1
Al112 AASLD ABSTRACTS GASTROENTEROLOGY, Vol. 108, No. 4 • ~ FCTIVE INIESTINPL DECONTAMI~TION WITH NORFLOXACIN BACIERI@£- T R ~ T I O N IN ASCITIC CIRRHOTIC RATS EXPOSED TO HE~IC SHOCK. JM Llovet, R Bartoll, R Planas, B Vi~ado, J P~rez, E Cabre J Arnal, I Ojanguren, V Ausina, MA Gassull. Departments of Gastroenterology, Microbiology and Pathology. Research Unit. Hospital Germans Trias i Pujol. Badalona. Catalunya. Spain. In Cirrhosis, hemorrhagic shock (HS) increases, probably favoring bacterial translocation (ST), the risk of serious infections due to bacteria of intestinal origin, Selective intestinal decontamination (SID) has proved to decrease bacterial infections after HS in Cirrhotic patients. AIM: To assess the effect of HS upon the incidence of BT in ascitic cirrhotic rats, and if SID reduces this incidence. METHODS: Six groups of Sprague-Dawley rats were studied: ascitic rats (Group i, n:12), aecitic rats exposed to HS (Group 2, n:i6), ascitic rats exposed to HS with previous SID (Group 3, n: 16), healthy rats (Group 4, n:lO), healthy rats exposed to HS (Group 5, n:iO) and healthy rats exposed to HS with previous SID (Group 6, n:lO). Cirrhosis was induced with intragastric CC14. HS (40 m~) was produced by femoral phlebotomy and maintained for 30 minutes. SID was obtained administering norflo×acin 400 mg/daily/7 days through orogastric tube. BT Study Consisted in ascitic fluid, portal and peripheral blood, mesenteric lymph nodes and liver cultures and gut histological studies. :, RESULTS: BT was higher in Group 2 than in Group I [11/16 (69%) vs 5/12 (41%);n.s. ] and in Group 5 than in Group 4 [5/10 (50%) vs O;p=O.Ol]. SID reduces significantly not only global BT but mainly BT due to gramnegative bacteria (GNB) in Group 3 vs Group 2 [5/16 (31%) vs 11/16 (69%); p--0.038, and 0/i6 vs 6/16 (3T/.);p=O.O08, respectively]. In addition, SID prevents BT in Group 6 (0/10; p=O.Ol vs Group 5). Accordingly, ~ dissapeared from fecal flora in all rats submitted to SID. Caecal submucosal edema 39/44 (88%) and chronic imflammatory infiltrate 31/44 (70%) were only observed in ascitid rats , whereas caecal subepithelial edema 7/32 (22"/.) were only found in HS ascitic rats. CONCLUSION: HS increases the incidence of BT both in ascitic cirrhotic and healthy rats. SIDwi£h norfloxacin reduces significantly the incidence of BT after HS, specially those caused by aerobic gramnegative bacilli. PROPHYLACTIC BANDING LIGATION OF HIGH-RISK ESOPHAGEAL VARICES: AN INTERIM REPORT GH Lo, ]H Hwu, KH Lal. Division of Gastroenterology, Department of Medicine, Veterans General Hospital-Kaohsiueg, Kaohsiung, Taiwan Endoscopic variceal ligation (EVL) has been proven to be a viable substitute for injection selerotherapy i n the management Of bleeding esophageal varic~s. It is still unknown whether EVL can prevent first episode of esophageal x, ariceal bleeding. The study was conducted to investigate this issuel During 2 years' period, a total of 102 cin'hot:c patients were randomized to receive EVL( 52 patients, EVL groap) or served as controls(50 patients, control group). All :the patients had esophageal varices F2 or F3. sizes, with red color signs. Both groups were comparable regarding demographic data. In the EVL group, EVL was performed at 2-3 weeks intervals until varices obliterated or too small to be ligated. RESULTS: EVL (N=52) Control(N=50) Etiology of cirrhosis Alcoholism 9 7 Post-hepatitic 38 37 Cryptogenic 5 6 Pugh's grade A/B/C 15/20/17 13/19/18 Pugh's score (mea") 8.1+ 2,4 8.2+ 2.6 Sessions of treatment 3.1 + 0.5 Obliteration of EV 45(86%) Patients with EV bleeding 4(7.7%) 11(22°,4)* Patients with mortality 6(11%) 12(24%)** * p =0.07 ** p > 0.i TWO patients with EVL-induced ulcer bleeding were encountered in the EVL group. Other complications were insifnificant. CONCLUSIONS: This interim report showed a trend favoring reduced frequency of