Complete heteronuclear NMR resonance assignments and secondary structure of core binding factor beta (1-141)

We report a patient who developed significant liver dysfunction following therapy with terbinafine. At the end of a 3 1/2-wk course of terbinafine, he developed progressive jaundice and pruritus. His serum bilirubin peaked at 30.9 mg/dl 3 wk after discontinuing terbinafine. A liver biopsy revealed mild to moderate mixed cellular infiltrate in the portal tracts, and hepatocellular and canicular cholestasis. His liver tests normalized 100 days after stopping terbinafine.     

Hepatocellular carcinoma complicating biliary cirrhosis caused by biliary atresia: report of a case

A case of hepatocellular carcinoma complicating biliary cirrhosis caused by biliary atresia is reported. The patient had persistent severe jaundice with hepatosplenomegaly. A liver tumor was suspected because of the elevated serum alpha-fetoprotein and was shown by ultrasonography at 6 years of age. The tumor was treated with percutaneous ethanol injection therapy (PEIT). Nine months after initiation of PEIT, the patient died of massive bleeding from a metastatic tumor.     

Hepatitis caused by antidepressive therapy with maprotiline and opipramol

There are few published reports of antidepressive therapy induced hepatotoxicity. In most cases antidepressants cause only slight elevation of liver enzymes without clinical relevance. However, our patient with recidivation of unipolar depressive disorder developed severe laboratory abnormalities and clinical symptoms during therapy with maprotiline (Ludiomil) and opipramol (Insidon). To our knowledge, this is the first case report of bioptically proven severe acute hepatitis caused by these antidepressants. After their withdrawal, the patient's fatigue symptoms, scleric jaundice, and marked increase of liver enzymes completely disappeared. Hepatic side effects should be considered during antidepressive therapy with maprotiline and opipramol especially when additional clinical symptoms emerge.     

Granulomatous hepatitis attributed to the combination pyrimethamine-chloroquine

After her holiday in South Africa, a 50-year-old woman was admitted because of fever and pain in the upper abdomen. The laboratory tests showed moderately increased serum liver enzyme activities. The liver biopsy showed a granulomatous hepatitis. Further investigations revealed no evidence for sarcoidosis, tuberculosis or infectious hepatitis, nor for other granulomatous diseases or infectious diseases relevant to South Africa. Upon discontinuation of the malaria prophylaxis with Daraclor (pyrimethamine and chloroquine (sulphate)) the symptoms disappeared and the liver function tests returned to normal. It was concluded that Daraclor was the probable cause of granulomatous hepatitis in this patient. This adverse effect was not published before.     

Mutations of p53 gene can be detected in the plasma of patients with large bowel carcinoma

A 55-year-old woman was admitted because of progressive jaundice. Blood examination on admission revealed markedly elevated serum levels of CA19-9 and SPAN-1. Abdominal computed tomography revealed a large tumor in the head of the pancreas. Although the patient's jaundice and elevated CA19-9 decreased after percutaneous franshepatic cholangio-drainage, her SPAN-1 level remained elevated. Open biopsy of the pancreatic tumor revealed non-Hodgkin's lymphoma (NHL) (diffuse medium, B cell type), Complete remission was obtained after one course of CHOP therapy. This case suggests that pancreatic tumor with elevated serum CA19-9 and SPAN-1 levels may involve NHL, and may be curable with chemotherapy.     

Polyethylene glycol-modified bilirubin oxidase improves hepatic energy charge and urinary prostaglandin levels in rats with obstructive jaundice

