On Endings and Authenticity.

As an introduction to the panel on "Aging, Dying, and the Analytic Process," and to the Focus of this issue of The Psychoanalytic Review, this article offers personal comments linked to affective neuropsychoanalytic theory, and advocates an ability to think about illness and death as an integral part of lived experience.

Sevelamer-Induced Gastrointestinal Disease in 12 Patients with End-Stage Renal Disease: A Case Series.

INTRODUCTION: Isolated case reports and case series have linked the use of sevelamer to severe gastrointestinal (GI) inflammation and perforation among patients with end-stage renal disease. METHODS: In this study, we identified 12 cases of biopsy-proven sevelamer-induced gastrointestinal disease from a large urban community hospital over the course of 5 years. We described baseline characteristics, sites and types of injury, histological findings, timing and dosing of sevelamer initiation compared with symptom onset, and in a smaller subset, endoscopic resolution post drug cessation. We also reviewed preexisting conditions to identify trends in populations at risk. RESULTS: Several of the patients reviewed had preexisting conditions of decreased motility and/or impaired mucosal integrity. The presentation of disease was broad and included both upper-GI and lower-GI pathologies and in varying severity. DISCUSSION: There is a broad phenotypic range of sevelamer-induced gastrointestinal disease. As this becomes a more frequently recognized pathology, clinicians should be aware of how it may present and which populations may be more susceptible.

A Case Series of Extrapulmonary Mycobacterium in Liver Transplant Recipients.

Liver transplant recipients are at increased risk of infection because of the immunosuppression required after transplantation. Infection by Mycobacterium species increases the morbidity and mortality of liver transplant recipients. The prompt recognition and diagnosis of opportunistic infection is necessary for good outcomes, particularly during periods of increased immunosuppression. The balance of immunosuppressive therapies during prolonged treatment with hepatotoxic medications has not been well studied and should be tailored for the unique clinical setting of each patient. The goal of treatment in these patients is to eradicate the disease and preserve allograft function.

On Need, Necessity, and the Source of Narcissism.

Even Freud had a difficult time explaining narcissism. It may account for why he only wrote one paper explicitly concerning this topic. The author proposes that the field of affective neuroscience has developed theoretical concepts that were not available to Freud, and that have created the potential for discussion of how narcissism may begin to explain much of the rampant disagreements among psychoanalysts studying the field of psychoanalysis. Specifically, the author suggests that a source of narcissism in the mammalian brain/mind is beginning to be knowable through advances in knowledge from the collective baseline of neurophysiology, affective as well cognitive neuroscience, and psychoanalysis.

Baseline Hepatic Levels of miR-29b and Claudin are Respectively Associated with the Stage of Fibrosis and HCV RNA in Hepatitis C.

We sought to determine if the baseline hepatic levels of miR-122, miR-29b, Claudin, Occludin, Protein Kinase R (PKR) or PKR activator (PRKRA) were correlated with HCV RNA or stage of fibrosis in patients with chronic hepatitis C (CHC). A total of 25 CHC patients (genotype 1) who were treatment naive at the time of sample collection enrolled in this study. By multivariate analysis, CLDN RNA was found as the single independent factor positively correlated with HCV RNA levels (p=0.003), while hepatic miR-29b levels was found as the single independent factor for predicting advanced stage of fibrosis (p=0.028). Conclusion: Our results highlight miR-29b and CLDN as novel predictors of advanced stage of liver fibrosis and baseline HCV RNA in CHC.

Flexible Sigmoidoscopy Rather than Colonoscopy Is Adequate for the Diagnosis of Ipilimumab-Associated Colitis.

OBJECTIVES: Treatment with ipilimumab, a cytotoxic T lymphocyte antigen-4 approved for metastatic melanoma can result in clinically significant immune-mediated drug injury in the form of colitis. Timely diagnosis and response are essential for optimal management. The aims of our study were to determine the percentage of our patients with ipilimumab-associated colitis in which the colitis could be diagnosed by flexible sigmoidoscopy only and to describe the variations in endoscopic and histologic findings as well as the patients' clinical courses. METHODS: We retrospectively reviewed 244 patients with metastatic melanoma, treated them with ipilimumab, and characterized the endoscopic and histologic features for those who developed colitis. RESULTS: Of the 68 patients who presented with diarrhea, 33 were diagnosed as having ipilimumab-associated colitis. Endoscopically, all of them had involvement of the left side of the colon; none of the patients were noted to have isolated right colon involvement. CONCLUSIONS: Ipilimumab-associated colitis can be diagnosed with a flexible sigmoidoscopy alone, obviating the need for full colonoscopy.

