Pyridoxine deficiency and peripheral neuropathy associated with long-term phenelzine therapy

A 51-year-old, nonalcoholic, nondiabetic woman with sensorimotor peripheral neuropathy and pyridoxine deficiency associated with long-term phenelzine therapy is described. Since phenelzlne, like hydralazine and isoniazid, is a hydrazine capable of reducing pyridoxine levels in the rat, it is suggested that phenelzine, like hydralazine and isoniazid, may cause a pyrldoxine-responslve peripheral neuropathy in humans.     

Chronic treatment with the monoamine oxidase inhibitor phenelzine increases hypothalamic-pituitary-adrenocortical activity in male C57BL/6 mice: relevance to atypical depression

Atypical depression has been linked to low hypothalamic-pituitary-adrenocortical axis activity and exhibits physical and affective symptoms resembling those of glucocorticoid deficiency. Because atypical depression has also been defined by preferential responsiveness to monoamine oxidase inhibitors (MAO-I), we hypothesized that MAO-I reverse these abnormalities by interfering with glucocorticoid feedback and increasing hypothalamic-pituitary-adrenocortical activity. To test this hypothesis, we measured plasma hormones and ACTH secretagogue gene expression in male C57BL/6 mice treated chronically with saline vehicle or phenelzine, a representative MAO-I. Changes in glucocorticoid feedback were evaluated using adrenalectomized (ADX) mice with and without corticosterone replacement. Antidepressant efficacy was confirmed by decreased immobility during forced swim testing. Phenelzine significantly increased circadian nadir and postrestraint plasma corticosterone levels in sham-operated mice, an effect that correlated with increased adrenocortical sensitivity to ACTH. Phenelzine increased circadian nadir, but not poststress ACTH in ADX mice, suggesting that phenelzine augmented corticosterone secretion in sham-operated mice by increasing stimulation and decreasing feedback inhibition of hypothalamic-pituitary activity. Consistent with the latter possibility, phenelzine significantly increased plasma ACTH and paraventricular hypothalamus CRH mRNA in ADX, corticosterone-replaced mice. Phenelzine did not increase paraventricular hypothalamus CRH or vasopressin mRNA in ADX mice lacking corticosterone replacement. We conclude that chronic phenelzine treatment induces sustained increases in glucocorticoids by impairing glucocorticoid feedback, increasing adrenocortical responsiveness to ACTH, and increasing glucocorticoid-independent stimulation of hypothalamic-pituitary activity. The resulting drive for adrenocortical activity could account for the ability of MAO-I to reverse endocrine and psychiatric symptoms of glucocorticoid deficiency in atypical depression.     

Caval backflow: a potential problem during blood sampling from the hepatic vein

A proper measurement of splanchnic metabolism involves sampling blood from the hepatic vein without backflow contamination of blood from the caval vein. We have investigated the potential problem of caval backflow in human volunteers with an indwelling hepatic vein catheter by sampling blood with different amounts of suction on the syringe (ie, sampling speeds). We also investigated the potential problem in pigs in which a balloon catheter was inserted in the hepatic vein. Pure hepatic vein samples were obtained with the balloon inflated and compared with samples obtained from the same catheter in the conventional manner. In overnight fasted humans, drawing blood samples from the hepatic vein with minimal suction ("slow" drawing) resulted in glucose values 9.6% higher than drawing the samples with greater suction ("fast" drawing). The calculated arterial-venous balance across the splanchnic bed was 4.8 times greater with "slow" blood drawing as compared with "fast" drawing. Values obtained from the pigs showed no concentration differences between pure hepatic vein samples and "slow" drawing from the hepatic vein. The current study indicates that it is possible to obtain a "true" hepatic vein sample, but backflow from the caval vein is a potential pitfall that can have a physiologically significant impact on calculated balance data.     

