Liver-cell adenomas with heavy iron deposition.

We report 3 unusual cases of liver cell adenomas with some uncommon features, corresponding to 3 women aged 45, 37, and 41 years, respectively. The diagnosis was incidental in 2 cases, and the third presented with abdominal pain. Radiologic findings were consistent with liver-cell adenoma, but gross examination failed to reveal the lesion until 24 hours of formalin fixation in 2 cases. Histopathological examination showed a striking deposition of iron pigment. In fact, Pearl's stain was the best way to visualize the limits of the neoplasm, which were irregular (pseudo-infiltrative). There was no evidence of other architectural or cytologic features suggesting an alternative diagnosis, particularly liver-cell carcinoma. Follow-up ranged from 9 months to 6 years and all patients are free of disease.

Liver disease in heavy drinkers with and without alcohol withdrawal syndrome.

BACKGROUND: Withdrawal syndrome is a hallmark of alcohol dependence. The characteristics of alcohol consumption, closely related to dependence, could influence the development of alcoholic liver disease. The study aimed to investigate if patients with severe alcohol withdrawal syndrome have a peculiar profile of liver disease. METHODS: The study included 256 heavy drinkers (aged 19-75 years, 70.3% males) admitted to an Internal Medicine Department. Patients admitted for complications of liver disease were not included. Severe alcohol withdrawal syndrome (seizures, disordered perceptions, or delirium) developed in 150 patients (58.6%). Alcohol consumption (daily quantity, duration, and pattern [regular or irregular]) was assessed by questionnaire. Liver biopsy was performed in all cases. RESULTS: Patients with alcohol withdrawal syndrome showed a lower prevalence of liver cirrhosis and a higher prevalence of alcoholic hepatitis than patients without it. The negative association of alcohol withdrawal syndrome with liver cirrhosis persisted after we adjusted for sex, daily intake, duration, and pattern of alcohol consumption. Alcoholic hepatitis was independently associated with the irregular pattern of alcohol consumption, which was closely associated with severe alcohol withdrawal syndrome. CONCLUSIONS: The profile of liver injury is different in heavy drinkers who develop and who do not develop a severe alcohol withdrawal syndrome when admitted to the hospital.

Inervación de la pars interarticularis en la espondilolistesis / Innervation of the pars interarticularis on spondylolisthesis

En relación con la espondilolistesis ístmica lítica se ha referido que existen terminaciones nerviosas en dicho defecto fibroso, que se estimulan con los micromovimientos, originando dolor, que podría ser tratado con la reparación directa de la pars, a falta de otras posibles fuentes de síntomas, sin sacrificar el movimiento de ninguna unidad funcional vertebral. Es posible que con la edad, además de aparecer otras fuentes de dolor (como el disco intervertebral en su proceso degenerativo), disminuya el número de tales terminaciones nerviosas (a semejanza de algunas pseudoartrosis) o que, cuanto menos, varíe la presencia relativa de cada tipo de terminación, en un hipotético proceso de adaptación progresiva de una pseudoartrosis más o menos estable mecánicamente (la espondilólisis). Objetivo. Estudiar la variación con la edad de las terminaciones nerviosas en el defecto de la pars, en número y distribución relativa de los diversos tipos de terminaciones presentes, en pacientes con una espondilolistesis ístmica lítica con dolor de espalda. Material y método. Se tomaron biopsias bilaterales del defecto de la pars en 15 pacientes consecutivos tratados quirúrgicamente por espondilolistesis ístmica lítica. Las muestras se estudiaron con microscopia óptica con tinción de hematoxilina-eosina e inmunohistoquímica con técnicas S-100 y para proteína glial ácida y neurofilamentos. Resultados. Se encontraron sólo terminaciones nerviosas libres, en las biopsias de 8 de los 15 pacientes, sin constatar ninguna variación atribuible a la edad. Conclusión. La presencia de terminaciones nerviosas en el defecto fibroso de la pars interarticularis podría no ser un hallazgo general (AU)

[Mutations in the HFE gene (C282Y, H63D, S65C) in alcoholic patients with finding of iron overload]. / Mutaciones en el gen HFE (C282Y, H63D, S65C) en pacientes alcohólicos con datos de sobrecarga de hierro.

