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PubMed1990

[Clinico-laboratory diagnosis of adverse reactions in children to antitubercular drugs in different combinations].

To clarify side effects in children, which resulted from the treatment of intrathoracic tuberculosis with rifampicin, 72 patients were examined. The findings were compared with those on 58 identical patients who received a routine combination of chemotherapeutic drugs. Hence, on the basis of this observation it was found that there were no differences in the incidence of adverse reactions in the compared groups, though their nature was varying. The children on rifampicin were observed to develop mild liver dysfunction 2.5 times more frequently. Besides, toxic-allergic reactions were recorded in the majority of the patients. The combination of isoniazid and rifampicin was proved to enhance their toxic and allergic effects. Liver dysfunction in the presence of different adverse reactions presented with a higher activity in the blood serum of indicator liver enzymes and its impaired protein-forming function.

Adolescent↗
PubMedDate not supplied

[Multicenter study on incidence of total parenteral nutrition complications in the critically-ill patient. ICOMEP study. Part I].

OBJECTIVE: To assess parenteral nutrition complications in a prospective cohort of patients admitted to the ICU. MATERIAL AND METHODS: Prospective, multicenter study of patients admitted to the ICU and that received total parenteral nutrition (TPN). A 14-item questionnaire was done. Total number of admissions and TPN-treated patients were recorded. Demographical data, diagnosis, APACHE II, multiorgan dysfunction index and TPN indications were included. Each complication was previously defined and was related to the route, administration, serum electrolytes unbalances, active ingredients, liver dysfunction, and nosocomial infections. An independent group managed the databases. Data were expressed in absolute values or by their median and percentile (25-75). The rate and incidence density of complications are determined. RESULTS: The number of admissions during the study period was 3409. Three hundred and seventy (11%) were valid cases that were treated with PN. Two hundred and thirty seven were men, 142 patients were admitted for medical causes, 195 for surgical causes and 33 for trauma. One hundred and twenty patients were moderately or severely underfed, 181 received PN for 7 days (3-11), and 189 received PN and EN. The main indication for PN was paralytic ileus, in 145 patients. TPN was withdrawn for switching to EN in 121 cases and for complications in 5 cases. PN summed up 3220 days. The incidence of complications was: access route 9.32%, maintenance 19.7% and 0.8 per 100 days. Administration, 5.6% and 6.4 per 100 days. Nutrients, 94.3% and 10.8 per 100 days. Catheter-induced sepsis, 54.6% and 0.44 bacteriemias per 100 days with catheter. Nosocomial infection, 54.6% and 6.27 per 100 days on TPN. CONCLUSIONS: hyperglycemia and liver dysfunction have a greater incidence. Hyperglycemia, electrolyte unbalances and catheter complications have a greater number of therapeutic interventions, but does not mean that TPN should be withdrawn.

Aged↗
PubMed2005

Off-pump coronary artery bypass attenuates transient hepatocellular damage after myocardial revascularization.

OBJECTIVE: Cardiopulmonary bypass (CPB) affects hepatocellular integrity and occasionally results in liver dysfunction after cardiac surgery. Performing coronary artery bypass graft surgery without CPB may help to reduce the risk of this complication and better preserve perioperative liver function. This study compared perioperative hepatocellular damage in patients undergoing on-pump and off-pump bypass surgery. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Patients scheduled for elective on-pump (n = 21) and off-pump (n = 17) coronary artery bypass surgery. MEASUREMENTS AND MAIN RESULTS: Liver function was assessed by serum levels of alcohol dehydrogenase (AD) and alpha-glutathione S-transferase (alpha-GST), which serve as more sensitive indices of hepatocellular injury than do conventional transaminases. Arterial blood was sampled at 6 stages: after induction of anesthesia (baseline); at the end of CPB in the on-pump group or on completion of the last distal anastomosis in the off-pump group; at the end of surgery; and 6 hours, 12 hours, and 24 hours after the end of anesthesia. The off-pump patients showed significantly lower increases in serum AD and alpha-GST levels than did the on-pump group. AD and alpha-GST values increased in the on-pump patients after the initiation of CPB and peaked at the end of surgery, with a return to baseline at 12 hours and 24 hours after the end of anesthesia. No clinically relevant liver dysfunction was observed in either group. CONCLUSIONS: CPB induced transient subclinical hepatocellular damage, whereas off-pump revascularization attenuated this damage.

