Disturbed Liver Function Research Articles

AN EXPERIMENTAL TRIAL FOR INFECTING THE SCAVENGER CATFISH CLARIAS LAZERA WITH TRICHINELLA SPIRALIS LARVAE WITH SPECIAL REFERENCE TO CERTAIN FISH BIOCHEMICAL REACTIONS.

Scavenger catfish Glorias gariepius were experimentally infected with viable infective Trichinella spiralis larvae (1000 larvae/fish), Examination of the intestinal contents revealed the presence of viable larvae (that infect albino rats, xenodiagnosis) up to 48 hours post infection. Adult worms were not detected in the intestines of any of the experimentally infected fish. Trichinella spiralis larvae were not detected neither in the muscles of the infected catfish nor in the diaphragms of albino rats fed on muscles obtained from the experimentally infected fish by the 40th day post infection. Thus, C. gariepius might be considered as a paratenic host for T. spiralis infection and could play a role in the epidemiology of trichinosis. Sequential serum samples from each fish were collected 7 and 40 days post infection. Small but statistically significant changes, in alanine aminotransferase and aspartate aminotransferase occurred after infection. Serum concentration of total protein remained constant, indicating little disturbance of liver function. Infection significantly lowered the relative mobility of serum protein fractions separated by polyacrylamide gel electrophoresis on the 40th day post infection. The relative intensities of the more mobile fraction (# 1) significantly rose, while fractions # 3, 5 and 11 decreased 40 days post infection. It is concluded that the immune response of C gariepius is probably held responsible for the failure of Trichinella spiralis larvae to establish in this abnormal host.

Temozolomide followed by combined immunotherapy with GM-CSF, low-dose IL2 and IFN alpha in patients with metastatic melanoma.

The purpose of this study is to determine the toxicity and efficacy of temozolomide (TMZ) p.o. followed by subcutaneous (s.c.) low-dose interleukin-2 (IL2), granulocyte–monocyte colony stimulating factor (GM-CSF) and interferon-α 2b (IFNα) in patients with metastatic melanoma. A total of 74 evaluable patients received, in four separate cohorts, escalating doses of TMZ (150–250 mg m−2) for 5 days followed by s.c. IL2 (4 MIU m−2), GM-CSF (2.5 μg kg−1) and IFNα (5 MIU flat) for 12 days. A second identical treatment was scheduled on day 22 and cycles were repeated in stable or responding patients following evaluation. Data were analysed after a median follow-up of 20 months (12–30 months). The overall objective response rate was 31% (23 out of 74; confidence limits 20.8–42.9%) with 5% CR. Responses occurred in all disease sites including the central nervous system (CNS). Of the 36 patients with responding or stable disease, none developed CNS metastasis as the first or concurrent site of progressive disease. Median survival was 252 days (8.3 months), 1 year survival 41%. Thrombocytopenia was the primary toxicity of TMZ and was dose- and patient-dependent. Lymphocytopenia (grade 3–4 CTC) occurred in 48.5% (34 out of 70) fully monitored patients following TMZ and was present after immunotherapy in two patients. The main toxicity of combined immunotherapy was the flu-like syndrome (grade 3) and transient liver function disturbances (grade 2 in 20, grade 3 in 15 patients). TMZ p.o. followed by s.c. combined immunotherapy demonstrates efficacy in patients with stage IV melanoma and is associated with toxicity that is manageable on an outpatient basis.

Late cytomegalovirus disease following liver transplantation.

The widespread use of antiviral prophylaxis or preemptive therapy among orthotopic liver transplantation (OLT) recipients has reduced the occurrence of early cytomegalovirus (CMV) disease. Late disease is increasingly reported. Little is known about CMV disease occurring beyond the first year after transplantation. The aim of this study was to evaluate the occurrence of CMV disease two or more years after OLT and to determine its risk factors and clinical features. Eighty-one consecutive OLT recipients followed for 2 years or longer after transplantation were included in the study. Data were collected on demographic and clinical variables, clinical presentation, treatment, and outcome of late CMV disease. Late CMV disease occurred in 7/81 liver recipients (8.5%) at a mean time of 5.9 years after OLT (range: 3.5--9.3, median: 6.3 years). All seven patients were women, with a mean age of 47.7 years (range: 26--60, median: 59 years). There was no association between the development of late CMV disease and the occurrence of rejection episodes, treatment with corticosteroids, or the early use of antiviral prophylaxis. Clinical presentation included fever and disturbed liver functions in all patients, one patient had concurrent CMV pneumonitis and one CMV retinitis. Though all patients responded to ganciclovir, two had recurrent disease episodes and one patient died of secondary bacterial sepsis. Late-onset CMV disease can occur several years after OLT. Although it manifests classic clinical features of early disease, it is not associated with traditional risk factors and its pathogenesis may differ from that of early disease.