INTRODUCTION: The pathogenesis of iron overload in alcoholic individuals is not fully elucidated. The frequency of mutations in hereditary hemochromatosis (HFE) is high in this population. Heterozygotes show data of iron overload similar to those in alcoholic individuals. OBJECTIVE: To analyze whether iron excess among alcoholic individuals is associated with mutations in C282Y, H63D or S65C in the HFE gene. Patients and methods. Thirty-two active alcoholic individuals (29 males and 3 females, age range 30-67 years) with data of iron overload (increased serum ferritin with or without saturation of increased transferrin) were studied. In all individuals, mutations C282Y, H63D and S65C were investigated. From 16 cases, liver histology was available. Data on iron overload were compared between patients with and without mutations. RESULTS: Twenty-two patients (68.8%) did not show any mutation, one (3.1%) was heterozygous for C282Y, three (9.4%) were homozygous for H63D, four (12.5%) were heterozygous for H63D, and two patients (6.3%) were heterozygous for C282Y/H63D. None of the patients was homozygous for C282Y or presented mutation in S65C. Transferrin saturation, serum ferritin and liver iron index were similar among with and without mutations. Three patients (9.3%) were diagnosed of hemochromatosis. One of them was homozygous for H63D, other patient was heterozygous for the combined C282Y/H63D, and in the remaining patient none of the mutations was found. CONCLUSIONS: In our setting, iron overload among alcoholic individuals seems to be independent of the presence of mutations C282Y, H63D and S65C in the HFE gene.

Mutaciones en el gen HFE (C282Y, H63D, S65C) en pacientes alcohólicos con datos de sobrecarga de hierro / Mutations in the HFE gene (C282Y, H63D, S65C) in alcoholic patients with finding of iron overload

Introducción. La patogenia de la sobrecarga de hierro en alcohólicos no está enteramente aclarada. La frecuencia de las mutaciones del gen de la hemocromatosis hereditaria (HFE) es alta en la población. Los heterocigotos presentan datos de sobrecarga de hierro similares a los de los alcohólicos. Objetivo. Analizar si el exceso de hierro en alcohólicos se asocia a las mutaciones C282Y, H63D o S65C del gen HFE. Pacientes y métodos. Se estudiaron 32 alcohólicos activos (29 varones y tres mujeres, de edades entre 30-67 años) que presentaban datos de sobrecarga de hierro (ferritinemia elevada con o sin saturación de transferrina aumentada). En todos se estudiaron las mutaciones C282Y, H63D y S65C. En 16 casos se dispuso de histología hepática. Se compararon los datos de sobrecarga de hierro en los pacientes con y sin mutaciones. Resultados. Veintidós pacientes (68,8 por ciento) no presentaban ninguna mutación, uno (3,1 por ciento) era heterocigoto-C282Y, tres (9,4 por ciento) eran homocigotosH63D, 4 (12,5 por ciento) eran heterocigotos-H63D y dos pacientes (6,3 por ciento) eran heterocigotos compuestos (C282Y/H63D). Ningún paciente era homocigotoC282Y ni presentó la mutación S65C. La saturación de transferrina, la ferritinemia y el índice de hierro hepático fueron similares en los pacientes con y sin alguna mutación. Tres pacientes (9,3 por ciento) fueron etiquetados de hemocromatosis. Uno era homocigoto-H63D, otro heterocigoto compuesto (C282Y/H63D) y en la restante no se encontró ninguna de las mutaciones. Conclusión. En nuestro medio la sobrecarga de hierro en alcohólicos parece independiente de la presencia de las mutaciones C282Y, H63D y S65C en el gen HFE (AU)

[Cocaine related fulminant liver failure]. / Fallo hepático fulminante asociado al uso de cocaína.

A 23-year-old woman developed biochemical signs of acute severe hepatitis together with confusion and flapping tremor after snorting a large dose of cocaine. Blood levels of cocaine were very high and liver biopsy performed few days later showed centrilobular necrosis. She recovered completely with conservative measures. Cocaine toxicity should be considered in similar cases of fulminant liver failure.

Fallo hepático fulminante asociado al uso de cocaína / Cocaine-related fulminant liver failure

Una paciente de 23 años presentó datos bioquímicos de hepatitis aguda grave asociados a confusión y asterixis pocas horas después de esnifar una dosis elevada de cocaína. Los niveles sanguíneos de cocaína se encontraban muy elevados y en la biopsia hepática realizada pocos dias más tarde se observó necrosis centrolobulillar. La recuperación fue completa con tratamiento conservador. La toxicidad de la cocaína se debe tener en cuenta en casos similares de insuficiencia hepática aguda grave (AU)

[Hepatitis C virus antibodies in alcoholic patients]. / Anticuerpos frente al virus C de la hepatitis en alcohólicos activos.

