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Biomedical subjects

R Wyllie

Publications and source records attributed to R Wyllie.

At least 37 records · Page 2Linked to original sources
PubMed1997

Use of conscious sedation for lower and upper gastrointestinal endoscopic examinations in children, adolescents, and young adults: a twelve-year review.

BACKGROUND: Over the past decade, many pediatric endoscopists have replaced general anesthesia with conscious sedation. Sedation is commonly used to minimize discomfort. METHODS: To evaluate the safety and efficacy of conscious sedation we reviewed 2711 reports of lower and upper gastrointestinal endoscopic examinations performed in 2026 patients between July 1981 and December 1992. RESULTS: Intravenous sedation was accomplished using meperidine and diazepam (914 examinations, 35%) or meperidine and midazolam (1427 examinations, 55%). Single agents were used for 83 examinations (3%), and 96 examinations (3.5%) were performed with the patient under general anesthesia. In the lower endoscopy group sedated intravenously (n = 713), the cecum was reached in 82% of examinations. The procedure could not be completed in 17 cases in which patients were uncooperative despite sedation. In the upper endoscopy group sedated intravenously (N = 1653), all but 91 endoscopies were completed to the descending duodenum. Esophagoscopy had been planned in 76% of these procedures. Minor complications occurred in 7 patients (0.3%). This included two episodes of significant oxygen desaturation that responded to oxygen administration and narcotic reversal. A major complication occurred in 1 patient (0.04%) who had a gastric perforation during esophageal dilation over a defective guide wire. There were no deaths, episodes of cardiorespiratory arrest, or pulmonary aspirations in our series. The combined major and minor complication rate was 0.3%. CONCLUSIONS: Intravenous conscious sedation is safe and effective in children undergoing endoscopic examination of the gastrointestinal tract. Selected patients will require general anesthesia.

Adolescent↗
PubMed1997

Delayed gastric emptying affects outcome of Nissen fundoplication in neurologically impaired children.

BACKGROUND: Nissen fundoplication (NF) has a relatively high failure rate in neurologically impaired children with gastroesophageal reflux (GER). In 1990 we began to use routine technetium 99m sulfur colloid emptying scans and pyloroplasty with NF for delayed gastric emptying (DGE) in our neurologically impaired patients. The aim of this study was to determine the influence of DGE and pyloroplasty on the outcome of NF in neurologically impaired children. METHODS: One hundred neurologically impaired children underwent NF by a single surgeon between August 1986 and July 1995. Beginning in January 1990 emptying scans were routinely obtained, and patients with DGE underwent pyloroplasty with NF. Outcome analysis was performed for recurrence/wrap failure and other parameters. Mean follow-up was 5.8 years, with a minimum of 18 months. RESULTS: DGE was found in 35 (65%) of the 54 children who had emptying scans. All 11 children with normal scans had successful NF without recurrent reflux (100%). Forty (93%) of 43 children who underwent pyloroplasty and NF had successful outcomes. Thirty-eight children underwent NF without evaluation of gastric emptying with success in 30 of them (78.9%). Overall success improved from 34 (83%) of 41 in the first half of the study, when 3 (7%) of 41 children underwent emptying scans, to 55 (93%) of 59 in the second half, when 51 (86%) of 59 of the children underwent emptying scans. CONCLUSIONS: DGE is common in neurologically impaired children with GER. NF in children with normal gastric emptying has a high probability of success. Pyloroplasty improves the outcome of NF in children with DGE. Neurologically impaired children should be evaluated for DGE before operation for GER.

Adolescent↗
PubMed1997

Cisplatin pharmacokinetics in children with cancer.