Role of platelet-activating factor in pathogenesis of galactosamine-lipopolysaccharide-induced liver injury

In an attempt to clarify the role of platelet-activating factor (PAF) in the pathogenesis of hepatic injury induced by galactosamine (GalN) plus lipopolysaccharide (LPS), effects of WEB 2086 (PAF receptor antagonist) on hepatic injuryin vivo as well as on neutrophil adherence to hepatic endothelial cellsin vitro have been investigated, as we have recently clarified the role of neutrophils in this experimental model of hepatic injury. Although an enhanced serum TNF- level after GalN-LPS administration was not reduced by WEB 2086, hepatic injury and hepatic neutrophil accumulation in the liver after GalN-LPS administration were attenuated by WEB 2086. Anin vitro study revealed that an enhanced neutrophil adhesion to hepatic endothelial cells by stimulation with the sera that were collected from the GalN-LPS-treated rats, was reduced in the presence of WEB 2086 in a dose-dependent manner. In addition, LPS, TNF-, and PAF were found to enhance the neutrophil adherence to hepatic endothelial cells, which was reduced in the presence of WEB 2086. These results suggest that PAF play an important role in the GalN-LPS induced hepatic injury and that PAF receptor antagonist reduces the neutrophil adherence to hepatic endothelial cells in the liver.     

Myocardial H2O2 production in the unanaesthetized rat Influence of fasting,myocardial load and inhibition of superoxide dismutase and monoamine oxidase

Summary Myocardial H₂O₂ production was studied by means of the in vivo administration of aminotriazole (AT), which inactivates the catalase-H₂O₂ complex compound I. Measurements of the residual catalase activity in male and female rats indicate that -oxidation of fatty acids in peroxisomes does not contribute in a substantial way to energy production in response to fasting or to an increased myocardial load, despite previous data on peroxisomes in myocardium.Superoxide dismutase (SOD) inhibition by diethyldithiocarbamate demonstrates that SOD participates in the production of H₂O₂ in physiological conditions. Such a role was not demonstrated for monoamine oxidase through inhibition by phenelzine.     

Phenelzine associated peripheral neuropathy—clinical and electrophysiologic findings

Phenelzine associated sensorimotor peripheral neuropathy is reported in two patients. Symptoms were predominantly sensory, and improvement occurred after withdrawal of phenelzine. Electrophysiologic findings were consistent with an axonal process.     

Vascularite de l’artère hépatique : à propos d’un cas d’atteinte d’organe isolée

Introduction

Vasculitis usually have a systemic involvement. Rare cases of localized vasculitis have been described, but the exclusive involvement of the hepatic artery is exceptional. We report the case of a patient who developed a vasculitis of the right and left hepatic arteries.

First results on the effects of MAO inhibition on cognitive functioning in elderly depressed patients

Elderly depressed patients who met the Research Diagnostic Criteria (RDC) for major depressive illness, were treated with phenelzine, a non-selective monoamine oxidase inhibitor, for a period of 2 to 7 wk, following 2 wk of placebo washout period. Possible pre- and post-treatment differences on the cognitive test battery were evaluated using the Wilcoxon test. Although recovery from depression was obtained in the majority of patients (Hamilton, Global and Self-rating Scales), none of the cognitive measures showed statistically significant changes over the course of the treatment period and the cognitive tests scores did not change as a result of treatment. It is of interest that tricyclic antidepressants (TCAs) are known to impair memory in geriatric patients, presumably due to their sedative and anticholinergic effects. The lack of an adverse cognitive effect for phenelzine therefore suggests a possible advantage of monoamine oxidase inhibitors over tricyclic antidepressants for the treatment of geriatric depression.     

Interaction of iron,insulin resistance,and nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) has emerged as a ubiquitous liver disorder with occasional serious overtones. Although diabetes and obesity were initially held culpable, insulin resistance (IR) is now considered the fundamental operative mechanism. IR is probably the "first step" in nonalcoholic steatohepatitis (NASH). Oxidative stress may be the elusive "second" of possibly multiple steps in the progression of steatosis to fibrosing steatohepatitis. Because hepatic iron promotes oxidative stress, it was mooted as a contributory cofactor in NASH. This proposal was strengthened by an association with hepatic fibrosis. Subsequent studies have shown neither a significant increase in hepatic iron nor an association between hepatic iron and any of the histologic determinants in NASH. Likewise, the increased prevalence of hemochromatosis gene (HFE) mutations in some studies appears to be largely irrelevant to the development of hepatic fibrosis. Excess hepatic iron may occur in insulin resistance-associated iron overload (IRHIO), characterized by hyperferritinemia with normal to mild increases in transferrin saturation. Although patients with IRHIO have a high prevalence of IR-related metabolic disorders, the relationship of IRHIO to NASH is unclear. A recent study showed improvement in insulin sensitivity with the use of venesection in patients with NAFLD, but this approach cannot be implemented without extensive review.     

