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Biomedical subjects

A Colantoni

Publications and source records attributed to A Colantoni.

At least 37 records · Page 2Linked to original sources
PubMed2000

Immunohistochemical analysis of estrogen receptors in breast carcinomas using monoclonal antibodies that recognize different domains of the receptor molecule.

Estrogen receptor (ER) analysis was performed in 46 primary breast carcinomas using four monoclonal antibodies (MABs) to ER (AER311, ER1D5, LH1, and LH2), each of which recognizes a distinct domain of the receptor protein. ER was expressed as the percentage of positively stained tumor cells. Statistical analysis was performed using the SPSS/PC+ program to set the cut off of positivity and the prognostic value of each MAB. A positivity >30% for each MAB possessed the best sensitivity/specificity ratio and was used as the cut-off value. Multivariate discriminant analysis showed that MABs AER311, ER1D5, and LH2 had significant prognostic value. Fourteen tumors showed positivity for these three MABs; 17 were positive for one or two of the three MABs, and 15 were negative for all three MABs. Survival analysis showed that patients with tumors negative for all three of these MABs had progression of the disease within 8 years from the diagnosis of the tumor, whereas all patients with tumors positive for all three MABs were alive 13 years after surgery. A significant correlation (P = 0.0006) between tumor grading and ER status was found; 71% of the tumors that were positive for all three MABs were grade 1, whereas tumors negative for all three MABs were mostly grades 2 and 3. No significant relationship was observed between ER status and tumor size. A significant correlation (P = 0.008) between lymph node status and ER was found; breast tumors positive for all three MABs were in the majority (92.9%) of cases pNO, whereas 67% of tumors negative for all three MABs were pN1. Results from the present study suggest that the use of a panel of MABs that target distinct epitopes within domains of the ER protein could offer a better approach for assessing the ER status in breast cancer patients, because it enables the recognition of breast tumors with intact or structurally defective ER proteins.

Adult↗
PubMed1999

Can hepatitis B core antibody positive livers be used safely for transplantation: hepatitis B virus detection in the liver of individuals who are hepatitis B core antibody positive.

A major impediment to the wider application of clinical liver transplantation is the paucity of acceptable organs. Most centers refuse organs that come from donors who are hepatitis B core antibody positive because of a fear of transmission of hepatitis B virus (HBV) infection to the recipient. The risk related to the use of such donor organs has never been assessed in an ordered manner. The presence or absence of polymerase chain reaction detectable HBV-DNA in liver tissue of individuals undergoing liver biopsy for clinical reasons was assessed in 133 consecutive patients. A total of 8.2% of these livers resulted positive for HBV-DNA; interestingly the rate was higher among those who were hepatitis B surface antibody positive (12.5%) as compared to those without detectable hepatitis B surface antibody (5.7%). These data provide measures of putative risk for HBV infection in liver transplant recipients associated with the use of organs obtained from a hepatitis B core antibody positive donor.

Adult↗
PubMed1998

Prevention of reoxygenation injury by sodium salicylate in isolated-perfused rat liver.

Sodium salicylate can be used as a chemical trap for hydroxyl radicals, the most damaging reactive oxygen species. Because reactive oxygen species are involved in the pathogenesis of hepatic hypoxia/reoxygenation injury, the goal of this study was to determine if trapping hydroxyl radicals with salicylate would prevent or at least ameliorate such injury. Isolated rat livers, continuously perfused with Krebs-Henseleit bicarbonate buffer in the presence or absence of salicylate (2 mM), were exposed, after 30 min of recovery, to 60 min of hypoxia, followed by 30 min of reoxygenation. During reoxygenation, control livers experienced a sharp increase in the rate of lactic dehydrogenase release, taken as index of cell injury, protein carbonyl content, and malondialdehyde, taken as index of protein oxidation and lipid peroxidation, respectively. The presence of salicylate in the solution perfusion significantly reduced the rate of lactic dehydrogenase release, protein carbonyl content, and malondialdehyde production during reoxygenation. Hepatic histology documented a significantly reduced cell injury in salicylate-perfused livers compared to control livers. These data suggest that the hydroxyl radical chemical trap sodium salicylate, acting as an antioxidant, may represents an effective agent to reduce liver injury due to hypoxia/reoxygenation in a model of isolated-perfused rat liver.