Liver function disturbances following laparoscopic cholecystectomy: incidence and significance.

Unexplained disturbances of liver function parameters after laparoscopic cholecystectomy have been reported in a few previous studies. We aimed to assess the incidence of these disturbances, and their relation to age, sex, duration of surgery, and type of gallbladder inflammation, as well as their clinical significance. All patients undergoing laparoscopic cholecystectomy at Dallah Hospital, Riyadh, Saudi Arabia, during the year 2001 were prospectively evaluated. In all the patients, six parameters of liver function (direct bilirubin, indirect bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase) were assessed before and 24 hours after surgery. Patients with suspected chronic liver disease or common bile duct pathology were excluded. Patients who showed more than a 100% increase in at least one parameter (group I) were compared with those who did not (group II) regarding age, sex, duration of surgery, and type of gallbladder inflammation. Of the patients, 67.1% showed more than a 100% increase in at least one parameter of liver function. No significant difference was noticed between the two groups regarding age, duration of surgery, or type of gallbladder inflammation. Female patients, however, showed a significantly higher incidence of liver function changes (P = .011). No clinical adverse reactions were reported in those who showed liver function changes. Changes in liver function parameters after laparoscopic cholecystectomy are common, carrying no clinical sequalae. They are more common in female patients and are not related to age, duration of surgery, or the acuteness of gallbladder inflammation. Assessment of direct bilirubin and alkaline phosphatase is sufficient for the routine evaluation of these patients postoperatively.

Neuroprotection Is Unlikely to Be Effective in Humans Using Current Trial Designs: An Opposing View

To summarize recent neuroprotective trials, there has been no useful balance of benefit over risk.1 It is premature to shoot the messenger without evidence either that the results have been misleading or that we have missed trends. Confirmatory trials and/or meta-analysis support the validity of the results, and similar designs have successfully revealed the risks and benefits of thrombolysis. Trial designs have been imperfect, but the message is accurate: the drugs or doses we tried were inadequate. We need safer and better drugs, we need to know when and how to use them, and we need to maximize the efficiency of our trials. All are possible with current designs.2 Originally, limited efficacy data from a single laboratory and an acceptable toxicity profile were sufficient to proceed to clinical development. Choice of dose range, the optimal duration of therapy, patient subgroup selection, and the likely extent of benefit were all reserved for testing in clinical trials. The misplaced optimism of such an approach is now recognized, however, and guidance on preclinical testing has been elaborated.3 Rigorous external scrutiny of preclinical data now occurs in the more informed companies,4 and clinical development is deferred pending resolution of any deficiencies. This is the first role of the (now mandatory) trial steering committee. The drug classes under investigation are evolving, and new approaches are still being discovered. Glutamate antagonists have been widely studied.1 While effective in small animal models, their short time window in the laboratory, failure to protect …

Studies on the influence of a Se-restricted diet on the effects of long-term increased copper intake in guinea pigs

Guinea pigs were exposed to Se-restriction/deficiency in combination with drinking water containing 200 or 300 mg Cu/l for 6-30 weeks. Under the influence of Se-restriction/deficiency Cu excretion by bile was diminished, the Cu content of the kidneys was increased and disturbances of liver function were seen in animals exposed for prolonged periods. Some parameters of the immune system, such as the phagocytic activity of peritoneal macrophages, mitogenicity of spleen lymphocytes and the amount of lymphatic spleen tissue were also adversely affected. These effects correlated in part with the liver damage and the copper content of the kidneys. Conclusion are drawn with respect to the Idiopathic Copper Toxicosis/Indian Childhood Cirrhosis.

Normal liver function in women in the general Japanese population subjected to environmental exposure to cadmium at various levels.