抗脂肪肝冲剂对大鼠乙醇性肝损伤防治的实验研究

目的：探讨抗脂肪肝冲剂对乙醇性肝损伤大鼠脂质代谢的影响,寻找针对乙醇所致脂肪肝的有效药物,方法：采用乙醇慢性肝损伤模型,观察大鼠肝组织总胆固醇（TC）,及甘油三酯（TG）的含量,结果：抗脂肪肝冲剂降低乙醇性肝损伤大鼠肝组织TC,TG的含量,与模型组比较P＜0．05（小剂量组）,P＜0．01（中,大剂量组）,病理检查,抗脂肪冲剂各剂量组与模型组比较P＜0．01,结论：抗脂肪肝冲剂能够降低乙醇性肝损伤大鼠肝组织TG,TC的含量,具有防治乙醇性脂肪肝的作用。     

Effect of phenformin on hepatic balances of gluconeogenic substrates in man

Summary The effect of a five day pretreatment with phenformin (3 x 50 mg daily) on hepatic metabolism was studied in six healthy volunteers. Arterial and hepatic venous concentrations of substrates and hepatic blood flow were estimated during a basal period and during a low-dose lactate infusion (0,03 mmol · kg^–1· min^–1). The results have been compared with those obtained from untreated normal subjects in a previous study (16). During the baseline period arterial concentration of alanine and the hepatic venous concentration ratios of alanine: pyruvate and-hydroxybutyrate: acetoacetate were significantly increased with phenformin treatment, while the balances of carbon dioxide and glucose and the fractional extraction of alanine were decreased compared to the values obtained in untreated subjects. During lactate infusion mean arterial lactate concentration was significantly increased and hepatic lactate extraction was decreased compared to untreated persons under the same conditions. In the phenformin-treated group lactate infusion resulted in hepatic output of pyruvate and the hepatic glucose balance remained unchanged compared to baseline. Since the rate of hepatic blood flow was not increased during lactate infusion a significantly smaller glucose output and lactate uptake was obtained with phenformin. These findings support the present view that the hypoglycaemic effect of biguanides is due, at least in part, to inhibition of hepatic gluconeogenesis.     

Complete eradication of hepatic metastasis from colorectal cancer by Yttrium-90 SIRT

Yttrium-90 (Y-90) radioembolization,also known as selective internal radiation therapy (SIRT),is a regional hepatic therapy used in the treatment of unresectable colorectal cancer (CRC) liver metastases. In SIRT,Y-90 impregnated microspheres are injected into the VASCULAR SUPPLY of hepatic tumor,leading to selective irradiation and necrosis of tumor TISSUE. While several studies demonstrate improved local control and survival with SIRT,the specific indications for this therapy have yet to be defined. Typically,SIRT is given in combination with chemotherapy as multimodal treatment for unresectable hepatic CRC. However,it HAS ALSO FOUND INCREASING USE as a salvage therapy in chemo-refractory patients. Herein,the authors describe their experience with SIRT as "stand alone" therapy in a surgically-prohibitive,chemotherapy naive patient with hepatic CRC metastasis. The results suggest that Y-90 SIRT may have potential applications beyond its usual role as a palliative or salvage therapy for unresectable hepatic CRC.     

