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Biomedical subjects

L Jeffers

Publications and source records attributed to L Jeffers.

At least 19 recordsLinked to original sources
PubMed2005

Liver enzymes elevation after HAART in HIV-HCV co-infection.

Hepatitis C virus (HCV) co-infection is common among human immunodeficiency virus (HIV) patients. The incidence and risk factors associated with hepatotoxicity in this population after high active antiretroviral therapy (HAART) is initiated are still not well-understood. We argued to evaluate the incidence and risk factors associated with liver enzyme elevation (LEE) and their clinical significance. A retrospective chart review of patients who started HAART and had follow up at our centre for at least 1 year was undertaken. The frequency and severity of alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation after treatment initiation were investigated and searched for clinical manifestations. Between January 1996 and March 2002, 85 HIV-HCV co-infected patients began HAART and continued follow up for at least 1 year. The incidence of severe toxicity [grades 3 + 4 LEE: >5 and >10 times the upper limit of normal (ULN) of ALT or AST] was calculated at 4% per person-years. There were no clinical manifestations of liver toxicity, and patients continued their treatment with a trend towards a decrease of their enzymes. No statistical differences in opportunistic infections or mortality were evident. The variables associated with severe hepatotoxicity were a higher baseline AST, higher international normalized ratio (INR) and lower albumin. A baseline AST < 2.1 ULN had a negative predictive value of 92% of leading to severe hepatotoxicity. In HIV-HCV co-infected patients therefore, the group at a higher risk of developing higher transaminase elevations is the one with a higher baseline AST, higher INR and lower albumin.

Adult↗
PubMed2001

The role of laparoscopy in the evaluation of liver transplant patients.

Diagnostic laparoscopy is safe and effective in the diagnosis of liver diseases. In liver transplant patients, laparoscopy has a valuable role in the early detection and staging of hepatic lesions. Laparoscopy is helpful in the early detection and staging of primary hepatic malignancy. With the increase of liver transplantation around the world, gastroenterology and hepatology programs should re-evaluate the role of laparoscopy in the diagnosis of liver diseases.

Contraindications↗
PubMed2001

Benign and solid tumors of the liver: relationship to sex, age, size of tumors, and outcome.

From 1983 through 1997, our center diagnosed 130 cases of benign neoplasms: 27 with focal nodular hyperplasia (FNH), 25 with hepatic adenoma, 71 with cavernous hemangioma, and seven with mixed tumors of different diagnoses. Most often these lesions were seen in females [female-to-male ratio (f/m): 5.5/1]. Hepatic adenomas and mixed tumors were seen exclusively in females and FNH predominantly in females (f/m: 26/1). Hemangiomas, however, were not uncommon in men (f/m: 52/19) relative to the other tumors (P < 0.001). Furthermore patients with hemangioma were older (mean age: 49 years) whereas patients with hepatic adenoma, FNH, and mixed tumors were often younger (mean age: 33, 35, and 44 years respectively; P < 0.004). Oral contraceptive steroid use was related by 21 of 25 patients (84%) with hepatic adenoma, 22 of 26 (85%) females with FNH, five of seven (71%) females with mixed tumors, and 10 of 52 (19%) patients with hemangioma. Ninety-five of the 130 patients (73%) had one or more symptoms. There was no statistically significant correlation between symptoms and the size of the lesion, the final diagnosis, and whether there were solitary or multiple masses. Three of 25 (12%) with hepatic adenoma presented with rupture, and one of 27 (4%) with FNH had such a consequence. None of the hemangiomas presented with rupture or progressed to such a state. One patient with hepatic adenoma (4%) had a focus of malignancy. Surgical removal of benign tumors was performed in 82 of 130 patients (63%), and there was one operative mortality (1.2%) in a patient who had a caudate lobe FNH. The types of surgical procedures included segmentectomy (62%), lobectomy (34%), and trisegmentectomy (4%). In two of 84 patients who had undergone laparotomy resection was not technically possible. Resection is recommended in all cases of hepatic adenoma because of fear of rupture or associated focus of malignancy. FNH was not observed to undergo a malignant transformation and will rarely rupture. Surgery is only recommended for symptomatic hemangioma, and size of the lesion is not a criterion for excision.

Adenoma, Liver Cell↗
PubMed2000

Hepatocellular carcinoma: an emerging problem with hepatitis C.

