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Biomedical subjects

G B Zibari

Publications and source records attributed to G B Zibari.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of dextran and pentoxifylline on hemorrhagic shock-induced P-selectin expression.

BACKGROUND: Dextran and pentoxifylline have been shown to prevent leukocyte-endothelium adherence encountered after hemorrhagic shock. P-Selectin is the first endothelial cell adhesion molecule to be upregulated after an ischemic insult. We investigated the effects of resuscitation with dextran 70 and administration of pentoxifylline during resuscitation on hemorrhagic shock-induced P-selectin expression. MATERIAL AND METHODS: Hemorrhagic shock was induced in C57BL/6 mice by withdrawing blood to reduce mean arterial blood pressure to 30 mm Hg for 45 min. Animals were resuscitated by infusing one of the following solutions (each n:5): (1) Ringer's lactate, (2) 6% dextran 70, (3) Ringer's lactate plus 50 mg/kg pentoxifylline, (4) 5% human albumin. Afterward shed blood was infused. In vivo P-selectin expression was determined using dual-radiolabeled monoclonal antibody technique in lung, heart, liver, kidney, mesentery, stomach, small bowel, and colon 5 h after resuscitation. RESULTS: P-Selectin was significantly upregulated in all of the organs studied in the Ringer's lactate resuscitation group (P < 0.001). Resuscitation with dextran 70 and administration of pentoxifylline during resuscitation prevented P-selectin upregulation. Resuscitation with human albumin caused significant attenuation but could not prevent P-selectin upregulation (p < 0.01). CONCLUSION: Our study implies that the prevention of hemorrhagic shock-induced leukocyte-endothelium adherence by dextran 70 and pentoxifylline observed in other studies may be mediated by prevention of P-selectin expression by these agents.

Animals↗
PubMed1999

Are all successful renal transplants really successful?

We previously described a small group of renal transplant recipients considered to have successful allografts statistically, but who did not benefit clinically. These were patients in whom the grafts survived greater than 6 months but less than 3 years. This expanded study evaluates 179 consecutive renal transplant recipients divided into three groups. Group 1 (n = 18), group 2 (n = 41), and group 3 (n = 120) have patients with graft survival less than 6 months, between 6 months and 3 years, and greater than 3 years, respectively. Mean age, cause of renal failure, HLA match, and immunosuppressive regimen were not statistically different in any group. The number of acute rejection episodes, number of hospitalizations, and number and seriousness of complications were significantly greater in group 2 patients compared with the other groups. Patients in group 2 experienced five times the number of acute rejections (P < 0.0001), three times the number of hospitalizations (P < 0.0001), and two times the number of complications (P < 0.0001) compared with group 3 patients. In conclusion, those transplant recipients whose grafts survived longer than 6 months but less than 3 years were the most unfortunate. They experienced repeated and serious complications and spent many days in the hospital at great expense. A study with more sensitive methods of detecting presensitization might impact on graft performance in the future.

Adult↗
PubMed1999

Role of P-selectin expression in hepatic ischemia and reperfusion injury.

BACKGROUND: Researchers have shown that reperfusion of ischemic tissues initiates a complex series of reactions that paradoxically injure tissues. Although several mechanisms have been proposed to explain the pathobiology of ischemic/reperfusion (I/R) injury, much attention has focused on adhesion molecules. Our research is intended to show the kinetics of P-selectin in the liver in response to I/R injury. METHODS: Left-lobar hepatic ischemia was induced for 30 min in 35 C57BL-6 mice and 20 P-selectin-deficient (K-O) mice. P-selectin expression was measured in these mice at 20 min, 2, 5, 12 and 24 h reperfusion times, as well as in control and sham animals. The animals were injected with radio-labeled P-selectin monoclonal antibody and the organs were harvested for counts/g tissue, expressed as the percentage injected dose. Serum liver enzymes were measured and pathological sections of ischemic and control livers were performed. The unpaired t-test was used for statistical analysis. RESULTS: P-selectin expression showed two peaks in this animal model. The first peak was at 20 min and the second peak at 5 h of reperfusion (p < 0.001). We documented an 8-fold increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels 10 h following I/R injury. Pathological specimens showed periportal necrosis consistent with an ischemic event. P-selectin K-O mice showed no up-regulation as a separate control group, and the liver enzymes were significantly lower than the wild-type mice at 10 h (p < 0.001). CONCLUSION: P-selectin has a bimodal expression following hepatic I/R injury. The first peak is attributed to the Weibel-Palade bodies and the second to new translational P-selectin. We noted no difference in the up-regulation of P-selectin in the ischemic and non-ischemic liver lobes in the same animal.