Dietary fructose augments ethanol-induced liver pathology.

Certain dietary components when combined with alcohol exacerbate alcohol-induced liver injury (ALI). Here, we tested whether fructose, a major ingredient of the western diet, enhances the severity of ALI. We fed mice ethanol for 8 weeks in the following Lieber-DeCarli diets: (a) Regular (contains olive oil); (b) corn oil (contains corn oil); (c) fructose (contains fructose and olive oil) and (d) corn+fructose (contains fructose and corn oil). We compared indices of metabolic function and liver pathology among the different groups. Mice fed fructose-free and fructose-containing ethanol diets exhibited similar levels of blood alcohol, blood glucose and signs of disrupted hepatic insulin signaling. However, only mice given fructose-ethanol diets showed lower insulin levels than their respective controls. Compared with their respective pair-fed controls, all ethanol-fed mice exhibited elevated levels of serum ALT; the inflammatory cytokines TNF-α, MCP-1 and MIP-2; hepatic lipid peroxides and triglycerides. All the latter parameters were significantly higher in mice given fructose-ethanol diets than those fed fructose-free ethanol diets. Mice given fructose-free or fructose-containing ethanol diets each had higher levels of hepatic lipogenic enzymes than controls. However, the level of the lipogenic enzyme fatty acid synthase (FAS) was significantly higher in livers of mice given fructose control and fructose-ethanol diets than in all other groups. Our findings indicate that dietary fructose exacerbates ethanol-induced steatosis, oxidant stress, inflammation and liver injury, irrespective of the dietary fat source, to suggest that inclusion of fructose in or along with alcoholic beverages increases the risk of more severe ALI in heavy drinkers.

Intrahepatic distribution of hepatitis B virus antigens in patients with and without hepatocellular carcinoma.

AIM: To study the intrahepatic expression of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in chronic hepatitis B patients with and without hepatocellular carcinoma. METHODS: A total of 33 chronic hepatitis B patients (mean age of 40.3 ± 2.5 years), comprising of 14 HBeAg positive and 19 HBeAg negative patients; and 13 patients with hepatitis B virus related hepatocellular carcinoma (mean age of 49.6 ± 4.7 years), were included in our study. Immunohistochemical staining for HBcAg and HBsAg was done using standard streptavidin-biotin-immunoperoxidase technique on paraffin-embedded liver biopsies. The HBcAg and HBsAg staining distributions and patterns were described according to a modified classification system. RESULTS: Compared to the HBeAg negative patients, the HBeAg positive patients were younger, had higher mean HBV DNA and alanine transaminases levels. All the HBeAg positive patients had intrahepatic HBcAg staining; predominantly with "diffuse" distribution (79%) and "mixed cytoplasmic/nuclear" pattern (79%). In comparison, only 5% of the HBeAg-negative patients had intrahepatic HBcAg staining. However, the intrahepatic HBsAg staining has wider distribution among the HBeAg negative patients, namely; majority of the HBeAg negative cases had "patchy" HBsAg distribution compared to "rare" distribution among the HBeAg positive cases. All but one patient with HCC were HBeAg negative with either undetectable HBV DNA or very low level of viremia. Intrahepatic HBcAg and HBsAg were seen in 13 (100%) and 10 (77%) of the HCC patients respectively. Interestingly, among the 9 HCC patients on anti-viral therapy with suppressed HBV DNA, HBcAg and HBsAg were detected in tumor tissues but not the adjacent liver in 4 (44%) and 1 (11%) patient respectively. CONCLUSION: Isolated intrahepatic HBcAg and HBsAg can be present in tumors of patients with suppressed HBV DNA on antiviral therapy; that may predispose them to cancer development.