Animals↗
PubMed1998

Q-T interval prolongation in cirrhosis: prevalence, relationship with severity, and etiology of the disease and possible pathogenetic factors.

Prolonged Q-T interval predicts severe arrhythmias and sudden death, and has been shown to occur in alcoholic liver disease and cirrhotic patients who are candidates for liver transplantation. This study first evaluated the prevalence of prolonged Q-T interval in a large population of unselected patients with cirrhosis, and assessed the relationship between abnormal Q-T, etiology, and severity of liver disease and mortality of patients. Possible causes of Q-T abnormality were also explored. Ninety-four patients with cirrhosis without overt heart disease and 37 control subjects with mild chronic active hepatitis were enrolled. Rate-corrected Q-T interval (Q-Tc) was assessed along with routine liver tests, Child-Pugh score, serum bile salts, electrolytes and creatinine, plasma renin activity, aldosterone, norepinephrine, atrial natriuretic factor and, gonadal hormones. Q-Tc was longer in patients with cirrhosis than in controls (440.3 +/- 3.2 vs. 393.6 +/- 3.7 ms; P < .001) and prolonged (> 440 ms) in 44 patients (46.8%) and 2 controls (5.4%; P < .001). Q-Tc length was not influenced by the etiology of cirrhosis and correlated with Child-Pugh score (r = .53; P < .001), liver tests such as prothrombin activity, and serum concentrations of albumin and bilirubin, plasma bile salts, and plasma norepinephrine. Multivariate analysis showed that only Child-Pugh score and plasma norepinephrine were independently correlated with Q-Tc duration. Over a median follow-up period of 19 months (range, 2-33 months), patients with Q-Tc longer than 440 ms had a significantly lower survival rate than those with normal Q-Tc. Q-T interval is frequently prolonged in patients with cirrhosis, regardless the etiology of the disease, worsens in parallel with the severity of the disease, and may have an important prognostic meaning. In addition to other undefined factors related to the severity of cirrhosis, sympathoadrenergic hyperactivity may play a pathogenetic role.

Electrocardiography↗
PubMed1998

Effect of ischemia--reperfusion on heat shock protein 70 and 90 gene expression in rat liver: relation to nutritional status.

Heat shock proteins are intracellular proteins associated with a generalized response of cells to stress. The purpose of this study was to assess RNA levels of heat shock protein 70 and 90 in fed or fasted rat livers during ischemia-reperfusion. Northern blot analysis of heat shock proteins was performed. Adenosine triphosphate and glutathione were assessed. In baseline conditions, livers of fasted rats showed a twofold increase in mRNA for both heat shock proteins and 38% and 43% reductions in adenosine triphosphate and glutathione, respectively, when compared with organs from fed rats. After ischemia, livers of fasted rats presented a twofold decrease in heat shock protein mRNA, while no changes were observed in livers of fed rats; reduced glutathione and adenosine triphosphate decreased 55% and 50% in fasted livers and 25% and 20% in fed organs, respectively. After 120 min of reperfusion, heat shock protein mRNA rose threefold in fasted livers, while a slight decrease was observed in the fed group; reduced glutathione and adenosine triphosphate returned to 65% and 70% of baseline values in fasted livers and 85% and 90% in fed organs, respectively. In conclusion, the nutritional status affects heat shock protein expression determined by reperfusion. The reduced antioxidant status leading to increased oxidative stress could be the mechanism underlying the phenomenon.

Adenosine Triphosphate↗
PubMed1998

Pathogenesis of hepatitis B and C-induced hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is estimated to have an annual worldwide incidence of 0.25 to 1.2 million new cases per year. Both the prevalence and incidence of HCC vary markedly as a function of geography and the local prevalence of chronic viral hepatitis. Both chronic hepatitis B and chronic hepatitis C are recognized as risk factors for HCC. The prevalence of cirrhosis in individuals with HCC and chronic hepatitis B or C is reported to be 80.9% and 75.8%, respectively. HCC occurs at a lower rate in chronic viral hepatitis in the absence of cirrhosis. Moreover, hepatitis C virus (HCV) rather than hepatitis B virus (HBV) is associated with the majority of non-cirrhotic cases of HCC. It is probable that the ongoing process of hepatocyte necrosis and liver cell renewal coupled with inflammation, which is characteristic of chronic viral hepatitis, causes not only nodular regeneration and cirrhosis but also progressive genomic errors in hepatocytes as well as unregulated growth and repair mechanisms leading to hepatocyte dysplasia and, in some cases, hepatic carcinoma. Current concepts concerning virus-induced HCC are reported and discussed in the following review.