Alanine Transaminase↗
PubMed1999

P-selectin contributes to the initial recruitment of rolling and adherent leukocytes in hepatic venules after ischemia/reperfusion.

We have recently reported that hepatic ischemia/reperfusion (I/R) is associated with a biphasic increase in the expression of P-selectin in the liver microvasculature, with peak expression levels observed at 20 min and 5 h after reperfusion. This I/R-induced upregulation of P-selectin expression is accompanied by leukocyte-endothelial cell adhesion in terminal hepatic venules (THV). The objective of this study was to determine whether the early expression of P-selectin contributes to the initial recruitment of rolling and adherent leukocytes in THV after liver I/R. Left hepatic lobe ischemia was induced for 30 min in anesthetized C57B1/6 and P-selectin knockout (KO) mice. The number of rolling, saltating, and adherent leukocytes in THV was measured at 0, 15, 30, 60, and 120 min after reperfusion using intravital video microscopy. Hepatic I/R elicited significant increases in the number of rolling, saltating, and adherent leukocytes, with peak values observed at 30 min after reperfusion. All of these responses were absent in P-selectin KO mice and in C57B1/6 mice treated with a blocking antibody to P-selectin. Our findings suggest that P-selectin is the primary determinant of leukocyte-endothelial cell adhesion observed in hepatic venules in the initial period after I/R. Hence, this adhesion molecule may represent a target for therapeutic intervention in liver transplantation and other conditions associated with hepatic I/R.

Animals↗
PubMed1999

Can low volume liver transplant centers be successful? The Regional Transplant Center of Willis-Knighton & Louisiana State University Medical Center. The first 120 liver transplants.

The development of orthotopic liver transplantation represents this century's most significant advance in the management of liver disease. In the 1980s the vast majority of liver transplants were performed at several large centers; however, in this decade, improvements in techniques and success rates have allowed live transplantation to expand to regional centers across the country, particularly in the southeast. This proliferation of regional centers and the widening disparity between organ availability and numbers of recipients have created tremendous controversy at the national level regarding the allocation scheme used to distribute livers to recipients. The large programs today are advocating change to a national waiting list which would eliminate local priority and jeopardize the existence of smaller regional centers. Furthermore, the large programs favor establishing a limited number of megacenters where all liver transplants would take place, arguing that low volume centers cannot perform liver transplants with acceptable complication and survival rates. At the Regional Transplant Center of Willis-Knighton Hospital and Louisiana State University Medical Center in Shreveport (WK/LSUMC) we performed 122 liver transplants between July 1, 1991 and December 31, 1997. The purpose of this study was to examine our complication and survival rates and compare them to national averages. The actuarial graft survival at 1, 2, and 3 years in this series compared to the national average respectively was 76% and 70%, 66% and 66%, 62% and 62%. The actuarial patient survival (WK/LSUMC vs National) at 1, 2, and 3 years was 80% and 80%, 75% and 75%, 70% and 74%. The rate of retransplantation was 8% with a national average of 10% to 20%. Our rate of graft primary non-function was 5% with the national average being 2% to 10%. The rate of vascular thrombosis of the graft in this series was 2% with a national rate of 5%. The differences in these results were not statistically significant (P < .05). Low volume transplant centers can perform liver transplant successfully, allowing the regionalization of the treatment of choice for end-stage liver disease.

Actuarial Analysis↗
PubMed1999

The use of FDG-positron emission tomography for the evaluation of colorectal metastases of the liver.

