[Pharmacological profiles of mycophenolate mofetil (CellCept), a new immunosuppressive agent].

Mycophenolate mofetil (MMF, CellCept), a semisynthetic derivative of mycophenolic acid (MPA) produced by a fungus, is an inhibitor of the inosine monophosphate dehydrogenase (IMPDH) enzyme (IC50 = 25 nM) that catalyzes the synthesis of guanosine monophosphate (GMP) from inosine. GMP is an essential nucleoside for purine synthesis during cell division. As T and B-lymphocytes almost exclusively use the de novo pathway of purine synthesis, these cells are particularly sensitive to the inhibitory action of MMF. It has a mechanism of action distinct from cyclosporine and tacrolimus. Although MMF does not affect cytokine production, by inhibiting the rate-limiting enzyme IMPDH in the de novo synthesis of purines, it inhibits the proliferation of T and B-lymphocytes, the production of antibodies, and the generation of cytotoxic T lymphocytes. Reversal of acute allograft rejection and increased survival of kidney, heart and bone marrow cell allograft has been shown in several animal studies. Moreover, it was suggested that MMF combined with CsA prevented the acute rejection, and approximately half of the animals became long-term survivors. The Ministry of Health and Welfare approved MMF in 1999 for use for rejection treatment in renal transplantation based on several prospective, randomized and blind efficacy trials.

[MR imaging of cerebral palsy].

We evaluated 35 patients with cerebral palsy on the basis of MR imaging findings in the brain. The types of palsy were spastic quadriplegia (n = 11), spastic diplegia (n = 9), spastic hemiplegia (n = 2), double hemiplegia (n = 1), athetosis (n = 10) and mixed (n = 2). Of all patients, 28 (80%) generated abnormal findings. In spastic quadriplegia, although eight cases revealed severe brain damage, two cases showed no abnormal findings in the brain. One of the three had cervical cord compression caused by atlanto-axial subluxation. In spastic diplegia, the findings were divided according to whether the patient was born at term or preterm. If the patient had been born prematurely, the findings showed periventricular leukomalacia and abnormally high intensity in the posterior limbs of the internal capsule on T2-weighted images. MR imaging in spastic hemiplegia revealed cerebral infarction. In the athetoid type, half of all cases showed either no abnormal findings or slight widening of the lateral ventricle. Three cases showed abnormal signals of the basal ganglia. The reason why athetoid-type palsy did not show severe abnormality is unknown. We believe that MR imaging is a useful diagnostic modality to detect damage in the brain in cerebral palsy and plays an important role in the differentiation of cerebral palsy from the spastic palsy disease.

[Complete remission in a case of concurrent breast and thyroid cancers with metastatic spinal paralysis].

UNLABELLED: A case of right breast and thyroid cancer is reported in which, despite metastasis to the spinal cord occurring 1 year after mastectomy, satisfactory therapeutic results were obtained. At the time of her first examination the patient had spastic paresis involving all segmental levels below Th7. Bone scintigraphy disclosed multiple hot areas in the spinal column, centering around Th5 6. On myelography, complete block was noted above the lower margins of the vertebral body of Th5. The paresis progressed to result in a complete loss of touch and pain sensations with flaccid paralysis of both lower extremities. Laminectomy of Th4-6 was therefore performed on the 20th day of hospitalization. Biopsy at that time demonstrated the metastasis to be from the breast cancer. Radiotherapy (Linac, 600 rad/w) was started at the 20th postoperative day, a total dose of 3,000 rad being given. Physicotherapy was instituted simultaneously. As drug therapy, OK-432 and FT-207 suppositories (750 mg) were used in addition to diethylstilbestrol, 300 mg/day. RESULTS: After 6 months of these combined therapeutic regimens the patient became capable of moving along the edge of the bed with the aid of a good hand and leg. After 7 months she underwent radical surgery for the thyroid cancer and 3 months later she was discharged asymptomatic.