bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ischemic Injury in Liver Transplantation: Difference in Injury Sites Between Warm and Cold Ischemia in Rats
Authors: Ikeda Tetsuo , Yanaga Katsuhiko , Kishikawa Keiji , Kakizoe Saburo , Shimada Mitsuo , Sugimachi Keizo 
Published: March 2007

Using liver allografts with warm or cold ischemia, we evaluated functional and morphological alterations in hepatocytes, sinusoidal endothelial cells and Kupffer cells in a rat transplantation model. All recipients of allografts with either 4 hr of cold or 30 min of warm ischemia lived more than 22 days and were judged viable. On the other hand, all recipients of grafts with 6 hr of cold or 60 min of warm ischemia died within 2 days and were therefore judged to be nonviable. With these viable and nonviable allograft models, hepatocyte function was evaluated by the bile output and serum glutamic–oxaloacetic transaminase, serum glutamic–pyruvic transaminase and serum lactate dehydrogenase levels; endothelial cell function was judged by the serum hyaluronic acid level, and Kupffer cell function was measured by an intravenous colloidal carbon clearance test.
Hepatocyte injury was the prominent feature in warm ischemic grafts, especially in the nonviable ones. On the other hand, serum hyaluronic acid values were significantly higher in the nonviable cold ischemic group, compared with the viable counterpart, suggesting that the functional depression of endothelial cells was predominant in cold, nonviable livers. Histological examinations coincided with the above findings. The phagocytic activity of Kupffer cells was depressed by warm or cold ischemia, whereas the number of Kupffer cells was reduced in the warm ischemia group. We conclude that in liver allografts the main site of injury in warm ischemia is the hepatocytes and suggest that cold ischemia is associated with endothelial cell damage. (Hepatology 1992;16:454-461.)
Inhibition of Rat Hepatic Lipocyte Activation in Culture by Interferon–γ
Authors: Rockey Don C. , Maher Jacquelyn J. , Jarnagin William R. , Gabbiani Giulio , Friedman Scott L. 
Published: March 2007

Hepatic lipocytes (perisinusoidal, Ito cells) are the primary matrix–producing cells in liver fibrosis. During liver injury they undergo activation, a process characterized by cell proliferation and increased fibrogenesis. We and others have established a culture model in which in vivo features of lipocyte activation can be mimicked by cells grown on plastic. Additionally, we recently showed that activation is associated with new expression of smooth muscle-specific α–actin both in vivo and in culture. Although interferon–γ is known to inhibit collagen production in some systems, its action as a general modulator of lipocyte activation has not been examined; this issue forms the basis for our study.
In culture–activated lipocytes, interferon–γ (1,000 U/ml) significantly inhibited lipocyte proliferation as assessed by [3H]thymidine incorporation assay and nuclear autoradiography. In time–course studies of activation, it also markedly reduced expression of smooth muscle-specific α–actin and its messenger RNA. In dose–response experiments, maximal inhibitory effects on smooth muscle-specific α–actin mRNA gene expression were achieved with as little as 10 U interferon–γ/ml. Inhibition of cellular activation was reversible; after interferon–γ withdrawal, messenger RNA levels of smooth muscle-specific α–actin returned to untreated control levels. The effect of interferon–γ extended to extracellular matrix gene expression, with reduction of type I collagen, type IV collagen and total fibronectin messenger RNAs to 3%, 24% and 15% of untreated control levels, respectively. In contrast to the marked effects on smooth muscle–specific α–actin and extracellular matrix gene expression, interferon–γ reduced total protein synthesis by only 17.7%. Moreover, maximal doses of interferon–γ had no effect on cell viability as determined by exclusion of propidium iodide. In summary, interferon–γ is a potent inhibitor of lipocyte activation and may prove useful in the treatment of fibrotic liver injury. (Hepatology 1992;16:776-784.)
The Perfused Liver Is Capable of Producing All Transferrin Glycan Variants Found in the Sera of Intact Rats
Authors: Hu Wei-Li , Chindemi Paul A. , Regoeczi Erwin 
Published: March 2007