BACKGROUNDS/AIMS: No study has so far been conducted to clarify whether the presence of hyperbilirubinemia is detrimental to liver and renal functions. In the present study, the effects of polyethylene glycol-modified bilirubin oxidase (PEG-BOX) therapy on liver and renal function tests, hepatic energy charge and urinary prostaglandin levels were evaluated in a rat model of obstructive jaundice. METHODS: Sprague-Dawley rats were used in the experimental model of obstructive jaundice. PEG-BOX or an equivalent amount of PEG alone was intravenously injected into the animals and sampling of blood and urine, and liver harvesting were done sequentially after bile duct ligation. RESULTS: Conventional liver function tests showed no difference between PEG-BOX and control groups. However, bilirubin concentrations in the peripheral blood and liver tissue specimens markedly decreased, and the hepatic energy charge significantly increased in the PEG-BOX group as compared to controls. The blood concentration of bile acid was lower, but its urinary excretion was higher in the PEG-BOX group than in the control group. In vitro incubation of PEG-BOX with serum from rats with obstructive jaundice decreased the concentration of bilirubin but not that of bile acid. The urinary levels of prostaglandin E2 and the thromboxane B2/6-keto-prostaglandin Fla ratio were significantly lower in the PEG-BOX group than in the control group. CONCLUSIONS: The systemic reduction of bilirubin concentration may contribute to normalization of the urinary levels of prostaglandins and thromboxane B2, to decrease in serum bile acid levels, and to improvement of the hepatic energy charge in obstructive jaundice. These findings suggest that preoperative improvement of jaundice may be beneficial to patients with obstructive jaundice.     

Techniques for rapid quantitative assessment of activity levels in small-group tutorials

OBJECTIVE: To describe a case of pemoline-induced liver failure resulting in liver transplantation. CASE SUMMARY: A 9-year-old white boy, diagnosed with attention deficit/hyperactivity disorder (ADHD) and treated with pemoline, developed signs and symptoms of liver failure. Pemoline therapy was discontinued, but the patient's liver function continued to decline. Ultimately, a liver transplantation was required. DISCUSSION: Pemoline, an agent used in ADHD treatment, has been associated with hepatotoxicity with the majority of cases occurring in pediatric patients. To our knowledge, this is the second reported case of pemoline-induced liver failure resulting in liver transplantation. The mechanism of action remains unclear, with several hypotheses being postulated including hypersensitivity reactions, dose-related phenomena, and autoimmune-mediated reactions. CONCLUSIONS: With increasing evidence linking pemoline to liver failure, this agent should not be considered first-line therapy for ADHD. Prior to initiating therapy, baseline liver function tests should be obtained and closely monitored, and parents and patients should be educated on the signs and symptoms of liver toxicity.     

Droxicam-induced hepatitis. Description of 3 new cases and review of the literature

Three new cases of cholestatic hepatitis caused by droxicam are described, along with a revision of the other eight cases published to date. Itching, asthenia, and jaundice were the most common symptoms. Average age was 62.8 years (range: 45-82 years), and the median time of exposition was 22.7 days (range: 5-50 days). Biochemistry of the liver showed primarily cholestasis and in 4/11 cases hypereosinophilia. Two patients presented elevated levels of cholesterol and triglycerides which disappeared within the month. Clinical manifestations persisted in one patient for eight weeks after the cessation of treatment. The three patients presented in the present series presented alteration in the biochemistry of the liver two months after initiation. Liver biopsy in three patients showed centrozonal cholestasis associated with portal inflammatory activity and presence of granulomas consistent with toxic hepatitis.     

Liver cell necrosis during administration of clozapine

A 38-year-old woman was treated for mutism with clozapine. After a week liver function disturbances developed, which disappeared when the treatment was discontinued. Histopathological investigation of a liver biopsy specimen revealed extensive liver cell necrosis. So far two patients have been described with cholestatic jaundice induced by clozapine, and one patient with toxic hepatitis due to clozapine.     

Lithium regulation of protein phosphorylation in rat cerebral cortex slices in vitro

