Bupropion in breast milk: an exposure assessment for potential treatment to prevent post-partum tobacco use

Objectives: To assess potential infant exposure to bupropion and its active metabolites in breast milk such as would occur during treatment to prevent post-partum relapse to tobacco use, and to compare the concentrations of bupropion in urine and saliva with plasma and breast milk.

Design and setting: Cohort study, outpatient clinical research centre.

Subjects: Ten healthy post-partum volunteers who agreed to take bupropion for seven days, pump and discard their breast milk, and have samples of breast milk, plasma, saliva, and urine analysed.

Intervention: Bupropion 150 mg a day for three days and then 300 mg a day for four days.

Main outcome measures: Concentrations of bupropion and its active metabolites (hydroxybupropion, erythrohydrobupropion, threohydrobupropion) in breast milk, plasma, saliva, and urine. Determination of average infant exposure.

Results: The calculated average dosage of bupropion in breast milk was 6.75 µg/kg/day. Therefore, the average infant exposure is 0.14 % of the standard adult dose of bupropion, corrected for the difference in body weight. Considering the sum of bupropion and its active metabolites, the average infant exposure is expected to be 2% of the standard maternal dose on a molar basis. The concentration of bupropion and its active metabolites in breast milk was not associated with age, body mass index, use of oral contraceptive pills, age of infant, or the frequency of breast feeding at the time the study was initiated. The coefficient of determination (r²) between the concentration of bupropion in breast milk and in urine was 0.77 (p < 0.01).

Conclusions: Bupropion and its active metabolites are present in the breast milk of lactating women. The concentrations of bupropion in breast milk and urine were highly correlated. These results indicate that the daily dose of bupropion and metabolites that would be delivered to an infant of a woman taking a therapeutic dose of bupropion is small. These results suggest that the effectiveness of bupropion to prevent post-partum relapse to tobacco use should be evaluated without excluding women who plan to breast feed.

     

Investigation of twin-wall structure at the nanometre scale using atomic force microscopy

The structure of twin walls and their interaction with defects has important implications for the behaviour of a variety of materials including ferroelectric, ferroelastic, co-elastic and superconducting crystals. Here, we present a method for investigating the structure of twin walls with nanometre-scale resolution. In this method, the surface topography measured using atomic force microscopy is compared with candidate displacement fields, and this allows for the determination of the twin-wall thickness and other structural features. Moreover, analysis of both complete area images and individual line-scan profiles provides essential information about local mechanisms of twin-wall broadening, which cannot be obtained by existing experimental methods. The method is demonstrated in the ferroelectric material PbTiO(3), and it is shown that the accumulation of point defects is responsible for significant broadening of the twin walls. Such defects are of interest because they contribute to the twin-wall kinetics and hysteresis.     

Certain ineffective parametric interactions

The letter discusses a situation where both reactances of a resonator are pumped together in unison. It is shown that this mode of pumping does not yield a parametric excitation. This result may be of practical relevance in treating certain microwave and optical systems.     

Reversal of pretreatment hypotension and control of hemorrhage in trauma patients by a simple device

The injection of a suspension of Walker 256 carcinoma cells into the carotid artery of rats produced a model of hematogenously spread cerebral metastases. Most animals died from massive extracerebral tumors of the head and jaw; brain tumors were present in only one-quarter. External carotid artery ligation prior to tumor inoculation did not increase the incidence of fatal brain tumor. When cyclophosphamide, 15 mg/kg, was injected as a single dose on the fourteenth day after tumor inoculation, most of the extracerebral tumor disappeared. Fifty percent of the animals so treated were cured of tumor, but 90% of the remainder died of large intracerebral tumors. Severe cytopathic changes resulting from cyclophosphamide were present in extracerebral or choroid plexus tumors but were mild or nonexistent in intracerebral tumors. These selective effects of cyclophosphamide suggest that water-soluble agents are less effective against tumor in the brain than against extracerebral tumors despite the fact that metastatic tumor breaks down the blood-brain barrier.     

Anomalous double blood supply to the lung

We report an unusual case in which an apparently normal upper lobe of the right lung was supplied by major systemic arterial and pulmonary arterial vessels. The anomalous artery arose from the descending aorta. Following interruption of this vessel, the machinery-like murmur previously present disappeared.     

Thyroid carcinoma after high-dose external radiotherapy for Hodgkin's disease: report of three cases

Three patients (two female and one male), who had received mantle irradiation for Hodgkin's disease eight, ten, and twelve years previously, developed papillary thyroid carcinoma. The radiation doses to the necks overlying the site of thyroid cancers were 3000, 4000, and 4100 rads, respectively. It has been stated that there is no risk of developing thyroid cancer with such high doses of external irradiation but apparently this complication will be encountered in a small number of patients.     

Discontinuities and senior management: assessing the role of recognition in pharmaceutical firm response to biotechnology

Despite an increasing emphasis on the role of senior managementcognition in shaping organizational action, there have beenfew attempts to link top management mental models to strategicchoice in the face of discontinuous innovation. This paper uses23 years of data covering 15 major pharmaceutical firms to explorethe degree to which each firm's response to the revolution inbiotechnology was shaped by the senior team's recognition ofbiotechnology's importance. Controlling for a number of importantalternative explanations, we show that recognition may be animportant predictor of action, suggesting that cognition atthe most senior level can play a critical role in shaping establishedfirms' response to discontinuities.     

Improved analysis of dissolved carbohydrates in stream water with HPLC-PAD

This paper describes improvements made to the determination of dissolved carbohydrates in stream water with high-performance liquid chromatography and pulsed amperometric detection (HPLC-PAD). We eliminated interference from dissolved oxygen, separated xylose and mannose along with other molecules, reduced the chromatographic peak shift associated with carbonate accumulation in the column to less than 1% for all samples, and achieved an 8% increase in recovery of hydrolyzed carbohydrates by replacing ion-exchange desalting cartridges with evaporative removal of HCl under N2. These modifications lowered detection limits to less than or equal to 0.4 nM for 10 different monosaccharides and enhanced our ability to follow the dynamics of these molecules in stream ecosystems. In the determination of dissolved free monosaccharides, average relative precision was 1.3% and recovery ranged from 92 to 109%. For dissolved total saccharides, average relative precision was 3.3%. Concentrations were stable when filtered (0.2 microm) stream water was stored for 1 day at 22 degrees C, 1 week at 4 degrees C, or 1.5 months at -20 degrees C.     

A simpler analysis of Burrows–Wheeler-based compression

In this paper, we present a new technique for worst-case analysis of compression algorithms which are based on the Burrows–Wheeler Transform. We mainly deal with the algorithm proposed by Burrows and Wheeler in their first paper on the subject [M. Burrows, D.J. Wheeler, A block sorting lossless data compression algorithm, Technical Report 124, Digital Equipment Corporation, Palo Alto, California, 1994], called bw0. This algorithm consists of the following three essential steps: (1) Obtain the Burrows–Wheeler Transform of the text, (2) Convert the transform into a sequence of integers using the move-to-front algorithm, (3) Encode the integers using Arithmetic code or any order-0 encoding (possibly with run-length encoding).