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J Y Lau

Publications and source records attributed to J Y Lau.

At least 19 recordsLinked to original sources

Generation of transmissible hepatitis C virions from a molecular clone in chimpanzees.

Multiple alignments of hepatitis C virus (HCV) polyproteins from six different genotypes identified a total of 22 nonconsensus mutations in a clone derived from the Hutchinson (H77) isolate. These mutations, collectively, may have contributed to the failure in generating a "functionally correct" or "infectious" clone in earlier attempts. A consensus clone was constructed after systematic repair of these mutations, which yielded infectious virions in a chimpanzee after direct intrahepatic inoculation of in vitro transcribed RNAs. This RNA-infected chimpanzee has developed hepatitis and remained HCV positive for more than 11 months. To further verify this RNA-derived infectivity, a second naive chimpanzee was injected intravenously with serum collected from the first chimpanzee. Infectivity analysis of the second chimpanzee demonstrated that the HCV infection was successfully transmitted, which validated unequivocally the infectivity of our repaired molecular clone. Amino acid sequence comparisons revealed that our repaired infectious clone had 4 mismatches with the isogenic clone reported by Kolykhalov et al. (1997, Science 277, 570-574) and 8 mismatches with that reported by Yanagi et al. (1997, Proc. Natl. Acad. Sci. USA 94, 8738-8743). At the RNA level, more mismatches (43 and 67, respectively) were identified; most of them were synonymous substitutions. Further comparisons with 16 isolates from different genotypes demonstrated that our repaired clone shares greater consensus than the reported isogenic clones. This approach of generating infectious HCV RNA validates the importance of amino acid sequence consensus in relation to the biology of HCV.

Amino Acid Sequence

Endoscopic retreatment compared with surgery in patients with recurrent bleeding after initial endoscopic control of bleeding ulcers.

BACKGROUND AND METHODS: After endoscopic treatment to control bleeding of peptic ulcers, bleeding recurs in 15 to 20 percent of patients. In a prospective, randomized study, we compared endoscopic retreatment with surgery after initial endoscopy. Over a 40-month period, 1169 of 3473 adults who were admitted to our hospital with bleeding peptic ulcers underwent endoscopy to reestablish hemostasis. Of 100 patients with recurrent bleeding, 7 patients with cancer and 1 patient with cardiac arrest were excluded from the study; 48 patients were randomly assigned to undergo immediate endoscopic retreatment and 44 were assigned to undergo surgery. The type of operation used was left to the surgeon. Bleeding was considered to have recurred in the event of any one of the following: vomiting of fresh blood, hypotension and melena, or a requirement for more than four units of blood in the 72-hour period after endoscopic treatment. RESULTS: Of the 48 patients who were assigned to endoscopic retreatment, 35 had long-term control of bleeding. Thirteen underwent salvage surgery, 11 because retreatment failed and 2 because of perforations resulting from thermocoagulation. Five patients in the endoscopy group died within 30 days, as compared with eight patients in the surgery group (P=0.37). Seven patients in the endoscopy group (including 6 who underwent salvage surgery) had complications, as compared with 16 in the surgery group (P=0.03). The duration of hospitalization, the need for hospitalization in the intensive care unit and the resultant duration of that stay, and the number of blood transfusions were similar in the two groups. In multivariate analysis, hypotension at randomization (P=0.01) and an ulcer size of at least 2 cm (P=0.03) were independent factors predictive of the failure of endoscopic retreatment. CONCLUSIONS: In patients with peptic ulcers and recurrent bleeding after initial endoscopic control of bleeding, endoscopic retreatment reduces the need for surgery without increasing the risk of death and is associated with fewer complications than is surgery.

Aged

Antibodies to hepatitis C virus envelope proteins correlate with hepatitis C viraemia after liver transplantation.

