Distribution, elimination, and action of d-tubocurarine in neonates, infants, children, and adults

The relation of plasma concentration of d-tubocurarine (dTc) to neuromuscular blockade, and the distribution and urinary excretion of dTc was determined in neonates (n = 4), infants (n = 6), children (n = 8), and adults (n = 8). The plasma concentration-time course curves to 24 hr are best described for all groups by three-compartment models. Both neonates and infants exhibit decreased plasma clearance (CLP), 1.1 +/- 0.08 and 1.0 +/- 0.06 ml X kg-1 X min-1, and in addition a prolonged t1/2 terminal phase, 311 +/- 44 and 306 +/- 35 (mean +/- SEM, min). The neonates' 24-hr urinary excretion, 27 +/- 2 (mean +/- SEM, % total dose) is significantly less than the adult value, 45 +/- 4% total dose. There was no significant difference seen in the log plasma concentration-evoked compound electromyogram (ECEMG) response between 20-80% paralysis for adults, children, infants, and five of the seven neonates studied. Two of the neonates had a significant shift of their log concentration-response curve to the right. There was also no significant difference between any of the groups in the time for 50% return of ECEMG stimulus height or the time required for recovery of the ECEMG from 25 to 75% of control value. for recovery of the ECEMG from 25 to 75% of control value.     

Overview: Epidemiology,indications, goals,extent, and nature of work-up

Each year in the United States, it is estimated that there will be 42,000 new cases of rectal cancer and 8,500 deaths^.1,2 Some patients present with an incurable rectal cancer but more often death follows development of recurrent rectal cancer after failed curative-intent therapy. Knowledge of the natural history of rectal cancer and limitations of treatment options coupled with sound clinical judgment and compassion are essential prerequisites for the clinician providing palliative care.     

Methotrexate, Azathioprine, Cyclosporine, and Risk of Fracture

We studied the fracture risk associated with use of methotrexate, azathioprine, and cyclosporine. The study was designed as a case-control study. All patients with a fracture (n = 124,655) in the year 2000 in Denmark served as cases. Information on fractures and confounders was retrieved from the National Hospital Discharge Register and a number of other national registers. For each case, three age- and gender-matched controls were randomly drawn from the general population (n = 373,962). Exposure was use of the drugs and a number of covariates including other immunosuppressive drugs, corticosteroids, any cancer, Crohn’s disease, ulcerative colitis, rheumatoid arthritis, psoriasis, liver and kidney disease, prior fracture, and alcoholism. Azathioprine was associated with an increase in overall fracture risk, but besides this, none of the drugs was significantly associated with overall fracture risk or risk of hip, spine, or forearm fracture. Liver [odds ratio (OR) = 1.55, 95% confidence interval (CI) 1.42–1.69] and kidney (OR = 1.26, 95% CI 1.16–1.37) diseases were significantly associated with increased risk of fractures. Azathioprine was associated with an increase in overall fracture risk but not in the risk of spine, hip, or forearm fractures. Methotrexate and cyclosporine were not associated with fracture risk. It thus seems that the underlying disease for which the treatment is administered may be responsible for much of the increase in fracture risk rather than the drugs used to treat the disorder in question.