Shunt surgery for treatment of portal hypertension in children

Shunt surgery in children suffering from portal hypertension (PH) is considered as an immediate and definite mode of prevention of recurrent gastrointestinal hemorrhage. Certain conditions must be met: (a) normal liver; (b) normal veins available within the portal system; (c) a sufficient portosystemic gradient of pressure; and (d) a surgical team with experience in portal venous surgery. In patients in whom PH is an epiphenomenon of severe liver disease, other means of hemostasis for bleeding esophageal varices should be sought. The difficult decision is in the child with specific liver alterations without major hepatocellular dysfunction but in whom the prognosis cannot be precisely foreseen. A few more years will be needed before one can tell if shunt surgery is the best choice for this category of patient.

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Resumen La cirugía derivativa (shunts portosistémicos) en los niños que sufren de hipertensión portal es considerada como una forma inmediata y definitiva de prevenir la hemorragia gastrointestinal recurrente. Ciertas condiciones deben existir para su realization: (a) hígado normal; (b) venas disponibles dentro del sistema porta; (c) suficiente gradiente en las presiones portosistémicas; y (d) disponibilidad de un equipo quirúrgico con experiencia en cirugía venosa portal. Otros medios de hemostasis de las várices esofágicas sangrantes deben ser utilizados en aquellos pacientes en quienes la hipertensión portal es un epifenómeno de enfermedad hepática severa. La decisión más difícil se presenta en el niño con alteraciones hepáticas específicas pero sin mayor disfunción hepatocelular en quien no se puede determinar con precisión el pronóstico. Todavía serán necesarios unos años más antes de poder afirmar que la cirugía derivativa representa la mejor escogencia para esta categoría de pacientes.

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Résumé La dérivation portale chez les enfants atteints d'hypertension portale constitue une méthode immédiate et définitive de prévention des hémorragies digestives récidivantes. Les conditions les plus favorables sont les suivantes: a) foie normal; b) veines disponibles dans le secteur porte pour l'anastomose; c) gradient de pression suffisant entre le système porte et le système cave et d) équipe entraînée à la chirurgie portale. Lorsque l'hypertension portale est un épiphénomène au cours d'une affection hépatique sévère, d'autres méthodes d'hémostase des varices oesophagiennes rompues doivent être envisagées. La décision du choix thérapeutique à adopter est difficile lorsqu'il existe une atteinte hépatique, sans altération hépatocellulaire majeure, mais de pronostic incertain à long terme. Quelques années encore seront nécessaires avant de pouvoir affirmer que la dérivation représente la meilleure opération pour traiter ce type d'hypertension portale.

     

Distinct immunopathological mechanisms of EBV-positive and EBV-negative posttransplant lymphoproliferative disorders

EBV-positive and EBV-negative posttransplant lymphoproliferative disorders (PTLDs) arise in different immunovirological contexts and might have distinct pathophysiologies. To examine this hypothesis, we conducted a multicentric prospective study with 56 EBV-positive and 39 EBV-negative PTLD patients of the K-VIROGREF cohort, recruited at PTLD diagnosis and before treatment (2013–2019), and compared them to PTLD-free Transplant Controls (TC, n = 21). We measured absolute lymphocyte counts (n = 108), analyzed NK- and T cell phenotypes (n = 49 and 94), and performed EBV-specific functional assays (n = 16 and 42) by multiparameter flow cytometry and ELISpot-IFNγ assays (n = 50). EBV-negative PTLD patients, NK cells overexpressed Tim-3; the 2-year progression-free survival (PFS) was poorer in patients with a CD4 lymphopenia (CD4⁺<300 cells/mm³, p <  .001). EBV-positive PTLD patients presented a profound NK-cell lymphopenia (median = 60 cells/mm³) and a high proportion of NK cells expressing PD-1 (vs. TC, p = .029) and apoptosis markers (vs. TC, p < .001). EBV-specific T cells of EBV-positive PTLD patients circulated in low proportions, showed immune exhaustion (p = .013 vs. TC) and poorly recognized the N-terminal portion of EBNA-3A viral protein. Altogether, this broad comparison of EBV-positive and EBV-negative PTLDs highlight distinct patterns of immunopathological mechanisms between these two diseases and provide new clues for immunotherapeutic strategies and PTLD prognosis.     

IMPORTANCE OF DONOR SELECTION IN RENAL TRANSPLANTATION

Renal transplantation has become a treatment of choice for patients with end stage renal disease. A successful transplant is the result of a combination of several factors acting synergistically, such as the degree of HLA compatibility between donor and the recipient, pretransplant blood transfusions, the recipient''s state of immunoreactivity and sensitization, immunosuppressive therapy given in post operative period etc. Donor selection appears to be the most critical factor for the long term success of the organ graft. In this brief review, some of the important parameters of donor selection in renal transplantation are highlighted.KEY WORDS: Histocompatibility (HLA) matching, Cross match, Sensitization     

Beta-amyloid precursor protein is detectable on monocytes and is increased in Alzheimer's disease

