glutathione peroxidase levels. Supplementation with selenium or vitamin E or both may be a beneficial therapeutic option in these patients to decrease the frequency of pancreatitis.

Adolescent↗
PubMed1995

Cyclophosphamide metabolism in children.

The alkylating agent cyclophosphamide is a prodrug which is metabolized in vivo to produce both therapeutic and toxic effects. Cyclophosphamide metabolism was investigated in 36 children with various malignancies. Concentrations of cyclophosphamide and its principal metabolites were measured in plasma and urine using a quantitative high-performance TLC method. The results indicated a high degree of inter-patient variation in metabolism. In contrast to previous adult studies on urinary metabolites, plasma carboxyphosphamide concentrations did not support the existence of polymorphic metabolism. Plasma concentrations of dechlorethylcyclophosphamide and carboxyphosphamide were correlated in individual patients, suggesting that the activity of both aldehyde dehydrogenase and cytochrome P450 enzyme(s) determine carboxyphosphamide production in vivo. The presence of ketocyclophosphamide in plasma was strongly associated with dexamethasone pretreatment and was also accompanied by a high clearance of the parent drug. Interpatient differences in metabolism reflect individual levels of enzyme expression and may contribute to variation in clinical effect.

Adolescent↗
PubMed1995

Comparison of continuous infusion and bolus administration of ifosfamide in children.

The pharmacological effects of ifosfamide (IFO) are dependent on its metabolism which may vary between different modes of administration. This was studied in 17 patients who received both a continuous infusion (9 g/m2 over 72 h) and repeated bolus administration (3 g/m2 every 24 h for 3 days). Concentrations of IFO and its metabolites were determined in plasma and urine. There was up to 70% less of the dechloroethylated metabolites in plasma following bolus administration compared to continuous infusion. Since dechloroethylation results in the formation of the toxic metabolite chloroacetaldehyde, this difference in metabolism may have an impact on the toxicity of IFO. There were no other consistent differences between the two modes of administration. Auto-induction of IFO metabolism, with an increase in dechloroethylated metabolites, was observed for both modes of administration. In conclusion, apart from dechloroethylation, there is little difference between these two modes of administration. However, during multiple cycles of IFO therapy such differences could have a significant effect.

Adolescent↗
PubMed1995

Acute and Chronic Pancreatitis.

Pancreatitis, once thought to be almost exclusively a disease of adults, is increasingly being found as the cause of abdominal pain in adolescents. The authors review the pathophysiology, diagnosis, managment, and complications of acute and chronic pancreatitis, noting that a high index of suspicion is needed to properly diagnose and provide optimal care to these patients.

Journal Article↗
PubMed1994

The results of strictureplasty in pediatric patients with multifocal Crohn's disease.

This study is a retrospective review of eight pediatric patients with multifocal intestinal Crohn's disease who underwent strictureplasty with or without concomitant bowel resection between January 1978 and April 1992. The patients ranged in age from 9.9 years to 18.5 years. Indications for surgery were partial intestinal obstruction (n = 6), failure of medial therapy or steroid dependence (n = 4), growth failure (n = 2), and enterocutaneous fistula (n = 2). Thirty-six strictureplasties were performed in the eight patients (median, 4.5 strictureplasties per patient; range, 1-12). Bowel resection was performed in six of the eight patients in areas where strictureplasty was not feasible. The mean length of resection was 40 cm (range, 15-82 cm). The only complication was intestinal hemorrhage, which was conservatively managed in two patients. The patients were followed for a mean of 19 months (range, 3-55 months). Five patients had a weight below the fifth percentile prior to surgery. Postoperatively, there was a weight gain in seven patients, including all five patients who were originally below the fifth percentile. A statistically significant weight gain was found when a paired t test analysis was applied to the entire group (p = 0.04). Five of six patients who were on steroid medication at the time of surgery were successfully weaned within 1.5-3 months (mean, 2.3 months) from the time of surgery. Seven of eight patients had relief of their intestinal symptoms. Strictureplasty with small-bowel resection, or perhaps strictureplasty alone, in pediatric patients with multifocal intestinal Crohn's disease can improve gastrointestinal symptoms, promote weight gain, and allow discontinuation of steroid medications.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Applications of gastrointestinal endoscopy in infants and children.