Hepatocellular carcinoma (HCC) is emerging as a major problem in the United States, primarily due to the development of liver cancer in patients with cirrhosis secondary to the hepatitis C virus. The diagnosis of HCC in patients with underlying cirrhosis can be achieved at an early stage if appropriate diagnostic measures are pursued by primary care physicians and gastroenterologists. African Americans are particularly vulnerable in developing HCC since their response to current therapy for chronic hepatitis C is less than optimal.

California↗
PubMed1999

The significance of hepatitis G virus in serum of patients with sporadic fulminant and subfulminant hepatitis of unknown etiology.

Excluding acute hepatic failure caused by drugs, the etiology of fulminant hepatitis (FH) remains unknown in many patients. There are conflicting data about a possible pathogenic role for the hepatitis G virus (HGV) in patients with cryptogenic fulminant hepatitis (non-A-E FH). We investigated the presence of circulating HGV in 36 patients with well-documented non-A-E fulminant and 5 patients with subfulminant hepatitis from 3 geographic locations in the United States. Serum HGV RNA was determined by reverse transcriptase-polymerase chain reaction using primers from the NS5 region of the HGV genome. HGV RNA was also measured before and after liver transplantation in 5 patients and at different time points in 7 patients. Serum samples were recoded and reanalyzed for HGV RNA using different primer sets to assess the validity of the HGV RNA assay. HGV was present in serum of 14 of the 36 patients (38.8%) with non-A-E fulminant hepatitis. Twenty percent of patients from the Northeast, 11% of the patients from the Southeast, and 50% from the Mid-Atlantic regions of the United States had circulating HGV RNA. The use of therapeutic blood products was significantly associated with the presence of serum HGV RNA (P <.02). Retesting for HGV RNA with different primers was positive in all but 1 case. HGV RNA is not causally related to non-A-E fulminant hepatitis. The finding of HGV RNA in serum from these patients is likely related to the administration of blood product transfusion after the onset of fulminant hepatitis.

Adolescent↗
PubMed1999

Multiple genetic alterations, 4q28, a new suppressor region, and potential gender differences in human hepatocellular carcinoma.

Primary hepatocellular carcinomas (HCCs) of different etiologies were studied to determine the rate of alteration of several genetic regions previously associated with the HCC phenotype. The focus of our study was to identify the frequency of genetic alterations within individual HCCs and their distribution among male and female cases. Genetic differences were evaluated between DNA isolated from tumor (T) and corresponding non-tumor (N) tissue using short tandem repeat (STR)-microsatellites and restriction fragment length polymorphism (RFLP) analyses. Twenty-eight HCC cases were studied with polymorphic markers from different parts of the genome. Three or more loci were identified with genetic alterations from 28 loci tested in 63% of HCC cases. The highest frequency of alteration occurred in the chromosome regions 1p36, 13q14, 17p13, and the 4q28 region identified in HCCs for the first time. High loss of heterozygosity (LOH) in 1p36, 4q28, 13q14, and 17p13 regions indicates important HCC suppressors within the regions. The study documents no association between cause and specific genetic change or their frequency in HCCs analyzed. The data document a significant gender distortion for genetic alteration in chromosome 13q14 and 17p13 regions and a concordant gender alteration rate in the 1p36 and 4q28 regions. An overall higher frequency of genetic alterations was identified in male cases. Future study with an extended number of HCC cases should substantiate the frequency of alteration between genders and identify tentative suppressors in the 1p36 and 4q28 regions.

Adult↗
PubMed1999

Experience with staging laparoscopy in pancreatic malignancy.