Aged↗
PubMed1992

[Pharmacokinetic studies of menogaril (TUT-7) with rats].

Menogaril (TUT-7) is a novel antitumor antibiotic belonging to anthracyclines. The pharmacokinetic parameters derived from plasma concentration-time profiles after repeated (for 14 days) or single oral administration of TUT-7 to rats were found to be not significantly different by either administration schedule. The rats with artificial liver dysfunction were obtained by subcutaneous application of carbon tetrachloride (CCl4, 1 ml/kg) for 3 days. After oral administration of TUT-7 to the rats with CCl4-induced liver toxicity (3 daily administrations of 1mg/kg, S.C.), the maximum plasma concentrations (Cmax) and AUC of both the unchanged drug and its metabolite N-Demethyl menogaril, were increased. Also over all elimination was slower in animals with liver dysfunction.

Administration, Oral↗
PubMed1993

Possible case of procainamide-induced intrahepatic cholestatic jaundice.

OBJECTIVE: To describe a possible case of procainamide-induced intrahepatic cholestatic jaundice that was recognized six weeks after the initiation of procainamide therapy and to summarize the five previously reported cases. CASE SUMMARY: A 77-year-old woman with a history of hypertension, insulin-dependent diabetes mellitus, temporal arteritis, and Wolff-Parkinson-White syndrome who had taken procainamide for six weeks presented to the hospital with disorientation and acute renal and hepatic dysfunction. In addition to disorientation, scleral icterus, and diffuse maculopapular rash, her physical examination was generally normal. There was no evidence of fever, nausea, vomiting, lymphadenopathy, or eosinophilia. Her liver enzyme concentrations increased significantly from baseline (beginning of procainamide therapy). Her N-acetylprocainamide (NAPA) concentration was elevated to 52 mg/L upon admission. Procainamide was discontinued and her NAPA concentration returned to within normal limits in two days. Diagnostic tests were performed to rule out active hepatitis, vasculitis, and liver malignancies. After procainamide was discontinued and prednisone treatment was started, she became more oriented and her liver enzyme concentrations slowly improved. DISCUSSION: Only five cases of procainamide-induced liver abnormalities have been previously reported; these included granulomatous hepatitis and intrahepatic cholestasis. The mechanism for liver dysfunction is not known; however, it is proposed to be a delayed hypersensitivity reaction. Clinical hallmarks of hypersensitivity include fever, eosinophilia, rash, and lymphadenopathy; nausea and vomiting also may be present. Of the five reported cases, all experienced fever and only one experienced pruritus. No patients had eosinophilia or lymphadenopathy. Because of the temporal increase in liver enzyme concentrations after six weeks of procainamide therapy, we believe that this case represents another possible procainamide-induced hypersensitivity reaction. CONCLUSIONS: Procainamide-induced liver dysfunction can occur from one day to six weeks after initiation of the drug and may subside one day to several weeks after discontinuation of therapy. Symptoms may include nausea, vomiting, rash, and fever. Liver enzyme concentrations are abnormal. It is important to recognize the possibility of such a reaction early so that procainamide therapy can be discontinued promptly to avoid further liver damage.

Aged↗
PubMed1999

Rabeprazole: pharmacokinetics in patients with stable, compensated cirrhosis.