BACKGROUND: Liver transplant recipients for hepatitis C virus (HCV)-related cirrhosis usually remain anti-HCV-seropositive after transplantation. The aim of this study was to characterize, longitudinally, the profile of HCV-specific antibodies and cryoglobulins in liver transplant recipients with recurrent HCV infection. METHODS: Serial serum samples were collected prospectively before, at 1 month after, and at 12 months after transplantation for HCV cirrhosis in 30 patients infected with genotype 1. The antibodies against HCV envelope proteins (E1 and E2) were quantitated by enzyme-linked immunosorbent assay and antibodies against core, E2/hypervariable region I (HVRI), NS3, NS4, and NS5A antigens by a line immunoassay. Sera were also tested for cryoglobulins. RESULTS: The titer of each anti-HCV antibody had fallen at 1 month after transplantation (P<0.05) with the exception of anti-E1 levels, which had risen in 16 patients with acute hepatitis C at that time (P=0.01). Anti-E1 and anti-E2 titers, but not antibodies against other HCV antigens, increased to pre-transplantation levels or higher at 12 months, which correlated with serum HCV RNA levels. Cryoglobulinemia was present in nine patients after transplantation (30%) and was associated with lower anti-E1 levels (P=0.04) and more severe graft damage. CONCLUSIONS: The early increase in antibodies to HCV envelope proteins in correlation with viremia suggests that the envelope-specific humoral immune response may be directly stimulated by HCV replication. Anti-E1 levels may be a useful marker in monitoring patients with recurrent HCV infection.

Cryoglobulins

Association of diabetes mellitus and chronic hepatitis C virus infection.

While patients with liver disease are known to have a higher prevalence of glucose intolerance, preliminary studies suggest that hepatitis C virus (HCV) infection may be an additional risk factor for the development of diabetes mellitus. To further study the correlation of HCV infection and diabetes, we performed a retrospective analysis of 1,117 patients with chronic viral hepatitis and analyzed whether age, sex, race, hepatitis B virus (HBV) infection, HCV infection, and cirrhosis were independently associated with diabetes. In addition, a case-control study was conducted to determine the seroprevalence of HCV infection in a cohort of 594 diabetics and 377 clinic patients assessed for thyroid disease. In the former study after the exclusion of patients with conditions predisposing to hyperglycemia, diabetes was observed in 21% of HCV-infected patients compared with 12% of HBV-infected subjects (P =.0004). Multivariate analysis revealed that HCV infection (P =.02) and age (P =.01) were independent predictors of diabetes. In the diabetes cohort, 4.2% of patients were found to be infected with HCV compared with 1.6% of control patients (P =.02). HCV genotype 2a was observed in 29% of HCV-RNA-positive diabetic patients versus 3% of local HCV-infected controls (P <.005). In conclusion, the data suggest a relatively strong association between HCV infection and diabetes, because diabetics have an increased frequency of HCV infection, particularly with genotype 2a. Furthermore, it is possible that HCV infection may serve as an additional risk factor for the development of diabetes, beyond that attributable to chronic liver disease alone.

Adult

Characterization of soluble hepatitis C virus RNA-dependent RNA polymerase expressed in Escherichia coli.

Production of soluble full-length nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) has been shown to be problematic and requires the addition of salts, glycerol, and detergents. In an effort to improve the solubility of NS5B, the hydrophobic C terminus containing 21 amino acids was removed, yielding a truncated NS5B (NS5BDeltaCT) which is highly soluble and monodispersed in the absence of detergents. Fine deletional analysis of this region revealed that a four-leucine motif (LLLL) in the hydrophobic domain is responsible for the solubility profile of the full-length NS5B. Enzymatic characterization revealed that the RNA-dependent RNA polymerase (RdRp) activity of this truncated NS5B was comparable to those reported previously by others. For optimal enzyme activity, divalent manganese ions (Mn2+) are preferred rather than magnesium ions (Mg2+), whereas zinc ions (Zn2+) inhibit the RdRp activity. Gliotoxin, a known poliovirus 3D RdRp inhibitor, inhibited HCV NS5B RdRp in a dose-dependent manner. Kinetic analysis revealed that HCV NS5B has a rather low processivity compared to those of other known polymerases.