BACKGROUND: The role of diagnostic laparoscopy in the staging of abdominal malignancies is not well defined. METHODS: We retrospectively reviewed the usefulness of diagnostic laparoscopy as a staging procedure in pancreatic malignancy. This experience between February 1988 and May 1997 involves 109 cases of suspected or proven pancreatic malignancy. All laparoscopies were performed with the patient under conscious sedation and local anesthesia in an endoscopy suite. RESULTS: Of the 109 patients with pancreatic cancer, 45 (42%) had metastatic disease. The use of computed tomography (CT) alone revealed the existence of liver metastases in 10 of 109 (9%) patients, which were confirmed laparoscopically. The further use of laparoscopy identified metastases in 29 more cases: hepatic, 23; hepatic and peritoneal, 3; peritoneal and mesenteric, 1; and mesenteric, 2. CT in conjunction with laparoscopy therefore revealed metastatic liver, peritoneal, or mesenteric lesions in 39 of 109 (36%) patients with pancreatic cancer. After staging laparoscopy, 67 of 69 patients underwent laparotomy. Metastatic disease was identified at laparotomy in 6 more patients; however, only 4 of these patients had metastases to the liver whereas 2 had metastases to the peripancreatic lymph nodes. Therefore, in patients with pancreatic malignancy, the negative predictive value for the diagnosis of metastases to the liver, peritoneum or mesentery was 94% (61 of 65 patients). The positive predictive value of laparoscopy alone for the detection of metastatic disease to the liver, peritoneum, or mesentery was 88% (29 of 33 patients). Laparoscopy was successfully performed without complications in all patients with pancreatic cancer; however, one had a technically unsatisfactory examination. The overall rate of resectability after staging by imaging studies and laparoscopy was 57% (35 of 61 patients). CONCLUSIONS: In patients with a negative CT for metastases, laparoscopic identification of metastases avoided unnecessary laparotomy in 29 of 99 (29%) patients with pancreatic cancer. Staging laparoscopy is indicated in all cases of pancreatic malignancy before an attempt at a surgical cure.

Aged↗
PubMed1999

Hepatitis C virus genotypes and viremia and hepatocellular carcinoma in the United States.

OBJECTIVE: Hepatitis C virus (HCV) is a well recognized cause of hepatocellular carcinoma (HCC). The pathogenic significance of HCV genotypes in hepatocarcinogenesis is undefined. The aim of this study was to investigate the genotypic distribution and viremic level of HCV in patients with HCV-associated cirrhosis with or without HCC. METHODS: A total of 28 HCV-infected patients with HCC (HCC+) and 38 patients with HCV-associated cirrhosis without HCC (HCC-) were studied. HCV genotype was assessed by the genotype-specific polymerase chain reaction (PCR) method of Okamoto and restriction fragment length polymorphism (RFLP) of the 5' untranslated region (5' UTR). Hepatitis C viremia was quantitated with the branched-chain DNA (bDNA) assay. RESULTS: Using the Okamoto method, we found genotype 1b in 64% of the HCC+ group and 74% of the HCC- group, 36% of the HCC+ group and 16% of the HCC- group were coinfected with a combination of genotype 1b and another genotype. Using the RFLP method, we found genotype 1b in 41% of the HCC+ group and in 24% of the HCC- group. Other genotypes accounted for 18% of the HCC+ group and 55% of the HCC- group; no combination genotypes were identified. Poor concordance occurred between the two genotyping methods. Mean bDNA levels were not significantly different between the two groups. CONCLUSIONS: Our study demonstrates that no particular HCV genotypes were associated with HCC and genotype did not appear to influence the development of HCV-associated HCC.

Carcinoma, Hepatocellular↗
PubMed1998

Percutaneous dilatation of biliary strictures through the afferent limb of a modified Roux-en-Y choledochojejunostomy or hepaticojejunostomy.

BACKGROUND: This report is a 13-year prospective evaluation of percutaneous balloon dilatation of benign biliary strictures through the subcutaneous or subfascially positioned afferent limb of a choledocho or hepaticojejunostomy in 30 patients. DATA SOURCE: Twenty-seven strictures developed after a common duct injury sustained at the time of cholecystectomy, two after hepatectomy reconstruction for trauma and one following a gastrectomy. Twelve injuries (40%) were recognized at operation. Of the 18 patients where the injury was unrecognized at the time of operation, 8 had not been reoperated at the time of referral, 7 had late repairs by the referring physician, and 3 had late repairs at our institution. The follow-up is 1 to 13 years. RESULTS: There has been 1 late death and 6 patients are lost alive. The jejunal-limb was accessed 50 times with two minor and no major complications. There have been two parajejunal hernia repairs, but there have not been any reoperations for recurrent biliary strictures. CONCLUSIONS: Benign biliary strictures can be effectively managed by repeat balloon dilatations thru the afferent limb of a choledocho or hepaticojejunostomy, thus eliminating the need for repeat surgical interventions.

Adult↗
PubMed1998

Detection of anti-hepatitis C virus antibodies in patients undergoing dialysis by utilizing a hepatitis C virus 3.0 assay: correlation with hepatitis C virus RNA.