This single-center, open-label study was undertaken to compare the tolerability and pharmacokinetic profiles of rabeprazole, a new proton-pump inhibitor (PPI), in healthy volunteers and in subjects with chronic cirrhosis. Thirteen healthy men and 10 men with stable, compensated cirrhosis documented by biopsy or liver/spleen scan received a single 20-mg rabeprazole dose. Blood samples were drawn before and up to 24 hours after drug administration for the determination of plasma rabeprazole concentrations using high-performance liquid chromatography. Adverse events, vital signs, electrocardiograms, physical findings, and clinical laboratory test results were monitored before and during treatment to determine how rabeprazole was tolerated. Chronic liver disease substantially altered the pharmacokinetic profile of rabeprazole. The maximum rabeprazole concentration (+/- SD) in subjects with cirrhosis (635+/-199 ng/mL) was approximately 50% higher than that in the healthy volunteers (401+/-246 ng/mL), and both area under the curve and elimination half-life were increased by approximately 100%. Oral clearance in subjects with cirrhosis was 38% of that in the healthy volunteers. Rabeprazole was well tolerated by both groups. Three subjects reported a total of 5 clinical adverse events that were judged as definitely or possibly related to rabeprazole treatment. Some minor changes in laboratory values were judged to be clinically insignificant. In patients with mild-to-moderate liver dysfunction, clearance of this PPI, as with other members of the class, was markedly reduced and plasma levels were increased. Although caution is always warranted in patients with severe liver disease, drug accumulation is unlikely with rabeprazole 20 mg once daily, and dose adjustment does not appear to be indicated in patients with mild-to-moderate liver dysfunction.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

[Cytomegalovirus antigenemia assay as a useful tool for early diagnosis and therapy for cytomegalovirus infections in three cases with collagen diseases].

We report here three cases of collagen diseases with cytomegalovirus infections. (1) A 21-year-old female, who had been diagnosed as systemic lupus erythematosus, lupus nephritis and lupus peritonitis, had fever. Cytomegalovirus antigenemia (CMV-Ag) assay was 10/8 positive. (2) A 33-year-old female, who had been diagnosed as Wegener glanulomatosis, had fever and liver dysfunction. CMV-Ag assay was 933/896 positive. (3) A 64-year-old female, who had been diagnosed as microscopic polyangitis, had fever, liver dysfunction and pneumonia. CMV-Ag assay was 6/2 positive. They were considered to be complicated with CMV infections. We could make early diagnoses of CMV infection by using CMV-Ag assay and treat them with anti-CMV therapy effectively.

Adult↗
PubMedDate not supplied

Laparoscopic microwave coagulation therapy for small hepatocellular carcinoma on the liver surface.

Six patients with small size (< or =2.0 cm in diameter) hepatocellular carcinoma (HCC) on their liver surface underwent laparoscopic microwave coagulation therapy (LMCT) in our institute. All cases showed complete necrosis after LMCT alone and there were no major complications during the LMCT. During the follow-up period, one patient had recurrent HCC at the LMCT-treated lesion site and two patients had lesions at sites distant to the LMCT-treated site. Two out of these three patients had presented with severe liver dysfunction at admission and died within the follow-up period. LMCT is believed to be a useful and safe treatment for small size HCC on the liver surface, and treatment can achieve complete tumor necrosis. However, in severe liver dysfunction, the use of LMCT may have a negative influence on patient survival.

Adult↗
PubMed1986

Serum bile acid concentrations as a liver function test in workers occupationally exposed to organic solvents.