Cisplatin is an important drug in the treatment of a number of paediatric cancers yet, despite widespread use, there are only very limited data on the pharmacokinetics of the drug in children. Cisplatin pharmacokinetics were studied in 21 patients following a 24 h infusion of 50-120 mg/m2 cisplatin. Total and free platinum (Pt) levels in plasma and Pt in urine, were measured by atomic absorption spectrophotometry. Pharmacokinetic parameters were determined by non-compartmental and compartmental analyses. There was 3-fold interpatient variability in free drug exposure (area under the plasma concentration versus time curve--AUC) for a given surface area-based dose of cisplatin. The mean (+/- SD) pharmacokinetic parameters for free Pt were: AUC 0.47 +/- 0.13 mg/ml.min/100 mg/m2, Vdss 12.5 +/- 2.7 l/m2, t1/2 39 +/- 9 min, Ke 0.019 +/- 0.006 min-1, Clrenal 62 ml/min/m2, Cltotal 233 +/- 455 ml/min/m2, Cpss 0.31 +/- 0.09 microgram/ml. The total free Pt clearance was 1.5-5.8-fold higher (3.4 +/- 1.0) than the glomerular filtration rate (GFR). The renal clearance of cisplatin was not related to GFR and cisplatin was subject to only limited urinary excretion (27% administered dose 0-48 h), indicating that there are other important pathways of clearance beside renal elimination. Patient and treatment heterogeneity precluded the investigation of pharmacokinetic-pharmacodynamic relationships; however, the degree of interpatient pharmacokinetic variability observed suggests that body surface area-based dosing of cisplatin in children is not satisfactory.

Adolescent↗
PubMed1997

The influence of ifosfamide scheduling on acute nephrotoxicity in children.

Nephrotoxicity is a significant problem in children after treatment with ifosfamide. Acute changes in renal function were compared in 16 children receiving 9 g m(-2) of ifosfamide as a 72-h continuous infusion on one occasion and, on another course, divided into three 1-h infusions on consecutive days. Subclinical acute nephrotoxicity was demonstrated with both schedules, but there were no significant differences in severity.

Adolescent↗
PubMed1997

The safety of gastrostomy in patients with Crohn's disease.

OBJECTIVE: To evaluate the safety of gastrostomy tube placement in patients with Crohn's disease. METHODS: We retrospectively reviewed the charts of 25 patients with Crohn's disease who underwent surgical or endoscopic gastrostomy tube placement. Additional follow-up information was obtained by contacting the patients by telephone. RESULTS: Twenty-five patients with Crohn's disease underwent either surgical or percutaneous gastrostomy tube placement for prolonged enteral nutrition or gastric decompression after abdominal surgery. Gastrostomies were placed without difficulty in all cases. No major complications occurred after the procedures. Minor complications occurred in five patients, including one case of local wound infection, one case of persistent pain at the gastrostomy site, and three cases of peristomal leakage. These minor complications occurred in 22% of those who underwent percutaneous gastrostomy tube placement and 16% of those who underwent surgical gastrostomy. There was a higher incidence of minor complications in those who underwent gastrostomy for gastrointestinal decompression than in those who underwent the procedure for nutritional supplementation (14% versus 3.5%). A prior history of fistula formation did not predispose to complications related to gastrostomy placement. After gastrostomy tube removal, rapid closure of the site occurred in 96%. No cases of gastrocutaneous fistula formation occurred during follow-up, which ranged from 45 days to 8.7 yr (mean = 2.6 yr). CONCLUSIONS: We conclude that gastrostomy placement is safe in patients with Crohn's disease and does not result in an increased incidence of peristomal disease or formation of prolonged gastrocutaneous fistulas after gastrostomy tube removal.

Abdomen↗
PubMed1996

The effect of treatment with high dose melphalan, cisplatin or carboplatin on levels of glutathione in plasma, erythrocytes, mononuclear cells and urine.