Whereas it is well established that environmental exposure to cadmium (Cd) may induce kidney dysfunction, less attention has been paid to the possible disturbance of liver function by Cd exposure. The possibility that liver function is adversely affected by current levels of environmental exposure to Cd as investigated in women in the general population in Japan, where the background level of exposure to Cd is known to be high. From 1991 to 1997, 24-h food duplicate, peripheral blood and morning spot urine samples were collected from 607 non-smoking and non-habitually drinking women (age range 19-78 years) at 30 survey sites (with no known environmental pollution from heavy metals) throughout Japan. Liver function parameters in serum were examined by conventional methods. After wet-ashing, the food duplicate, blood and urine samples were analyzed for Cd intake via food (Cd-F), Cd in blood (Cd-B), and Cd in urine (Cd-U) by inductively-coupled plasma mass spectrometry. The geometric mean values for Cd-F, Cd-B, and Cd-U were 24.7 (27.1) microg/day, 1.76 (2.07) microg/l, and 3.94 (4.61) microg/g creatinine (values in parentheses for 41- to 60-year-old women), respectively. It as found that the three parameters of ALP, ALT, and AST activity were positively and significantly related to the age of the subjects (whereas no association as detected in cases of gamma-GTP, LAP, and albumin). Accordingly, a further analysis as made with 367 women selected by age (41-60 years; about 60% of the total population). Essentially, no Cd dose-dependent changes in liver function parameters were observed in the selected population of this narrower age range. Overall, it seemed prudent to conclude that liver function as not disturbed by the current environmental exposure to Cd in Japan.

Serum gastrin and gastrin-immunoreactive cells in the antral mucosa of patients with alcoholic liver disease.

Hypergastrinaemia has been reported in liver cirrhosis; meanwhile, it is unclear whether it is associated with an increase in gastrin cell function. The serum gastrin concentration and the number of gastrin cells in antral biopsies were studied in patients with alcoholic liver disease. Immunocytochemical and quantification techniques were used to localize and determine the number of gastrin cells. Slight non-significantly higher serum gastrin values were observed in the alcoholic liver disease patients compared with controls, but the individual variation within the groups was considerable. The frequency of gastrin cells did not differ between groups. However, the size of the gastrin cell nuclei was larger in patients with liver disease than in controls, indicating increased cellular activity. Alcoholic liver disease, with a disturbed liver function, influences the gastrin cells. The observed alterations may reflect the effect of alcohol and/or malnutrition, or may be secondary to the influence of liver disease on other regulatory peptides.

Atypischer Verlauf einer akuten Leberfunktionsstörung mit schwerer Thrombozytopenie im dritten Trimester

The authors diagnosed disturbance of liver-function associated with severe thrombopenia in a pregnant woman in the third trimester. Principally, acute fatty liver of pregnancy can be characterized by existing symptoms, e.g. nausea, vomiting, epigastric pain, jaundice, hyperbilirubinemia, moderately elevated SGOT and SGPT levels, thrombopenia, leukocytosis, low fibrinogen level and disseminated intravascular coagulopathy, but hepatomegaly, purpura and petechia on lower and upper extremities, and high ALP and GGT levels during postpartum period do not confirm suspicion of this diagnosis. The present report draws attention to the difficulties of differential diagnosis of pregnancy-induced elevated liver enzymes diseases associated with low platelets, as there are several identical pathophysiological processes. Although causes and exact pathophysiology of disorders are unknown, similar symptoms during the process of diseases leave the question open whether they are different diseases or whether they are different manifestations of the same disease, and what kind of relationship exists between these diseases and preeclampsia. This case suggests careful evaluation of the whole clinical picture, moreover it is emphasized that prompt, aggressive treatment of hemostatic disturbance and the expeditious delivery can save maternal life.

The Liver in Hereditary Hemorrhagic Telangiectasia (Weber-Rendu-Osler Disease)

Background: Hereditary hemorrhagic telangiectasia (HHT, Osler disease) is an inborn error in the structure of different vessels. This leads to vascular malformations in multiple organ systems. In the liver vascular abnormalities are associated with a marked fibrosis and/or cirrhosis. Methods and Results: We found hepatic manifestation of Osler disease in four women and one man (51-63 years old) presenting initially with slight disturbances of liver function. In three patients progressive liver insufficiency developed. The characteristic histologic and sonographic findings are described and discussed. Conclusion: Ultrasonography with color and Doppler analysis is diagnostic, replacing more extensive procedures like angiography, computer tomography, or magnetic resonance tomography.

Dexamethasone-induced hepatomegaly in three children

High-dose treatment with dexamethasone led to reversible hepatomegaly with disturbance of liver function in three children. After withdrawal of dexamethasone, liver size and function returned to normal. These observations were compared with previously published data. The authors conclude that if this condition occurs, dexamethasone should be discontinued.