Liver injury has long been associated with occupational exposure to a wide variety of chemicals. The controversial data existing in relation to hepatotoxicity of organic solvents might be explained as a consequence of the different exposures or it may well be that the tests used for evaluating liver function might not be sensitive enough to detect any mild changes at an early stage. To study liver function during exposure to solvent mixtures, we determined serum bile acid (SBA) concentrations as compared with conventional liver function tests in a selected group of workers (n = 30) occupationally exposed to a mixture of organic solvents (mostly toluene, xylene, acetone, n-butylacetate, n-butanol, ethylacetate) and in a reference group (n = 20). The mean levels of liver enzyme activities and bilirubin concentrations in the two groups were similar, whereas mean SBA levels increased in the exposed group (8.0 +/- 6.0 mumol/l vs 2.8 +/- 1.4 mumol/l) and the difference as compared with the controls was significant (P less than 0.01). In 73% of the exposed workers, SBA levels were higher than 5.6 mumol/l (the cut-off value) as compared with 5% of the controls. These results demonstrate the higher sensitivity in detecting liver dysfunction achieved with the SBA test as compared with conventional hepatic function tests. As increased SBA concentrations are considered to reflect an impairment of anion transport across the liver, higher SBA levels in the group of workers exposed to organic solvents might be explained as a slight and early sign of liver dysfunction. Therefore, SBA determination in biological monitoring of workers exposed to potentially hepatotoxic chemicals might be proposed.

Adult↗
PubMedDate not supplied

Acetaminophen overuse in the Ohio Medicaid population.

OBJECTIVE: To examine patterns of use of acetaminophen in patients with and without risk factors for hepatotoxicity in the Ohio Medicaid population. DESIGN: Retrospective, cross-sectional analysis of claims data. SETTING: Ohio. PATIENTS: Ohio Medicaid patients (n = 22,496) who received at least 6 prescriptions for acetaminophen from November 1998 through April 1999. MAIN OUTCOME MEASURE: Overuse of acetaminophen, defined as an average daily dose (ADD) greater than or equal to 4 grams/day or an ADD of greater than or equal to 3 grams/day along with diagnosis codes suggesting underlying liver dysfunction. RESULTS: We identified 687 patients (3.05%) who received either greater than or equal to 4 grams/day or greater than or equal to 3 grams/day and had diagnosis codes suggesting underlying liver dysfunction (n = 128). CONCLUSION: Although the number is relatively small, some Ohio Medicaid patients are receiving acetaminophen doses that exceed safety recommendations. Because acetaminophen overuse is the leading cause of liver failure, health care professionals should be alert to the possibility of acetaminophen overuse.

Acetaminophen↗
PubMed2003

Coil embolization of a patent ductus venosus in a 52-day-old girl with congenital heart disease.

We present the case of 52-day-old girl with a common atrioventricular canal. Severe liver dysfunction persisted following complete repair of the cardiac defect. A patent ductus venosus appeared to be the source of the hemodynamic disturbance responsible for hepatic dysfunction. Given her critical condition, coil embolization of the ductus venosus was performed, after which the patient improved rapidly. The ductus venosus should be tested for patency when liver dysfunction persists after the corrective cardiac surgery, and coil embolization is the treatment of choice in gravely ill children.

Abnormalities, Multiple↗
PubMedDate not supplied

Retrospective monocentric study of 17 patients with adult Still's disease, with special focus on liver abnormalities.

BACKGROUND/AIMS: Adult Still's disease is one of the febrile disorders of unknown etiology, characterized by high fever, transient cutaneous rash and leukocytosis. Liver dysfunction in adult Still's disease has been described in some case reports. The objective of this study was to analyze the pattern and the frequency of liver abnormalities in a monocenter series of adult Still's disease patients. METHODOLOGY: Data of 17 patients with adult Still's disease (fulfilling Yamaguchi's diagnostic criteria) were retrospectively reviewed. These patients were followed in an Internal Medicine Department over a period of 7 years. RESULTS: The median age was 27 years with a sex ratio M/F of 1.4. Fever was present in 100% of the cases and hepatomegaly occurred in 47% of the cases. Abnormalities in liver biochemistry, apparent in 76% of the subjects were characterized from moderate (elevation of transaminases between 2 and 5 N) (65%) to severe cytolysis (level of transaminases > 5 N) (12%), cholestasis (elevation of gamma GT and/or PAL) (65%), and increase in the level of LDH (35%). All of these symptoms disappeared either spontaneously or under treatment (83%), within a median period of 18 days. CONCLUSIONS: This study confirms the high frequency of liver dysfunction in adult Still's disease patients. Although it is moderate and asymptomatic in most cases, severe cytolytic hepatitis has been described. This study especially puts forward the need for exploring the possibility of adult Still's disease in the presence of a fever and hepatic cytolysis.