Mixed Hepatocellular Carcinoma, Neuroendocrine Carcinoma of the Liver.

We present the case of a 76-year-old male found to have a large tumor involving the left lateral lobe of the liver, presumed to be hepatocellular carcinoma (HCC). After resection, pathologic features demonstrated both high-grade HCC and high-grade neuroendocrine carcinoma (NEC). Areas of NEC stained strongly for synaptophysin, which was not present in HCC component. The HCC component stained strongly for Hep-Par 1, which was not present in the NEC component. The patient underwent genetic analysis for biomarkers common to both tumor cell types. Both tumor components contained gene mutations in CTNNB1 gene (S33F located in exon 3). They also shared mutations in PD-1, PGP, and SMO. Mixed HCC/NEC tumors have been rarely reported in the literature with generally poor outcomes. This patient has been referred for adjuvant platinum-based chemotherapy; genetic biomarker analysis may provide some insight to guide targeted chemotherapy.

MiR-122 decreases HCV entry into hepatocytes through binding to the 3' UTR of OCLN mRNA.

BACKGROUND & AIMS: Analysis in silico suggests that occludin (OCLN), a key receptor for HCV, is a candidate target of miR-122; the most abundant hepatic micro RNA. We aimed to determine if miR-122 can decrease HCV entry through binding to the 3' UTR of OCLN mRNA. DESIGN: Huh7.5 cells were cotransfected with luciferase construct containing 3' UTR of OCLN (pLuc-OCLN) and with selected miRNAs (0-50 nM) and luciferase activity was measured. Huh7.5 cells were also infected by viral particles containing lenti-miR122 genome or control virus. After 48 h, the cells were infected with HCV pseudo-particles (HCVpp) and VSV pseudo-particles (VSVpp). After 72 h of infection, luciferase activity was measured and HCVpp activity was normalized to VSVpp activity. RESULTS: miR-122 binds to the 3'-UTR of OCLN and down-regulates its expression; cotransfection of miR-122 mimic with pLuc-OCLN resulted in a significant decrease in luciferase activity [by 55% (P < 0.01)], while a non-specific miRNA and a mutant miR-122 did not have any effect. miR-122 mimic significantly down-regulated [by 80% (P < 0.01)] OCLN protein in Huh7.5 cells. Accordingly, patients with chronic hepatitis C and higher levels of hepatic miR-122 have lower hepatic expression of OCLN. Immuno-fluorescence imaging showed a decrease in colocalization of OCLN and CLDN following miR-122 over-expression in HCV infected cells. Huh7.5 cells transiently expressing Lenti-miR122 system showed 42% (P < 0.01) decrease in HCV entry. CONCLUSION: This study uncovers a novel antiviral effect of miR-122 on human liver cells and shows that over-expression of miR-122 can decrease HCV entry into hepatocytes through down-regulation of OCLN.

Drug-induced liver injury with autoimmune features.

Drug-induced liver injury (DILI) with features of autoimmunity (AI) represents an important category of hepatotoxicity due to medication exposure. Drugs repeatedly associated with AI-DILI include diclofenac, α-methyl DOPA, hydralazine, nitrofurantoin, minocycline, and more recently statins and anti-TNF-α agents. Usually, symptoms of acute liver injury occur within a few months after initiation of a culprit medication, but a longer latency period is possible. Like idiopathic autoimmune hepatitis, circulating autoantibodies and a hypergammaglobulinemia are frequently present in sera from patients with AI-DILI. If performed, a liver biopsy should demonstrate interface hepatitis with a prominent plasma cell infiltrate. The severity of AI-DILI is variable, but a complete resolution after withdrawal of the offending medication is the expectation. A response to corticosteroid therapy supports the diagnosis, whereas a lack of recurrence of symptoms or signs following corticosteroid cessation distinguishes AI-DILI from idiopathic autoimmune hepatitis.

Psychoanalytic education in the twenty-first century: a syllabus for all seasons.