ABSTRACT

The single oligosaccharide attachment in rat transferrin exhibits marked structural microheterogeneity. In this study we examined whether all microheterogeneous forms of rat transferrin found in plasma are derived from a single organ, such as the liver. To this end we analyzed the glycans of rat transferrin synthesized by the isolated perfused rat liver by a method established earlier for rat transferrin isolated from rat plasma.
Our observations provide evidence that the liver can and does produce all variant rat transferrin glycans present in plasma. However, this discovery does not preclude the possibility that extrahepatic sources with an active rat transferrin gene may contribute to the circulation rat transferrin molecules, which bear glycan variants identical to those made by the liver. The glycan spectra of rat transferrin in plasma and in liver perfusate compared closely with each other in a quantitative sense. Nevertheless, rat transferrin in the perfusate was sialylated to a lesser extent and fucosylated to a greater extent than rat transferrin in plasma. These differences could not be eliminated by supplementation of the medium with insulin, dexamethasone, pyruvate and adenine or adenosine either alone or in combinations, nor could it be eliminated by use of a fluorocarbon O2 carrier. In contrast, epidermal growth factor normalized both parameters. The pH of the perfusing medium also influenced sialylation and fucosylation in such a way that higher pH brought these parameters closer to their values in plasma rat transferrin. Lower pH, on the other hand, reduced sialylation and left the fucosylation index unchanged. (HEPATOLOGY 1992;16:1049-1054.)
Pregnancy and Cholelithiasis: Pathogenesis and Natural Course of Gallstones Diagnosed in Early Puerperium
Authors: Valdivieso Vicente , Covarrubias Carmen , Siegel Freddy , Cruz Francisco 
Published: March 2007

Several recent reports have indicated an increased prevalence of gallstones in association with pregnancy. If these reports are true, the early puerperium should be a favorable time to detect the disease in its initial stages and follow its natural course. Accordingly, the gallbladder was examined by ultrasound in 980 women during the immediate postpartum period and in 150 nulliparous, age-matched healthy volunteers. Gallstones were detected in 12.2% of the puerperal women and in 1.3% of the control group.
In 70 patients who had stones in a functioning gallbladder, 22 (31%) had had attacks of biliary colic. The history of pain was more common in patients with stones greater than 10 mm in diameter. Forty-one women with small stones (<10 mm) were followed clinically and ultrasonographically for between 6 and 24 (mean = 8.7) mo. All remained pain-free, and in twelve subjects (29%) the stones disappeared.
Gallbladder bile was examined in 11 normal volunteers (controls) immediately after delivery and in 19 women with small stones 39 ± 6 days postpartum. Bile was saturated with cholesterol in the controls and was unsaturated in patients with gallstones.
We conclude that in our population pregnancy is a very important pathogenetic factor favoring gallstone formation. Attacks of biliary colic appear early and frequently in young Chilean women with this disease. Unexplained disappearance of small stones frequently occurs: in some cases it is likely to be the result of spontaneous dissolution because bile becomes unsaturated within a few weeks of delivery. (Hepatology 1993;17:1-4.)
Aplastic anemia and hepatitis C: Molecular biology exonerates another suspect
Authors: Gumucio Jorge J. , Bachwich Dale , Dienstag Jules 
Published: March 2007