Amino Acid Sequence

Helicobacter pylori and the null genotype of glutathione-S-transferase-mu in patients with gastric adenocarcinoma.

BACKGROUND: Chronic Helicobacter pylori infection now is recognized as an important causative agent for gastric carcinoma. However, only a small minority of infected individuals develop the malignancy, even in areas with a high prevalence of gastric carcinoma. It has been postulated that the absence of glutathione-S-transferase-mu (GST-mu), which impairs detoxification of exogenous carcinogens, might predispose some infected individuals to the development of gastric carcinoma. METHODS: Patients with histologically confirmed adenocarcinoma of the stomach were tested for H. pylori infection and the GST-mu genotype. Prevalence of GST-mu gene deletion was compared with the H. pylori status of the patients. A group of gender- and age-matched control subjects with known H. pylori-related nonulcer dyspepsia also were tested for the GST-mu genotype and compared with patients with H. pylori positive carcinoma. RESULTS: Fifty-one patients with gastric adenocarcinoma were enrolled into the study. Thirty-five were found to have H. pylori in the resected specimens. The null genotype of GST-mu was significantly more common among those patients with H. pylori positive carcinoma compared with the H. pylori negative group (65.7% vs. 31.3%; P < 0.05). Homozygous deletion of GST-mu was significantly higher in the H. pylori positive carcinoma patients than in the H. pylori-infected, nonmalignant control group (65.7% vs. 37.1%; P < 0.05). CONCLUSIONS: The null genotype for GST-mu is found more commonly in gastric carcinoma associated with H. pylori infection. The absence of the GST-mu enzyme may increase the risk of the development of gastric carcinoma in these patients.

Adenocarcinoma

A randomized study comparing ribavirin and interferon alfa monotherapy for hepatitis C recurrence after liver transplantation.

Hepatitis C virus (HCV) infection usually recurs after orthotopic liver transplantation (OLT), and most patients develop graft damage. This study compared the efficacy of interferon alfa (IFN-alpha) and ribavirin monotherapies in liver transplant recipients with chronic hepatitis C in the graft. Thirty OLT recipients with chronic hepatitis C were randomized to receive either IFN-alpha (3 MU three times a week) or ribavirin (up to 1.2 g daily) for 24 weeks. Virological, biochemical, and histological responses to treatment were assessed. Twenty-eight patients completed the treatment regimen, two ribavirin-treated patients being withdrawn because of severe hemolysis. Normalization of serum aspartate aminotransferase was achieved in 13 of 14 patients receiving ribavirin (93%) and 6 of 14 patients receiving IFN-alpha (43%; P=.01). Lobular inflammation was reduced in 9/14 ribavirin-treated (64%) and 3 of 14 IFN-alpha-treated patients (21%; P=.05), each of whom had a biochemical response. However, the total histological activity index did not improve in either the interferon (P=.43) or the ribavirin (P=.96) group. Posttreatment viremia levels were significantly reduced in IFN-alpha-treated (P=.05) but not in ribavirin-treated (P=.88) patients. Hemolysis occurred in all ribavirin-treated patients, with serum hemoglobin decreasing to < 10 g/dL in 50%. Total leukocyte and lymphocyte counts decreased significantly during ribavirin treatment (P=.02 and P=.004, respectively). We concluded that in patients with chronic hepatitis C after OLT, IFN-alpha retains an antiviral effect whereas ribavirin is superior in achieving normalization of serum aspartate aminotransferase levels and reducing lobular inflammation, but not the total histological activity index. These findings provide a rationale for combination therapy in the post-OLT setting, although patients must be carefully monitored for hemolysis.

Adult

Intrahepatic hepatitis C virus-specific cytotoxic T lymphocyte activity and response to interferon alfa therapy in chronic hepatitis C.

Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes (CTL) have been shown to play a role in host defense and pathogenesis of chronic HCV infection. Our aim was to test the hypothesis that intrahepatic HCV-specific CTL activity may impact subsequent response to interferon alfa (IFN-alpha) therapy. Of the 37 patients that we have prospectively evaluated for HCV-specific CTL activity in liver, 21 received IFN therapy, and 19 completed a 6-month course and attended 6 to 18 months of follow-up. Intrahepatic CD8+ cells were isolated from liver biopsy tissue and tested against target cells expressing HCV antigens to determine intrahepatic CTL activity. The relationship between treatment response and HCV-specific CTL activity and other factors known to associate with response (genotype, viremia, histology) was analyzed. HCV-specific CTL activity was detected in 9 of 21 patients (and 9 of 19 who completed therapy). After 6 months of IFN therapy, 8 of 19 (42%) patients had normal serum alanine transaminase (ALT) (complete responders). After 18 months of follow-up, only 3 patients (16%) had a sustained biochemical response. Of the 9 patients with detectable HCV-specific CTL activity in their liver before treatment, 7 (78%) developed a complete response. In contrast, only 1 of the 10 patients with no detectable HCV-specific CTL activity developed a complete response to IFN (P < .01). In 6 of 8 patients with a complete response, including the 3 sustained responders, the CTL response appeared to be directed predominately to the HCV core region. These data suggest that the host immune response, particularly that mediated by CD8+ CTL, may be important in determining the outcome of IFN therapy for chronic HCV infection. Further understanding of the mechanism of action of IFN should impact the design of better therapeutic strategies against chronic HCV infection.

Adult

The efficacy of prophylactic interferon alfa-2b in preventing recurrent hepatitis C after liver transplantation.

Clinical recurrence of hepatitis C after liver transplantation can lead to cirrhosis, liver failure, and death. In patients undergoing liver transplantation for hepatitis C, we assessed the efficacy of interferon alfa-2b (IFN) in preventing recurrent hepatitis. We randomized 86 patients to either an IFN group (3 MU three times a week starting within 2 weeks after transplantation and continued for 1 year) or a control (no IFN) group. Recurrence, the primary end point, was diagnosed on biopsy performed at 1 year or for abnormal biochemistries. HCV RNA levels were measured by branched-chain DNA (bcDNA) assay and arbitrarily defined as low, moderate, or high (< 10 x 10(5), 10-100 x 10(5), or > 100 x 10(5) Eq/mL, respectively). Data on 30 IFN patients and 41 no-IFN patients who survived > or = 3 months were reviewed. Mean follow-up was 669 +/- 228 days for IFN patients and 594 +/- 254 days for no-IFN patients. IFN patients were less likely to develop recurrent hepatitis (8 IFN vs. 22 no-IFN patients, P = .017, log rank analysis). IFN and 1-month HCV RNA level were independent predictors of recurrence. IFN reduced the risk of recurrence by a factor of 0.4 (P = .04, Cox proportional hazards model); HCV RNA level > 100 x 10(5) Eq/mL at 1 month after transplantation increased the risk by a factor of 3.1 (P = .01). Low, moderate, and high viral levels at 1 and 3 months were associated with significantly different rates of recurrence in IFN patients (P = .05 at 1 month and P = .003 at 3 months) but not in untreated patients (P = .28 at 1 month and P = .25 at 3 months). In patients with two or more rejections, the risk of recurrence was increased by a factor of 2.17 (P = .05). On 47 1-year biopsies (24 IFN; 23 no IFN), piecemeal necrosis was more common in untreated patients (P < .02). One- and 2-year patient survival, respectively, was 96% and 96% with IFN and 91.2% and 87.2% without (P = NS). Prophylactic IFN reduced the incidence of recurrent hepatitis after transplant. Although IFN was most effective in patients with low HCV RNA levels, we also noted an effect in patients with moderate levels. IFN did not prevent viremia, suggesting that it may work through alternative mechanisms.