Using the anti-beta-amyloid precursor protein (betaAPP) monoclonal antibodies 4G8, 6E10 and 22C11 and flow cytometry, we report that human circulating peripheral blood monocytes display surface immunoreactivity for betaAPP. In contrast, circulating lymphocytes do not possess cell surface betaAPP immunoreactivity, despite similar levels of betaAPP expression. Immunoblotting analysis showed that monocytes, but not lymphocytes, possess an 82 kDa C-terminal betaAPP fragment consistent with a processed transmembrane species. Monocyte surface betaAPP was upregulated approximately threefold by activation with lipopolysaccharide and interferon-gamma, activation did not produce detectable betaAPP on the cell surface of lymphocytes. Surface betaAPP immunoreactivity was reduced in a normal aged population compared to normal young controls (Young = 81.07 +/- 13.67 mean fluorescence units, Aged = 36.74 +/- 3.81, p < 0.01), but was significantly increased in AD subjects compared to age-matched healthy controls (AD = 60.31 +/- 7.42, p < 0.05). Our data suggest that a proportion of peripheral A beta may be derived from monocyte/macrophages, and that defects in brain cell processing of betaAPP in AD may be shared by this readily accessible peripheral cell.     

The discriminative stimulus effects of naloxone and naltrexone in morphine-treated rhesus monkeys: comparison of oral and subcutaneous administration

  Rationale: Opioid antagonists are used to reverse the toxic effects of opioids, to diagnose opioid dependence and to treat opioid and other (alcohol) drug abuse. Objectives: This study compared the discriminative stimulus effects of two opioid antagonists (naloxone and naltrexone), after parenteral and oral administration. Methods: The discriminative stimulus effects of naloxone and naltrexone were evaluated every 15 min over a 2-h period in four morphine-treated (3.2 mg/kg per day) rhesus monkeys discriminating between subcutaneous (SC) injections of naltrexone (0.01 or 0.032 mg/kg) and saline, while responding under a fixed-ratio 5 schedule of stimulus shock termination. Results: Within 15 min of SC administration, naloxone and naltrexone produced greater than 90% drug-appropriate responding at doses of 0.032 and 0.01 mg/kg, respectively. The largest dose of naloxone (3.2 mg/kg) administered orally produced 82% drug-appropriate responding within 90 min; the same dose of naltrexone administered orally produced greater than 90% drug-appropriate responding within 30 min. Although both drugs were at least 100-fold more potent when administered SC, as compared to orally, there was little difference (3-fold) between the potency of naloxone and naltrexone by either route. Conclusions: These results fail to support the view that naloxone has reduced bioavailability after oral administration, as compared to naltrexone, or that its pharmacokinetic profile is particularly advantageous for some therapeutic settings (e.g. Talwin Nx). Received: 15 July 1998 / Final version: 21 December 1998     

Comparison of immunochemical and biological properties of human anti thrombin during blood clotting and upon interaction with exogenous thrombin

Modification of immunological and biological properties of human antithrombin were studied in plasma-serum pairs and in defibrinated plasma supplemented with human thrombin. Modified antithrombin obtained through whole-blood clotting or upon addition of exogenous thrombin appeared the same with regards to its electrophoretic or biological properties. However, amounts of thrombin higher than that physiologically available, had to be used to obtain a "serum-like" antithrombin in thrombin supplemented plasma suggesting different pathways for this transformation. This was in agreement with the observation in plasma of a modification of antithrombin antigenic properties upon thrombin addition whereas no difference was demonstrated when comparing serum to normal plasma. It may be concluded that the inactivation of antithrombin and the appearance of electrophoretically modified forms in normal serum is not mainly due to the formation of enzyme-inhibitor complexes and therefore that proteolytically modified, enzyme-free forms of antithrombin demonstrated in purified systems (Fish et al. 1979) could be of physiological relevance.     

Monitoring universal precautions: a new assessment tool.

OBJECTIVES: Two pilot studies were conducted to produce efficacy data on an observational tool designed to assess the use of Universal Precautions (UP) in patient care settings. The instrument addresses barrier precautions, hand-washing, handling of sharps, and avoidance of unprotected mouth to mouth resuscitation. DESIGN: The Universal Precautions Assessment Tool was submitted to a panel of 3 experts to establish consensual validity. It was pilot tested by 2 simultaneous observers to establish interrater reliability. SETTING: Pilot Study I was conducted in 3 different units within a 100-bed U.S. Army hospital. Pilot Study II was conducted in the emergency department of a large university-based hospital. PARTICIPANTS: Subjects observed were registered nurses providing acute patient care. RESULTS: Two simultaneous raters calculated UP compliance rates of 76.4% and 78.6%, respectively, for 9 nurses in Pilot Study I, and 62% and 65%, respectively, for 5 nurses in Pilot Study II. The intraclass correlation coefficient for the raters' scores in Pilot Study I was 0.992 with a 95% confidence interval (0.979, 0.997). Consensual validity was established. CONCLUSIONS: The instrument has acceptable interrater reliability under the conditions used. Limitations to use include the possibility of a Hawthorne effect and the fact that assessing proper implementation of UP occasionally relies on a "judgment call" by the observer. With test conditions adjusted to minimize these limitations and with proper consideration of sample size, the tool can be used by researchers and by monitors of hospital quality control to measure UP compliance of caregivers individually or collectively.