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Early radioactively labeled proteins (P) in dog bile (B)
303
EARLY RADIOACTIVELY LABELEDPROTEINS (P) IN DOG BILE (B). K. Weiqand Department of Clinical Pharmacology, University of Berne, Switzerland.
I t has been demonstrated that the quantitatively most important P in B, albumin and IgA,are derived from plasma.However,it is unknown whether hepatocytes can also secrete P d i r e c t l y into B.If P were exclusively tranferred from plasma into B radioactive P would not be detectable in B e a r l i e r than in plasma after injection of a radioactive precursor amino acid.To determine i f hepatocytes "lose" newly formed P directly into B, we studied the secretion of radioactive P into B and plasma.ldentical experiments were performed in 2 unanesthetized female boxer dogs.A B duct catheter was placed through a Thomas cannula and B was collected at 2 min intervals. B flow was kept constant by infusion of 20 ~mol taurocholate per min. After i.v. injection of 250 ~Ci 1-14-C-leucine (59 mCi/mmol), a dose high enough for measurement of secretion time, plasi~,a samples were drawn every 2 min. Radioactively labeled P was detected in plasma 18 and 20 min resp.,after injection of 14-C-leucine (Mans+ Novelli).Thereafter i t increased exponential]y. In contrast,radioactivel~ labeled P in B was detectable as early as 10 and 14 min after injection with a f i r s t peak after 20 and 30 min (1700 and 950 dpm/ml) and a subsequent decrease. A rapid increase of radioactively labeled P in B,parallelling the rise in plasma,was observed after 50 min. B flow,B salt concentration (enzymatic),and b i l i a r y P concentration (adapted Lowrymethod) remained constant during the experimental period.The biphasic appearanceof radioactively labeled P in B with a minor peak after about 12 min and a steep increase after 50 min indicates that most B proteins are derived from plasma,a small amount,however,is secreted by hepatocytes or b i l i a r y epithelium directly into B.An attempt to i d e n t i f y these P by SDS gel electrophoresis and fluorography was not successful owing to the very small amounts secreted. The secretion time for plasma P is 18 min,the transit time for P from plasma into 8 is about 30min.
304
THE R E C U R R E N C E O F V A R I C E S F O L L O W I N G INITIAL O B L I T E R A T I O N BY S C L E R O T H E R A P Y D Westaby# BRD MacDougall~ Roger W i l l i - m s The L i v e r Unit, King's C o l l e g e Hospital & School of M e d i c i n e & Dentistry D e n m a r k Hill, L o n d o n SE5 9HS
To d e t e r m i n e the incidence and s i g n i f l e ~ n c e of r e c u r r e n c e of varlces f o l l o w i n g o b l i t e r a tion by sclerotherapy, 147 patients (99 cirrhosis, 48 n o n - c l r r h o s i s ) were p r o s p e c t i v e l y followed for periods up to 6 years after initial o b l i t e r a t i o n had been achieved. Routine endoscopic examinations were undertaken at intervals of S - 4 months for the first year and 6 monthly thereafter. 'New' varioes d e v e l o p e d i n 9 9 o a s e s (67%) a l t h o u g h these were the cause of bleeding i n o n l y 28 p a t i e n t s o f whom 3 d i e d . Twenty-five o f t h e 28 p a t i e n t s rebleeding did so within 12 m o n t h s o f i n i t i a l obliteration of varices. A median of 2 courses of sclerotherapy ( r a n g e 1 - 4) w e r e r e q u i r e d to again achieve obliteration. I n 20 p a t i e n t s a second recurrence of varioes occurred with bleeding in 8 cases but no associated deaths. There was no correlation between the aetiology of cirrhosis or the severity of the underlying liver disease and the development of 'new' varioes. The high rate of recurrence of varices applied equally to those with a portal vein thrombosis. The results indicate that recurrenoe of varices can be expected in the majority of patients following initial obliteration by sclerotherspyo However, the frequency of bleeding may be minimised by regular f o l l o w up e n d o s c o p y , and injection of 'new' varices, particularly during the first 12 m o n t h p e r i o d .
