Dickson, E. Rolland

Patients with severe, inoperable cholestasis and intractable pruritus not responding to conventional medical therapy might benefit from a depletion of their bile acid pool by sorbent perfusion since accumulated bile acids are possibly responsible for their itching. In vitro, USP-charcoal-coated glass beads removed bile acids from human plasma far better than any other sorbent tested. In order to demonstrate the safety and efficacy of charcoal plasmaperfusion in vivo, five dogs underwent plasmapheresis one week following cholecystectomy and bile duct ligation, and 2.2 ± 0.2 (x̄ ± SD) times their plasma volume was passed over a column containing 400 ml of charcoal-coated glass beads prior to reinfusion. During the procedure the plasma bile acid concentration was reduced by 40.2 ± 4.0% and the bilirubin level by 48.2 ± 3.3%. The columns, whose capacity was far from being saturated, retained 1.3 ± 0.4 times the pre-perfusion plasma pool of bile acids (1.1 ± 0.2 for bilirubin) suggesting that substantial amounts of bile acids and bilirubin were mobilized from tissue stores. The procedure was well tolerated by the animals and might have promising clinical applications.

Abstract The syndrome of primary biliary cirrhosis and limited scleroderma (the CREST syndrome) is described in 22 patients. The syndrome is expanded to include a serologic marker - the anticentromere antibody - and keratoconjunctivitis sicca. The acronym ‘PACK’ (primary biliary cirrhosis, anticentromere antibody, CREST syndrome, and keratoconjunctivitis sicca) with ‘syndrome’ is suggested to facilitate recall of the various components of this entity.

Cyclosporine induces hypertension and wide-spread vasoconstriction after transplantation in addition to reducing kidney function. We studied hemodynamic, renal, and hormonal effects of monotherapy with nifedipine XL (n = 37) in liver transplant recipients within a year after transplant (median, 4.4 months). Systemic hemodynamics were determined with thoracic electrical bioimpedance. Blood pressure before therapy was 172 +/- 4/108 +/- 2 mm Hg. Sixty-four percent of recipients achieved blood pressures less than 140/90 mm Hg mediated by a fall in systemic vascular resistance index (2427 +/- 245 dyne.s.cm-5.m-2 in responders versus 2905 +/- 281 in nonresponders, P < .01). Despite the fall in systemic vascular resistance, glomerular filtration rates were not changed during nifedipine therapy, as measured by both creatinine and iothalamate clearances. Urinary prostacyclin (6-ketoprostaglandin F1 alpha) was suppressed below normal from 2468 +/- 323 ng/d before transplant to 1103 +/- 99 ng/d (P < .01) after transplant and did not change during nifedipine therapy. Urinary thromboxane B2 and plasma renin activity also fell after transplant and remained low during nifedipine. These data demonstrate that nifedipine can reverse systemic vasoconstriction associated with hypertension after transplantation. Systemic effects were not transmitted to the kidney sufficiently to improve glomerular filtration rate or reverse hormonal changes within the kidney. Hence, vascular and functional regulation of the kidney was dissociated from the systemic circulation during nifedipine administration after transplantation.