Each year at least 130,000 people in the United States are diagnosed with colorectal carcinoma. Approximately 14,000 of these patients will have liver metastases, and 20 per cent of these patients will die from these metastases. Surgical resection is the only possible chance for cure in patients with only intrahepatic metastases, and extrahepatic disease is a contraindication to glucose metabolism. Positron emission tomography (PET) allows the in vivo study of the uptake and use of glucose in human cells. Here, we review our experience with the use of PET imaging for the diagnosis and management of colorectal metastases of the liver. We conducted a retrospective chart review of 14 patients undergoing PET imaging for known or suspected hepatic metastases from colorectal carcinoma. Results of CT, magnetic resonance imaging, and PET images were compared with pathological specimens. CT scan identified 7 lesions, and PET identified 31 intrahepatic lesions. Of the 6 patients who underwent surgery, CT identified 4 (20%) and PET identified 17 (85%) of the 20 intrahepatic metastases histologically confirmed. The accuracy (number of lesions) of CT and PET was 20 per cent and 85 per cent, respectively. CT scans had a sensitivity (number of patients) of 50 per cent, and PET had a sensitivity of 100 per cent in patients undergoing surgical resection. PET imaging altered the management in 49 per cent of patients. Twenty-one per cent of patients had their surgery cancelled due to previously undiagnosed extrahepatic metastases. Twenty-one per cent of patients had negative CT scans and underwent surgery on the basis of their PET images, and all had histologically proven disease. One patient avoided a second-look laparotomy when PET revealed a lesion seen on CT to be false positive. PET is an ideal imaging modality to detect intra- and extrahepatic metastases from colorectal carcinomas and would aid in the surgical management of these patients.

Adult↗
PubMed1998

Small-bowel tumors.

BACKGROUND: The rarity, delayed presentation, and diagnostic difficulty of small-bowel tumors prompted this study. STUDY DESIGN: Charts were reviewed retrospectively for 85 patients with 89 small-bowel tumors (22 primary malignant, 23 primary benign, and 44 metastatic) over a 10-year period (1986-1996) at Louisiana State University Medical Center-Shreveport and two affiliated hospitals in Shreveport. RESULTS: Of the primary malignant tumors, 10 carcinoids and 11 duodenal adenocarcinomas were identified. Most primary benign tumors were adenomatous or hyperplastic polyps, diagnosed by esophagogastroduodenoscopy. Metastatic tumors accounted for nearly 50% of all small-bowel tumors. Across all three tumor types, the most common presenting signs and symptoms were abdominal pain and nausea and vomiting. In addition, patients with benign tumors were more commonly presented with gastrointestinal hemorrhage, and those with metastatic tumors were more likely to present with obstruction. The mean interval from the onset of signs and symptoms to operation was 54 days for primary malignant tumors and 330 days for primary benign tumors. Esophagogastroduodenoscopy and computed tomography of the abdomen were occasionally helpful in diagnosis. Among the 22 primary malignant tumors, curative resections were performed in 11 patients (for 9 carcinoids and 2 adenocarcinomas) and palliative resections were performed in 10 patients (for 9 adenocarcinomas and 1 myxoliposarcoma). One patient had carcinomatosis from colon cancer and an incidentally discovered ileal carcinoid; this carcinoid was not included in this group of resections for primary malignant small-bowel tumors. All operations for 39 (of 44) patients with metastatic tumors were palliative. The remaining 5 (of 44) patients had metastatic duodenal cancer (confirmed by esophagogastroduodenoscopy or endoscopic retrograde cholangiopancreatography with biopsy) and did not undergo laparotomy. Surgical complications occurred more commonly with metastatic than with primary malignant tumors. Patients with primary malignant tumors had a 5-year survival rate of 36%. CONCLUSIONS: These findings demonstrate that small-bowel tumors are difficult to diagnose because of delayed presentation, nonspecific signs and symptoms, and lack of accurate diagnostic studies. If the overall survival of patients with small-bowel tumors is to be improved, clinicians must have a high index of suspicion and be willing to perform exploratory celiotomy early.

Adenocarcinoma↗
PubMed1998

Surgical and nonsurgical management of primary and metastatic liver tumors.

