Defining the limitations of transcutaneous bilirubin measurement in late preterm newborns.

OBJECTIVE: The objective of this study is to determine the impact of postnatal age on the bias between transcutaneous (TcB) and total serum bilirubin (TSB), and evaluate a TcB screening protocol. STUDY DESIGN: Preterm and term infants had paired TcB and TSB performed on days 1 to 3 of life; a subset of preterm infants had measurements on days 4 to 7. Sensitivity and specificity of TcB (plotted on an age-specific TSB nomogram) for prediction of high-intermediate (HIR) or high-risk TSB were calculated. RESULTS: Median TcB bias was 2.6 and 2.5 mg dl-1 for term and preterm infants in the first 3 days of life, respectively. However, median bias was 2.2 mg dl-1 for preterm infants at 4 to 7 days of life. TcB in preterm infants predicted HIR or high-risk TSB with 94% sensitivity and 56% specificity. CONCLUSION: TcB screening protocols developed for term infants can be used for late preterm infants in the first 3 days of life.

Comparison of in vitro and in vivo efficiencies of a novel unit-dose liquid aerosol generator and a pressurized metered dose inhaler.

Gamma scintigraphic imaging was employed in 10 healthy volunteers to compare the total and regional lung deposition of aerosols generated by two delivery platforms that permitted microprocessor-controlled actuation at an optimal point during inhalation. An aqueous solution containing 99mTc-DTPA was used to assess the deposition of aerosols delivered by inhalation from two successive unit-dosage forms (44 microl volume) using a prototype of a novel liquid aerosol system (AERx Pulmonary Delivery System). This was compared with aerosol deposition after inhalation of two 50 microl puffs of a 99mTc-HMPAO-labeled solution formulation from a pressurized metered dose inhaler (MDI). The in vitro size characteristics of the radiolabeled aerosols were determined by cascade impaction. For the AERx system, the predicted lung delivery efficiency based on the product of emitted dose (60.8%, coefficient of variation (CV)=12%) and fine particle fraction (% by mass of aerosol particles <5.7 microm in diameter) was 53.3% (CV=13%). For the solution MDI, the emitted dose was 62.9% (CV=13%) and the predicted lung dose was 44. 9% (CV=15%). The AERx system demonstrated efficient and reproducible dosing characteristics in vivo. Of the dose loaded into the device, the mean percent reaching the lungs was 53.3% (CV=10%), with only 6. 9% located in the oropharynx/stomach. In contrast, the lung deposition from the solution MDI was significantly less (21.7%) and more variable (CV=31%), with 42.0% of the radiolabel detected in the oropharynx/stomach. Analysis of the regional deposition of the radioaerosol indicated a homogeneous pattern of deposition after delivery from the AERx system. A predominantly central pattern of distribution occurred after MDI delivery, where the pattern of deposition was biased towards a central zone depicting the conducting airways. The AERx system, in contrast to MDIs, seems highly suited to the delivery of systemically active agents via pulmonary administration.

Inhalation delivery systems with compliance and disease management capabilities.

Non-compliance with prescribed medication is a major reason for poor therapeutic outcomes, leading to unnecessary contributions to healthcare costs. Poor technique in self-administration of inhalation therapy is a special type of non-compliance associated with this route of administration. However, pulmonary drug delivery has fundamental advantages for therapy of diseases of the respiratory tract because it is site-directed. The lung is also a promising portal for drug delivery into the systemic circulation. Incorporation of microprocessors into pulmonary drug delivery systems facilitates sophisticated compliance management of chronic diseases such as asthma and diabetes. Microprocessor-assisted systems afford control of patients' administration technique during the therapeutic inhalation event, thus leading to efficient and reproducible regional deposition of the inhaled drug or diagnostic agent. SmartMist is a hand-held asthma disease management device that aids patients to use optimally metered dose inhalers. It also measures pulmonary lung function and provides a long term downloadable electronic record of the therapeutic and diagnostic events. The AERx pulmonary delivery system utilizes similar microprocessor capabilities; however, it employs a novel means of generating aqueous aerosols from unit dose packages, thus providing a broad inhalation technology base for delivery of a wide variety of therapeutic and diagnostic agents into the respiratory tract, and via the lung into the systemic circulation.