Histamine type 2 receptor antagonists (H2RAs) have been found to alter gastric motility. The aims of this study were to determine if H2RAs affect antral contractility in vitro and the mechanism of this effect. Guinea pig antral muscle strips were pinned in an organ bath after removing the mucosa, and circular muscle tension was measured using an isometric force transducer. Gastric myocytes were isolated from guinea pig stomach using collagenase digestion, and cell lengths were measured using an image analysis system. In muscle strips, ranitidine and nizatidine increased the amplitude of spontaneous phasic antral contractions in a concentration-dependent fashion with threshold concentrations of 5 microM. The order of potency for the H2RAs was ranitidine = nizatidine > cimetidine > famotidine. The contractile effects of ranitidine and nizatidine were reduced, but not abolished, by tetrodotoxin and omega-conotoxin GVIA and nearly abolished by atropine. In isolated cells, ranitidine and nizatidine, but not famotidine or cimetidine, induced concentration-dependent cell shortening, with maximal shortening at 10 microM. These contractile effects of ranitidine and nizatidine in isolated cells were inhibited by atropine. Ranitidine and nizatidine increase antral contractility; this effect appears to be mediated by an interaction between ranitidine and nizatidine on cholinergic pathways with both direct effects on smooth muscle cholinergic receptors and indirect effects by increasing cholinergic neurotransmission.     

Effect of standard and high dose ranitidine on [13C]urea breath test results

OBJECTIVE: It has been suggested that standard dose H2 blockers will affect the [14-C]urea breath test. The aim of this study was to evaluate the effect of standard and high dose ranitidine on the [13C]urea breath test in a prospective cross-over study. METHODS: Volunteers found to be positive for H. pylori by IgG serology and [13C]urea breath test were given either ranitidine 150 mg b.i.d. or 300 mg b.i.d. for 14 days. Repeat breath tests were completed on the last day of antisecretory dosing and study patients were immediately crossed over to the other ranitidine dose. The third breath test was performed at 14 days after initiation of the new dose. RESULTS: A total of 20 volunteers were enrolled. Using the established cut-off of 2.4% for the commercial breath test, only one patient developed negative results on H2 blockers. This patient had negative breath tests on both ranitidine doses and remained test-negative off all medications 6 wk after study completion, suggesting either a false positive baseline test or an unexpected bacterial eradication. No specific trend in breath test results was observed for the group (p=NS). On ranitidine 300 mg, six of 19 patients elevated their breath results from 23% to 112% (mean 76%) above baseline. CONCLUSION: Ranitidine at standard or high doses did not generate a reproducible decline in breath test results. Histamine 2 blockers do not need to be discontinued before urea breath testing.     

Evaluation of somatostatin analogues for the detection and treatment of gastrinoma in a dog

Gastrinomas in dogs are difficult to diagnose, localise and treat. In humans, somatostatin analogues have improved localisation and treatment of gastrinomas. The somatostatin analogues pentetreotide and octreotide were evaluated for the detection and treatment of gastrinoma in a dog. 111indium-pentetreotide scintigraphy revealed multiple areas of activity in the patient's mid-ventral abdomen which were consistent with masses in the pancreas and liver at laparotomy. Immunohistochemistry, electron microscopy and binding of 125I-[Tyr3]-octreotide in vitro confirmed the lesion as a gastrinoma which expressed somatostatin receptors. Octreotide at doses of 2, 4 and 8 micrograms/kg caused transient decreases in circulating gastrin. Plasma somatostatin peaked at one hour after octreotide and was still detectable at four and six hours after administration of octreotide. Combination therapy with famotidine, omeprazole, sucralfate and increasing doses of octreotide allowed patient survival for 14 months.     

The isolated choroid plexus cyst

A 48-year-old asymptomatic male hepatitis B virus carrier presented with a 2-day history of fever, chills, right upper quadrant abdominal pain, and jaundice. Shock was detected on admission. Emergency abdominal computed tomography (CT) scanning without contrast enhancement showed the features of acute pancreatitis. Hemobilia, edematous pancreatitis, cholestasis and cholecystitis were found on exploratory laparotomy. Neither stone nor active bleeding were detected on intraoperative choledochoscopic examination. Postoperative T-tube cholangiography one month later revealed non-opacification of the left intrahepatic duct. The patient's abdominal pain and hemobilia recurred. Celiac angiography and CT scanning with contrast showed two hepatocellular carcinomas (HCC) in the left lobe of the liver. This is the first case report in the English literature of HCC presenting as jaundice, hemobilia, and acute pancreatitis.     

