Structural and functional changes in the rat small intestine following localized hyperthermia were examined. In anaesthetized male Sprague-Dawley rats a 10 cm segment of mid-small intestine was temporarily exteriorized, suspended in a cup containing Krebs-Ringer solution, and either heated at 43.5 degrees C or sham-heated at 38 degrees C for 45 min. The intestinal segments were studied 1, 4, 7, 21 and 42 days later by histopathological examination, determination of wet weight, dry weight and gross segment area, and by measuring absorption of 15 mM D(+)-glucose containing 14C-labelled D(+)-glucose as a tracer. Intestinal glucose transport was assessed by two different techniques: the everted sac method (in vitro) and luminal perfusion-recirculation (in vivo). After 1 day, heated intestinal segments exhibited marked mucosal damage, consisting of loss of epithelial cells and destruction of villi. Re-epithelialization had occurred by day 4, but mucosal architecture remained abnormal throughout the observation period. Hyperthermia caused significant thickening of the intestinal wall: at 4 days the thickening was due to oedema, whereas at 42 days tissue mass per cm2 in heated segments had increased by approximately 53 per cent compared with sham-heated control segments. At 1 day, net glucose transport in vitro in heated segments was reduced to 20 per cent and the serosal/mucosal concentration ratio to 57 per cent of that of control segments. In vivo, glucose transport in heated intestine at 4 days was 45 per cent of that of controls. From 4 days on, glucose transport improved gradually, and at 42 days there was no significant difference between heated and sham-heated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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Gentamicin and tobramycin pharmacokinetics in patients with cystic fibrosis.

Pharmacokinetic variables were compared in patients with cystic fibrosis receiving gentamicin or tobramycin for the treatment of a pseudomonas pulmonary infection. Sixty-nine pediatric patients receiving gentamicin sulfate (n = 31) or tobramycin sulfate (n = 38) were studied. Doses were administered every six hours. All patients received concurrent ticarcillin therapy, had a mild fever, and normal hematocrit and serum creatinine values. Amino-glycoside pharmacokinetic variables were calculated. Tobramycin and gentamicin serum concentrations were determined by radioimmunoassay. The mean (+/- S.D.) half-lives for the tobramycin and gentamicin patients were 1.2 +/- 0.5 and 1.4 +/- 0.4 hr, respectively. The average volume of distribution and clearance values for the tobramycin and gentamicin patients were 0.33 +/- 0.20 liters/kg and 2.98 +/- 0.80 ml/min/kg, and 0.35 +/- 0.15 liters/kg and 2.79 +/- 0.75 ml/min/kg, respectively. There were no significant differences between the kinetic variables in the patients receiving gentamicin or tobramycin. To achieve steady-state peak concentrations between 7 and 9 micrograms/ml and trough concentrations below 2 micrograms/ml, gentamicin patients required 10.3 +/- 3.2 mg/kg/day and tobramycin patients required 11.1 +/- 3.9 mg/kg/day. Because of the large amount of interpatient variability in maintenance dosage requirements, therapy should be initiated with 2.5 mg/kg of gentamicin or tobramycin given every six hours and then individualized on the basis of serum concentrations and clinical response.

Adolescent↗