The medical records of 267 patients who had liver tumors, primary and metastatic, from 1988 to 1995 were retrospectively reviewed. Two hundred thirteen patients (80%) had metastatic disease, and 54 patients (20%) had primary liver disease. Their clinical manifestations and laboratory values were evaluated as factors predictive of diagnosis and survival. There was a significant increase in the occurrence of upper abdominal pain, weight loss, extrahepatic symptoms due to the metastatic origin, and hepatomegaly. Metastases from colorectal primary lesions were synchronous in 34 patients and metachronous in 31 patients. Stomach, lung, and pancreatic primaries were more commonly synchronous. Breast metastases were more commonly metachronous. Elevated serum glutamic-oxaloecetic transaminase and alkaline phosphatase and decreased albumin were the most common liver test abnormalities at diagnosis. Carcinoembryonic antigen values were elevated in the majority of colon cancer patients. Eighty-one percent of patients with primary liver cancer had elevated levels of alpha-fetoprotein, 40 per cent were seropositive for hepatitis B, and 23 per cent were seropositive for hepatitis C. Seventy-nine patients (30%) underwent surgery for their cancer, 37 (47%) had resections, 38 (48%) were unresectable, and 4 (5%) underwent liver transplantation. The patients who underwent surgery had a 32 per cent 5-year survival rate compared to a 0 per cent 5-year survival in the patients who did not have surgery (p = 0.0001). The patients who had resections had a better survival rate than those deemed unresectable at surgery (62% versus 0% at 5-years with p = 0.0008). The perioperative morbidity rate was 16 per cent, with lobectomies having the best rate and trisegmentectomies having the worst. Perioperative mortality rate was zero for all liver resections. Hepatic resection and, in selected patients, liver transplantation are the only two available therapeutic modalities that produce long-term survival with a possible cure in patients with primary and metastatic liver tumor.

Adolescent↗
PubMed1998

Aggressive surgical management of necrotizing fasciitis serves to decrease mortality: a retrospective study.

Necrotizing fasciitis is an aggressive soft-tissue infection that in the past has carried a significant mortality rate. One of the most important determinants of outcome is recognition of the disease process. This is followed by aggressive resuscitation measures and radical debridement at the initial operation to control the infectious spread at the outset. The objective of this study is to help reveal the benefits of aggressive early surgical debridement in the treatment of necrotizing fasciitis. A retrospective review of the medical records of 68 patients between the years 1980 and 1996 with the diagnosis of necrotizing fasciitis was performed. The patients were assigned to two groups, Group A (21; 31%), who had delay in therapy or inadequate preliminary therapy and Group B (47; 69%), who underwent aggressive surgical debridement from the outset. Concomitant disease processes were noted. The medical records of 68 patients were studied. Age ranged from 13 to 67 (mean, 52) years of age. There were 38 (56%) females, 21 (64%) of the patients were African-American, 24 (73%) of the patients had concomitant disease processes, 29 (42%) of the patients had a history of tobacco use, 11 (16%) of the patients had a history of alcohol consumption, and 11 (16%) of the patients were obese. Mortality in Group A was 8 of 21 patients (38%). Mortality in Group B was 2 of 47 patients (4.2%). The difference in mortality was found to be statistically significant (P = 0.0007). Early recognition and expeditious initial wide excision and debridement along with appropriate antibiotic coverage and support of systemic effects of necrotizing fasciitis serve to decrease morbidity and mortality. We believe the above is an absolute necessity followed by frequent washing and minor debridement of the wound until granulating tissue is observed. This can then be followed by procedures to close/cover the surgical defect (i.e., split-thickness skin grafts or various coverage flaps).

Adolescent↗
PubMed1998

Colorectal cancer in the young patient.

Although predominantly a disease of older adults, colorectal cancer affects the younger population with an incidence of two to six per cent. It is thought to carry a less favorable prognosis in the young than in the general population. This may be due to advanced stage of the tumor at diagnosis. This study is composed of 37 patients, aged 40 and younger, treated over a 20-year period for colorectal cancer at Louisiana State University Medical Center-Shreveport and E. A. Conway Hospital. It was performed to investigate the incidence, stage at diagnosis, and prognosis of colorectal cancer in these young patients. The location of the primary tumor was fairly evenly distributed throughout the colon and rectum in this population. Pain, weight loss, rectal bleeding, and nausea and vomiting were the most common presenting symptoms. A family history of colon cancer or premalignant lesions were not risk factors in this study. Seventy per cent of all patients were treated with curative intent, and 42 per cent of these patients developed recurrent disease. The patients in this review presented with a higher incidence of advanced disease. Thirty-seven per cent of the lesions were Duke's C and 22 per cent were Duke's D, with poor 5-year survival (11% and 0%, respectively) when compared with national studies. The absolute 5-year survival for all young patients with colorectal cancer was 26 per cent (5 of 19 patients). It is important for the surgeon to be aware of the potential for colorectal cancer in young patients and to take an aggressive approach to the diagnosis and early treatment of the disease.

