Liver transplantation

Purpose of review: Liver transplantation continues to change as we further define appropriate criteria for allocation and utilization of this scarce resource. The following review highlights new trends and ideas in this evolving field. Recent findings: Although the model for end-stage renal disease (MELD) scoring system appears to fairly accurately predict mortality while waiting for transplant, the system may be less accurate in predicting outcomes following transplantation. MELD scores offer an additional advantage to patients with hepatocellular carcinoma (HCC), bringing them to transplant sooner with overall better survivals. However, despite its advantages, the MELD scoring system does not resolve the disparity in the allocation of organs between various organ procurement organizations. Several variables appear to affect patients with hepatitis C undergoing liver transplantation. Selection of appropriate donors appears to be important when transplanting patients with hepatitis C virus (HCV) infection as increasing donor age is associated with poorer outcomes. However, the controversy over whether a living donor liver transplant (LDLT) results in poorer outcomes in HCV infected patients remains. Post-transplant medical treatment of HCV may result in both a sustained virologic response and improved histology. With improved overall survival in patients undergoing orthotopic liver transplant (OLT), increasing attention has been focused on the medical complications following transplant. Identifying specific contributing factors in the development of renal dysfunction and devising strategies to prevent its occurrence are critical to further improvements in outcome following OLT. Summary: As the gap between patients and available organs remains, continued investigation into appropriate allocation and maximization of outcomes following liver transplant will continue. © 2005 Lippincott Williams & Wilkins

The effect of partial portacaval transposition on the canine liver

The influence of nonhepatic splanchnic venous blood on dog liver morphology and biochemical content was investigated by performing partial portacaval transposition, anastomosing the supra-adrenal inferior vena cava to either the right or left branch of the main portal vein. In the resulting preparation, nonhepatic splanchnic venous blood supplies one portion of the liver and systemic venous blood perfuses the remaining fraction,. Seven dogs were studied for 70 to 94 days, 3 with right and 4 with left transposition. No clinical abnormalities were noted. Transient enzyme elevations were seen early after operation but reverted to normal. The most striking feature was the gross and microscopic atrophy and deglycogenation which occurred in the part of the liver receiving systemic venous blood. Blood flow studies were performed in 8 additional dogs with an electromagnetic square wave flowmeter. Flow was measured in both right and left portal vein branches before and 1 to 4 hours after partial transposition to either the right (4 dogs) or left (4 dogs) main branch. Flow rates were increased in 11 instances and remained essentially the same in 5. In 2 more dogs, a jugular venous autograft was placed between the abdominal aorta and the right or left main portal vein branch. Atrophy and deglycogenation in the portion receiving arterial blood was comparable to that described above in liver fractions perfused with systemic venous blood. The evidence from these and earlier experiments that splanchnic venous blood contains a hepatotrophic substance is discussed. © 1967

Sociolinguistic variation in the nativisation of BSL fingerspelling

British Sign Language (BSL) is a visual-gestural language distinct from spoken languages used in the United Kingdom but in contact with them. One product of this contact is the use of fingerspelling to represent English words via their orthography. Fingerspelled loans can become “nativised”, adapting manual production to conform more closely to the native lexicon’s inventory of phonemic constraints. Much of the previous literature on fingerspelling has focused on one-handed systems but, unlike the majority of sign languages, BSL uses a two-handed manual alphabet. What is the nature of nativisation in BSL, and does it exhibit sociolinguistic variation? We apply a cross-linguistic model of nativisation to BSL Corpus conversation and narrative data (http://bslcorpusproject.org) obtained from 150 signers in 6 UK regions. Mixed effects modelling is employed to determine the influence of social factors. Results show that the participants’ home region is the most significant factor, with London and Birmingham signers significantly favouring use of fully nativised fingerspelled forms. Non-nativised sequences are significantly favoured in signers of increasing age in Glasgow and Belfast. Gender and parental language background are not found to be significant factors in nativisation. The findings also suggest a form of reduction specific to London and Birmingham

The origin, hormonal nature, and action of hepatotrophic substances in portal venous blood