Adult

A randomized comparison of acute phase response and endotoxemia in patients with perforated peptic ulcers receiving laparoscopic or open patch repair.

BACKGROUND: In patients with peritonitis from perforated peptic ulcers, we compared acute stress responses, endotoxemia, and bacteremia following laparoscopic or open surgery. PATIENTS AND METHODS: Consecutive patients with peritonitis from perforated peptic ulcers were randomized to receive laparoscopic sutured or open omental repair. Undiluted peritoneal fluid was obtained at surgery for quantitative bacterial and endotoxin (Limulus Amoebocyte Lysate) assay. Serial blood samples were taken at 0, 30, 60, 90, 120, and 180 minutes, and at 12, 24, 48, 72, and 120 hours for determinations of quantitative bacterial and endotoxin assays, interleukin-6 (IL-6), C-reactive protein (CRP), and cortisol. RESULTS: Twenty-two patients were randomized: laparoscopy group (n = 12), open repair group (n = 10). Conversions were required in 3 patients assigned to laparoscopy, leaving 9 patients for analysis. The two groups were comparable in their demographic data, median duration of perforation (13.5 hours versus 10 hours), severity of peritoneal contamination as indicated by viable bacterial count (5.9 x 102 versus 1.5 x 10(2) colony forming unit/mL) and endotoxin concentration in peritoneal fluid (27.2 versus 24.6 EU/mL). No significant endotoxemia or bacteremia was detected in these patients. Median interleukin-6 was highest at 0 hour (1520 versus 962 pg/mL) and fell rapidly following surgery. C-reactive protein peaked at 24 hours and plateaued thereafter. Cortisol was highest intraoperatively and fell thereafter. No difference was noted between the two treatment groups with respect to these inflammatory markers (IL-6 P = 0.19, CRP P = 0.14, cortisol P = 0.56, multivariate analysis of variance). CONCLUSION: Endotoxemia and bacteremia are insignificant in most patients with perforated peptic ulcers. In patients with perforated peptic ulcers, laparoscopic patch repair does not reduce acute stress responses when compared with open surgery.

Acute-Phase Proteins

Tissue injury of Injection Gold Probe.

BACKGROUND: The Injection Gold Probe, which incorporates an injection needle and a bipolar electrocoagulation probe, potentially offers better anchoring of the probe for electrocoagulation. This study compares the tissue injury caused by the Injection Gold Probe with or without protrusion of the needle. METHODS: A 10F Injection Gold Probe was applied perpendicularly on the antrum of porcine stomach. At each site of testing, one pulse of treatment at 12 W was given for 10 seconds. The extent of tissue injury was studied under different forces of application (light touch or maximal force) and different probe conditions (needle-in, needle-out, needle-out plus 1 mL saline solution injection). Each maneuver was repeated 8 times. The depth and width of tissue injury were assessed histologically by a pathologist blinded to the treatment. RESULTS: The depth and width of tissue injury did not differ significantly with needle-in, needle-out, or needle-out plus 1 mL saline solution injection on both light touch. But the tissue injury was significantly deeper and wider with maximal force applications than with light touch under the same probe condition. CONCLUSION: The extent of tissue injury inflicted by electrocoagulation using the Injection Gold Probe is not affected by the position of the injection needle.

Analysis of Variance

Does eradication of Helicobacter pylori impair healing of nonsteroidal anti-inflammatory drug associated bleeding peptic ulcers? A prospective randomized study.