Adult↗
PubMed2003

[EB virus-associated peripheral T cell lymphoma presenting with hemophagocytic syndrome and hepatic cell necrosis].

A 72-year-old woman was admitted with left cervical lymphadenopathy, high fever, pancytopenia and liver dysfunction. Bone marrow aspiration showed infiltration of large atypical lymphoid cells and hemophagocytic histiocytes, thus suggesting a diagnosis of lymphoma associated hemophagocytic syndrome (LAHS). An abdominal CT scan revealed multiple low-density areas in the liver, and the patient's liver function rapidly deteriorated. Histologically, the cervical biopsy showed lymphoma cell infiltration with prominent necrosis and karyorrhectic debris. The lymphoma cells expressed CD3+, CD4-, CD8+, CD20-, CD56+/-, TIA-1+, granzyme B+, and EBER was positive using in situ hybridization. DNA analysis of the TCR beta and gamma chain gene with the Southern blot showed rearranged bands. These findings were compatible with those of EB-virus associated peripheral T-cell lymphoma. After chemotherapy with the THP-COP regimen, the patient's liver dysfunction improved rapidly, but she died from bacterial peritonitis due to perforation of a recurrent duodenal ulcer. Post-mortem examination of the liver showed multiple irregular massive necroses of the hepatocytes, where no lymphoma cell infiltration was present. Hemophagocytic histiocytosis was remarkable in the bone marrow, spleen, lymph nodes, and liver. Marked elevation of serum levels of cytokines such as TNF-alpha or IFN-gamma suggests that these cytokines played an important role in the pathogenesis of the hepatic cell necrosis.

Aged↗
PubMed1996

Effects of the endothelin receptor antagonist, SB 209670, on circulatory failure and organ injury in endotoxic shock in the anaesthetized rat.

1. This study investigates the effects of the non-selective ETA/ETB receptor antagonist, SB 209670, on systemic haemodynamics, renal function, liver function, acid-base balance and survival in a rat model of endotoxic shock. 2. Injection of E. coli lipopolysaccharide (LPS, 10 mg kg-1, i.v.) resulted in increases in the serum levels of tumour necrosis factor-alpha (TNF-alpha, maximum 60 min after LPS), endothelin-1, (ET-1; maximum 120 min after LPS), and interferon-gamma (IFN-gamma, maximum 180 min after LPS). 3. Injection of LPS also resulted in a fall in blood pressure from 113 +/- 3 mmHg (time = 0) to 84 +/- 4 mmHg at 360 min (n = 15) as well as a hyporeactivity to the vasoconstrictor responses elicited by noradrenaline (NA, 1 microgram kg-1, i.v.). Pretreatment of rats with a continuous infusion of SB 209670 (3 mg kg-1, i.v. bolus + 100 micrograms kg-1, i.v. infusion commencing 15 min prior to LPS) significantly augmented the hypotension as well as the vascular hyporeactivity to NA caused by endotoxaemia. 4. Pretreatment of LPS-rats with SB 209670 (3 mg kg-1, i.v. bolus given 15 min prior to LPS) or infusion of SB 209670 (bolus dose and infusion as above) resulted in a reduction in 6 h-survival from 71% (control) to 30% and 13%, respectively. 5. Endotoxaemia for 4 h resulted in rises in the serum levels of urea and creatinine (indicators of renal failure), but not in the serum levels of bilirubin, GPT and GOT (indicators of liver dysfunction and/or hepatocellular injury). Pretreatment of LPS-rats with SB 209670 (3 mg kg-1, i.v. bolus 15 min prior to LPS) significantly augmented the serum levels of creatinine, bilirubin, GPT and GOT caused by endotoxin. In addition, endotoxaemia caused, within 15 min, an acute metabolic acidosis (falls in pH, HCO3- and base excess) which was compensated by hyperventilation (fall in PaCO2). Pretreatment of LPS-rats with SB 209670 (3 mg kg-1, i.v. bolus) significantly augmented the metabolic acidosis caused by LPS. 6. Thus, the non-selective ETA/ETB receptor antagonist, SB 209670, augments the degree of (i) hypotension, (ii) vascular hyporeactivity to noradrenaline, (iii) renal dysfunction and (iv) metabolic acidosis caused by endotoxin in the anaesthetized rat. In contrast to rats treated with LPS alone, LPS-rats treated with SB 209670 exhibited liver dysfunction and hepatocellular injury. We propose that the release of endogenous ET-1 serves to maintain blood pressure and subsequently organ perfusion in septic shock.