The hepatotrophic factors previously reported to be in splanchnic venous blood are pancreatic hormones and specifically insulin and glucagon. Of these, insulin is anabolic and glucagon is mainly catabolic but not exclusively so, since glucagon also has the anabolic effect of stimulating gluconeogenesis. The insulin glucagon relationship and the interrelationship of these hormones to others, such as epinephrine, in the moment to moment regulation of nutrient and hepatic homeostasis is a central fact of liver physiology that should reconcile a number of previously divergent opinions about portoprival syndromes, mechanisms of hepatic atrophy and hyperplasia, and the control of liver regeneration

Abnormal Epidermal Keratinization in the repeated epilation mutant mouse

Repeated epilation (Er) is a radiation-induced, autosomal, incomplete dominant mutation in mice which is expressed in heterozygotes but is lethal in the homozygous condition. Many effects of the mutation occur in skin: the epidermis in Er/Er mice is adhesive (oral and nasal orifices fuse, limbs adhere to the body wall), hyperplastic, and fails to undergo terminal differentiation. Skin from fetal +/+, Er/+ and Er/Er mice at ages pre- and postkeratinization examined by light, scanning, and transmission electron microscopy showed marked abnormalities in tissue architecture, differentiation, and cell structure; light and dark basal epidermal cells were separated by wide intercellular spaces, joined by few desmosomes, and contained phagolysomes. The numbers of spinous, granular, and superficial layers were highly variable within any given region and among various regions of the body. In some areas, 2-8 layers of granular cells, containing large or diminutive keratohyalin granules, extended to the epidermal surface; in others, the granular layers were covered by several layers of partially keratinized or nonkeratinized cells. In rare instances, a single or small group of cornified cells was present among the granular layers but was not associated with the epidermal surface. Both the granular and nonkeratinized/partially keratinized upper epidermal layers Er/Er skin gave positive immunofluorescence with antiserum to the histidine-rich, basic protein, filaggrin. Proteins in epidermal extracts from +/+, Er/+ and Er/Er mice were separated and identified by radio- and immunolabeling techniques. The Er/Er extract was missing a 26.5- kdalton protein and had an altered ratio of bands in the keratin region. The 26.5-kdalton band was histidine-rich and cross-reacted with the antiserum to rat filaggrin. Several high molecular weight bands present in both Er/Er and +/+ extracts also reacted with the antiserum. These are presumed to be the precursors of filaggrin and to account for the immunofluorescence om Er/Er epidermis even though the product protein is absent. The morphologic and biochemical data indicated that the genetic defect has a general and profound influence on epidermal differentiation, including alteration of two proteins (filaggrin and keratin) important in normal terminal differentiation, tissue architecture, and cytology. Identification of epidermal abnormalities at early stages of development (prekeratinization) and defective structure of other tissues and gross anatomy suggest that the mutation is responsible for a defect in same regulatory step important in many processes of differentiation and development

Fire effects on aquatic ecosystems: an assessment of the current state of science

Fire is a prevalent feature of many landscapes and has numerous and complex effects on geological, hydrological, ecological, and economic systems. In some regions, the frequency and intensity of wildfire have increased in recent years and are projected to escalate with predicted climatic and landuse changes. In addition, prescribed burns continue to be used in many parts of the world to clear vegetation for development projects, encourage desired vegetation, and reduce fuel loads. Given the prevalence of fire on the landscape, authors of papers in this special series examine the complexities of fire as a disturbance shaping freshwater ecosystems and highlight the state of the science. These papers cover key aspects of fire effects that range from vegetation loss and recovery in watersheds to effects on hydrology and water quality with consequences for communities (from algae to fish), food webs, and ecosystem processes (e.g., organic matter subsidies, nutrient cycling) across a range of scales. The results presented in this special series of articles expand our knowledge of fire effects in different biomes, water bodies, and geographic regions, encompassing aquatic population, community, and ecosystem responses. In this overview, we summarize each paper and emphasize its contributions to knowledge on fire ecology and freshwater ecosystems. This overview concludes with a list of 7 research foci that are needed to further our knowledge of fire effects on aquatic ecosystems, including research on: 1) additional biomes and geographic regions; 2) additional habitats, including wetlands and lacustrine ecosystems; 3) different fire severities, sizes, and spatial configurations; and 4) additional response variables (e.g., ecosystem processes) 5) over long (>5 y) time scales 6) with more rigorous study designs and data analyses, and 7) consideration of the effects of fire management practices and policies on aquatic ecosystems