Pharmacologic treatment of hyperthyroidism during lactation

QUESTION I have a patient who has hyperthyroidism due to Graves disease. She was taking methimazole but discontinued when she found out she was pregnant. She is currently close to delivery and might require antithyroid therapy in the postpartum period. Can methimazole cross into human milk, and is breastfeeding safe for her infant?ANSWER The exposure of infants to methimazole or propylthiouracil through breast milk is minimal and not clinically significant. Women with hyperthyroidism using methimazole or propylthiouracil should not be discouraged from breastfeeding, as the benefits of breastfeeding largely outweigh the theoretical minimal risks.     

Trends of medication errors in hospitalized children

Medication errors are a major cause of morbidity and mortality among hospitalized children. Due to the small volumes of stock solution involved, even a large error may look as an unsuspiciously small dose. Strategies were implemented to reduce medication errors in a large tertiary pediatric hospital in Toronto. Starting in 1993, several initiatives were taken, including a new hospital computer system for medication ordering, a review process to remove hazardous drugs from wards where they are not needed immediately, and in the training of pediatric residents. The rates of reported medication errors were compared before and after these initiatives were taken. Compared to baseline, there was a steady and a statistically significant decrease in medication errors through the decade. Total errors (actual and potential) decreased for nurses and physicians by half and for pharmacists by 75%. Actual incidents decreased by half. Moderate and severe errors decreased by more than 70%. It was concluded that a combination of several initiatives to decrease system and human errors has resulted in more than a 50% reduction of medication errors reaching the pediatric patient.     

Inhibition of p53-induced apoptosis without affecting expression of p53-regulated genes

Using DNA microarray and clustering of expressed genes we have analyzed the mechanism of inhibition of wild-type p53-induced apoptosis by the cytokine interleukin 6 (IL-6) and the calcium mobilizer thapsigargin (TG). Clustering analysis of 1,786 genes, the expression level of which changed after activation of wild-type p53 in the absence or presence of IL-6 or TG, showed that these compounds did not cause a general inhibition of the ability of p53 to up-regulate or down-regulate gene expression. Expression of various p53 targets implicated as mediators of p53-induced apoptosis was also not affected by IL-6 or TG. These compounds thus can bypass the effect of wild-type p53 on gene expression and inhibit apoptosis. IL-6 and TG activated different p53-independent pathways of gene expression that include up-regulation of antiapoptotic genes. IL-6 and TG also activated different differentiation-associated genes. The ability of compounds such as cytokines and calcium mobilizers to inhibit p53-mediated apoptosis without generally inhibiting gene expression regulated by p53 can facilitate tumor development and tumor resistance to radiation and chemotherapy in cells that retain wild-type p53.     

Toward further expansion of the organ pool for adult liver recipients: splitting the cadaveric liver into right and left lobes

BACKGROUND: Current methods of living donor right lobe transplantation can be expanded for use in the cadaveric setting. The aim of this study is to discuss alternative methods for the management of large-for-size cadaveric livers and determine the feasibility of splitting these organs into left and right hemi-livers using similar techniques to those used in the living donor setting. METHODS: The indication for an in situ right-left split procedure was an offer of a large liver for a small recipient with a recipient-donor ratio of greater than 1.5. A total of three livers were split. Mean donor age was 33.3 (range, 22-40) years. Mean weight was 118 (range, 90-150) kg. All donors were without significant medical history and were hemodynamically stable, with normal liver function and short hospital stay. Mean duration of the procurement procedure was 235 (range, 210-270) min. Mean cold ischemia time was 8.5 hr. Mean recipient weight was 58.3 kg, and mean donor to recipient weight ratio was 2.0 (1.6-2.6). United Network for Organ Sharing statuses at the time of transplantation were 1 (n=1), 2A (n=1), and 2B (n=4). RESULTS: Immediate graft function was seen in five recipients. Delayed nonfunction was identified in one recipient of a left lobe, who did not undergo transplantation because of sepsis that resulted in death at 30 days. A second mortality occurred in a left lobe recipient, from a fungal brain abscess at 90 days. Complications related to the split included bile leaks in two patients, one necessitating operative revision. CONCLUSIONS: Splitting of livers from appropriate brain-dead donors into right and left lobes is technically and logistically feasible. The large-for-size organ provides a more substantial amount of liver tissue to each of the adult recipients, which may result in a greater graft to recipient weight ratio than the current standard that is used in the living donor grafting. The importance of this variable will need to be studied, because it may positively impact on the ability of the reduced-size graft to withstand donor-related organ system stress and injury, which is associated with brain death and the inevitable longer period of cold preservation.