Abdominal Pain↗
PubMed1998

Spontaneous bacterial peritonitis in liver failure.

Cirrhosis of the liver results from a variety of mechanisms that cause progressive hepatic injury. It is the sixth leading cause of death in all patients between the ages of 35 and 55. This study attempts to correlate the morbidity and mortality of spontaneous bacterial peritonitis in liver failure patients to numerous etiologic and clinical variables. A retrospective review of 26 patients with spontaneous bacterial peritonitis associated with chronic liver disease was performed in a university hospital. Demographics (age and gender), clinical variables (etiology of liver failure, Child's classification, prior history of ascites, fever, abdominal pain, encephalopathy, and upper gastrointestinal hemorrhage), and laboratory variables (ascitic polymorphonuclearcyte count and cultures, serum albumin, bilirubin, creatinine, and prothrombin time) were studied. All of the patients had Child's C liver disease. Mortality rate was 46 per cent. Alcohol (46%) and hepatitis (30%) were the most common etiologies. Escherichia coli and Klebsiella pneumoniae were the most common culture isolates. All of the infections were monomicrobial. The only significant predictor of mortality (P < 0.05) in this study was the peritoneal fluid polymorphonuclear (PMN) cell count. PMN count >1000 PMN/mm3 was associated with a mortality of 88 per cent. Few patients with spontaneous bacterial peritonitis are ultimately transplanted.

Adolescent↗
PubMed1997

Serologic allogeneic chimerism.

BACKGROUND: At least some transplanted livers secrete soluble human leukocyte antigens (sHLA) of donor phenotype into the body fluids of recipients. The individuals in whom this phenomenon occurs are by definition serologic allogeneic chimeras. Because an allogeneic transplanted liver may induce tolerance to itself and other organs in animals of the donor strain, and because maintenance of a soluble antigen in the circulation of any animal in sufficient quantity for a sufficient period generally leads to tolerance, this phenomenon may be biologically important. This study was performed to determine how common this phenomenon is and whether it occurs after transplantation of organs other than the liver. METHODS: We studied 445 serum samples obtained from transplant recipients (liver, n=12; kidney, n=18; and heart, n=8) before and at various intervals after transplantation. All patients studied had allografts that had functioned for more than 1 year. We used an enzyme-linked immunosorbent assay to quantitate sHLA-A2 and sHLA-A1/A3/A11 (as a cross-reacting group). Donor and recipient combinations were selected in which measurable allotypes in donors were not present in recipients. In some instances, an additional allotype was present in a recipient but not in a donor. RESULTS: All liver transplant recipients had detectable donor sHLA in their serum samples after transplantation. In 72% of kidney and 50% of heart transplant recipients, donor sHLA was found persistently in serum samples obtained after transplantation. Interestingly, all heart transplant recipients of HLA-A3, but none of HLA-A2, had detectable donor sHLA in their serum samples, a finding that may be due to technical reasons. High and stable serum concentrations of donor sHLA characterize long-term stable allograft function. CONCLUSIONS: Donor sHLA is produced by all transplanted livers, most transplanted kidneys, and at least half of (but probably more) transplanted hearts. The hypothesis that donor sHLA may be tolerogenic to liver transplants can be expanded to include kidney and heart transplants.

Antibodies, Monoclonal↗
PubMed1997

Quantification of P-selectin expression after renal ischemia and reperfusion.