Pregnancy and delivery after liver transplantation

The first case of pregnancy in a patient after an orthotopic liver transplantation (OLT) in Poland is presented. A 21-year-old woman was liver grafted 3 years prior to the pregnancy. Before having conceived the patient's graft function was stable. The woman was on immunosuppressive therapy with cyclosporine A and prednisolone. During pregnancy no significant changes in biochemical tests of liver function and liver blood flow were noted. Starting at the second trimester, a slight anemia occurred and the quantity of blood platelets continued to decrease, the latter having been observed immediately after the transplantation. The intrauterine growth of the fetus was monitored by ultrasound and the assessment of blood flow to the placenta was made. No abnormality was observed. In the second and third trimester the presence of HCV-RNA in the serum was found. In the 41-st week of pregnancy labor commenced. The threat of intrauterine infection indicated a cesarean delivery. The newborn weighed 4180 g and had an Apgar score of 10. The cesarean section, as well as puerperium, was normal. The immunosuppressive therapy was continued, and antibiotics were administered for prophylactic reasons. During the first month the infant was treated with antibiotics because of pneumonia and the suspicion of meningitis. Nine months after the delivery, the patient's health is satisfactory and the baby is making normal progress.     

Hong Kong''s eastern and western medical history

BACKGROUND: Some clinical studies suggest that a combination of an H1- and H2-antagonist may be effective in the prophylaxis of allergic reactions. OBJECTIVE: The efficacy of pretreatment with an H1/H2-antagonist combination, H1-antagonist alone, or placebo in the prophylaxis of local and systemic adverse reactions to specific immunotherapy with Hymenoptera venom was compared. METHODS: In a prospective, randomized, double-blind, placebo-controlled study, 121 patients with Hymenoptera venom allergy were treated with rush immunotherapy and pretreatment with one of the following: 120 mg of terfenadine plus 300 mg of ranitidine, 120 mg of terfenadine alone, or placebo. The incidence of unwanted systemic adverse and local reactions was recorded for up to 50 weeks. RESULTS: In seven patients (6%), six in the placebo group and one in the terfenadine group, systemic side effects required cessation of therapy (p = 0.005). Subjective symptoms occurred in four patients (10%) in the terfenadine plus ranitidine group and in three patients (7%) in the terfenadine group. Regarding local reactions, significantly fewer patients treated with a combination of terfenadine and ranitidine and with terfenadine alone as compared with placebo had severe local symptoms of erythema (29%, 29%, and 49%), edema (24%, 18%, and 41%), and pruritus (13%, 11%, and 31%) at week 1 (p < 0.05). This therapeutic benefit was limited to the first 4 weeks of treatment. Treatment with a combination of terfenadine and ranitidine was not superior to treatment with terfenadine alone. CONCLUSIONS: Pretreatment with H1-antihistamines with or without H2-antihistamines significantly reduced local and systemic adverse reactions to immunotherapy with Hymenoptera venom and may therefore be helpful in the management of immunotherapy.     

Should recurrent Cytomegalovirus infections in patients with liver transplantation be treated?

Cytomegalovirus (CMV) is the single most important viral pathogen in organ transplantation. Treatment strategy for CMV infection and disease is not well established in transplantation. We report a case of primary CMV infection and two relapses in a woman with a liver transplant in whom spontaneous clearing of the second CMV relapse was seen. A 23 year-old CMV-seronegative woman received a liver transplant with a CMV-negative organ. Six weeks after transplantation she had her primary CMV infection proved by seroconversion and virus isolation. She had no clinical symptoms. Treatment with ganciclovir for five weeks resulted in declining CMV-antigen positive cells from 300/200.000 PMNs to CMV-antigen negativity. Only a slight antibody response was seen. At week 13 the first relapse occurred evidenced by antigenaemia. Ganciclovir was reinstituted for six weeks resulting in reduced antigenaemia. At week 22 liver biopsy was performed due to slightly elevated ALAT. The biopsy showed evidence of focal CMV hepatitis and blood analysis showed 120 CMV-antigen positive cells/200.000 PMNs. In spite of this, ganciclovir was not reinstituted, but the immunosuppressive treatment was reduced to a minimum to stimulate the patient's immune response to CMV. During the following months the patient gradually developed IgG antibody, cleared the antigen and levels of liver enzymes returned to normal. We suggest that ganciclovir treatment, may be omitted in cases of relapse with minimal clinical symptoms, slight antigenaemia and a beginning antibody response and that, the immunosuppressive treatment should be reduced instead. Such an approach requires careful clinical monitoring of the patient.     

