First human trial of FTY720, a novel immunomodulator, in stable renal transplant patients

FTY720 is a novel immunomodulator to be developed for use in organ transplantation. The primary objective of this study was to measure safety, single-dose pharmacokinetics, and pharmacodynamics in stable renal transplant patients-the first human use of FTY720. This study used a randomized, double-blind, placebo-controlled design that explored single oral doses of FTY720 from 0.25 to 3.5 mg in 20 stable renal transplant patients on a cyclosporine-based regimen. Safety assessments and blood samples were taken predose and at multiple time points during a 96-h period postdose. Standard pharmacokinetic parameters were derived from the FTY720 whole blood concentrations, measured by HPLC/MS/MS. FTY720 was well tolerated, with no serious adverse events. Transient, asymptomatic bradycardia occurred after administration in 10 of 24 doses of FTY720. Pharmacokinetics are characterized by a prolonged absorption phase; the terminal elimination phase started 36 h after the administration, with elimination half-life (t(1/2)) ranging from 89 to 157 h independent of dose. Maximum plasma concentration and AUC were proportional to dose with low intersubject variability, the apparent volume of distribution (V(d)/F) ranged from 1116 to 1737 L. FTY pharmacodynamics were characterized by a reversible transient lymphopenia within 6 h, the nadir being 42% of baseline. The lymphocyte count returned to baseline within 72 h in all dosing cohorts except the highest. Single oral doses of FTY720 ranging from 0.25 to 3.5 mg were well tolerated and caused a reversible selective lymphopenia. Transient, but asymptomatic bradycardia was the most common adverse event. The long t(1/2) suggests less frequent dosing intervals. The size of V(d)/F is in excess of blood volume, consistent with widespread tissue distribution     

Total gastric necrosis in a neonate.

Necrosis of the entire stomach is extremely rare in neonates. We report a case of total gastric necrosis in a full-term neonate. The possible pathophysiology, diagnostic features and therapeutic options for gastric necrosis in a newborn are discussed.     

Heterotopic spinal cord?

Unusual morphological findings were encountered in a high cervical meningomyelocele sac of a neonate. Magnetic resonance imaging revealed a massive liquid-filled sac traversed by a linear structure. The spinal cord was seen to be located normally within the spinal canal. At operation, a spinal cord-like structure was identified within the sac. This cord terminated posteriorly at the neural tissue lining the meningomyelocele sac. There were fibrous strands connecting the cord to the sac like the rigging of a ship. The anterior end of this cord terminated in a fibrous band. It extended upwards into the spinal canal through the narrow neck of the meningoyelocele sac above the arch of the atlas. The whole of this cord, along with the meningomyelocele sac, was excised. Histological analysis confirmed that this spinal cord-like structure consisted of glial tissue with an ependymal-lined cavity. The excised sac was lined by neural tissue.     

Male breast carcinoma: an updated experience at a Veterans Administration Hospital and review of the literature

Ten cases of male breast carcinoma are reviewed. Male patients with breast cancer on the average are 10 years older than females, and they delay twice as long as females after noting a breast mass before seeking medical attention. Because of this patient's delay, male breast cancer tends to be more advanced at the time of diagnosis and initial therapy than female breast cancer.     

Pathogenesis of unilateral proptosis

A series of 34 patients presenting with unilateral proptosis has been studied in order to evaluate the mechanism of proptosis. It is observed that symmetrical (axial) proptosis is usually the result of generalised increase in intraorbital contents and occurs in thyroid disease and with intracranial lesions lying remote from the orbit. Rarely, in myasthenia gravis, it may be caused by myogenic paralysis of the extraocular muscles. Asymmetrical proptosis is the result of localised increase in intraorbital contents, and this occurs with expanding lesions of the orbit and in lesions arising from neighbouring structures and enroaching the orbit.