S152
EARLY RADIOACTIVELY LABELEDPROTEINS (P) IN DOG BILE (B). K. Weiqand Department of Clinical Pharmacology, University of Berne, Switzerland.
I t has been demonstrated that the quantitatively most important P in B, albumin and IgA,are derived from plasma.However,it is unknown whether hepatocytes can also secrete P d i r e c t l y into B.If P were exclusively tranferred from plasma into B radioactive P would not be detectable in B e a r l i e r than in plasma after injection of a radioactive precursor amino acid.To determine i f hepatocytes "lose" newly formed P directly into B, we studied the secretion of radioactive P into B and plasma.ldentical experiments were performed in 2 unanesthetized female boxer dogs.A B duct catheter was placed through a Thomas cannula and B was collected at 2 min intervals. B flow was kept constant by infusion of 20 ~mol taurocholate per min. After i.v. injection of 250 ~Ci 1-14-C-leucine (59 mCi/mmol), a dose high enough for measurement of secretion time, plasi~,a samples were drawn every 2 min. Radioactively labeled P was detected in plasma 18 and 20 min resp.,after injection of 14-C-leucine (Mans+ Novelli).Thereafter i t increased exponential]y. In contrast,radioactivel~ labeled P in B was detectable as early as 10 and 14 min after injection with a f i r s t peak after 20 and 30 min (1700 and 950 dpm/ml) and a subsequent decrease. A rapid increase of radioactively labeled P in B,parallelling the rise in plasma,was observed after 50 min. B flow,B salt concentration (enzymatic),and b i l i a r y P concentration (adapted Lowrymethod) remained constant during the experimental period.The biphasic appearanceof radioactively labeled P in B with a minor peak after about 12 min and a steep increase after 50 min indicates that most B proteins are derived from plasma,a small amount,however,is secreted by hepatocytes or b i l i a r y epithelium directly into B.An attempt to i d e n t i f y these P by SDS gel electrophoresis and fluorography was not successful owing to the very small amounts secreted. The secretion time for plasma P is 18 min,the transit time for P from plasma into 8 is about 30min.
304
THE R E C U R R E N C E O F V A R I C E S F O L L O W I N G INITIAL O B L I T E R A T I O N BY S C L E R O T H E R A P Y D Westaby# BRD MacDougall~ Roger W i l l i - m s The L i v e r Unit, King's C o l l e g e Hospital & School of M e d i c i n e & Dentistry D e n m a r k Hill, L o n d o n SE5 9HS
To d e t e r m i n e the incidence and s i g n i f l e ~ n c e of r e c u r r e n c e of varlces f o l l o w i n g o b l i t e r a tion by sclerotherapy, 147 patients (99 cirrhosis, 48 n o n - c l r r h o s i s ) were p r o s p e c t i v e l y followed for periods up to 6 years after initial o b l i t e r a t i o n had been achieved. Routine endoscopic examinations were undertaken at intervals of S - 4 months for the first year and 6 monthly thereafter. 'New' varioes d e v e l o p e d i n 9 9 o a s e s (67%) a l t h o u g h these were the cause of bleeding i n o n l y 28 p a t i e n t s o f whom 3 d i e d . Twenty-five o f t h e 28 p a t i e n t s rebleeding did so within 12 m o n t h s o f i n i t i a l obliteration of varices. A median of 2 courses of sclerotherapy ( r a n g e 1 - 4) w e r e r e q u i r e d to again achieve obliteration. I n 20 p a t i e n t s a second recurrence of varioes occurred with bleeding in 8 cases but no associated deaths. There was no correlation between the aetiology of cirrhosis or the severity of the underlying liver disease and the development of 'new' varioes. The high rate of recurrence of varices applied equally to those with a portal vein thrombosis. The results indicate that recurrenoe of varices can be expected in the majority of patients following initial obliteration by sclerotherspyo However, the frequency of bleeding may be minimised by regular f o l l o w up e n d o s c o p y , and injection of 'new' varices, particularly during the first 12 m o n t h p e r i o d .
S152