Acid-Base Equilibrium↗
PubMed2000

S-Methylisothiourea sulfate improves renal, but not hepatic dysfunction in canine endotoxic shock model.

OBJECTIVE: Excess production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathophysiology of septic shock. This study was designed to see whether S-methylisothiourea sulfate (SMT), a selective inhibitor for iNOS, prevents cardiovascular changes and multiple organ damage in the canine endotoxic shock model. DESIGN: Prospective, comparable, experimental study. SETTING: Laboratory at a university hospital. SUBJECTS: Twenty male mongrel dogs were studied under pentobarbital anesthesia. INTERVENTIONS: Dogs were divided into three groups: bacterial lipopolysaccharide (LPS) group (n = 7) receiving continuous infusion of LPS (2 mg/kg/h for 1 h); LPS plus SMT group (n = 7) receiving LPS and SMT (1 mg/kg, bolus i. v., followed by continuous infusion of 1 mg/kg/h for 1 h); and vehicle plus SMT group (n = 6). MEASUREMENTS AND RESULTS: Hemodynamics, blood gas parameters, and urine output were measured during 6 h observation periods. Serum levels of lactate, transaminases, and bilirubin were measured at baseline, 1 and 6 h. Creatinine and free water clearance, urine sodium excretion and fractional excretion of sodium were calculated. LPS caused a profound hypotension associated with decreases in cardiac output and oxygen delivery, lactic acidosis, renal and liver dysfunction, and thrombocytopenia. SMT prevented the LPS-induced hypotension and renal dysfunction, whereas it did not affect the LPS-induced decreases in cardiac output or oxygen delivery, hyperlactatemia, liver dysfunction, or thrombocytopenia. SMT alone had no appreciable effects on hemodynamics, blood gases, liver or renal functions. CONCLUSIONS: These findings show that SMT improves renal, but not hepatic dysfunction, in dogs with endotoxic shock, suggesting that iNOS-derived NO plays differential roles in sepsis-associated multiple organ dysfunction.

Animals↗
PubMed1983

Ascites-induced LeVeen shunt coagulopathy.

Ten of 11 patients undergoing peritoneovenous (LeVeen) shunt placement for intractable ascites had disseminated intravascular coagulation (DIC) following the shunt procedure. Intraoperative ascitic fluid specimens revealed fibrin split products (FSP) in high titer (1:100-1:1600) in all patients. Endotoxin was found in 6 of 11 ascitic fluid samples but in no plasma samples. Activated clotting factors, clot inhibitors, excess protein, and fibrinolytic activity were not found in ascitic fluid. Clotting factor levels were much lower than in plasma. Bleeding occurred after operation in two patients; this appeared to be related to the severity of liver dysfunction as demonstrated by elevations of bilirubin, serum glutamic oxalocetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and preoperative DIC. It is concluded that the LeVeen shunt coagulopathy is DIC, and may be related to exposure of the systemic circulation to FSP-rich ascitic fluid that may activate the coagulation mechanism. Bleeding complications do not appear to be related to the severity of the post shunt coagulopathy, but rather to the severity of liver dysfunction and presence of preoperative DIC (probably caused by the liver disease).

Adult↗