Glutathione(GSH) has been implicated as an important factor in the detoxification of many electrophilic xenobiotics, including agents used in cytotoxic chemotherapy. Maintenance of high levels of GSH in normal tissues is believed to be important in the prevention of drug-induced toxicity. Previous studies have indicated that exposure of cells to some toxic electrophiles both in vitro and in vivo can cause a temporary decrease in intracellular levels of GSH. In this paper we report that in a series of 22 children and young adults treated with high dose melphalan (ten courses studied, all 200 mg/m2), cisplatin (eight courses, 80-104 mg/m2) or carboplatin (seven courses, 507-750 mg/m2) there was no significant alteration in the level of plasma, erythrocyte or urine GSH in the period immediately following drug administration. Fluctuations in the level of GSH in mononuclear cells were observed in some patients but did not follow any consistent pattern and were similar to those observed in a series of nine normal adult controls over the same time course. These results suggest that for melphalan, cisplatin and carboplatin, drug-GSH adduct formation is insufficient to cause a measurable decrease in intracellular GSH levels in normal peripheral haematopoietic cells during the course of treatment.

Adolescent↗
PubMed1996

Intrasubject variation in children of ifosfamide pharmacokinetics and metabolism during repeated administration.

The aim of this study was to investigate intrasubject variability in ifosfamide (IFO) pharmacokinetics and metabolism which may influence clinical effect, since the pharmacology of this drug is dependent on metabolism. A group of 11 patients (ages 1-16 years) were studied on at least two occasions. IFO, 9 gm-2 was administered as a continuous infusion over 72 h. Plasma and urine samples were collected and concentrations of IFO and its metabolites were determined. Comparisons were made between courses in the same subject, allowing for differences in age and prior IFO treatment. There was a wide variation in drug (twofold) and metabolite (up to tenfold) AUCs between courses in the same patient. Although some patients did show an increase in clearance between courses (up to threefold), there was no significant consistent change in overall pharmacokinetics among the different courses studied in the same patient. There was a significant decrease (up to 63%) in the AUC of the inactive metabolite 3-dechloroethylifosfamide (3-DCI) in later courses compared with the first course studied (P = 0.032, paired t-test). This was matched by an increase in the AUC of the total dechloroethylated metabolites with course (P = 0.015, paired t-test). None of the other metabolites measured showed any consistent change in plasma or urine levels between courses. Overall, the AUC of parent drug correlated with age (r2 = 0.86, P = 0.011), and postinfusion half-life correlated with plasma bilirubin (r2 = 0.89, P = 0.007). This study demonstrated large and seemingly unpredictable intrasubject variability in IFO pharmacokinetics and metabolism during repeated administrations. Investigations relating the clinical effects of IFO to pharmacokinetics and metabolism must take this variation into account.

Adolescent↗
PubMed1996

Therapeutic intervention for nonvariceal gastrointestinal hemorrhage.

The choice of therapeutic endoscopic technique depends on the training and equipment available to the endoscopist. If the technique is properly performed, the results are similar using injection, thermal coagulation, or laser therapy. We recommended that pediatric endoscopists concentrate on one thermal and one injection technique, since individual bleeding lesions may be more amenable to one method than another based on their anatomic location or briskness of bleeding.

Child↗
PubMed1996

Cyclophosphamide pharmacokinetics in children.

1. Cyclophosphamide pharmacokinetics were measured in 38 children with cancer. 2. A high degree of inter-patient variation was seen in all pharmacokinetic parameters. Cyclophosphamide half-life varied between 1.1 and 16.8 h, clearance varied between 1.2 and 10.61 h-1 m-2 and volume of distribution varied between 0.26 and 1.48 1 kg-1. 3. The half-life of cyclophosphamide was prolonged at high dose levels (P = 0.008). 4. Children who had received prior treatment with dexamethasone showed a mean increase in clearance of 2.51 h-1 m-2 (P = 0.001) presumably as a result of CYP450 enzyme induction. 5. Treatment with allopurinol or chlorpromazine was associated with a significant increase in cyclophosphamide half-life (P < 0.001 in both cases). 6. Dose and concurrent treatment may influence cyclophosphamide metabolism in vivo and thus potentially alter the drugs therapeutic effect.

Adolescent↗