The results of the present study indicate that NaC1 transport by in vitro rabbit gallbladder must be a consequence of a neutral coupled carriermediated mechanism that ultimately results in the active absorption of both ions; pure electrical coupling between the movements of Na and C1 can be excluded on the grounds of electrophysiologic considerations. Studies on the unidirectional influxes of Na and CI have localized the site of this coupled mechanism to the mucosal membranes. Studies on the intracellular ion concentrations and the intracellular electrical potential are consistent with the notion that (a) the coupled NaCI influx process results in the movement of C1 from the mucosal solution into the cell against an apparent electrochemical potential difference; (b) the energy for the uphill movement of CI is derived from the Na gradient across the mucosal membrane which is maintained by an active Na extrusion mechanism located at the basolateral membranes; and (¢) C1 exit from the cell across the basolateral membranes is directed down an electrochemical potential gradient and may be diffusional. Finally, as for the case of rabbit ileum, the coupled NaC1 influx process is inhibited by elevated intracellular levels of cyclic 3~,5r-adenosine monophosphate. A working model for transcellular and paracellular NaCI transport by in vitro rabbit gallbladder is proposed.

Metoclopramide tablets have been approved for use in the acute and chronic management of diabetic gastroparesis. Its efficacy as an antiemetic has been well documented. We measured the acute and chronic effects of oral metoclopramide on gastric liquid emptying in 12 diabetic patients with symptoms of stasis using scintiscanning techniques. We found that liquid emptying in these subjects was abnormal, as determined by residue area determination when compared to normal volunteers (P less than 0.01). Metoclopramide 10 mg orally acutely enhanced emptying, restoring it to control values (P less than 0.01). In contrast, when gastric emptying was evaluated following one month of chronic liquid metoclopramide use, 10 mg before each meal, the acute effect of the drug on emptying could no longer be demonstrated and residue areas returned to baseline values, suggesting that chronic oral administration of metoclopramide may result in a loss of the gastrokinetic properties of this drug.

Veratridine modification of Na current was examined in single dissociated ventricular myocytes from late-fetal rats. Extracellularly applied veratridine reduced peak Na current and induced a noninactivating current during the depolarizing pulse and an inward tail current that decayed exponentially (~ = 226 ms) after repolarization. The effect was quantitated as tail current amplitude, /tail (measured 10 ms after repolarization), relative to the maximum amplitude induced by a combination of 100 IzM veratridine and 1 ~M BDF 9145 (which removes inactivation) in the same cell. Saturation curves for Itail were predicted on the assumption of reversible veratridine binding to open Na channels during the pulse with reaction rate constants determined previously in the same type of cell at single Na channels comodified with BDF 9145. Experimental relationships between veratridine concentration and Itau confirmed those predicted by showing (a) haftmaximum effect near 60 ~M veratridine and no saturation up to 300 ~M in cells with normally inactivating Na channels, and (b) haft-maximum effect near 3.5 p,M and saturation at 30 ~M in cells treated with BDF 9145. Due to its known suppressive effect on single channel conductance, veratridine induced a progressive, but partial reduction of noninactivating Na current during the 50-ms depolarizations in the presence of BDF 9145, the kinetics of which were consistent with veratridine association kinetics in showing a decrease in time constant from 57 to 22 and 11 ms, when veratridine concentration was raised from 3 to 10 and 30 I.LM, respectively. As predicted for a dissociation process, the tail current time constant was insensitive to veratridine concentration in the range from 1 to 300 o,M. In conclusion, we have shown that macroscopic Na current of a veratridine-treated cardiomyocyte can be quantitatively predicted on the assumption of a direct relationship between veratridine binding dynamics and Na current and as such can be successfully used to analyze molecular properties of the veratridine receptor site at the cardiac Na channel.

Human liver transplantation has been possible since 1967. We report our experience in 32 adult patients who received liver transplants at the University of Pittsburgh over a 16-month period. Survival data, method utilized for patient selection, costs, and morbidity of the procedure are discussed.Orthotopic liver transplantation for humans with advanced liver disease has been possible since 1967 when the first extended survival of such a patient was reported. Since then, more than 400 procedures have been performed; the majority (360) were performed by two groups; one in London (Calne) and the other in the United States (Starzl). At the time of this writing, 237 orthotopic liver transplants have been performed by Starzl; 170 at the University of Colorado and 67 at the University of Pittsburgh. We report the results in adults at the University of Pittsburgh and discuss patient selection, morbidity, cost, and institutional commitment. PATIENT SELECTIONFrom February 1, 1981 through May 30, 1982, 32 orthotopic liver transplants were performed in adults at the University of Pittsburgh School of Medicine; the indications are shown in Table 1. The major indication, accounting for nearly one-third of the cases, was post-necrotic cirrhosis. The second and third most common indications for liver transplantation were advanced primary biliary cirrhosis and hepatocellular carcinoma respectively.The 32 patients were selected from 115 individuals who were evaluated for liver transplantation. All were referred specifically for consideration for possible liver transplantation. Sixty-eight were considered acceptable candidates based upon the severity of liver disease and the absence of factors known to contradict transplantation.The disease categories of the potential candidates is shown in Table 2. Of the 68 acceptable candidates, only one refused transplantation after having been accepted for this procedure.Acceptance for transplantation was determined by consensus of the Transplantation Committee. The committee meets weekly and discusses each patient only after completion of an in-hospital evaluation. The committee also reviews potential candidates, discusses the course of each patient in hospital, and receives periodic reports concerning previously transplanted patients who are not in the hospital. Outpatient data are provided by a follow-up nurse coordinator and various physicians who are actively caring for these individuals elsewhere. Copyright © 1982 The number of patients and the reasons for rejecting referred patients for liver transplantation are shown in Table 4. The major reasons for rejecting patients for possible transplantation were that they were not sick enough with their primary hepatic disease, or had metastatic hepatocellular or cholangiolar carcinoma beyond the limits of the liver. Only three patients were refused surgery because they were "too ill." One man had α 1 -antitrypsin deficiency with advanced pulmonary and renal disease, compounded by advanced pancreatitis and pancreatic insufficiency. A...

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