It has been reported that chronic alcoholics show a high prevalence of hepatitis C virus (HCV) infection, with a possible role in the pathogenesis and severity of underlying liver disease. Thus, the present study was aimed to evaluate the prevalence of HCV antibodies (anti HCV-Ab) in a group of patients admitted to an Internal Medicine Department, as well as to compare characteristics of anti-HCV-Ab(+ve) respect to anti-HCV(-ve) patients. The presence of anti-HCV-Ab was prospectively studied in 180 alcoholic patients admitted during a 16-month period using a second generation ELISA. Intravenous drug abusers were excluded. Reasons for admittance were as follows: alcohol withdrawal syndrome (92 cases), complications of liver cirrhosis (mainly ascites) (54 cases), acute pancreatitis (12 cases) and miscellaneous causes (22 cases). Sixty-six patients were cirrhotics, 23 had fatty liver, 27 had liver fibrosis and 28 alcoholic hepatitis (36 patients were not evaluable concerning liver lesion). Twelve patients (6.7%) were anti-HCV-Ab(+ve). Prevalence was higher in patients admitted because of complications of cirrhosis (16.7%) than that of those admitted due to alcohol abstinence syndrome (1.1%, p < 0.01). Likewise, the proportion of HVC-Ab(+ve) patients was higher in patients with liver cirrhosis (16.7%) respect to those with lesser degrees of liver injury (1.3%; p < 0.01). In the latter group, the prevalence of anti-HCV-Ab(+ve) was similar to that of the normal population. Anti-HCV-Ab patients were older than anti-HCV-Ab(-ve) cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Nifedipine in rat liver cirrhosis.

Rat liver cirrhosis induced by CCl4+ethanol was employed to assess the effectiveness of nifedipine in reducing liver injury. Nifedipine reduced the severity of hepatocellular necrosis, significantly decreased Mallory bodies (p < 0.01), decreased polymorphonuclear inflammatory infiltrate (p < 0.05) and reduced perivenular fibrosis. Plasma lactic acid levels were significantly increased in the CCl4+ethanol group (p < 0.01). Lactacidaemia remained at normal values when the calcium antagonist blocker was employed. Nifedipine did not significantly alter the incidence of cirrhosis in this experimental model.

[Hypophosphatemic osteomalacia secondary to a vascular fibrous histiocytoma]. / Osteomalacia hipofosfatémica secundaria a histiocitoma fibroso vascular.

Management of an adult woman with a 3 years untractable low back pain, allowed us to discover the existence of hypophosphatemic osteomalacia, due to a benign mesenchymal tumor (vascular fibrous histiocytoma). The prognosis of this form of osteomalacia, as in the present case, is excellent after total removal of the tumor.

Comparative effect of nifedipine and S-adenosylmethionine, singly and in combination on experimental rat liver cirrhosis.

An experimental rat liver cirrhosis, by means of carbon tetrachloride and ethanol during 8 weeks, was employed to assay the effect of Nifedipine (a calcium antagonist blocker), S-Adenosylmethionine (a precursor of glutathione); singly and in combination on rat liver cirrhosis. A slight decrease of cirrhosis (N.S.) was observed with the pharmacological therapy employed singly. The combination therapy (Nifedipine+S-Adenosylmethionine) significantly inhibited liver cirrhosis (p < 0.01).

Immunohistochemical location of prothymosin alpha in regenerating human hepatocytes and hepatocellular carcinomas.

In the present paper we analysed the presence of prothymosin alpha (ProT) in human liver. In normal liver, ProT immunostaining was found in the nuclei of bile duct cells, but not in the hepatocytes. In contrast an intense immunoreactivity was observed in regenerative hepatocytes of chronic hepatitis, cirrhosis and in hepatocellular carcinomas. In all cases the immunostaining was restricted to the nuclei, but the nucleoli were always negative. Similar results were obtained for proliferating cell nuclear antigen. These findings confirm that ProT is related to cell proliferation and provides a new immunohistochemical proliferation marker for routinely processed samples.

Effect of nifedipine and S-adenosylmethionine in the liver of rats treated with CCl4 and ethanol for one month.

