Relation of long chain n-3 polyunsaturated fatty acid intake to serum high density lipoprotein cholesterol among Japanese men in Japan and Japanese-American men in Hawaii: the INTERLIPID study

Epidemiologic evidence shows an inverse relationship between fish consumption and coronary heart disease (CHD) mortality. Associations between dietary intake of long chain n-3 polyunsaturated fatty acids (PUFA) and serum high density lipoprotein (HDL) cholesterol concentration are unknown. In this study, the association between n-3 PUFA (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA)) intake and serum HDL cholesterol among Japanese men and women in Japan and Hawaii was examined. The study population consisted of Japanese ancestries from five research centers of the International Study of Macronutrients and Blood Pressure (INTERMAP) study, in Japan and Hawaii (672 men and 676 women), surveyed between 1996 and 1998. Four 24-h dietary recalls and one set of serum lipid measurements were performed. For men, n-3 PUFA intake and HDL cholesterol were higher in Japan than in Hawaii (n-3 PUFA: 1.32 g/day versus 0.47 g/day, p<0.001). For women, n-3 PUFA intake was higher in Japan than in Hawaii (p<0.001) but HDL cholesterol was not significantly different (p=0.752). After adjustment for age, body mass index, physical activity, number of cigarettes per day, alcohol intake, and hormone replacement therapy (for women), n-3 PUFA intake was positively associated with serum HDL cholesterol in men (4.6 mg/dl higher HDL cholesterol with 1%kcal higher n-3 PUFA intake, p=0.011). This association was not observed in women. This positive association of dietary n-3 PUFA with serum HDL cholesterol may partially explain the low mortality from CHD among Japanese men.     

Oxidative stress is associated with adiposity and insulin resistance in men

To investigate the direct relationship of oxidative stress with obesity and insulin resistance in men, we measured the plasma levels of 8-epi-prostaglandin F2alpha (PGF2alpha) in 14 obese and 17 nonobese men and evaluated their relationship with body mass index; body fat weight; visceral, sc, and total fat areas, measured by computed tomography; and glucose infusion rate during a euglycemic hyperinsulinemic clamp study. Obese men had significantly higher plasma concentrations of 8-epi-PGF2alpha than nonobese men (P < 0.05). The plasma levels of 8-epi-PGF2alpha were significantly correlated with body mass index (r = 0.408; P < 0.05), body fat weight (r = 0.467; P < 0.05), visceral (r = 0.387; P < 0.05) and total fat area (r = 0.359; P < 0.05) in all (obese and nonobese) men. There was also a significant correlation between the plasma levels of 8-epi-PGF2alpha and glucose infusion rate in obese men (r = -0.552; P < 0.05) and all men (r = -0.668; P < 0.01). In all subjects, the plasma levels of 8-epi-PGF2alpha were significantly correlated with fasting serum levels of insulin (r = 0.487; P < 0.01). In brief, these findings showed that the circulating levels of 8-epi-PGF2alpha are related to adiposity and insulin resistance in men. Although correlation does not prove causation, the results of this study suggest that obesity is an important factor for enhanced oxidative stress and that this oxidative stress triggers the development of insulin resistance in men.     

Possible association of vigorous hepatitis B virus replication with the development of fulminant hepatitis

A 49 year-old man was referred to our hospital for fear of developing fulminant hepatic failure. There had been an outbreak of fulminant hepatitis B in a dialysis clinic in the western part of Honshu, Japan, that resulted in four deaths among six patients. After the sixth patient contracted severe hepatitis, all patients in the unit were screened biweekly for hepatitis B surface antigen (HBsAg) to detect newly infected patients as soon as possible. Our patient was the seventh victim, and on the day he gave a positive result for HBsAg, his hepatitis B virus (HBV) DNA level had reached 1.1 × 10¹¹ copies/ml as assessed by real time polymerase chain reaction. Sequence analysis of the causal HBV revealed the presence of a mutation in the precore region (nt 1896), two mutations in the core promoter (nt 1762 and nt 1764), and some minor mutations in the P gene that were restricted to the upstream region. These mutations are indicative of a virus with a high replicative rate that cannot secrete HBeAg. Taken together, these findings indicate that it is very likely that the replicative ability of the causal virus was as vigorous as that of HBV in hepatitis B e antigen-positive asymptomatic carriers with markedly high viral titers. The present case report provides clinical evidence of a possible association between the rapid spread of highly replicative HBV before host immunological recognition and the development of fulminant hepatitis.     