I am suggesting that psychoanalytic training facilities restructure their curriculum to include opposing views, in an effort to avoid the inevitable disintegration of the field at large. Without a sense of requirement for any particular viewpoint, I have suggested the model of class modules, usually based around three differing positions, be applied in as many classes as possible. This method enhances the very nature of psychoanalysis while it extends the educational provenance of each separate institute, and specifically each teacher of psychoanalysis. In so doing, candidates across the board will feel and think in a more collegial manner, and may find that learning psychoanalysis is to learn something new and exciting.

[Poverty, youth and consumption of tobacco in Mexico]. / Pobreza, jóvenes y consumo de tabaco en México.

OBJECTIVE: To characterize tobacco use according to level of poverty in a random, nationally representative sample of adolescents (10 to 21 years old), living in urban areas with less than 50,000 inhabitants. The study was done in 2001 as part of the baseline assessment of the evaluation of the governmental program, Oportunidades. MATERIAL AND METHODS: A questionnaire was applied to 29,548 adolescents living in 30 000 selected households and it included specific questions on individual tobacco use among other questions. RESULTS: The prevalence of smokers was 3.5% (95% CI: 3.3%-3.7%) and experimenters 9.9% (95% CI: 9.6%-10.2%). A logistic regression model for clustered data was constructed in order to evaluate the associated factors that distinguish a smoker from an experimenter. After adjusting for level of poverty of the household and use of alcohol and drugs, a significant association (OR = 1.5, p <0.01) was found with having a paid job and a differential association was found between gender and age group. CONCLUSIONS: The results of this study suggest that the additional availability of money that an adolescent has, could increase the prevalence of tobacco smoking and that the program Oportunidades should include prevention campaigns directed specifically at this population group.

Pobreza, jóvenes y consumo de tabaco en México / Poverty, youth and consumption of tobacco in Mexico

OBJETIVO: Caracterizar el consumo de tabaco de acuerdo con el nivel de pobreza en una muestra probabilística nacional de jóvenes de 10 a 21 años de edad que viven en zonas suburbanas de México. El estudio forma parte de la evaluación del programa gubernamental Oportunidades (2001). MATERIAL Y MÉTODOS: Se entrevistaron a 29 548 jóvenes residentes en 30 000 hogares. Se calcularon la prevalencia de fumar y los factores relacionados que diferencian al fumador habitual del experimentador. RESULTADOS: La prevalencia de fumadores y experimentadores fue de 3.5 por ciento (IC95 por ciento 3.3-3.7) y 9.9 por ciento (IC95 por ciento 9.6-10.2), respectivamente. El nexo entre los diferentes factores que se vinculan con las condiciones de fumador y experimentador se evaluó a través de modelos de regresión logística para datos agrupados. Después de ajustar por nivel de pobreza del hogar y consumo de alcohol y drogas, se detectó una relación significativa (RM = 1.5, p <0.01) con tener un trabajo remunerado y una diferencial entre el género y el grupo de edad. CONCLUSIONES: La disponibilidad de dinero por parte del joven es un factor que contribuye a explicar la transición entre experimentar y fumar. Dado que el programa Oportunidades incluye transferencias monetarias a los hogares incorporados al programa, es necesario instituir campañas de prevención para evitar que la disponibilidad adicional de dinero en los jóvenes se utilice en la compra de cigarillos.

Functional assessment using the step-up-and-over test and forward lunge following ACL reconstruction.

This investigation compared lower extremity function of a control group and a group of patients who underwent anterior cruciate ligament (ACL) reconstruction using a repeated measures post-test only control group design. The ACL reconstruction group consisted of 18 patients at least 6 months postoperative (mean 58+/-19 weeks) and the control group consisted of 18 healthy, recreationally active individuals. Both groups performed a step-up-and-over test and a forward lunge on a long force plate. During the step-up-and-over test, the control group produced significantly more force during the initial step than the ACL reconstruction group. Also, when the ACL reconstruction patients led with the involved extremity, they were significantly slower. During the forward lunge test, the impact index and force impulse measurements were significantly greater for the uninvolved leg than the involved leg in the ACL reconstruction group. The implications are that force generation during functional tests may remain compromised for >1 year following reconstruction. The aforementioned tests are promising for evaluation of function following ACL reconstruction.