Carcinoma, Hepatocellular↗
PubMed1998

Ageing affects anoxia/reoxygenation injury in rat hepatocytes.

BACKGROUND: The reoxygenation phase after a period of anoxia leads to oxyradical formation, responsible for damage to cell membranes. Ageing is associated with functional and structural changes in liver cells, which modify their sensitivity to reoxygenation injury. The aim of this study was to determine the effects of ageing on the sensitivity of hepatocytes to anoxia/reoxygenation. METHODS: Oxyradical formation and cell injury were evaluated in hepatocytes isolated from rats of different ages exposed to 2 h of anoxia and 1 h of reoxygenation. Anion superoxide was measured by lucigenin-enhanced chemiluminescence, hydrogen peroxide by luminol-enhanced chemiluminescence, and cell damage by lactate dehydrogenase (LDH) release. RESULTS: During anoxia, oxyradical production dropped to background levels in both groups. LDH release was significantly greater in ageing hepatocytes. During reoxygenation, a massive generation of anion superoxide and hydrogen peroxide, followed by a sharp increase in LDH release, was observed in both groups. However, both oxyradicals and cell injury were significantly greater in liver cells obtained from ageing rats. CONCLUSIONS: The data confirm that hepatocytes produce high levels of free radicals during post-ischemic reoxygenation and suggest that ageing cells are more sensitive to reperfusion injury.

Aging↗
PubMed1998

Immunosuppressive drug-induced leukoencephalopathy in patients with liver transplant.

Organ transplantation has become a practical and effective option for patients with acute and/or chronic irreversible organ disease. However, solid organ transplantation is associated with many different complications which depend upon the specific surgical procedure and/or confounding medical problems (e.g. rejection, infection, adverse effect of immunosuppressive agents) experienced by a given patient. Tacrolimus and cyclosporin A are immunosuppressive drugs used to prevent rejection following allogeneic solid organ transplantation. Adverse events are common with both drugs and include long-term organ dysfunction, opportunistic infections, haematopoietic alterations, nephrotoxicity and neurotoxicity. Neurological complications, both central and peripheral, occur in 10-42% of transplant recipients using either of these two immunosuppressive agents. Two cases of reversible posterior leukoencephalopathy manifested by headache, nausea and seizures associated with the use of immunosuppressive drugs following liver transplantation are reported.

Adolescent↗
PubMed1997

Rat hepatocytes isolated from alcohol-induced fatty liver have an increased sensitivity to anoxic injury.

The aim of this study was to determine whether rat hepatocytes isolated from steatotic or nonsteatotic livers have different thresholds for injury due to anoxia-reoxygenation. Rats were fed ethanol or control diets for 8 weeks. Histology showed that more than 75% of the hepatocytes in alcohol-fed and less than 3% in control animals contained fatty vacuoles. The glycogen content was significantly reduced in steatotic livers. Isolated hepatocytes were cast in agarose gel threads and perfused with Krebs-Henseleit bicarbonate buffer. Cell viability was determined by Trypan Blue (TB) exclusion; cell injury was determined by lactate dehydrogenase (LDH) release; and superoxide anion (O2.-) was determined by lucigenin-enhanced chemiluminescence (LCL). During the pre-anoxic basal perfusion the following occurred: viability was 86% +/- 1% and 85% +/- 1%; LDH release was 16 +/- 3 and 15 +/- 3 mU/min; and LCL was 4 +/- 1 and 5 +/- 1 nA in steatotic and nonsteatotic hepatocytes, respectively. Cell viability decreased slightly under 4 hours of aerobic perfusion without differences between the two groups. In contrast, fatty hepatocytes died much faster than did control hepatocytes during anoxia; after 3 hours viability was 17% +/- 8% vs. 60% +/- 2% (P < .001), respectively. With reoxygenation following 2 hours of anoxia, the changes in viability, in LDH release, and in LCL were similar in both groups. These results indicate that in hepatocytes isolated from alcohol-fed rats when compared with control hepatocytes: 1) cell viability under aerobic conditions is not influenced; 2) anoxic injury is significantly increased; 3) a reduction in the hepatic glycogen stores, which may contribute to the enhanced sensitivity to anoxia, can be demonstrated; and 4) O2.- generation and cell injury occurring immediately after reoxygenation do not appear to be affected.