An experimental model of toxic liver injury in rats was employed to assay the effect of Nifedipine (a calcium antagonist blocker) and S-Adenosylmethionine (a precursor of glutathione). An important decrease in both perivenular fibrosis and cirrhosis was found. Furthermore, a significant decrease in lactic acid levels was found in the group of animals treated with pharmacologic therapy, although no correlation was seen between lactic acid levels and the different degrees of perivenular fibrosis. No significant variations in ALT and AST enzymes were observed between both groups, as opposed to a significant decrease in LDH enzyme in the Nifedipine+S-Adenosylmethionine group. The results indicate an improvement in the histologic picture of the liver in rats treated by means of pharmacological association, without any change in inflammatory infiltrate and with a slight decrease in necrosis, indicating an action mechanism via creeping fibrosis (instead of a hepatitis pathway).

[Toxic hepatitis from cinchophen: report of 3 cases]. / Hepatitis tóxica por cincofeno: descripción de tres enfermos.

Three cases of hepatic toxicity due to cincophen (a uricosuric drug used for the treatment of gout) are reported. The three patients were females aged 57, 60 and 67 years, respectively, who were treated with cincophen because of renoureteral urate stones. The mean dose was 300 mg/day for a mean duration of 3-4 months before the hepatotoxic features first developed. Cincophen induces hepatic necrosis through a hypersensitivity or metabolic idiosyncrasy mechanism with histologic abnormalities similar to those due to isoniazid, anticonvulsants, halothane and methyldopa. In two patients the disease presented as acute hepatitis. One had severe hepatic failure and died. Cincophen had been widely used in Europe and severe hepatotoxicity reactions have been reported since then (with a mortality rate of about 50%). It is still commercially available in Spain in two preparations as lithium cincophenate and piperacine. The present study has the aim of recalling the severe problems associated with cincophen hepatotoxicity, so that new cases can be prevented.

[Alagille's syndrome: a family case and its association with hepatocellular carcinoma]. / Síndrome de Alagille: presentación familiar y asociación con carcinoma de células hepáticas.

Two cases of Alagille syndrome are reported, father and son. This, a 6-year-old boy, presented with neonatal cholestasis but thereafter evolved with progressively decreasing jaundice and persisting pruritus. A liver biopsy confirmed the absence of intrahepatic bile ducts with preservation of hepatic architecture and no fibrosis. The patient had a characteristic phenotype: short stature, triangular face, deep eyes with hypertelorism, partial embryotoxon and data of peripheral pulmonary artery stenosis. His father died 43-year-old by a hepatocarcinoma. His liver biopsy showed also absence of intrahepatic bile ducts. In addition to the association Alagille's syndrome hepatocarcinoma (previously reported in six cases, three into the same family), it should be stressed in this case the long survival and the fact he had many children: the case with Alagille's syndrome, five children in good health, and one who died shortly after birth.

Immunohistochemical demonstration of neuronal and astrocytic markers and oncofoetal antigens in retinoblastomas.

General opinion is that retinoblastomas, though not everyone agrees with that view. Some authors suggest that retinoblastomas are derived from a primitive retinal cell able to differentiate into both neuronal and glial cell lines. The aim of the present work was to study immunohistochemically the expression of neuronal and astrocytic markers in retinoblastomas and at the same time the presence of the oncofoetal antigens carcinoembryonic antigen (CEA) and alpha Foeto Protein (AFP), since patients with retinoblastomas often show high oncofoetal antigen in serum levels. For this purpose we employed the streptavidin-biotin immunoperoxidase technique in 13 cases of retinoblastoma to evaluate the presence and distribution of neuron-specific enolase (NSE), neurofilament protein (NF), glial fibrillary acidic protein (GFAP), S-100 protein, CEA and AFP. All 13 tumours studied stained for NSE. Seven of them showed GFAP- and S-100 positive perivascular glial cells as well as cells distributed randomly in the tumour that were interpreted as non tumour cells. All 13 retinoblastomas lacked detectable NF, CEA, and AFP. These results support the idea that retinoblastomas are neuronal tumours, although retinal glial cells may become incorporated in the tumour and proliferate in response to the tumour.

[Whipple's disease and splenomegaly with negative intestinal biopsies]. / Enfermedad de Whipple y esplenomegalia con biopsias intestinales negativas.

A case is presented of a patient with a picture of acute gastroenteritis and splenomegaly. Microscopic study of the spleen and a lymph node showed the characteristic findings of Whipple's disease, although no digestive alteration was found, in spite of performing several duodenal and jejunal biopsies. The etiopathogenesis of this entity is commented on and discussed.

[Hepatic cystadenoma: report of a case]. / Cistoadenoma hepático: presentación de un caso.

A case is presented of bilobar hepatic cystadenoma. This is a rare benign tumor in which an adequate preoperative diagnosis is important for correct treatment. A review is made of the literature and controversial aspects of this infrequent lesion are discussed.