Objective. - To test the hypothesis that the rare, often fatal, syndrome of hepatitis-associated aplasia is associated with hepatitis C virus infection.
Design. - Case series.
Setting.-Tertiary referral centers in the United States, Japan, Italy, and Germany.
Patients. - Twenty-eight patients with onset of aplastic anemia within 90 days after seeking medical attention for jaundice, or having serum transaminase levels 150% or more of normal (hepatitis-associated aplasia patients) and three patients who developed aplastic anemia following liver transplantation for non-A, non-B, hepatitis.
Outcome Measures. - Presence of hepatitis C in serum, bone marrow, and liver samples, detected by the polymerase chain reaction; antibody testing; and percentage of activated peripheral cytotoxic T lymphocytes determined by immunophenotyping.
Results. - Hepatitis ribonucleic acid was present in the serum samples of 10 (36%) patients with hepatitis-associated aplasia. However, hepatitic C virus viremia was associated with transfusions received after the onset of aplasia: seven (58%) of 12 patients with hepatitis-associated aplasia who had received 21 or more units of blood products at the time of serum sampling were viremic, compared with only three (19%) of 16 patients with hepatitis-associated aplasia who had received 20 or less units of blood products (P <.05). Hepatitis C virus was not found in blood and bone marrow samples of three National Institutes of Health case patients tested at the time of diagnosis. None of three livers from non-A, non-B hepatitis patients who developed aplastic anemia after liver transplantation contained hepatitis C virus ribonucleic acid. Activated CD8+ T lymphocytes were elevated three- to 20-fold early in the course of hepatitis-associated aplasia.
Conclusions. - Our results implicate a novel, non-A, non-B, and non-C agent in both hepatitis-associated aplasia and fulminant hepatitis.
Acute Hepatitis A: An endangered species
Authors: Sjogren Maria H. 
Published: March 2007

Background:
Although inactivated hepatitis A vaccine is known to be well tolerated and immunogenic in healthy children and adults, its efficacy has yet to be established.

Methods:
To evaluate the efficacy of the hepatitis A vaccine in protecting against clinically apparent disease, we conducted a double-blind, placebo-controlled trial in a Hasidic Jewish community in upstate New York that has bad recurrent outbreaks of hepatitis A. At the beginning of a summer outbreak, 1037 healthy seronegative children 2 to 16 years of age were randomly assigned to receive one intramuscular injection of a highly purified, formalin-inactivated hepatitis A vaccine or placebo. A case was defined by the presence of typical signs and symptoms, a diagnostic increase in IgM antibody to hepatitis A, and a serum concentration of alanine aminotransferase at cast twice the upper limit of normal. Cases occurring ≥ 50 days after the injection were included in the evaluation of efficacy. The children were followed for a mean of 103 days.

Results:
A total of 519 children received vaccine, and 518 received placebo. The vaccine was well tolerated, with no serious adverse reactions. From day 50 after the injection, 25 cases of clinically apparent hepatitis A occurred in the placebo group and none in the vaccine group (P < 0.001), confirming that the vaccine had 100 percent protective efficacy. Before day 21, seven cases occurred in the vaccine group and three cases in the placebo group. After that time, there were no cases among vaccine recipients and 34 cases among placebo recipients.

Conclusions:
The inactivated purified hepatitis A vaccine that we tested is well tolerated, and a single dose is highly protective against clinically apparent hepatitis A.
To ligate or sclerose: Beginning of a new era in the management of esophageal varices?
Authors: Sarin S. K. , Bhatia V. 
Published: March 2007

Background.
Endoscopic sclerotherapy is an accepted treatment for bleeding esophageal varices, but it is associated with substantial local and systemic complications. Endoscopic ligation, a new form of endoscopic treatment for bleeding varices, may be safer. We compared the effectiveness and safety of the two techniques.

Methods.
In this randomized trial we compared endoscopic sclerotherapy and endoscopic ligation in 129 patients with cirrhosis who had proved bleeding from esophageal varices. Sixty-five patients were treated with sclerotherapy, and 64 with ligation. Initial treatment for acute bleeding was followed by elective retreatment to eradicate varices. The patients were followed for a mean of 10 months, during which we determined the incidence of complications and recurrences of bleeding, the number of treatments needed to eradicate varices, and survival.

Results.
Active bleeding at the first treatment was controlled by sclerotherapy in 10 of 13 patients (77 percent) and by ligation in 12 of 14 patients (86 percent). Slightly more sclerotherapy-treated patients had recurrent hemorrhage during the study (48 percent vs. 36 percent for the ligation-treated patients, P = 0.072). The eradication of varices required a lower mean (± SD) number of treatments with ligation (4 ± 2 vs. 5 ± 2, P = 0.056) than with sclerotherapy. The mortality rate was significantly higher in the sclerotherapy group (45 percent vs. 28 percent, P = 0.041), as was the rate of complications (22 percent vs. 2 percent, P < 0.001). The complications of sclerotherapy were predominantly esophageal strictures, pneumonias, and other infections.