Bright basal ganglia in T1-weighted magnetic resonance images are frequent in patients with portal vein thrombosis without liver cirrhosis and not suggestive of hepatic encephalopathy

Background/Aims: Deposition of paramagnetic substances in basal ganglia, resulting in increased signals in T1-weighted magnetic resonance images (bright basal ganglia), is frequently seen in liver cirhrosis. The present study describes the prevalence of bright basal ganglia and its clinical significance in patients with long-standing portal vein thrombosis in the absence of liver cirrhosis. Methods: Six patients with angiographically proven complete portal vein thrombosis and cavernomatous transformation without signs of acute or chronic liver disease were studied by magnetic resonance imaging of the brain, neuropsychiatric evaluation, psychometric tests, electroencephalography, and determination of arterial ammonia levels and of serum manganese concentrations from peripheral venous blood. Results: Five out of six patients demonstrated increased signal intensity in the basal ganglia. Overt portal-systemic encephalopathy was not noted prior to or at the time of evaluation. Normal EEG results were recorded in all patients. Only one of the six patients had pathological results in at least two out of four psychometric tests. This latter patient had had a large right-sided brain infarction. Arterial ammonia concentrations were normal in four of the six patients; one patient with increased ammonia levels had concomitant renal insufficiency with azotemia. The other four patients had no relevant concomitant diseases. Serum manganese levels were non-significantly increased compared with control group ( p=0.06), but they were significantly correlated to basal ganglia signal intensity (R=0.88; p=0.02). Conclusions: Our results demonstrate that bright basal ganglia primarily represent shunt-induced alterations. They are not directly associated with disturbed liver function nor with portal-systemic encephalopathy.

Aetiology of oral cancer: alcohol

The effect of alcohol alone on the oral mucosa and its association with the development of oral cancer is difficult to establish, principally because alcohol consumption histories are difficult to verify, alter over time, both with respect to beverage type and quantity, and are frequently confounded by tobacco use. This review considers the various pathways by which alcohol may exert such an influence. Namely, due to topical exposure (e.g. direct effect on cell membranes, altered cell permeability, variation in enzymes that metabolise alcohol) and/or systemic effects (e.g. nutritional deficiency, immunological deficiency, disturbed liver function). Finally, the numerous papers that have sought to establish the relative risk for oral cancer in association with alcohol intake are reviewed.

A RANDOMISED STUDY ON THE EFFECTS OF CONVERSION OF CYCLOSPORINE/PREDNISONE TO CYCLOSPORINE/AZATHIOPRINE 6 MONTHS AFTER KIDNEY TRANSPLANTATION

234 Purpose: Recently, Opelz suggested that 5 year kidney graft survival was better with an immunosuppressive protocol consisting of cyclosporine (CsA) and azathioprine (Aza) compared to the combination of cyclosporine and prednisone (P). We analyzed the results of a randomised study in which P was switched to Aza 6 months after kidney transplantation(KTx), in comparison with continuation of CsA/P treatment. Methods: Patients were randomised for 1. continuation of the initial regimen consisting of CsA and P 0, 15 mg/kg (CsA/P group, 34 patients), or 2. replacement of P by Aza 3 mg/kg (CsA/Aza group, 34 patients). Exclusion criteria were: unstable graft function, HLA-identical living related donor, liver function disturbances and leuco- or thrombopenia. The groups were comparable for baseline creatinine, age, sex, number of rejections since KTx, mean arterial pressure (MAP), number of antihypertensive drugs, hemoglobin (Hb), proteinuria and CsA dose and level. Follow-up was available until 24 months after KTx. Analysis was performed on an intention-to-treat basis. Results: In the CsA/Aza group P was successfully replaced by Aza in 15/34 patients. In 19/34 patients P was reintroduced because of: anaemia, leuco- or thrombopenia (11 patients), possible hypocorticism (8 patients) or other reasons (9 patients). After randomisation 5 rejections occurred: 4 in the CsA/P group and 1 in the CsA/Aza group (NS). Graft loss occurred in 3 patients in the CsA/P group and in none in the CsA/Aza group(NS). One year after KTx, higher values were found in the CsA/P group for Hb(8,3 vs 7,5 mmol/l; p<0,01), MAP (114 vs 104 mm Hg; p<0,01) and number of antihypertensive drugs (2,1 vs 1,5; p<0,05). No differences were found for weight, creatinine, CsA level and proteinuria. Two years after KTx no differences were detected between the two treatment groups. Conclusion: CsA/P can be converted safely to CsA/Aza 6 months after KTx; however reintroduction of P frequently is necessary.

Prognostic factors in perforating diverticulitis of the large intestine

Morbidity and mortality after emergency procedures in 105 patients with perforated colonic diverticulitis were evaluated in a retrospective study. In different stages of diverticulitis (Hinchey classification: I, 8.6%; II, 14.3%; III, 57.1%; IV, 20.0%) mortality was 12.4%. Preoperative sepsis syndrome with leucopenia and disturbed liver function, cardiac risk factors and obesity were independent prognostic factors in multiple logistic regression. Accompanied by immunosuppression the mortality rate remarkably increased to 33%. The stage of peritonitis showed no influence on the prognosis. In multivariate analysis, surgical procedure (primary resection 12.4%. Hartmann's procedure 61.9%, non-resection procedures 25.7%) showed influence only on increased general complications.

