Hydroxyurea in the treatment of sickle-cell anemia.

Sickle-cell anemia is a congenital hemolytic anemia characterized by sickle-shaped RBCs. The deformed RBCs become distorted and rigid and may occlude small arterioles and capillaries leading to tissue ischemia and infarction. Sickled RBCs are too fragile to withstand the trauma of circulation, and hemolysis occurs after they enter the circulation. RBCs with a high level of Hb F are resistant to sickling. Hydroxyurea has been shown to stimulate Hb F synthesis, leading to a reduction in the incidence of hemolytic and vaso-occlusive manifestations; however, hydroxyurea has no role in the treatment of crises already in progress. The National Heart, Lung, and Blood Institute announced in January 1995 that treatment with hydroxyurea leads to an increase in Hb F production within RBCs and a reduction in the frequency of painful crises in patients with sickle-cell anemia. Although the mechanism by which hydroxyurea increases Hb F is not known, one possible explanation is that hydroxyurea is cytotoxic to the more rapidly dividing late erythroid precursors, leading to the recruitment of early erythroid precursors that have demonstrated increased capacities to produce Hb F. Clinical trials have demonstrated that hydroxyurea results in an increase in Hb F concentrations; however, this increase may not dramatically affect the progressive vascular changes associated with sickle-cell anemia; thus, patients may still experience complications related to sickle-cell anemia. At North Carolina Baptist Hospital in Winston-Salem, NC, compliant patients with sickle-cell anemia are started on hydroxyurea. There are no specific criteria for patient selection or monitoring. The dosage is started at 10-15 mg/kg/d. Platelet count, complete blood count, and Hb F are monitored and hydroxyurea dosages are adjusted accordingly. Although hydroxyurea has been effective in the treatment of sickle-cell anemia, large double-blind, placebo-controlled clinical trials are needed to determine whether the risks of long-term administration outweight the risk of vaso-occlusive disease in untreated patients.

Another go at the experiment.

A number of states have experimented with legislation that would allow unlicensed international medical graduates to become physician assistants. These attempts have failed. The authors conducted a pilot evaluation study in California in response to legislative efforts. They examined the medical knowledge of a group of unlicensed international medical graduates and compared their clinical skills with those of a control group of recent graduates from a physician assistant training program. The unlicensed international medical graduates were below standard in medical knowledge and clinical skills and failed to make critical diagnoses in the tests with standardized patients. The authors conclude that unlicensed international medical graduates need additional training to be incorporated into the U.S. health care system as physician assistants.