Regional Variation and Use of Exception Letters for Cadaveric Liver Allocation in Children with Chronic Liver Disease

The Pediatric End-Stage Liver Disease (PELD) score was designed to reduce subjectivity in liver allocation and to advantage patients with a higher probability of waiting list mortality. The aims of this study were to determine the impact of PELD implementation for children with chronic liver disease and to assess whether PELD met its goal of standardization of liver allocation for children. This study used data reported to the United Network for Organ Sharing (UNOS) registry for children with chronic liver disease receiving primary cadaveric liver transplant between January 2000 and December 2001 (pre-PELD) and March 2002 and July 2003 (PELD). PELD reduced the percentage of children transplanted while in an intensive care unit and as status 1. A calculated PELD score was used for allocation in only 52% of recipients. Thirty percent were status 1 at transplant and PELD scores granted by exception were used for allocation in 18% of patients. There was regional variation in PELD score at allocation and use of exception scores with a significant relationship between PELD score and percentage of exception cases. Regional variation suggests that PELD has not resulted in standardization of listing practices in pediatric liver transplantation.     

Assessment of the scatter fraction evaluation methodology using Monte Carlo simulation techniques

To evaluate scatter fraction and scatter pair spatial distribution, experimental methods are generally used. These methods make use of a line source, placed along the FOV axis, inserted in a cylindrical phantom filled with air or water. The accuracy of these experimental methodologies can be tested by the use of a Monte Carlo method. In fact, the simulation allows the shape of the scatter event projection and the scatter fraction to be defined. An example of this application is the simulation package PETSI (PET SImulation). In this paper the comparison between the predicted scatter fraction and the experimentally evaluated one, obtained using an ECAT III PT 911/02 double ring whole body scanner are presented. PETSI permits additional data to be obtained: a) the true and scatter component of the energy spectrum; b) the spatial distribution, in the FOV plane, of the detected scatter events at different energy thresholds; c) the scatter to total detected events ratio; d) the predicted scatter fraction at both energy thresholds and FOV diameters. This information is very useful for optimizing both energy threshold and FOV size and to improve the accuracy of the currently used methods for the scatter fraction evaluation. Preliminary results of the predicted scatter fraction in a uniform phantom are presented.This article was presented at the 1st EEC workshop on accuracy determination in PET, January 19–20th. 1989 Pisa, Italy (COMAC-BME Concerted Project Characterization and Standardization of PET Instrumentation)     

Human isolated small intestine: motor responses of the longitudinal muscle to field stimulation and exogenous neuropeptides

Summary (1) Longitudinal muscle strips from the human small intestine (jejunum/ileum) responded to electrical field stimulation (1–50 Hz) with frequency-related primary contractions which were largely atropine- (3 M) sensitive. When the tone was raised by addition of galanin (0.3 – 1 M), prostaglandin (PG) E₂ (1–10 M) or neurokinin A (NKA, 0.1 M), a frequency-related relaxation was evident which was potentiated by atropine. All the responses to field stimulation were abolished by tetrodotoxin (1 M), thus indicating their neural origin. (2) The atropine-sensitive primary contraction to field stimulation was virtually abolished by omega conotoxin fraction GVIA (CTX, 0.1–0.3 M) while the relaxations were CTX-resistant. The field stimulation-induced relaxations, which were observed in the presence of atropine and guanethidine (3 M), were also unaffected by apamin (0.1 M). (3) NKA and substance P (SP) produced a concentration- (1 nM–1 M for both peptides) related contraction, NKA being about 53 times more potent than SP. [Pro⁹]SP sulphone and [MePhe⁷]-NKB, selective agonists of the NK-1 and NK-3 receptor, respectively, were barely effective. On the other hand, [\Ala⁸]NKA(4–10), a selective NK-2 receptor agonist, had a potent contractile activity, similar to that of NKA. (4) Galanin (1 nM–1M) produced an atropine- and tetrodotoxin-resistant concentration-related contraction of longitudinal muscle of human isolated small intestine. The response to galanin did not show any sign of fading and was particularly suitable to study the evoked relaxations. (5) Calcitonin gene-related peptide (CGRP) (10–100 nM) consistently inhibited the nerve-mediated contractions of strips from the ileum while the effect on the jejunum was less pronounced. Vasoactive intestinal polypeptide (VIP, 0.1–1 M) inhibited nerve-mediated contractions both in the ileum and the jejunum. (6) These experiments indicate that both cholinergic excitatory and non-adrenergic non-cholinergic nerves affect motility of the longitudinal muscle of the human small intestine. Furthermore, several neuropeptides produce potent motor effects, the contractile response to tachykinins being apparently mediated by activation of NK-2 receptors.     

Sigmoidin F, a new prenylated flavonoid from Erythrina sigmoidea

Sigmoidin F, a new prenylated flavanone, as well as abyssinone IV and 5,7,4'-trihydroxy-3'-methoxy-5'-(1"-prenyl) flavonone have been isolated from the stem and bark of Erythrina sigmoidea. The structure of 1 has been confirmed by a combination of 1H-nmr and other spectroscopic techniques.     