variceal bleeding and mortality in high-risk cirrhotic patients receiving prophylactic EVL. @ ALCOHOL INTAKE AND HCV REPLICATION INt:LUENCE THE PLASMA GLUTATHIONE -TRANSFERASE ACTIVITY. C.Loouercio, F.Morisco, L.M.Valenza*. C.Tuccillo, C.Guerriero, G.Del Vecchio- Blanco, N r Caporaso, C.Del Vecchio-Blanco. Gastroenterology - 2" UniversibJ of Naples, * Internal Medicine-Hospital of Palermo, Italy. Alpha-glutathione transferases (GSH-T) are an important detoxifiyng system of the hepatic cells, ubiquitary distributed across the liver Iobule. The plasma values of GSH-T are considered an early and sensitive index of hepatocellular damage induced by toxic agents, drugs, alcohol, and acute viral infection. AIM of this study was to evaluate the GSH-T plasma levels in 42 subjects with ;)ersistent absence of signs of liver damage during almost one year of clinical and laboratory follow-up. Thirteen of these subjects were chronic alcohol abusers. HCV-RNA negatives, all males ( median age 42 years, range 30-51), 19 were no drinkers and healthy carriers of HCV- RNA (10 males, aged between 18-66 years, median 47) and 10, all males, (median age 40 years, range 28-49) negatives for serological markers of hepatic virus infection and alcohol consumption served as control group. No subject assumed any drug at least 1 month before the study. GSH-T were determined on the venous plasma sample obtained at 8 a.m. after an overnight fast by Kit Alfa -Biotech-ltaly- Biotrin International; on the same sample plasma alcohol levels were assayed using the Kit Alcohol Color Monoassay ( Boehringer- Mannheim-Germany) and the HCV-RNA by RT-PCR method. The table reports the number of subjects m which GSH-T resulted higher than the maximal value considered normal (8ng/ml). CONTROLS 0/10 (0,0%) ALCOHOL ABUSERS 5/13 (38.4%) HCV-RNA CARRIERS 10/19 (52.6%) The alcoholemia resulted positive only in 4 of the 5 alcohol abusers with high levels of GSH-T. suggesting in these cases a recent alcohol intake. In HCV-RNA+ subjects we did non find an exogenous factor that may induce GSH-T increase. Therefore it is possible to hypothesize that viral replication is the cause of GSH-T increase. ALTERATIONS OF GLUTATHIONE METABOLISM IN RED BLOOD CELLS OF PATIENTS WITH LIVER CIRRHOSIS. C.Loguercio,F.Del Veechio Blaneo*,P.Piscopo,A.Parente*,C.Del Vecehio Blanco. Gastroenterology and *Biology Institute=2°University=Napoli = Italia. Previous studies of our group showed a marked decrease of glutathione (GSH) content inthe red blood cells (r.b.c.) of patients with liver cirrhosis;This may be caused by an altera tion of GSH synthesis in these cells,as documented by a slm~ taneous significant increase of cysteine and a decrease of GSH=synthetase activity.On the contrary no change has been o= bserved in ~=glutamyl=cysteine=synthetase activity.In this study we evaluate the content of glutamic acid and glycine in r.b.c.from 18 patients affected by liver cirrhosis (12 males, age range 30=68 years,median 52)and i0 controls(7 males),with comparable age.Free aminoacids were evaluated by Aminoacid A= nalyzer,system Gold=Bec~nann,usin E post=column reaction with ninydrin.The blood samples were taken from all subjects at 8 a.m. and hemolised with distilled water.Results are reported in the table (nmol/ml;mean~ S.E.). Glutamic acid Glycine Controls 25.6 + 527 31.7 + 4.9 Cirrhotics 47.8 + 7.1" 45.2 + 2.7* *P(O.02 In r.b.c, of cirrhotic patients both glutamic acid and glyci= ne were si~ificantly higher in respect to values of controls. These data further confirm that the alteration of the GSH syn thesis in the erythrocytes of cirrhotics is dependent on the decrease of the activity of the GSH=synthetase,while the oth= er enzymatic activities involved in the GSH metabolism are normal.The consequence is the significant increase of all ~he aminoacids forming the GSH (cys£eine,glutamic acid and glyci= ne).