Animals↗
PubMed1997

Daily profile of plasma endothelin-1 and -3 in pre-ascitic cirrhosis: relationships with the arterial pressure and renal function.

BACKGROUND/AIMS: Measurements of plasma endothelin-1 and -3 in pre-ascitic cirrhosis have provided controversial results. Similarly, the role of the endothelin system in the pathogenesis of volume and hemodynamic disturbances of cirrhosis is still debated. To provide a further insight into this issue, we assessed the daily fluctuations of plasma endothelins and their relationship with arterial pressure and renal function in pre-ascitic cirrhosis. METHODS: Endothelin-1 and -3, plasma renin activity, atrial natriuretic peptide, noradrenaline and mean arterial pressure were measured at 11 pm, 7 am, 9 am and 6 pm in 10 patients with pre-ascitic cirrhosis and in 10 healthy subjects on normal sodium diet and carrying on their usual activities (supine from 10 pm to 7 am, standing and mobile after 7 am). Glomerular filtration rate and daily renal sodium excretion were assessed during the supine period, and from 7 am to 12 am and from 12 am to 10 pm during the standing period. RESULTS: Endothelin-1 was higher in patients than in control subjects (p=0.000) and did not change during the study. Endothelin-3 was also higher in patients (p=0.002) and showed slight fluctuation in control subjects. The mean daily level of plasma renin activity was lower (p=0.016) and that of atrial natriuretic peptide higher (p=0.000) in patients with cirrhosis. Norepinephrine and mean arterial pressure did not differ significantly between the two groups. No correlations were found between endothelins and either hemodynamic or neuro-hormonal and renal function parameters in the two groups. CONCLUSIONS: Despite the presence of increased effective volemia (as suggested by the reduced plasma renin activity and elevated atrial natriuretic peptide) and normal adrenergic tone, patients with pre-ascitic cirrhosis show elevated levels of endothelin-1 and endothelin-3 throughout the day. In early cirrhosis circulating endothelins, although elevated, do not appear to play a more prominent role in setting arterial pressure than in normal subjects, and endothelin elevation is not detrimental to renal function.

Adult↗
PubMed1997

Proteins but not nucleic acids are molecular targets for the free radical attack during reoxygenation of rat hepatocytes.

Isolated rat hepatocytes generate large amounts of reactive oxygen species and suffer a significant cell injury during postanoxic reoxygenation. The aim of this study was to determine whether oxidation of proteins and nucleic acids occurs during reoxygenation and whether their damage is related to the development of hepatocyte injury. Isolated perfused rat hepatocytes were exposed sequentially to 1 h of aerobic control, 2.5 h of anoxia, and 2 h of reoxygenation. Protein oxidation was determined by measuring the hepatocyte protein carbonyl content. DNA and RNA oxidation was assessed by measuring the 8-hydroxydeoxyguanosine and 8-hydroxyguanosine adducts, respectively. The control preanoxic carbonyl content was 6.48 +/- 1.03 nmol/mg protein. The preanoxic 8-8 hydroxydeoxyguanosine and 8-hydroxyguanosine levels were 4.76 +/- 1.22 pmol/ml and 14.19 +/- 2.17 pmol/ml, respectively. During anoxia, protein and nucleic acid oxidation did not change significantly. With reoxygenation, the protein carbonyl content increased significantly within 30 min, reaching a value of 10.25 +/- 1.58 nmol/mg. The nucleic acid oxidation level remained stable. Perfusion with 100 muM of during reoxygenation abolished protein oxidation. These results indicate that in rat hepatocytes during the early phase of reoxygenation: (1) the protein oxidation level increased significantly above the preanoxic aerobic values; (2) DNA and RNA oxidation does not appear to occur; and (3) free metal-mediated free radical reactions are involved in the oxidative protein damage.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1997

Intermittent anoxia reduces oxygen free radicals formation during reoxygenation in rat hepatocytes.