“Unexplained” disturbances in liver function are common following laparoscopic cholecystectomy. Is intraabdominal hypertension the reason?

“Unexplained” disturbances in liver function are common following laparoscopic cholecystectomy. Is intraabdominal hypertension the reason?

Does Isoniazid Reduce Side Effects of Intravesical Bacillus Calmette-Guerin Therapy in Superficial Bladder Cancer? Interim Results of European Organization for Research and Treatment of Cancer Protocol 30911

We analyzed the influence of the tuberculostatic agent isoniazid on the incidence and severity of adverse effects of intravesical bacillus Calmette-Guerin (BCG) therapy in patients with superficial bladder cancer. In a prospective randomized multicenter study the side effects of intravesical instillations with Tice strain BCG with and without isoniazid were compared in patients with stages pTa and pT1 bladder tumors. Isoniazid was given orally at a dose of 300 mg. daily at every instillation in an attempt to decrease the side effects of BCG. No differences in local or systemic adverse reactions after intravesical immune therapy with BCG could be observed between patients treated with or without prophylactic isoniazid therapy. However, analysis of liver function tests after BCG with isoniazid showed slightly more liver toxicity compared to BCG alone. Prophylactic administration of isoniazid during BCG instillations provides no decrease in any known side effect of BCG. In contrast, transient liver function disturbances are encountered slightly more frequently when isoniazid is administered. The use of prophylactic isoniazid in patients treated with BCG is not recommended.

Comparison of Sandimmun with a new cyclosporin derivative (IMM 125) in renal transplant patients with stable renal function

Abstract A double-blind switchover study was carried out on 70 renal transplant patients to assess the value of a new cyclosporin derivative, IMM 125. Preclinical in vitro and in vivo studies indicated that IMM 125 was as equally immunosuppressive as Sandimmun, but that its therapeutic index should be superior. The duration of the treatment was 24 weeks. The assumption that the dosage of IMM 125 could be 2.5 times lower than Sandimmun proved to be false; three patients suffered acute rejection episodes, probably as a consequence of the low dosage, and dosage adjustments had to be made for all patients receiving IMM 125 after only a few weeks. Although IMM 125 is an effective immunosuppressive agent, it does not appear to offer advantages over Sandimmun with regard to renal function. In addition, IMM 125 causes some disturbances in liver function.

Spontaneous ovarian hyperstimulation mimicking an ovarian tumour

Ovarian hyperstimulation syndrome in a spontaneous singleton pregnancy is exceedingly rare. We report a case of ovarian hyperstimulation presenting as bilateral ovarian masses in association with spontaneous pregnancy, occurring in a woman with disturbed liver function. A possible mechanism is discussed.

Ticlopidine

Ticlopidine is a thienopyridine derivative which reduces the risk of reversible ischaemia and stroke in patients who have previously experienced a cerebral ischaemic episode. In comparison with aspirin, ticlopidine produced a significant reduction in the risk of stroke in a multicentre clinical trial involving more than 3000 patients with previous transient or persistent minor ischaemia, and was superior to placebo for the prevention of stroke recurrence in more than 1000 patients who had experienced a major thrombotic stroke. The cost-utility ratio for ticlopidine in comparison with aspirin was estimated to be $US31 200 to 55,000 per quality-adjusted life-year gained. Diarrhoea is the most common adverse event in ticlopidine recipients (20 to 22% incidence versus about 10% with placebo), although skin rash, nausea, dyspepsia, bleeding events, abnormal liver function and haematological disturbances were also observed in clinical trials. Severe neutropenia is the most serious event: this developed in 0.85% of patients receiving ticlopidine in 2 large clinical studies (n = 4098) but resolved after treatment withdrawal. Fatal neutropenia, although rare, has been reported in some patients receiving ticlopidine. Thus, ticlopidine is effective in reducing the risk of recurrent cerebral ischaemia and stroke. It appears to provide a gain over aspirin for the prevention of stroke after reversible ischaemia, particularly during the first year of treatment (when the risk of stroke is greatest), although further data on its absolute relative benefit would be useful. The extent to which ticlopidine is prescribed will probably depend on individual clinicians' perception of its risk/benefit and cost-effectiveness profiles. Ticlopidine is likely to be particularly useful for stroke prophylaxis in patients who do not tolerate aspirin or who have an ischaemic episode during aspirin treatment, and for the prevention of stroke recurrence in patients who have previously experienced a major stroke.