Conclusions.
Patients with cirrhosis who have bleeding esophageal varices have fewer treatment-related complications and better survival rates when they are treated by esophageal ligation than when they are treated by sclerotherapy. N Engl J Med 1992;326:1527-1532.
Restructuring American health care financing: First of all, do no harm!
Authors: Berk Paul D. 
Published: March 2007

Health care costs are climbing throughout the western world. Aging populations and the costs of advanced technology are the principal forces behind much of this global increase. No country has yet succeeded in containing these growing costs other than by some form of rationing. A variety of experimental strategies, including managed competition, are being considered or tested, but none is clearly effective.
American health care expenditures differ, not in that they are rising, but in their enormously high starting point. Among other things, our higher costs reflect administrative costs of more than 20%, double those of Canada and nearly triple the European average; a malpractice system that, whatever its possible advantages, costs more than 10 times as much as it pays out to the injured; the enormous medical costs of poverty; maldistribution of physician specialties and incomes; and reimbursement systems that eliminate consumer input and oversight.
Restructuring the system of health care financing to bring administrative costs in line with those of other nations could save at least $70 billion annually; another $25 billion or more could be saved by replacing the malpractice system with more cost-effective alternatives. These savings could defray the costs of insuring all those not now covered, without increasing either costs to the middle class, through taxation of benefits, or total health care expenditures. With all Americans covered, the necessary restructuring of the system of health care delivery could be conducted without the current pressure for immediate drastic reform, which carries with it the risk of serious error.
In dealing with the sick, physicians are taught to apply two maxims: “primum non nocere” or “first of all, do no harm!”; and the rule of therapeutic restraint. The latter states that a severe chronic illness may respond better, and with fewer complications, to gradual corrective measures than to highly aggressive therapy. Both rules could well be applied to curing the American health care system.
Constipation: Is it a risk factor for cholesterol gallstones?
Authors: Gumucio Jorge J. , Watkins James L. , Wiley Thelma E. , Layden Thomas J. 
Published: March 2007

Many cases of gallstones can be explained in terms of the established risk factors, especially obesity. However, gallstones develop in some women who are not obese, and the causes are unknown. Biochemical studies have shown that slow intestinal transit is associated with lithogenic bile. We have tested the hypothesis that intestinal transit is abnormally slow in normal-weight women with gallstones.
In a population survey, 1058 women aged 25-69 years, registered with general practitioners in Bristol, UK, underwent cholecystosonography. Gallstones were identified in 48 women, of whom 15 were of normal weight (body mass index ≤ 25 kg/m2). These women and age-matched controls with healthy gallbladders then underwent measurement of whole-gut transit time (WGTT); the measurement was done directly when possible, or calculated from records of three defaecations. The mean WGTT was significantly longer in the women with gallstones than in the controls (82 vs 63 h; mean difference 19, 95% Cl (2-37 h). Stool output was also lower in the women with gallstones (74 [SD 54] vs 141 [56] g per 24 h, p = 0.015). There was no significant difference between cases and controls in body mass index, waist-hip circumference ratio, parity, plasma triglyceride concentration, or alcohol intake.
Normal-weight women with gallstones tend to have slow intestinal transit and this feature could explain why they have gallstones.
What should we clinicians do for healthy, asymptomatic, hbsag-positive carriers?
Authors: McMahon Brian J. 
Published: March 2007

Objective:
To assess the long-term outcome in hepatitis B surface antigen (HBsAg) carriers who have normal liver function tests, focusing on survival and the development of severe liver disease and hepatocellular carcinoma.

Design:
Cohort study with a mean follow-up of 130 months.

Setting:
Liver clinic of a referral center.

Patients:
Ninety-two HBsAg-positive blood donors with normal liver function tests.

Measurements:
Histologic evaluation of liver specimens at baseline; clinical, biochemical, and serologic follow-up; and repeat liver biopsy if clinically indicated or after 10 years of follow-up.