Morphine pharmacokinetics after pulmonary administration from a novel aerosol delivery system.

BACKGROUND: Successful pharmacotherapy of pain often depends on the mode of drug delivery. A novel, unit dose, aqueous aerosol delivery system (AERx Pulmonary Drug Delivery System) was used to examine the feasibility of the pulmonary route for the noninvasive systemic administration of morphine. METHODS: The study had two parts: (1) a dose-ranging study in four subjects with three consecutive aerosolized doses of 2.2, 4.4, and 8.8 mg (nominal) morphine sulfate pentahydrate at 40-minute intervals, and (2) a crossover study, on separate days, in six subjects with 4.4 mg (nominal) aerosolized morphine sulfate administered over 2.1 minutes on three occasions and intravenous infusions of 2 and 4 mg over 3 minutes. Subjects were healthy volunteers from 19 to 34 years old. Arterial blood was sampled for a total of 6 hours and plasma morphine concentrations were measured by gas chromatography-mass spectrometry. RESULTS: In part 1, plasma morphine concentrations were proportional to dose. In part 2, the mean +/- SD peak plasma concentration (Cmax) occurred at 2.7 +/- 0.8 minutes after the aerosol dose, with mean values for Cmax of 109 +/- 85, 165 +/- 22, and 273 +/- 114 ng/ml for the aerosol and 2 and 4 mg intravenous doses, respectively. The bioavailability [AUC(0-360 min)] of aerosol-delivered morphine was approximately 100% relative to intravenous infusion, with similar intersubject variability in AUC for both routes (coefficient of variation < 30%). CONCLUSION: The time courses of plasma morphine concentrations after pulmonary delivery by the AERx system and by intravenous infusions were similar. This shows the utility of the pulmonary route in providing a noninvasive method for the rapid and reproducible systemic administration of morphine if an appropriate aerosol drug delivery system is used.

The normal posterior atlantoaxial relationship.

The relationship of the posterior aspects of the atlas and the axis were studied in 100 normal adult volunteers. The ratio of the height of the atlantal spinolaminar line to the atlantoaxial interspinous distance was found to be remarkably constant and was less than 2.0 in all men and women. This ratio should prove helpful in detecting hyperflexion injuries isolated to the atlantoaxial level.

Erosion of portal vein catheter into the biliary system.

Transcatheter intraportal infusion of chemotherapy in a patient with metastatic liver disease resulted in erosion of the tip of the catheter into the biliary system within six months of its placement. This unusual complication adds to the disadvantages of direct portal administration of chemotherapeutic agents in the treatment of hepatic tumors.

Modulation of the thermic effect of food by fenfluramine.

The thermogenic effect of fenfluramine was examined in rats following either fasting or the ingestion of a large meal. Fenfluramine did not produce a thermogenic effect in the fasting animal, but significantly potentiated the thermogenic effect of the meal. Furthermore, fenfluramine was found to produce a significant thermogenic effect when accompanied with a glucose meal, but not with one consisting of fat. These data demonstrate the importance of drug and nutrient interactions in the analysis of thermogenesis and suggest that substrate cycling may play a role in the thermogenic effect of fenfluramine.

Insensible weight loss as an indicator of metabolic rate.

Insensible weight loss has been used in large animals as an index of metabolic rate. By using the microprocessor controlled electronic balance to minimize the effects of movement, the feasibility of utilizing insensible weight loss as an estimate of metabolic rate in the rat is considered in terms of convenience and accuracy. Using various metabolic stimulants, a high correlation between insensible weight loss and metabolic rate was obtained. Moreover, a calculation is described that corrects for respiratory water loss and results in even higher correlations. These findings support the use of insensible weight loss as an indicator of metabolic rate in controlled situations for small animals.