The sensitivity of liver cells to anoxia is a major problem afflicting liver preservation and transplantation. Intermittent ischemia has been proposed to reduce reperfusion injury. The aim of the study was to assess oxygen free radical formation and cell injury during continuous or intermittent anoxia/reoxygenation in rat hepatocytes. Anion superoxide was measured by lucigenin-enhanced chemiluminescence and cell damage by LDH release and trypan blue uptake. During anoxia, superoxide generation dropped to background level in both groups; trypan blue uptake and LDH release, which increased progressively, were significantly greater in hepatocytes exposed to continuous compared to intermittent anoxia. During reoxygenation, a massive generation of superoxide anion formation, followed by a sharp increase in LDH release, was observed in both groups. However, both oxyradical generation and cell injury were significantly greater in cells exposed to continuous compared to intermittent anoxia. The data, showing that intermittent oxygen deprivation reduce liver cell injury and oxygen free radical formation determined by anoxia/reoxygenation, suggest a novel possible approach to the reduction of reperfusion injury.

Animals↗
PubMed1997

Interferon treatment of cirrhotic patients with chronic hepatitis C.

Hepatitis C virus (HCV) infection is one of the more important infectious diseases yet to be conquered. An estimated 3.5 million people in the USA have chronic HCV. Each year, 8000 to 10000 of these chronically infected patients die of a liver-related complication of their infection. The introduction of effective blood screening assays has resulted in a remarkable decrease in the incidence of post-transfusion HCV infection. Nonetheless it is essential to have a treatment programme for chronic HCV disease that prevents the development and the progression of compensated cirrhosis to either decompensated cirrhosis or hepatocellular carcinoma, as many individuals present to the health care system with chronic active hepatitis or cirrhosis. A completely safe and effective treatment strategy for chronic HCV, with or without cirrhosis, remains to be developed. Of the various treatment alternatives currently available, only interferon (IFN) has been evaluated extensively. IFN therapy has been shown to induce remissions of the hepatic inflammatory process and also to eliminate the viral infection in some treated cases. As a result, the selection of patients for treatment and the dose and the duration of therapy with IFN are still controversial issues. It is widely held that cirrhotic individuals do not respond to IFN therapy and that treatment of decompensated cirrhotic individuals with HCV infection is dangerous. Here we review data regarding the available experience with IFN treatment of HCV-positive individuals with cirrhosis and compare the response rates of cirrhotics to those reported for individuals with chronic active HCV.

Chronic Disease↗
PubMed1997

The cardiac evaluation of liver transplant recipients: a single center's experience.

OBJECTIVE AND BACKGROUND: Orthotopic liver transplantation is both a difficult and a demanding surgical procedure. It is not unexpected that cardiovascular dysfunction is present in some individuals being evaluated for liver transplantation. Thus, all potential liver transplant recipients seen at this center undergo a full cardiac evaluation prior to being accepted for transplantation. The goal of this report was to review the components of the cardiovascular evaluation utilized at the Oklahoma Transplantation Institute and to determine their overall usefulness as well as the ability of the process to identify individuals at high risk for a cardiac misadventure during liver transplantation. MATERIALS AND METHODS: Between June 25, 1993 and June 30, 1995, a total of 154 consecutive patients with chronic liver disease were evaluated. The primary liver disease of each was established utilizing specific serologic and biochemical tests, ultrasonographic and abdominal tomographic findings, as well as hepatic histology results and hepatic iron and copper level determinations. Each liver transplant candidate underwent a full cardiac evaluation consisting of the following: nuclear ventriculography to estimate the left ventricular ejection fraction (at rest and during exercise), right ventricular ejection fraction, cardiac output, stroke volume and cardiac index; uptake images using thallium and adenosine to identify foci of cardiac ischemic or fixed defects; echocardiography to define the dimensions of the various cardiac chambers, wall thicknesses, cardiac contractility and morphology of the cardiac valves. Finally, coronary arteriography was performed in 26 patients (16.9%) who were suspected of having clinically important coronary artery disease. It should be noted that all of the cardiac evaluations were performed by a single cardiologist. RESULTS: Eight of the 154 potential liver transplant candidates (5.2%) were determined as not being eligible for liver transplantation because of an inadequate cardiac status based upon an initial history and physical examination. Forty-one of the remaining 146 patients (28.1%) underwent liver transplantation. The remaining 105 subjects have not been transplanted for reasons not related to the cardiac status. Eight of the 41 (19.5%) transplanted patients had a clinically advanced cardiac problem recognized prior to liver transplantation. Four of these eight required a specific cardiac intervention prior to liver transplantation consisting of coronary bypass surgery (n = 1), coronary artery balloon dilation (n = 2) or pericardiectomy (n = 1). The remaining four patients required no pretransplant cardiac intervention and were transplanted. None of these experienced any cardiac complications during, or in the 3 months following, the liver transplant procedure. Only one patient experienced a specific postoperative cardiac complication, consisting of an episode of high grave A-V block requiring transplant placement of a cardiac pacing device. This patient had hemochromatosis. CONCLUSIONS: Based upon this experience, it can be concluded that coronary artery disease per se is not an absolute contraindication for liver transplantation. With appropriate treatment, liver transplantation can be performed safely in individuals with confounding cardiac disease. Nuclear ventriculography and echocardiography are essential procedures in evaluating potential liver transplant recipients in an effort to exclude those with occult cardiomyopathy. Coronary arteriography is indicated only in selected cases with evidence of cardiac ischemia or infarction.

