We propose that the liver is a stem cell and lineage system with many parallels to lineages in the bone marrow, gut, and epidermis, varying from them only in kinetics. All are organized with three compartments: a slow cycling stem cell compartment with cells expressing a fetal phenotype and responding slowly to injury; an amplification compartment with cells of intermediate phenotype rapidly proliferating in response to regenerative stimuli or acute injuries; and a terminal differentiation compartment in which cells increasingly differentiate and gradually lose their ability to divide. In all systems, both those with slow or rapid kinetics, the various compartments are positioned in a polarized organization, are associated with a gradient in the chemistry of the extracellular matrix, and show lineage-position-dependent growth responses, gene expression, pharmacological and toxicological responses, and reaction to viruses and radiation. In general, known oncogens selectively kill cells in the differentiation compartment inducing chronic regenerative responses of the cells in stem cell and/or amplification compartment. Tumors arise by subsequent transformation of the activated stem cells or early precursor cells. The evidence for a lineage model consists of the data implicating gradients in cell size, ploidy, growth potential, and antigenic and gene expression in the liver parenchyma along the sinusoidal plates. The traditional explanation for this heterogeneity is that it represents adaption of cells to a changing sinusoidal microenvironment dictated by the direction of blood flow. However, we review the extant data and suggest that it more readily supports a lineage model involving a maturation process beginning with stem cells and precursors in the periportal zone and ending with sensescing parenchyma near the central vein. Support for this theory is provided by the studies on phenotypic heterogeneity in liver, investigations into the embryology of the liver, and analyses of the responses of liver to chemical and viral oncogens that induce rapid proliferation of small cells with oval-shaped nuclei, "oval cells," now thought to be closely related to liver stem cells. The lineage model provides clarity and insights into many aspects of liver biology and disease including the limited proliferative ability of in vitro parenchymal cultures, liver regeneration, gene expression, viral infection, hepatocellular carcinogenesis, liver cell transplantation, and aging.

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Applying MARS treatments to patients with acute exacerbation of chronic liver disease can detoxify blood, improve cerebral circulation, and reduce brain edema, as reflected by the reduction in intracranial pressure and jugular bulb oxygen saturation values in our patients. A partial reversal of the characteristic hyperdynamic circulation was also achieved. Despite our encouraging results, further testing is needed to determine the reliability of the system.

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Further research is needed to combine methods of investigation in order to assist the health care system in personalizing services to the trajectories of decline, and in enabling caregivers to prepare for the EOL experience.

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Aspiration pneumonias are frequent complications of cerebrovascular accidents (CVA). They occur mainly in patients suffering from swallowing disorders following the CVA. These patients can be diagnosed using a bedside swallowing evaluation. This evaluation is based on observation of some components of the oral and pharyngeal stages of the swallowing process and on a drinking test of 50 ml3 of clear liquids. Changing the mode of swallowing and the consistency of the diet according to the swallowing evaluation following CVA can reduce significantly the frequency of aspiration pneumonias. In our patient cohort, consisting of 180 patients admitted for stroke rehabilitation, aspiration pneumonias occurred in 10% and swallowing disorders were found in 28%. The administration of a structured swallowing evaluation was associated with a gradual reduction of frequency of pneumonia from 16% in the first group of 60 patients to 3% in the last group of 60 patients or, if considering only patients suffering from dysphagia, from 27% in the first group of patients to none in the last group of patients.