Prophylactic banding ligation of high-risk esophageal varices: An interim report

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Page 1: Prophylactic banding ligation of high-risk esophageal varices: An interim report

A l 1 1 2 AASLD ABSTRACTS GASTROENTEROLOGY, Vol. 108, No. 4

• ~ FCTIVE INIESTINPL DECONTAMI~TION WITH NORFLOXACIN BACIERI@£- T R ~ T I O N IN ASCITIC CIRRHOTIC RATS

EXPOSED TO H E ~ I C SHOCK. JM Llovet, R Bartoll, R Planas, B Vi~ado, J P~rez, E Cabre J Arnal, I Ojanguren, V Ausina, MA Gassull. Departments of Gastroenterology, Microbiology and Pathology. Research Unit. Hospital Germans Trias i Pujol. Badalona. Catalunya. Spain.

In Cirrhosis, hemorrhagic shock (HS) increases, probably favoring bacterial translocation (ST), the risk of serious infections due to bacteria of intestinal origin, Selective intestinal decontamination (SID) has proved to decrease bacterial infections after HS in Cirrhotic patients. AIM: To assess the effect of HS upon the incidence of BT in ascitic cirrhotic rats, and if SID reduces this incidence. METHODS: Six groups of Sprague-Dawley rats were studied: ascitic rats (Group i, n:12), aecitic rats exposed to HS (Group 2, n:i6), ascitic rats exposed to HS with previous SID (Group 3, n: 16), healthy rats (Group 4, n:lO), healthy rats exposed to HS (Group 5, n:iO) and healthy rats exposed to HS with previous SID (Group 6, n:lO). Cirrhosis was induced with intragastric CC14. HS (40 m~) was produced by femoral phlebotomy and maintained for 30 minutes. SID was obtained administering norflo×acin 400 mg/daily/7 days through orogastric tube. BT Study Consisted in ascitic fluid, portal and peripheral blood, mesenteric lymph nodes and liver cultures and gut histological studies. :, RESULTS: BT was higher in Group 2 than in Group I [11/16 (69%) vs 5/12 (41%);n.s. ] and in Group 5 than in Group 4 [5/10 (50%) vs O;p=O.Ol]. SID reduces significantly not only global BT but mainly BT due to gramnegative bacteria (GNB) in Group 3 vs Group 2 [5/16 (31%) vs 11/16 (69%); p--0.038, and 0/i6 vs 6/16 (3T/.);p=O.O08, respectively]. In addition, SID prevents BT in Group 6 (0/10; p=O.Ol vs Group 5). Accordingly, ~ dissapeared from fecal flora in all rats submitted to SID. Caecal submucosal edema 39/44 (88%) and chronic imflammatory infiltrate 31/44 (70%) were only observed in ascitid rats , whereas caecal subepithelial edema 7/32 (22"/.) were only found in HS ascitic rats. CONCLUSION: HS increases the incidence of BT both in ascitic cirrhotic and healthy rats. SIDwi£h norfloxacin reduces significantly the incidence of BT after HS, specially those caused by aerobic gramnegative bacilli.

PROPHYLACTIC BANDING LIGATION OF HIGH-RISK ESOPHAGEAL VARICES: AN INTERIM REPORT GH Lo, ]H Hwu, KH Lal. Division of Gastroenterology, Department of Medicine, Veterans General Hospital-Kaohsiueg, Kaohsiung, Taiwan

Endoscopic variceal ligation (EVL) has been proven to be a viable substitute for injection selerotherapy i n the management Of bleeding esophageal varic~s. It is still unknown whether EVL can prevent first episode of esophageal x, ariceal bleeding. The study was conducted to investigate this issuel During 2 years' period, a total of 102 cin'hot:c patients were randomized to receive EVL( 52 patients, EVL groap) or served as controls(50 patients, control group). All :the patients had esophageal varice s F2 or F3. sizes, with red color signs. Both groups were comparable regarding demographic data. In the EVL group, EVL was performed at 2-3 weeks intervals until varices obliterated or too small to be ligated. RESULTS: EVL (N=52) Control(N=50)

Etiology of cirrhosis Alcoholism 9 7 Post-hepatitic 38 37 Cryptogenic 5 6

Pugh's grade A/B/C 15/20/17 13/19/18 Pugh's score (mea") 8.1+ 2,4 8.2+ 2.6 Sessions of treatment 3.1 + 0.5 Obliteration of EV 45(86%) Patients with EV bleeding 4(7.7%) 11 (22°,4)* Patients with mortality 6(11%) 12(24%)**

* p =0.07 ** p > 0.i TWO patients with EVL-induced ulcer bleeding

were encountered in the EVL group. Other complications were insifnificant. CONCLUSIONS: This interim report showed a trend favoring reduced frequency of variceal bleeding and mortality in high-risk cirrhotic patients receiving prophylactic EVL.