Incidence, risk factors and outcomes of bronchiolitis obliterans after allogeneic stem cell transplantation

Bronchiolitis obliterans (BO) after allogeneic stem cell transplantation (allo-SCT) is a late-onset, life-threatening respiratory complication that significantly reduces a patient's quality of life. We retrospectively analysed the incidence of and risk factors for BO in allo-SCT recipients. In 2087 patients who underwent allo-SCT between January 1994 and June 2005 and survived >90 days after transplantation, 57 patients developed BO with a 5-year cumulative incidence of 2.8%. The median time interval from transplantation to BO diagnosis was 335 days (range 83-907 days). The 5-year cumulative incidence of BO was 1.62% in bone marrow transplantation (BMT) from related donors, 3.83% in peripheral blood stem cell transplantation (PBSCT) from related donors (R-PBSCT), 2.91% in BMT from unrelated donors and 2.65% in unrelated cord blood transplantation. The incidence of BO after R-PBSCT was significantly higher than that after any other type of allo-SCT (p = 0.02). R-PBSCT (p = 0.019) and preceding chronic graft-versus-host disease (GVHD) (p < 0.001) were BO-associated risk factors. Overall 5-year survival of patients with BO from the time of diagnosis was 45.4%, significantly less than those without (77.5% from day 335, p < 0.001). R-PBSCT recipients with existent chronic GVHD have a high risk of developing BO, and need extensive care and repeated pulmonary function tests.     

Accurate prediction of fulminant hepatic failure in severe acute viral hepatitis: multicenter study

Background: We have attempted to predict the development of fulminant hepatic failure at the stage of severe acute hepatitis before the onset of coma. This prediction is valuable because it may be used to block the development of fulminant hepatic failure with appropriate medical treatment. Methods: To establish a discrimination formula, we retrospectively compared 13 clinical and laboratory variables in 36 patients with acute viral hepatitis and prothrombin levels of 40% or less of the control value who later developed fulminant hepatic failure with these variables in 12 patients who recovered spontaneously. A prospective study of 58 patients who developed fulminant hepatic failure and 18 who spontaneously recovered confirmed the validity of this formula. Results: In the retrospective study, we established the following discrimination equation: Z = −0.89 + 1.74 × (causal viruses, 1 point for type A or type B in acute hepatitis B virus [HBV] infection, 2 points for others) + 0.056 × (total bilirubin, mg/dl) −0.014 × (cholinesterase, U/ml). A positive Z value indicates that fulminant hepatic failure will develop. In the prospective study, the specificity, sensitivity, predictive accuracy, and positive and negative predictive values were 0.833, 0.983, 0.947, 0.950, and 0.938, respectively. Conclusions: The present study indicated that fulminant hepatic failure can be predicted, by a simple discrimination equation, at the stage of severe acute hepatitis. Received: September 4, 2001 / Accepted: May 31, 2002 Acknowledgments. Supported by a grant from the Ministry of Health and Welfare of Japan. Reprint requests to: M. Yoshiba     

Mucinous cystadenoma of the pancreas 17 years after excision of gallbladder because of a choledochal cyst

A 56-year-old woman who had undergone excision of the gallbladder because of a choledochal cyst had a tumorous lesion of the pancreas identified by upper abdominal ultrasonography, but an operation was not carried out, because there was no apparent increase in the cystic mass and no elevation of serum tumor markers. In October 2001, she was admitted to our hospital to check for malignancy because of elevated levels of the tumor marker Dupan-2. Abdominal enhanced computed tomography and upper abdominal ultrasonography revealed a large multilocular cystic mass in the body to tail of the pancreas. Endoscopic retrograde cholangiopancreatography showed elongation of the common duct that communicates with the common bile duct and the main pancreatic duct, indicating an anomalous arrangement of the biliary and pancreatic duct system. No apparent communications between the cystic mass and the main pancreatic duct were observed. In January 2002, the patient underwent a spleen-preserving distal pancreatectomy, and histopathological and immunohistochemical examinations led to the diagnosis of pancreatic mucinous cystadenoma with ovarian-like stroma. The mucinous cystadenoma was detected 17 years after the operation for the choledochal cyst. To the best of our knowledge, no documented case reports of mucinous cystadenoma of the pancreas associated with a choledocal cyst have been reported to date. We present here the first case report of pancreatic mucinous cystadenoma occurring in the body to tail of the pancreas, associated with a choledocal cyst.     