BACKGROUND: Despite the widely accepted view that Helicobacter pylori is the most important cause of peptic ulcer disease, recent studies have suggested that the microbe protects against nonsteroidal anti-inflammatory drug (NSAID)-associated gastroduodenal lesions and promotes ulcer healing. We investigated the effects of H. pylori eradication on the healing of NSAID-associated bleeding peptic ulcers. METHODS: Chronic NSAID users presenting with peptic ulcer haemorrhage underwent endoscopy to secure haemostasis and to document H. pylori infection by rapid urease test and culture. They were prospectively randomized to receive either omeprazole (20 mg once daily) for 8 weeks or a 1-week course of triple therapy (bismuth subcitrate 120 mg, tetracycline 500 mg, metronidazole 400 mg, all given four times daily) plus omeprazole (20 mg once daily) for 8 weeks. Endoscopy was repeated after 8 weeks. Final H. pylori status was determined by a 13C-urea breath test that was performed at least 4 weeks after discontinuation of omeprazole. RESULTS: 195 H. pylori-infected NSAID users, complicated by bleeding ulcers, were randomized to receive omeprazole alone (102) or triple therapy plus omeprazole (93). 174 patients returned for second endoscopy at 8 weeks (91 in the omeprazole group, 83 in the triple therapy group). Urea breath test was negative in 14% in the omeprazole group vs. 92% in the triple therapy group (P < 0.001). Complete ulcer healing was achieved in 88 (97%) patients in the omeprazole group and 77 (93%) in the triple therapy group (P=0. 31). On intention-to-treat analysis, ulcers were healed in 86% of the omeprazole group and 83% of the triple therapy group (P=0.50). There was no significant difference in the healing rates of gastric or duodenal ulcers between the two groups. CONCLUSION: Eradication of H. pylori did not impair the healing of NSAID-associated bleeding peptic ulcers.

Adult

Serologic and virologic profiles of hepatitis C infection in renal transplant candidates. New England Organ Bank Hepatitis C Study Group.

The development of policies to prevent nosocomial transmission of hepatitis C virus (HCV) infection in hemodialysis units is critically dependent on the understanding of the relationship between tests for anti-HCV, HCV RNA, and HCV genotype and the patients' clinical characteristics. We tested sera from all patients on the renal transplant waiting list at the New England Organ Bank between November 1986 and June 1990 for anti-HCV by a third-generation enzyme-linked immunosorbent assay (ELISA3) and a third-generation recombinant immunoblot assay (RIBA3). All ELISA3-positive sera were tested for HCV RNA by reverse transcriptase "nested" polymerase chain reaction, and the genotype was characterized by restriction fragment length polymorphism. Sera were available in 1,544 of 3,243 (48%) patients on the waiting list, of whom 287 (19%) tested positive for anti-HCV by ELISA3. Two hundred eighty-six randomly selected, anti-HCV-negative patients served as controls. Compared with anti-HCV-negative controls, anti-HCV-positive patients had a longer duration since initiation of renal replacement therapy, higher number of previous kidney transplants and blood transfusions, higher proportion of patients with anti-HBc, history of liver disease, history of non-A, non-B hepatitis, and elevated serum alanine aminotransferase, and lower serum albumin concentrations. Of the 287 anti-HCV-positive sera, 261 (91%) were reactive by RIBA3, 21 (7%) were indeterminate, and five (2%) were nonreactive. HCV RNA was detected in 224 of 275 (81%) ELISA3-positive patients, in whom additional sera were available. There were no significant differences in clinical or laboratory characteristics between ELISA3-positive patients with and without HCV RNA. Genotypes 1a, 1b, 2a, 2b, 3a, and 4 were present in 53%, 23%, 8%, 10%, 4%, and 2% of patients, respectively. Infection with one, two, or three different HCV genotypes was present in 92%, 7%, and 1%, respectively. There was no significant association between the type or number of HCV genotypes and RIBA3 reactivity. There were no major differences in clinical or laboratory characteristics between genotypes or between single and mixed infection. In summary, this study provides detailed information regarding the relationship between tests for anti-HCV, HCV RNA, and HCV genotypes and the clinical and laboratory characteristics of a large, well-characterized cohort of patients referred for renal transplant.

Enzyme-Linked Immunosorbent Assay

Common bile duct stones become smaller after endoscopic biliary stenting.