Hepatitis C virus (HCV) infection is endemic in long-term dialysis units. We assessed the performance of a recently developed HCV 3.0 assay for the detection of HCV antibodies in patients undergoing dialysis. The study evaluated 128 patients undergoing long-term maintenance hemodialysis. Anti-HCV was detected by 2.0 and 3.0 enzyme immunoassay (EIA). Results were confirmed with recombinant immunoblot assays (RIBA 2.0 and RIBA 3.0). HCV RNA was detected by using reverse transcriptase-polymerase chain reaction (RT-PCR). Thirty-two patients (25%) were HCV EIA 2.0 positive. Of these, 1 was RIBA 2.0 negative (PCR positive), 3 were indeterminate (3 PCR positive), and 28 were positive (23 PCR positive). Thirty-five (27%) were HCV EIA 3.0 positive. One was RIBA 3.0 negative (PCR positive), 1 was indeterminate (c33c, PCR positive), and 33 were positive (27 PCR positive) by RIBA 3.0. Thus only 1 PCR-positive patient was negative with RIBA 2.0 and 3.0 assays. Two of the 3 RIBA 2.0 indeterminate samples were positive with RIBA 3.0. One remained indeterminate but was HCV RNA positive. In summary, HCV 3.0 EIA detected 4 additional viremic patients but was positive in 6 PCR-negative subjects. A high correlation of the presence of antibody to c33c with HCV RNA (28 of 34, 82%) was found, and it was found in all anti-HCV positive samples and in 1 indeterminate sample. We conclude that the HCV EIA 3.0 test with the supplemental confirmatory RIBA 3.0 test may improve the sensitivity for the detection of anti-HCV. Nevertheless, in potentially immunocompromised patients undergoing dialysis, PCR continues to be the only reliable test for detecting viremia.

Adult↗
PubMed1997

Effects of the polyamine analogues BE-4-4-4-4, BE-3-7-3, and BE-3-3-3 on the proliferation of three prostate cancer cell lines.

PURPOSE: Polyamines are biologic cations necessary for normal cell growth. Polyamine analogues have been shown to be effective inhibitors of tumor growth. We tested the effect of the polyamine analogues 1,1 9-bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4), N1,N11-bis(ethyl)norspermine (BE-3-3-3) and 1,15-bis(ethylamino)-4,12-diazapentadecane (BE-3-7-3) on the growth of the prostate cancer cell lines DU145, LNCaP and PC-3 in vitro. We also tested the effect of BE-4-4-4-4 on androgen-independent DU145 cells in vivo via a nude mouse xenograft model. METHODS: In vitro, cell proliferation was measured using a DNA assay or a colony-formation assay. In vivo, mice were given saline or BE-4-4-4-4 3 mg/kg or 5 mg/kg intraperitoneally twice daily on days 7-10 and 14-17 (cycle 1), days 49-52 and 56-59 (cycle 2) and days 91-94 and 98-101 (cycle 3). RESULTS: The proliferation of DU145, LNCaP and PC-3 prostate cancer cell lines was inhibited in a dose-dependent manner by BE-4-4-4-4. Intracellular putrescine, spermidine and spermine levels in all three cell lines declined after only 24 h exposure to BE-4-4-4-4 in vitro. Animals receiving BE-4-4-4-4 showed inhibition of tumor growth which continued throughout the experiment with 74% (3 mg/kg) and 81% (5 mg/kg) growth inhibition seen on day 101. No overt toxic reactions besides weight loss were observed in BE-4-4-4-4-treated animals. Tumor tissue from animals treated with BE-4-4-4-4 showed a dose-dependent decrease in spermidine and spermine levels but no decline in putrescine levels as compared with control. BE-4-4-4-4 levels were highest in tumors on day 63 with levels reaching 0.33 and 1.45 nmol/mg protein from animals treated at the 3 mg/kg and 5 mg/kg doses, respectively. CONCLUSION: These results show the polyamine analogues BE-4-4-4-4, BE-3-3-3 and BE-3-7-3 to be effective inhibitors of prostate cancer cell growth in vitro and BE-4-4-4-4 to be an effective inhibitor of DU145 cells in vivo with minimal toxicity.

Animals↗
PubMed1997

Recombinant factor VIIa corrects prothrombin time in cirrhotic patients: a preliminary study.