Neutrophils are important in ischemia and reperfusion injury. Multiple factors may be responsible for the adhesion of granulocytes to endothelial cells. P-selectin is a carbohydrate-binding glycoprotein that is stored preformed in endothelial cells as Weibel-Palade bodies. This preformation implies a very early role of P-selectin in the leukocyte adhesion process. Previous studies of P-selectin have not quantified its expression. The purpose of this study is to quantitate the expression and time course of P-selectin in response to renal ischemia and reperfusion injury. P-selectin was measured in 34 C57BL-6 mice after 30 minutes of occlusive left renal ischemia followed by 20 minutes, 2, 5, 10, and 24 hours of reperfusion. This was also performed in control and sham laparotomy groups. P-selectin was quantified using a new double radiolabeled 125I/131I monoclonal antibody technique and reported as percent injected dose per gram of tissue. P-selectin expression peaked at 20 minutes, plateaued up to 5 hours, and fell at 10 hours. Additionally, genetically altered mice that do not express P-selectin showed no up regulation after 5 hours of reperfusion. Pathology results confirmed significant renal injury. Renal ischemia and reperfusion injury caused significant upregulation of P-selectin. Expression of P-selectin at the short reperfusion time of 20 minutes reinforces the premise that P-selectin is one of the earliest adhesion molecules expressed. This early peak is probably caused by the release of preformed P-selectin. The delineation of these mechanisms of injury may be important in understanding and preventing renal injury in transplantation, sepsis, and shock.

Animals↗
PubMed1997

Preoperative vancomycin prophylaxis decreases incidence of postoperative hemodialysis vascular access infections.

The role of vancomycin in the treatment of infected arteriovenous chronic dialysis access is well established. However, the role of preoperative vancomycin administration in preventing infection in newly placed, revised, or surgically thrombectomized grafts has not been determined. We performed a prospective randomized study to examine whether vancomycin prophylaxis can decrease the incidence of postoperative graft infections. Over a 5-year period, 206 patients undergoing 408 permanent vascular access procedures were randomized into two groups. Group 1 (206 procedures) received a single intravenous dose of 750 mg of vancomycin approximately 6 to 12 hours before vascular access placement procedures, while group 2 (202 procedures) did not. Patients were evaluated for access infection within the following 30 days and before use of the access for chronic dialysis. Access infection developed in two patients (1%) in group 1 and in 12 patients (6%) in group 2 (P = 0.006). All 14 infections occurred in upper extremity polytetrafluoroethylene grafts. We conclude that the use of preoperative single-dose intravenous vancomycin prophylaxis for hemodialysis vascular graft procedures reduces the risk of postoperative access infection.

Adolescent↗
PubMed1997

Soluble fraction of class I human histocompatibility leukocyte antigens in the serum of liver transplant recipients.

In previous studies we reported a solid-phase, enzyme-linked immunoassay (ELISA) that can be used to quantitate the soluble fraction of human histocompatibility leukocyte class I antigens (S-HLA-I) and study their relevance in transplantation. In this study we determined the concentration and distribution of S-HLA-I in patients with end-stage liver disease (ESLD), as well as in liver transplant recipients. Sera were obtained from 51 patients with ESLD and 40 donor-recipient pairs. We analyzed the S-HLA-I in sera obtained from liver donors, as well as from liver transplant recipients (patients with ESLD), with sera from the latter obtained before and at various intervals up to 3 yr after transplantation. The results of the analyses justify the following conclusions: 1) Patients with ESLD had mean values of S-HLA-I (909 +/- 596 ng/ml) greater than those for the normal population (643 ng/ml) (P < 0.05); the S-HLA-I secretion decreased with increasing severity of liver disease. 2) Patients with tumors had mean S-HLA-I levels (399 ng/ml) significantly lower than those in patients with ESLD related to other causes. 3) In liver transplant recipients the S-HLA-I levels stabilized at approximately 1 month after transplant and remained relatively stable thereafter (mean level 950 +/- 536 ng/ml). The observed levels were also greater than those for the normal population (P < 0.05). 4) Preoperative and postoperative S-HLA-I values in liver transplant recipients demonstrated a biphasic distribution, dividing patients into high- and low-secretor groups. 5) During the post-transplant observation period, of these selected liver transplant recipients there was no difference between high- and low-secretor groups in the incidence of rejection (high, 70%; low, 67%), graft survival (high, 95%; low, 94%), or patient survival (high, 95%; low, 94%). 6) Measurement of the total amount of S-HLA-I, containing yet undefined ratios of both donor and recipient S-HLA-I, cannot be used to predict a state of tolerance in liver transplant recipients.

Enzyme-Linked Immunosorbent Assay↗