Early experience employing a linear hepatic parenchyma coagulation device

Background. In recent years, hepatic resection for primary and metastatic disease has been facilitated by improved anesthetic and surgical techniques, as well as by the application of new technologies. Historically, the major complications associated with hepatic resection have been postoperative bleeding, bile leak, and liver failure. Resection techniques and devices that minimize hemorrhage and bile leak, and enable the preservation of functional hepatic parenchyma, have been useful in the surgical management of liver tumors.Methods. Herein, the use of a radiofrequency powered device for the pretransection coagulation of hepatic tissue that simultaneously seals blood vessels and bile ducts 3?mm in diameter or smaller is described.Results. Early results from our single-center experience with the use of this linear radiofrequency device are reported. Seven patients underwent liver resection for either hepatocellular carcinoma or colorectal cancer metastases. There were no postoperative bile leaks, hemorrhage, or hepatic insufficiency. No transfusions were required, and the mean estimated blood loss for the parenchymal transection phase was less than 165?cc.Conclusions. The linear radiofrequency device is expedient for the pretransection coagulation of hepatic tissue and, thus, facilitates liver resection.     

Effects of antihyperlipidemic agents on hepatic insulin sensitivity in perfused Goto-Kakizaki rat liver

Background We previously reported that the Goto-Kakizaki (GK) rat, an animal model of type 2 diabetes, has hepatic insulin resistance using a perfused rat liver model. Pioglitazone, eicosapentaenoic acid (EPA), and fenofibrate are antihyperlipidemic agents and improve glucose tolerance. There have been few studies showing that these agents directly improve hepatic insulin sensitivity in type 2 diabetes mellitus. The aim of this study was to explore the effects of these agents on hepatic insulin sensitivity directly using a perfused GK rat liver model.Methods GK rats were treated with oral pioglitazone (6 or 10mg/kg body weight), EPA (1 or 2g/kg body weight), or fenofibrate (30mg/kg body weight) for 2 weeks. Livers were perfused in situ with glucagon or with glucagon and insulin, and hepatic glucose outputs were measured.Results In the pioglitazone-treated GK rats, blood glucose levels were significantly decreased. In the pioglitazone- and EPA-treated GK rats, insulin infusion significantly attenuated hepatic glucose output stimulated by glucagon. In the fenofibrate-treated GK rats, fat deposits in the hepatocytes were decreased, and glucose output elicited by glucagon was significantly decreased compared with that in the untreated GK rats, whereas insulin infusion did not affect glucose output by glucagon.Conclusions These findings suggest that pioglitazone and EPA may improve glucose tolerance by directly increasing hepatic insulin sensitivity, while fenofibrate may improve glucose tolerance by improving hepatic glycogen metabolism in the GK rats.     

Surgical Improvement of Hepatic Venous Mixing to Resolve Systemic Arterial Hypoxemia Associated with Post-Fontan Pulmonary Arteriovenous Fistulae

Pulmonary arteriovenous fistulae are known to develop in patients who have functional single-ventricle heart disease and interruption of the inferior vena cava with direct hepatic drainage to the heart, in which a bidirectional Glenn shunt is the only source of pulmonary blood flow. The progressive systemic arterial hypoxemia that is associated with pulmonary arteriovenous fistulae can have important clinical consequences. Baffling the hepatic venous return to the pulmonary circulation can alleviate pulmonary arteriovenous fistulae.Herein, we present the case of a 13-year-old patient with modified Fontan anatomy and pulmonary arteriovenous fistulae, in whom redirection of a previously placed hepatic venous-to-right pulmonary artery conduit was required in order to increase systemic arterial oxygen saturation. Revision of the conduit improved mixing of hepatic venous effluent with blood flow from the bidirectional Glenn shunt. Three years after this revision, the patient''s oxygen saturation remained stable at 90%, and his physical activity was markedly improved. We present our rationale for selected redirection of the conduit and discuss other surgical options that can improve hypoxemia that is associated with pulmonary arteriovenous fistulae.Key words: Arteriovenous fistula/physiopathology/surgery, arteriovenous malformations/etiology/surgery, Fontan procedure/adverse effects/methods, heart defects, congenital/surgery, hepatic veins/physiology/surgery, postoperative complications/etiology/physiopathology/surgery, vena cava, inferior/abnormalities/surgery, pulmonary artery/surgery, regional blood flow/physiology, reoperationPulmonary arteriovenous fistula (PAVF) can develop in patients who have undergone placement of a bidirectional Glenn shunt for single-ventricle heart disease that is associated with interruption of the inferior vena cava (IVC) and direct hepatic venous drainage to the heart.^1,2 The progressive systemic arterial hypoxemia that is associated with PAVF can have important clinical manifestations. It has been reported that baffling hepatic venous return to the pulmonary circulation can alleviate PAVF. Here, we present and discuss the case of a 13-year-old modified-Fontan patient with PAVF, in whom redirection of a previously placed hepatic venous-to-right pulmonary artery (PA) conduit was required in order to overcome unfavorable streaming and to increase systemic arterial oxygen saturation levels.     