BACKGROUND & AIMS: Cirrhotic patients with a prolonged prothrombin time (PT) are known to have low levels of factor VII. Because the current modalities to correct this problem are not ideal, recombinant factor VIIa (rFVIIa) may be useful in correcting the prolonged PT observed in the coagulopathy of cirrhosis. The aim of this study was to evaluate the effectiveness of rFVIIa in nonbleeding volunteer patients with the coagulopathy of cirrhosis. METHODS: A preliminary, single-center, dose-escalation trial was performed. Cirrhotic patients with a PT of > 2 seconds above the upper limit of the reference value received an intramuscular injection of vitamin K. Ten patients whose PT did not correct to within 2 seconds above the control of the upper limit of the reference value were given three successive dosages of rFVIIa (5, 20, and 80 micrograms/kg) during a 3-week period. RESULTS: The mean PT transiently corrected to normal in all three dosage groups. No adverse effects were noted. There was no evidence of the induction of disseminated intravascular coagulation. CONCLUSIONS: This preliminary trial shows rFVIIa to be effective in transiently reversing the prolonged PT in a select group of nonbleeding cirrhotic patients. These preliminary observations support conducting a large-scale efficacy trial.

Adult↗
PubMed1997

Laparoscopic evaluation of liver disease in chronic renal failure prior to renal transplantation.

BACKGROUND: Diagnostic laparoscopy with liver biopsy has been shown to be safe and effective in the evaluation of patients with chronic liver disease. Patients with end-stage renal disease may be more prone to bleeding complications secondary to liver biopsy as a result of multiple factors directly related to their underlying renal condition. METHODS AND PATIENTS: From January 1994 to June 1996, 16 patients with end-stage renal disease and hepatic dysfunction (6 women and 10 men) underwent diagnostic laparoscopy with liver biopsy prior to renal transplantation at the University of Miami School of Medicine. Laparoscopy was performed using a 5 mm video laparoscope with a left paramedian approach. The mean patient age was 46 years. Fourteen patients had chronic hepatitis C with a reactive anti-HCV by ELISA; one patient had chronic hepatitis B with reactive HBsAg, and one patient was co-infected with both hepatitis B and C viruses. RESULTS: Two patients developed hypotension related to the procedure and one patient developed an intra-abdominal hemorrhage 5 days after laparoscopy that did not require surgical intervention. Biopsy findings were as follows: 13 patients had mild chronic hepatitis; 2 patients had chronic hepatitis with bridging fibrosis; and 1 patient was cirrhotic. Prior kidney transplantation or peritoneal dialysis did not preclude the performance of laparoscopy. CONCLUSION: Diagnostic laparoscopy can be safety performed in patients with end-stage renal disease with acceptable morbidity and mortality.

Abdomen↗
PubMed1996

Early graft loss secondary to massive hemorrhagic necrosis following orthotopic liver transplantation. Evidence for cytokine-mediated univisceral Shwartzman reaction.

Massive hemorrhagic necrosis (MHN) of the liver following orthotopic liver transplantation (OLT) occurs infrequently during an otherwise uneventful recovery 1 week after OLT. It is characterized by fever and sudden deterioration of allograft function leading to failure in the absence of vascular thrombosis. The etiology is unknown, although it is usually preceded by some degree of allograft rejection. Between 6 and 8 days after OLT, four patients (out of 150) became febrile, hypotensive, and experienced a rapid rise in transaminases within 48 hr. Two patients had evidence of mild rejection; the other two had moderate to severe acute cellular rejection. All patients were ABO identical, crossmatch negative. Bolus steroids were given followed by OKT3 in the two patients with severe rejection. Although sepsis was suspected, antibiotic therapy did not ameliorate the clinical course. Each patient progressed to MHN with severe centrilobular necrosis and variable portal infiltrate. High levels of interferon-gamma and tumor necrosis factor-alpha occurred prior to the rise in transaminases in each MHN patient (155 +/- 39 pg/ml and 414 +/- 201 pg/ml, respectively) compared with levels in OLT patients with severe rejection (14 +/- 4 pg/ml and 26 +/- 5 pg/ml, respectively, P < 0.05). These data support the concept of a cytokine-mediated inflammatory response leading to a univisceral Shwartzman reaction in the transplanted liver. Early recognition of this syndrome and retransplantation are critical for survival.

Adult↗
PubMed1995

The role of transjugular intrahepatic portosystemic shunt for treatment of portal hypertension and its complications: a conference sponsored by the National Digestive Diseases Advisory Board.

TIPS is a new and exciting modality for treatment of portal hypertension and its complications. Indications for TIPS remain to be better defined in terms of efficacy and cost-benefit in relationship to other established modes of therapy of portal hypertension. Prospective, randomized controlled trials are needed for these comparisons. Until the role of TIPS in the routine management of the complications of portal hypertension is better defined, TIPS should be used only in situations in which conventional medical and endoscopic therapies have failed.

Humans↗