BACKGROUND AND STUDY AIMS: Endoscopic biliary stenting is often used for large or difficult common bile duct (CBD) stones that cannot be extracted at one session. We compared the sizes of the CBD stones after a period of stenting. PATIENTS AND METHODS: Over a 6-year period, a total of 444 patients with large CBD stones (> 2 cm diameter) or difficult CBD stones were managed in our endoscopy unit, of which 46 were treated by endoscopic stenting. Twenty-eight had second ERCP for stone removal after a median period of 63 days (range 17-1002 days). The largest diameter of the stones and the CBD (after correction of magnification) before and after stenting were compared using the Wilcoxon signed test. RESULTS: Before stenting the largest diameters of CBD stones were 11-46 mm (mean 24.9 mm) and decreased to 5-46 mm (mean 20.1 mm) after stenting. The difference in stone sizes was statistically significant although the CBD diameter pre- and post-stenting was not significantly different. The reduction in stone sizes was not significantly correlated with the duration of stenting. CONCLUSION: CBD stones became smaller after stenting. As the difficulty of stone extraction increases with stone size, a period of stenting may make subsequent removal easier for patients with large or difficult CBD stones.

Aged

The evolution of stigmata of hemorrhage in bleeding peptic ulcers: a sequential endoscopic study.

BACKGROUND AND STUDY AIMS: Stigmata of hemorrhage in bleeding peptic ulcers have prognostic characteristics. In the present study, the evolution of these stigmata was studied prospectively using daily endoscopic examinations. PATIENTS AND METHODS: From January 1989 to October 1989, 778 consecutive patients with bleeding peptic ulcers underwent endoscopy within 24 hours of admission. The bleeding peptic ulcers were assigned by three endoscopists to five categories, those with: a) active bleeding, b) a nonbleeding visible vessel, c) adherent clot, d) dot, or e) a clean base. Actively bleeding ulcers were treated by epinephrine injection. Ulcers with nonbleeding visible vessels, adherent clots, or dots were left untreated. Daily endoscopic examinations were carried out for three subsequent days, or until the ulcer base became clean. RESULTS: On day 0, there were 56 actively bleeding ulcers (7%), 62 ulcers with visible vessels (8%), 104 with adherent clots (13%), 182 with flat dots (23%), and 374 with a white base (48%). On the subsequent three days, 24 of 62 ulcers with visible vessels (39%), 30 of 104 with adherent clots (29%), 24 of 182 with dots (13%), and 19 of 374 with a clean base (5%) on day 0 re-bled endoscopically or clinically, or both. The overall rebleeding risk was 9.9%, 4.9%, and 2.7% on days 1, 2, and 3, respectively. CONCLUSIONS: Stigmata of hemorrhage in bleeding peptic ulcers are predictive of rebleeding. They represent intermediate phases in the evolution of bleeding vessels into clean-based ulcers. The associated rebleeding risk diminishes as the vessel disappears from the ulcer base.

Endoscopy, Gastrointestinal

Apoptosis and viral hepatitis.

Viral hepatitis is a diffuse inflammatory reaction of the liver caused by hepatotropic viruses. Pathomorphologic studies have shown acidophilic bodies and hepatocyte dropout, features that are compatible with apoptosis. Using in situ terminal transferase labeling, the number of hepatocytes showing features of apoptosis in patients with chronic hepatitis B and C was found to be small but higher than healthy subjects, indicating that apoptosis is involved in the pathogenesis of these diseases. There is evidence that the immune (cytotoxic T lymphocyte)-mediated pathways of apoptosis are activated, suggesting that the apoptosis of liver cells may at least in part be related to the host immune defense. Whether other cytokine-mediated and cellular constitutive apoptotic pathways are involved or not remains to be studied. There are recent data suggesting that hepatitis B and C viral proteins may modulate apoptosis. The exact role of these observations in relation to pathogenesis remains to be established.

Apoptosis