Application of phage display peptide library to autoimmune diabetes: identification of IA-2/ICA512bdc dominant autoantigenic epitopes

Autoantigenic epitope mapping represents a critical issue in autoimmune diseases. The islet tyrosine phosphatase-like protein IA-2/ICA512bdc is a major autoantigen in type 1 diabetes (IDDM), but the epitopes responsible for autoantibody binding have been only partially defined. The aim of our study was to identify ICA512bdc epitopes, and in particular mini-epitopes, utilizing a novel strategy for autoimmune diseases. The study was performed in three sequential steps: (1) construction of a lambda-phage surface-displayed ICA512bdc cDNA library with the methodology of tagged random priming with peptides displayed as a fusion to the C terminus of the capsid protein D; (2) affinity selection of the resulting library, followed by immunoscreening, enzyme-linked immunosorbent assay and sequence analysis of positive clones, and (3) radioimmunoprecipitation to detect autoantibodies to the selected clones. This strategy resulted in the identification of two epitopes (IA-2 residues 761 - 964 and 929 - 979), which were recognized by 100 % and 62.9 % ICA512bdc-positive IDDM patients, respectively. Interestingly, the larger clone was detected also by a proportion (16.7 %) of new onset ICA512bdc-negative patients, thus suggesting that this region contains not only the main autoantigenic repertoire of ICA512bdc molecule, but is able to detect IA-2 autoantibodies in even higher percentages of patients. In addition, this study showed the existence of multiple epitopes located in the C-terminal domain of the IA-2 protein, one of which is formed by the 50 C-terminal amino acids, and provided evidence that the strategy used represents a valid tool for identification of epitopes within autoantigenic molecules.     

Levothyroxine treatment in thyroid peroxidase antibody-positive women undergoing assisted reproduction technologies: a prospective study

BACKGROUND: Infertile women positive for thyroid antibodies suffer from a poor pregnancy/delivery outcome, although conflicting data have been published. Our objective was to investigate if levothyroxine (LT4) exerts any effect on pregnancy and/or delivery rates in thyroid peroxidase antibody (TPOAb)-positive (+) women undergoing assisted reproductive technologies. METHODS: Patients undergoing treatment were screened for TPOAb, thyroid-stimulating hormone (TSH) and free thyroxine (FT4). A total of 72 (15%) out of the 484 euthyroid women selected were TPOAb (+). These 72 patients were randomly divided into two groups: group A (n = 36) underwent LT4 treatment, group B (n = 36) placebo. Group C consisted of 412 women (85%) who were TPOAb negative (-). All patients received controlled ovarian stimulation. The endpoints of treatment were pregnancy rate, miscarriage rate and delivery rate. RESULTS: No differences in pregnancy rate were observed between the three groups. Miscarriage rate was higher in TPOAb (+) in comparison to TPOAb (-) [relative risk: 2.01 (95% CI = 1.13-3.56), P = 0.028]. CONCLUSIONS: The pregnancy rate is not affected either by presence of TPOAb or treatment with LT4. However, TPOAb (+) women show a poorer delivery rate compared to TPOAb (-). LT4 treatment in TPOAb (+) does not affect the delivery rate.     

Effect of interferon-alpha therapy on epitope-specific cytotoxic T lymphocyte responses in hepatitis C virus-infected individuals.

The majority of hepatitis C virus (HCV)-infected individuals fail to resolve the infection and become chronically infected despite the presence of HCV-specific CTL responses directed to different HCV-derived peptide antigens. Only a minority of individuals is able to clear the virus by mounting efficient CTL responses early after acute infection, but at present it is not clear whether viral clearance is associated with CTL responses of defined specificity. To elucidate those responses associated with improvement of the disease, we analyzed CTL responses to 16 different HLA-A2-presented, HCV-derived epitopes in 12 chronically infected patients, 14 chronically infected patients treated with interferon-alpha, and in one patient with acute symptomatic disease. We show here that the majority of chronically infected individuals present CTL responses directed to an NS4-derived peptide antigen (amino acids 1789-1797). Treated patients presented stronger HCV-specific CTL responses and therapy-induced changes in CTL target choice. In particular, 13 out of 14 individuals responded to an NS3-derived epitope (amino acids 1073-1081). By longitudinal analysis we show that five individuals responding to IFN-alpha therapy with decreases in alanine aminotransferase levels presented a strong CTL activity directed to the NS3-derived epitope. One patient that spontaneously resolved the infection presented a generally strong CTL activity specific for HCV-derived epitopes with a dominant response to the NS3-derived peptide antigen. This suggests that CTL responses directed to this NS3-derived antigen may be beneficial for the control of HCV infection. Improvement of these responses may represent a therapeutic intervention in chronic HCV infection.