Gastrointestinal endoscopy has become an integral part of defining and treating gastrointestinal disease in children. Premalignant conditions that have been identified by endoscopy with histologic evaluation include Barrett's esophagus, juvenile polyposis coli, generalized juvenile polyposis, familial polyposis, Gardner's syndrome, and Turcot's syndrome. Advances in endoscopic instrumentation has allowed successful endoscopic retrograde cholangiopancreatography (ERCP) to be performed in infants and children. Therapeutic ERCP has been performed to remove stones, ligate strictures, and place stents. This review focuses on selected advances in gastrointestinal endoscopy and related diseases.

Age Factors↗
PubMed1994

Chronic pancreatitis in late childhood and adolescence.

Acute pancreatitis is unusual in pediatric patients, and chronic pancreatitis is even less common. Between 1983 and 1988, we diagnosed 24 patients in late childhood and adolescence with chronic pancreatitis. Our review revealed that chronic pancreatitis presents as recurrent abdominal pain in late childhood and adolescence. Individual laboratory and radiological investigations may be normal during acute exacerbations of pain, but the determination of serum amylase and lipase concentrations--combined with ultrasonography--will accurately identify most patients. We found that endoscopic retrograde cholangiopancreatography is a valuable tool in the diagnosis of structural abnormalities. Surgical intervention may reduce symptoms in patients with structural abnormalities. There is a tendency toward decreased frequency and severity of pain as the patients increase in age.

Adolescent↗
PubMed1994

Colonoscopy and therapeutic intervention in infants and children.

Colonoscopy is an established procedure for the investigation of large bowel and terminal ileal disease in infants and children. Specific indications vary with the child's age. Preparation and sedation of the pediatric patient and colonoscopy techniques must be tailored to the age and physical stature of the patient.

Child↗
PubMed1993

Pharmacokinetics and metabolism of ifosfamide administered as a continuous infusion in children.

The pharmacokinetics and metabolism of ifosfamide was investigated in a group of 16 pediatric patients (5 girls) aged 1-17 years. Each received a dose of 3 g/m2/day for up to 3 days by continuous infusion. Plasma and urine were collected, and concentrations of ifosfamide and its principal metabolites were determined by a quantitative high-performance thin layer chromatography method. During 3 days of continuous infusion, the plasma concentrations of parent drug decreased. This was accompanied by a continuous increase in dechloroethylated products in plasma but not in urine. Estimated pharmacokinetic parameters (clearance, volume of distribution, and half-life) were dependent on body size and age but not any other patient variable. Renal clearance was a relatively minor route of elimination for parent drug and corresponded to < 25% of glomerular filtration rate. Metabolite data from plasma and urine indicated a high degree of interindividual variation in metabolism. Comparison of metabolite recoveries in urine indicated a positive correlation between activation and inactivation routes of metabolism. Prior exposure to ifosfamide was associated with a higher recovery in urine of dechloroethylated metabolites. The severity of hematological toxicity was inversely correlated with glomerular filtration rate but not to parameters of ifosfamide metabolism. There was marked variation in levels of the carboxy metabolite, which could not be detected in the plasma of 5 subjects. However, evidence for a polymorphism in metabolism to this metabolite was weaker than that seen with the isomeric oxazaphosphorine cyclophosphamide. There appeared to be a higher clearance of ifosfamide in pediatric patients compared to adults. The significance of this, and of the variation in metabolism of ifosfamide, for clinical outcome remains to be established, but the increase in the dechloroethylation route of metabolism may be associated with an increased risk of toxicity.

Adolescent↗