Effect of stimulation in the ventral intermediate nucleus of the thalamus on limb control in Parkinson's disease: a case study.

This study focuses on upper extremity strength and movement control in a patient with Parkinson's disease who had stimulating electrodes surgically implanted in the ventral intermediate nucleus (VIM) of the left thalamus. We examined torque generation and control of movement distance in single degree-of-freedom elbow movements under three different stimulation conditions: (a) no stimulation, (b) high stimulation, in which tremor was minimized but there was also tingling and perceived weakness, and (c) moderate stimulation, in which tremor was partially reduced, but there was also a subjective sense of increased strength compared with the high-stimulation condition. The patient's ability to generate both steady torque and rapid movements was poorest with no stimulation. The patient generated the largest torques with moderate stimulation and performed the fastest movements with high stimulation. However, even with tremor minimized, the patient's electromyogram (EMG) burst patterns were not typical of those of neurologically healthy subjects, although the movements were clearly improved.

Recombinant human erythropoietin stimulates erythropoiesis and reduces erythrocyte transfusions in very low birth weight preterm infants.

DESIGN AND METHODS: We hypothesized that treatment with recombinant human erythropoietin (r-HuEPO) would stimulate erythropoiesis and would thereby reduce the need for erythrocyte transfusions in preterm infants. We treated 157 preterm infants born at 26.9 +/- 1.6 weeks of gestation who weighed 924 +/- 183 g at birth with either subcutaneous r-HuEPO (100 U/kg/d, 5 days per week) or placebo for 6 weeks in a randomized, double-blind, controlled clinical trial. All patients received oral iron and were managed according to uniform conservative transfusion guidelines. RESULTS: Treatment with r-HuEPO was associated with fewer erythrocyte transfusions (1.1 +/- 1.5 per infant in the r-HuEPO group versus 1.6 +/- 1.7 per infant in the placebo group; P = .046) and with a reduction in the volume of packed erythrocytes transfused (16.5 +/- 23.0 mL versus 23.9 +/- 25.7 mL per infant; P = .023). Overall, 43% of the infants in the r-HuEPO group and 31% of placebo-treated infants were transfusion-free during the study (P = .18). The volume of blood removed for laboratory tests and the need for respiratory support at the start of treatment had major effects on transfusion requirements independent of r-HuEPO. Reticulocyte counts were higher during treatment in the r-HuEPO group (P = .0001), and r-HuEPO-treated infants had higher hematocrit values at the end of the study (32% versus 27.3% in the placebo group; P = .0001). We found no differences in the incidence of major complications of prematurity between the treatment groups. CONCLUSION: We conclude that treatment with r-HuEPO at a weekly dose of 500 U/kg stimulates erythropoiesis, moderates the course of anemia, is associated with a reduction in erythrocyte transfusions, and appears safe in very low birth weight preterm infants who are receiving iron supplements. Conservative transfusion criteria, minimization of phlebotomy losses, and treatment with r-HuEPO are complementary strategies to reduce erythrocyte transfusions in these infants.

Enhancement of erythropoiesis by recombinant human erythropoietin in low birth weight infants: a pilot study.

We randomly assigned eight concurrently symptom-free premature infants (birth weight less than or equal to 1250 gm) at high risk of requiring erythrocyte transfusions for anemia of prematurity to 6 weeks of intensive treatment with either subcutaneous recombinant human erythropoietin (r-HuEPO group) or a placebo (control group). Treatment with r-HuEPO was initiated at a dose of 100 units/kg per day 5 days a week, and was increased to 200 units/kg per day after 2 or 3 weeks if target reticulocyte counts were not achieved. All patients were given supplemental oral iron therapy at a dose of 6 mg/kg per day, as tolerated. Mean reticulocyte counts in r-HuEPO-treated and control infants were 64,600 versus 67,500 cells/mm3 at entry; were 245,600 versus 78,000 cells/mm3 after 1 week; and averaged 262,600 versus 136,400 cells/mm3 during the study. Mean reticulocyte counts in r-HuEPO-treated infants were 251,200 cells/mm3 during the week when r-HuEPO, 100 units/kg per day, was given, and were 269,500 cells/mm3 after the dose was increased to 200 units/kg per day. Mean hematocrit values at entry were 33.4% in babies who received r-HuEPO versus 33.6% in the control subjects, and were 31.4% in r-HuEPO-treated and 25.2% in the control subjects at the end of treatment. One r-HuEPO-treated and three control babies received transfusions during the study; the total volume of blood given was 17 ml in the r-HuEPO group and 101 ml in the control subjects. The percentage of hemoglobin F increased in infants not given transfusions. We conclude that r-HuEPO stimulates endogenous erythropoiesis in small premature babies who are receiving supplemental oral iron therapy. A controlled multicenter trial has been undertaken to confirm these promising preliminary observations.

Recombinant erythropoietin in pediatrics: a clinical perspective.

Recombinant human erythropoietin represents a potential therapeutic alternative to red blood cell transfusions in a number of pediatric anemias. It is effective in correcting anemia associated with chronic renal failure and may significantly reduce the morbidity associated with childhood CRF. Most exposures to allogeneic blood products in pediatrics for treatment of anemia with blood transfusions occur in neonatal intensive care units. If proven effective in treating anemia in premature babies, r-HuEPO will be responsible for a major reduction in the use of blood transfusions in clinical neonatology. Carefully designed, placebo-controlled clinical trials will be required to establish the role of r-HuEPO in anemia of prematurity. Recombinant human erythropoietin also may be useful to increase the amount of blood that can be collected before elective surgical procedures. Another potential indication is to raise the hematocrits of infants with large intracardiac shunts who develop congestive heart failure coincident with the developmental fall in hemoglobin concentration after birth. Finally, r-HuEPO may one day play a role in modifying the expression of globin genes and, thereby, ameliorate the course of sickle cell disease and beta thalassemia. Many questions surrounding the use of r-HuEPO in infancy and childhood are being addressed in ongoing clinical trials.