A report on three patients with <Emphasis Type="Italic">Echinococcus multilocularis</Emphasis>: Lessons learned

Echinococcus multilocularis (EM) is the most virulent species of the genus Echinococcus. It causes a highly lethal helminthic disease in humans. The disease may present as hepatic mass mimicking a malignant neoplasm. Due to the vascular and neural invasion, protean clinical manifestations including Budd-Chiari syndrome (BCS) may be the clinical presentation of this condition. We herein report three cases of Echinococcus multilocularis; the first case presenting as multiple hepatic space-occupying lesions, second as liver mass infiltrating the nerve bundles, and the third as a hepatic mass infiltrating the large vessels including inferior vena cava and right hepatic vein presenting as BCS. EM is a parasite with capabilities of mass-forming effect, neural and vascular invasion. Though cases of BCS have been described, most of these are due to secondary compression and rarely by direct parasitic invasion.     

Effect of hepatic iron concentration reduction on hepatic fibrosis and damage in rats with cholestatic liver disease

AIM: To assess the effect of iron reduction after phlebotomy in rats with "normal" hepatic iron concentration (HIC) on the progression of hepatic fibrosis, as a result of bile duct ligation (BDL). METHODS: Rats underwent phlebotomy before or after sham operation or BDL. Animals undergone only BDL or sham operation served as controls. Two weeks after surgery, indices of hepatic damage and fibrosis were evaluated. RESULTS: Phlebotomy lowered HIC. Phlebotomy after BDL was associated with body weight increase, lower hepatic weight, less portal hypertension, less periportal necrosis, less portal inflammation, lower hepatic activity index score and higher albumin levels. On the other hand, phlebotomy before BDL was associated with body weight decrease and hepatic activity index score increase. Phlebotomy after sham operation was not associated with any hepatic or systemic adverse effects. CONCLUSION: Reduction of HIC after induction of liver damage may have beneficial effects in BDL rats. However, iron deficiency could induce impairment of liver function and may make the liver more susceptible to insults like BDL.     

Hepatic abscesses as a complication of the sump syndrome: combined surgical and endoscopic therapy. Case report and review of the literature

The "sump syndrome" is an unusual complication of side-to-side choledochoduodenostomy in which the portion of the common bile duct distal to the anastamosis acts as a sump and may collect bile, stones, food, and other debris. Partial or complete obstruction of the stoma and resultant bacterial proliferation may result and lead to recurrent cholangitis or pancreatitis. A single hepatic abscess as a complication of the sump syndrome has been reported only once. We have recently seen a patient presenting with multiple hepatic abscesses as a complication of the sump syndrome. This is the first report of endoscopic treatment of this syndrome associated with a hepatic abscess. The literature on the endoscopic approach to this problem will be reviewed.     

Adenosine influences the high-affinity uptake of transmitter glutamate and aspartate under conditions of hepatic encephalopathy

The high-affinity uptake of transmitter glutamate and aspartate in hippocampal slices incubated in sera from patients with hepatic encephalopathy was dramatically reduced in neuropil areas by more than 50 % compared with the control level. Adenosine compensates for these reduction in reuptake capacity in a concentration-dependent fashion reaching normal values at 500 M adenosine. The renormalization of glutamate and aspartate uptake caused by adenosine might reasonably be expected to have potential therapeutic implications for the treatment of hepatic encephalopathy.