The role of preoperative biliary decompression in the treatment of bile duct cancer

Usefulness of preoperative biliary decompression by percutaneous transhepatic biliary drainage (PTBD) in patients with obstructive jaundice remains controversial. We determined bile and bile acid outputs in patients with complete biliary obstruction following biliary decompression by PTBD. Bile and bile acid outputs correlated well with the decline index of serum bilirubin. Patients with a poor decline index tended to have low bile acid output in spite of high bile output, i.e., secretion of watery bile. Daily bile acid output reflecting daily bile acid synthesis remained low or increased only slowly in almost all cases, indicating that recovery of liver function is considerably delayed. We stress the importance of bile acid output as a function of bile acid synthesis as an index of the recovery of liver function. Although many studies comparing operative intervention alone and PTBD followed by operation have already been carried out, and because of the increasing use and greater safety of a 2-staged approach with ultrasound-guided PTBD, the advantages and disadvantages of preoperative PTBD should continue to be reevaluated with respect to technical improvement and a concomitant decrease in complications.

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Resumen La utijidad de la descompresión biliar preoperatoria mediante el drenaje percutáneo transhepático (DPTH) en pacientes con ictericia obstructiva sigue siendo motivo de controversia. La disminución del nivel de bilirrubina sérica es función del balance entre la productión y la excretión de la bilirrubina acumulada en el organismo y no necesariamente coincide con la recuperación real de la función hepática. Por otra parte, puesto que la síntesis de ácido biliar tiene lugar exclusivamente en el hepatocito, ésta viene a ser el reflejo de un aspecto específico de la función hepática. En el presente estudio se realizó la determinación de la secretión de bilis y de ácido biliar en pacientes con obstrucción biliar completa después de descompresión por DPTH. La secretión de bilis y de ácido biliar apareció bien correlacionada con la disminución del índice de bilirrubina sérica. Los pacientes con menor disminución del índice presentaron tendencia a una secreción baja de bilis a pesar de elevados niveles de secretión de ácido biliar, o sea que secretaron una bilis acuosa. La secretión diaria de ácido biliar, que es reflejo de la síntesis diaria de ácido biliar, permaneció baja o se incrementó apenas en forma lenta en casi todos los casos, lo cual es indicativo de considerable retardo en la recuperación de la función hepática. Hacemos énfasis en la importancia del volumen de secretión de ácido biliar vis-a-vis la síntesis como un índice de recuparación de la función hepática. Aunque muchos estudios comparativos entre la intervención quirÚrgica sin drenaje previo y el DPTH seguido de operación han sido realizados, principalmente en virtud del creciente uso del enfoque terapéutico en 2 etapas con el más seguro DPTH guiado por ultrasonido, debe continuarse la reevaluación de las ventajas y desventajas del DPTH preoperatorio en relación al mejoramiento técnico del procedimiento y la disminución conomitante de las complicaciones.

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Résumé L'utilité du drainage biliaire pré-opératoire par voie percutanée et transhépatique chez les patients atteints d'ictère par obstruction reste controversée. Les auteurs ont étudié après drainage l'excrétion de la bile et des acides biliaires chez les malades qui présentaient une obstruction biliaire complète. L'excrétion de la bile et des acides biliaires est en corrélation précise avec celle de l'abaissement du taux de la bilirubine sérique. Les sujets chez qui ce dernier est peu important ont une excrétion biliaire faible bien que l'excrétion des acides soit importante et ils secrètent de la bile blanche. L'excrétion quotidienne des acides biliaires qui reflète leur synthèse quotidienne reste faible ou s'élève lentement dans la majorité des cas, ces faits traduisant un retard considérable dans l'amélioration des fonctions hépatiques altérées. Les auteurs soulignent l'importance de l'excrétion des acides biliaires en tant qu'expression de leur synthèse et facteur de pronostic de la fonction hépatique. Bien que de nombreuses études comparatives de l'intervention chirurgicale d'emblée et de l'intervention chirurgicale différée après drain age biliaire préalable aient été étudiées en raison du développement de l'opération en 2 temps pratiquée avec une plus grande sécurité grâce au guidage du cathéter sous échographie, les avantages et les désavantages du drainage biliaire percutané et trans-hépatique doivent Être appréciés avec rigueur pour améliorer la technique de cette méthode et réduire ses complications éventuelles.