Results:
At baseline, 69 subjects had normal histologic findings or only minor abnormalities, 18 had chronic persistent hepatitis, and 5 had mild chronic active hepatitis. Serum enzyme levels remained normal in 58 of 68 patients who had regular follow-up. Three patients had biochemical changes consistent with hepatitis B virus (HBV) infection; in one of these patients, a later histologic evaluation showed progression to chronic active hepatitis. One patient developed alcoholic cirrhosis. Six other patients had mild or transient transaminase elevations, with no evidence of HBV replication, hepatitis D virus infection, hepatitis C virus (HCV) infection, or histologic deterioration. Liver histologic findings also remained unchanged in 21 patients who showed no biochemical changes during 10 years of follow-up and consented to have repeated liver biopsy. Ten patients showed loss of HBsAg; 2 of these patients acquired antibody to hepatitis B surface antigen (anti-HBs). All patients who did not have regular follow-up, except 1, were interviewed by telephone during 1990; All denied having liver disease. No patients developed hepatocellular carcinoma.

Conclusions:
Italian HBsAg carriers with initially normal liver function tests have an excellent prognosis: Delta superinfection is infrequent and the risk for developing hepatocellular carcinoma is low.
Prevention of posttransfusion hepatitis B and C by screening for antibody to hepatitis C virus and antibody to HBcAg
Authors: Chung Hau Tim , Lee Joseph Sai Kit , Lok Anna Suk Fong 
Published: March 2007

Screening of blood donors by testing for antibody to HBcAg and antibody to hepatitis C virus is commonly done. However, the applicability of these screening tests may vary depending on the prevalence of hepatitis B virus and hepatitis C virus infection in various populations. We have therefore prospectively evaluated 158 adult patients who received blood or blood products during open-heart surgery in Hong Kong to compare the efficacy of various serological screening tests in the prevention of posttransfusion hepatitis. Serum from five (0.5%) donors was positive for antibody to hepatitis C virus by second-generation enzyme immunoassay; in two, optical-density readings in enzyme immunoassay were greater than 2.0, but only one was positive for hepatitis C virus RNA by reverse transcription-polymerase chain reaction. The latter donor was also positive for antibody to HBcAg and had elevated serum ALT activity. The recipient of a unit of this donor’s blood was the only one in whom posttransfusion hepatitis C developed (0.1% per unit transfused). Screening with antibody to hepatitis C virus was more specific than that with antibody to HBcAg or ALT in excluding donors from transmitting hepatitis C (99.6%, 79.4% and 98.8%, respectively). Both the sensitivity and negative predictive value of screening for antibody to hepatitis C virus were 100%, but the positive predictive value was only 20%.
Forty-five blood recipients were considered susceptible to hepatitis B virus infection because testing for hepatitis B serology in serum (HBsAg, antibody to HBsAg and antibody to HBcAg) was negative before being transfused. Asymptomatic hepatitis B seroconversion developed in three (6.7%) recipients (1.1% per unit transfused). One was transiently positive for HBsAg, and all three became positive for antibody to HBsAg and antibody to HBcAg during follow-up. One patient received a unit of blood that was positive for antibody to HBcAg and hepatitis B virus DNA by polymerase chain reaction. The second patient received a unit of blood with antibody to HBcAg but negative for hepatitis B virus DNA. The blood administered to the third patient was negative for hepatitis B markers, including hepatitis B virus DNA by polymerase chain reaction. Exclusion of donors with isolated antibody to HBcAg had the highest sensitivity and specificity for prevention of posttransfusion hepatitis B (66.7% and 96.1%, respectively). This approach yielded a positive predictive value of 16.7% and a negative predictive value of 99.6%. Antibody to hepatitis C virus should be screened in all blood donors to minimize the risk of posttransfusion hepatitis C. In hepatitis B virus-endemic areas, further reduction of the risk of posttransfusion hepatitis B with blood from HBsAg-negative volunteer donors is difficult. Our data suggest that excluding donors with isolated antibody to HBcAg may be the most effective approach. (HEPATOLOGY 1993;18:1045-1049).