@ ALCOHOL INTAKE AND HCV REPLICATION INt:LUENCE THE PLASMA GLUTATHIONE -TRANSFERASE ACTIVITY. C.Loouercio, F.Morisco, L.M.Valenza*. C.Tuccillo, C.Guerriero, G.Del Vecchio- Blanco, N r Caporaso, C.Del Vecchio-Blanco. Gastroenterology - 2" UniversibJ of Naples, * Internal Medicine-Hospital of Palermo, Italy.

Alpha-glutathione transferases (GSH-T) are an important detoxifiyng system of the hepatic cells, ubiquitary distributed across the liver Iobule. The plasma values of GSH-T are considered an early and sensitive index of hepatocellular damage induced by toxic agents, drugs, alcohol, and acute viral infection. AIM of this study was to evaluate the GSH-T plasma levels in 42 subjects with ;)ersistent absence of signs of liver damage during almost one year of clinical and laboratory follow-up. Thirteen of these subjects were chronic alcohol abusers. HCV-RNA negatives, all males ( median age 42 years, range 30-51), 19 were no drinkers and healthy carriers of HCV- RNA (10 males, aged between 18-66 years, median 47) and 10, all males, (median age 40 years, range 28-49) negatives for serological markers of hepatic virus infection and alcohol consumption served as control group. No subject assumed any drug at least 1 month before the study. GSH-T were determined on the venous plasma sample obtained at 8 a.m. after an overnight fast by Kit Alfa -Biotech-ltaly- Biotrin International; on the same sample plasma alcohol levels were assayed using the Kit Alcohol Color Monoassay ( Boehringer- Mannheim-Germany) and the HCV-RNA by RT-PCR method. The table reports the number of subjects m which GSH-T resulted higher than the maximal value considered normal (8ng/ml). CONTROLS 0/10 (0,0%) ALCOHOL ABUSERS 5/13 (38.4%) HCV-RNA CARRIERS 10/19 (52.6%) The alcoholemia resulted positive only in 4 of the 5 alcohol abusers with high levels of GSH-T. suggesting in these cases a recent alcohol intake. In HCV-RNA+ subjects we did non find an exogenous factor that may induce GSH-T increase. Therefore it is possible to hypothesize that viral replication is the cause of GSH-T increase.

ALTERATIONS OF GLUTATHIONE METABOLISM IN RED BLOOD CELLS OF

PATIENTS WITH LIVER CIRRHOSIS.

C.Loguercio,F.Del Veechio Blaneo*,P.Piscopo,A.Parente*,C.Del

Vecehio Blanco.

Gastroenterology and *Biology Institute=2°University=Napoli =

Italia. Previous studies of our group showed a marked decrease of

glutathione (GSH) content inthe red blood cells (r.b.c.) of

patients with liver cirrhosis;This may be caused by an altera

tion of GSH synthesis in these cells,as documented by a slm~

taneous significant increase of cysteine and a decrease of

GSH=synthetase activity.On the contrary no change has been o=

bserved in ~=glutamyl=cysteine=synthetase activity.In this

study we evaluate the content of glutamic acid and glycine in

r.b.c.from 18 patients affected by liver cirrhosis (12 males,

age range 30=68 years,median 52)and i0 controls(7 males),with

comparable age.Free aminoacids were evaluated by Aminoacid A= nalyzer,system Gold=Bec~nann,usin E post=column reaction with

ninydrin.The blood samples were taken from all subjects at 8

a.m. and hemolised with distilled water.Results are reported

in the table (nmol/ml;mean~ S.E.). Glutamic acid Glycine

Controls 25.6 + 527 31.7 + 4.9

Cirrhotics 47.8 + 7.1" 45.2 + 2.7*

*P(O.02

In r.b.c, of cirrhotic patients both glutamic acid and glyci=

ne were si~ificantly higher in respect to values of controls.

These data further confirm that the alteration of the GSH syn

thesis in the erythrocytes of cirrhotics is dependent on the

decrease of the activity of the GSH=synthetase,while the oth=

er enzymatic activities involved in the GSH metabolism are

normal.The consequence is the significant increase of all ~he

aminoacids forming the GSH (cys£eine,glutamic acid and glyci=

ne).