Adult↗
PubMed1997

Polymerase chain reaction for the detection of HCV-RNA: cryoglobulinaemia as a cause for false negative results.

Polymerase chain reaction is widely used in clinical practice as a reliable assay for the detection and quantitation of hepatitis C virus RNA in serum and tissue. Due to the high sensitivity of the test, both false positive and false negative results can occur. The presence of cryoglobulins in serum samples represents a variable that can influence the result of a polymerase chain reaction assay leading to false negative results. In cases of hepatitis C virus infection associated with cryoglobulinaemia, it is extremely important to very carefully process the samples to be tested in order to avoid cryoglobulin precipitation and the consequent removal of the virus from the sample.

Cryoglobulinemia↗
PubMed1996

Clinical and pathologic features of hepatocellular carcinoma in young and older Italian patients.

BACKGROUND: It is not known whether putative etiologic factors and clinical and pathological features of hepatocellular carcinoma (HCC) differ between young adult and older white patients. METHODS: We examined the characteristics of 498 consecutive patients with HCC age < 50 years (Group 1: 54 patients) and age > or = 50 (Group 2: 444 patients), an age beyond which the tumor occurrence rate briskly increases. RESULTS: Demographic characteristics, alcohol and coffee intake, and cigarette smoking did not differ between the two groups. Group 1 had a greater prevalence of the hepatitis B surface antigen (HBsAg) carriers (P = 0.006), while the prevalence of either past hepatitis B virus infection (P = 0.008) or antivirus C antibodies (P = 0.016) was higher in Group 2. The lack of both hepatitis B and C virus serologic markers was more common in Group 1 (P = 0.018). In these patients, HCC was less frequently superimposed on cirrhosis (P = 0.002) and was more advanced at the time of diagnosis. In fact, despite a better histologic differentiation grade (P = 0.019), monofocal (solitary and massive) tumors were larger (P = 0.012), small lesions (< or = 5 cm) less frequent (P = 0.028), and either diffuse (P < 0.001) or massive (P = 0.011) types more common. An elevation of serum alpha-fetoprotein was less frequent in group 1 (P = 0.016), but this difference disappeared when the "diagnostic" cut-off of 400 ng/mL was considered. Albeit the prevalence of presenting symptoms did not significantly differ between the two groups, the clinical stage was more advanced in young patients (P = 0.004). The 9-year cumulative rate of survival was similar in the 2 groups. CONCLUSIONS: An early exposure to the virus and/or an accelerated hepatocarcinogenesis in HBsAg carriers can be inferred. Moreover, in the period of life at low risk for hepatoma: (1) the impact of nonalcoholic chemical carcinogenesis seems to be greater; (2) the tumor occurrence is less dependent on cirrhosis development; (3) although histologically better differentiated, the neoplasm is more advanced at the time of diagnosis; and (4) the long term survival is similar to that of the patients age 50 years or older.

Adolescent↗