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The metabolism of alpha-aminobenzo(b)thiophene-3-propionic acid (the sulfur analog of tryptophan) in the rat.

The biotransformation of 3H-labeled alpha-aminobenzo[b]thiophene-3-propionic acid (the sulfur analog of tryptophan) was investigated in rats. Forty-eight hours after ip administration, 80% of the radioactive dose was recovered in the urine and 5% in the feces; tissue levels of radioactivity accounted for the remainder of the administered dose. The urinary metabolites were identified by a combination of thin-layer chromatography, gas chromatography, and gas chromatography-mass spectrometry, and were quantitated by thin-layer chromatography and liquid-scintillation counting to give, as percentages of the administered dose, unchanged alpha-aminobenzo[b]thiophene-3-propionic acid (20.6%), benzo[b]thiophene-3-acetic acid (1.3%), benzo[b]thiophene-3-pyruvic acid (14.2%), benzo[b]thiophene-3-lactic acid (4.9%), and N-(benzo[b]thiophene-3-acetyl)glycine (46.2%).

Tracheal agenesis in infants with VATER association.

Four newborns had tracheal agenesis and numerous features of the VATER (vertebral defects, imperforate anus, tracheoesophageal fistula, and radial and renal dysplasia) association. Forty-two additional reported cases of tracheal agenesis have been reviewed to establish whether this defect usually occurs in association with other VATER abnormalities. Since tracheal agenesis usually is accompanied by other VATER-associated defects and since similar abnormalities in embryological mechanisms and timing are implicated, according to current theories of development, we propose that tracheal agenesis should be considered a component of the VATER association.

Pharmacokinetics of netilmicin in premature infants.

The pharmacokinetics of netilmicin were studied in 12 premature infants with proven or presumed sepsis during the first month of life. Eleven of 12 patients received netilmicin 2.5 mg/kg intravenously every 12 h while one 770-gram birth weight infant received 2.5 mg/kg every 18 h. Mean steady-state peak and trough concentrations were 8.9 micrograms/ml and 2.8 micrograms/ml, respectively. Of twelve patients, 11 had trough serum concentration above 2 micrograms/ml and four had trough serum concentrations above 3 micrograms/ml. Mean total body clearance of netilmicin was 0.84 ml/min/kg. The mean clearance of 0.72 ml/min/kg was substantially lower in patients with a mean postnatal age of 2.7 days than the clearance of 1.10 ml/min/kg in patients with a mean postnatal age of 23 days. The mean apparent volume of distribution was 0.63 l/kg; and the mean elimination halflife was 8.6 h. A three-fold interpatient variation in pharmacokinetic parameters was seen. These data suggest the need for careful monitoring of netilmicin serum concentration in premature infants.

Alterations in cerebral blood flow and oxygen consumption during prolonged hypocarbia.

The effect of prolonged (2 h) hypocarbia on cerebral blood flow, oxygen delivery, extraction, and consumption was studied in eight, 1- to 4-day-old piglets. Hyperventilation to PaCO2 less than 20 mm Hg acutely (30 min) decreased cerebral blood flow and oxygen consumption. Cerebral oxygen consumption was subsequently restored via increases in cerebral blood flow and thus, cerebral oxygen delivery. Cerebral oxygen extraction rose from a normocarbic baseline of 50 to 75% with acute hypocarbia and was maintained at this level. The percent decrease in blood flow to the cerebrum was greater than that to other brain regions during hypocarbia.

Budd-Chiari syndrome in a premature infant receiving total parenteral nutrition.

A premature infant who developed Budd-Chiari syndrome as a complication of total parenteral nutrition through an inferior vena cava catheter is presented. A novel approach to the treatment of this otherwise lethal condition is described. This very unusual complication in pediatric patients may be seen with increased frequency as more premature infants are treated with central vein total parenteral nutrition.

The effect of naloxone on the hemodynamics of the newborn piglet with septic shock.

Naloxone has been shown to reverse the hemodynamic sequelae of experimental septic shock in adult animal models. Its effectiveness in the newborn has not been studied. To further investigate the efficacy of naloxone, we instrumented 18 piglets for continuous measurement of mean arterial pressure, mean pulmonary arterial pressure, central venous pressure, heart rate, left ventricular pressure, contractility, cardiac output, and O2. Oxygen consumption, systemic vascular resistance, and pulmonary vascular resistance were calculated. Following a stabilization period, group B beta-hemolytic Streptococci were infused over 30 min. Following the infusion, naloxone (1 mg/kg) was given followed by a continuous infusion of 1 mg/kg/h in nine treatment animals. Nine control animals were given an equal volume of saline. Both groups developed significant increases in mean pulmonary arterial pressure followed by a return to baseline. Oxygen consumption, cardiac output, contractility and mean arterial pressure decreased in both groups. Treatment with naloxone was associated with a cessation in the fall in the mean arterial pressure and the contractility. The difference in mean arterial pressure and contractility between groups was significant. The naloxone group had significantly improved 5-h survival. We speculate that naloxone may reverse some of the hemodynamic sequelae and improve survival in newborns with septic shock.