Effects of intravenous lansoprazole on acute gastric mucosal lesions and acid secretion

The effects of lansoprazole given intravenously on gastric mucosal lesions, gastric bleeding and acid secretion were investigated in rats in comparison with those of omeprazole, famotidine and ranitidine. Lansoprazole inhibited the formation of gastric mucosal lesions in rats induced by water-immersion stress or aspirin with ID50 values of 0.26 and 0.99 mg/kg, respectively, and also inhibited gastric bleeding induced by hemorrhagic shock or water-immersion stress with ID50 values of 0.46 and 1.22 mg/kg, respectively. Lansoprazole was more potent than omeprazole, famotidine and ranitidine in inhibiting gastric mucosal lesions and hemorrhagic shock- or stress-induced bleeding. Famotidine and ranitidine showed negligible inhibition of water-immersion stress-induced gastric bleeding. Lansoprazole strongly inhibited water-immersion stress-stimulated acid secretion in rats, whereas famotidine and ranitidine did not show a potent inhibitory effect. These results indicate that lansoprazole exerts prominent inhibitory actions against the formation of gastric mucosal lesions and gastric bleeding by inhibiting acid secretion, and they show that it is superior to histamine H2-receptor antagonists in inhibiting stress-induced gastric bleeding.     

DEFPARAM: a program package for aligning elliptical sections of biological objects containing an n-fold symmetry

BACKGROUND: Oesophageal candidiasis is the most common cause of oesophageal symptoms in patients with AIDS. Antifungal therapy, given as a suspension, may be better tolerated than capsules or tablets in children or patients with oesophageal symptoms. We performed a prospective study of the safety and efficacy of fluconazole suspension. METHODS: Patients with HIV infection; odynophagia, dysphagia, or retrosternal pain; endoscopic evidence of white plaques or exudate in the oesophagus; and microscopic confirmation of fungal infection on biopsy or brushing specimens were eligible. Patients received fluconazole oral suspension (200 mg loading dose followed by 100 mg q.d.s.). Therapy was continued for 2 weeks after symptom resolution. Repeat endoscopy was performed after completion of therapy. RESULTS: Forty-two patients enrolled in the study: 40 were male, mean (+/- s.e.) age was 37 +/- 2 years and mean CD4 cell count was 67 +/- 14/mm3. One patient was not evaluable because he received amphotericin during the first week of therapy. Symptoms resolved in all 41 evaluable patients; 17 (41%) had resolution by 1 week, 37 (90%) by 2 weeks, and 40 (98%) by 3 weeks. Endoscopic resolution occurred in 35 (95%) of 37 patients who underwent repeat endoscopy. Adverse events (skin rash in 1, nausea/vomiting in 2, elevated liver tests in 2) led to early termination of therapy in 5 patients, all of whom had clinical and endoscopic cure. CONCLUSIONS: Symptoms resolved in 100% of patients with AIDS and oesophageal candidiasis receiving an oral suspension of fluconazole, and 90% of patients had symptom resolution within 2 weeks. Determining whether the more rapid clinical cure in this study, compared with a previous trial which employed capsules, is related to an additional topical antifungal effect of the suspension, will require further study.     

Severe hepatocellular damage after administration of paracetamol and chlorzoxazone in therapeutic dosage

A 64 year old patient developed severe hepatocellular damage with jaundice and coagulopathy during ingestion of a combination of paracetamol and chlorzoxazone in therapeutic dosage. The risk factors for the development of liver cell necrosis following ingestion of paracetamol in therapeutic dosage are discussed. In particular in patients with risk factors (e.g. alcoholics and patients with heart failure) paracetamol-induced liver failure has to be considered in the presence of high transaminases, even when paracetamol was ingested in therapeutic dosage. Chlorzoxazone itself rarely can induce an idiosyncratic hepatocellular damage.