Computer-aided morphometry of liver inflammation in needle biopsies.

AIM: To introduce a computer-aided morphometric method for quantifying the necro-inflammatory phase in liver biopsy specimens using fractal geometry and Delaunay's triangulation. METHODS: Two-micrometer thick biopsy sections taken from 78 chronic hepatitis C virus-infected patients were immunohistochemically treated to identify the inflammatory cells. An automatic computer-aided image analysis system was used to define the inflammatory cell network defined on the basis of Delaunay's triangulation, and the inflammatory cells were geometrically classified as forming a cluster (an aggregation of a minimum of three cells) or as being irregularly distributed within the tissue. The phase of inflammatory activity was estimated using Hurst's exponent. RESULTS: The proposed automatic method was rapid and objective. It could not only provide rigorous results expressed by scalar numbers, but also allow the state of the whole organ to be represented by Hurst's exponent with an error of no more than 12%. CONCLUSION: The availability of rigorous metrical measures and the reasonable representativeness of the status of the organ as a whole raise the question as to whether the indication for hepatic biopsy should be revised by establishing clear rules concerning the contraindications suggested by its invasiveness and subjective interpretation.

Serum marker of type III procollagen in patients with idiopathic hemochromatosis and its relationship to hepatic fibrosis.

A radioimmunoassay for serum procollagen III aminopeptide (sPIIIP) was proposed recently for monitoring hepatic fibroplasia in patients with various inflammatory hepatic lesions. To determine whether sPIIIP also can detect fibroplasia in noninflammatory liver disorders, we measured this index in 16 patients with idiopathic hemochromatosis (IHC) at various stages of the disease and iron overload. Interestingly, we found normal levels of sPIIIP in 12 out of 16 patients examined (75%), despite clear histologic features of fibrosis or cirrhosis. The levels of sPIIIP exhibited no relationship to any of the clinical, laboratory, or histologic parameters of the disease. Thus, unlike other types of cirrhosis, in which sPIIIP is increased, the liver disease in IHC may be a fibrotic process unrelated to type III collagen stimulation. Accordingly, the determination of sPIIIP in these patients is of no value for monitoring the fibrosis associated with the liver disease.

Leucocyte migration inhibition in liver disease.

Clinical and histological features provide evidence that immunological reactions of the cell-mediated type are abnormal in some forms of chronic liver disease. By using the leucocyte migration test of Søborg and Bendixen (1967), a correlate of cellular hypersensitivity in vitro, the authors studied the production of the migration inhibitory factor by lymphocytes exposed to a fetal liver homogenate in 88 patients with acute and chronic liver disease. Abnormality of leucocyte migration was found in aggressive chronic hepatitis (inhibition in 67% of patients), cryptogenic cirrhosis (inhibition in 43%, stimulation in 13% of patients), and primary biliary cirrhosis (stimulation in two, inhibition in two out of six patients). The results are compatible with the hypothesis that cellular immune response to liver antigens is important in the pathogenesis of such diseases.

Serum total lipids, lipoprotein cholesterol, and apolipoprotein A in acute viral hepatitis and chronic liver disease.

Serum total lipids, lipoprotein cholesterol, apolipoprotein A (Apo A), and liver function tests have been investigated in patients with acute viral hepatitis and chronic liver disease. Hypertriglyceridaemia, absence of alpha and pre beta bands on the lipoprotein electrophoresis pattern, low level of Apo A, and presence of abnormal lipoproteins (beta-VLDL and beta2-LP) were observed in the early phase of acute hepatitis. A positive correlation was found between Apo A and high-density lipoprotein cholesterol, and a negative one between Apo A and triglyceride, bile acids, total bilirubin, and serum alanine aminotransferase. Lipoprotein abnormalities found in the early phase of acute hepatitis are probably due to low lecithin-cholesterol acyltransferase activity. The reappearance of alpha lipoprotein and the increase of Apo A are sensitive indices of improvement of liver function. In chronic liver disease low levels of cholesterol and Apo A indicate the severity of liver cell injury.

Rosette inhibition test in chronic liver disease.

A role has recently been assigned to cell-mediated immunity in chronic liver diseases in addition to the well-known alterations of humoral immunity. We now report the results of the rosette inhibition test for the evaluation of T-lymphocyte "sensitization" in patients with different chronic liver disorders. A cell-mediated immune reaction was found in 81% of patients with chronic active hepatitis and in 71% with primary biliary cirrhosis, whereas patients with chronic persistent hepatitis showed no reaction. The correlation with the incidence of hepatitis B antigen showed that T-lymphocyte sensitization was more frequent in the group of HB-positive patients. Finally, improvement of the test was observed in four out of nine patients given immunosuppressive treatment.

Serum total lipids, lipoproteins cholesterol, apoproteins A and B in cardiovascular disease.

Serum total lipids and lipoproteins cholesterol were determined in 33 survivors of myocardial infarction (MI) and in 75 subjects with peripheral vascular disease (PVD). Measurements were also made by a quantitative immunological assay of Apoprotein A (Apo A) and B (Apo B). Apo A levels were significantly lower in cases than in controls. In those cases with low levels of Apo A, high density lipoprotein has a higher cholesterol content as compared with controls. A negative correlation between high density lipoprotein cholesterol and low density lipoprotein cholesterol was found in controls and PVD subjects. The findings suggest that Apo A is associated to MI and PVD and its quantitative determination is predictive of cardiovascular disease.

Modeling of biological and medical systems: a systemic strategy.

A strategy in the frame of General System Theory is proposed for the study of biological systems for medical purposes. Its definition and use requires in each experiment the collaboration between physician and system scientists and hence the definition of a common language, by which the real system under study is described. The strategy is based on three intermingled steps: first an ingenuous model is proposed, gathering all the medical knowledge about the studied system, organized within an informal frame derived from the state space approach. Next, a functional model is derived, enlightening the organization of the relations in the medical model. Finally, this organization is formalized by the most suitable algebraic tools, which are thereafter translated into APL programs. This last version is used for simulation, which is exploited not only as a tool to describe and make provisions on the dynamics of the models, but also to deepen and improve the knowledge about the observed system.

Simultaneous staining of cytoplasmic iron and collagen matrix in human liver biopsy specimens.

One of the major liver fibrogenic activators is the cellular iron overload that can severely damage parenchymal and non-parenchymal cells. The aim of this study was to investigate a histochemical staining technique that allows the simultaneous detection of the irregular deposition of matrix collagen and both the amount and distribution of iron in liver cells on the same histological section. The method was evaluated using 3-microm histological sections obtained from ten standard liver biopsy specimens taken from patients with hepatitis C virus-related diseases and simultaneous liver cell iron overload. The results indicate that the double-staining technique is simple, sensitive and rapid, and can be routinely applied to liver biopsy specimens for diagnostic purposes. Furthermore, it may also facilitate the study of the complex relationship between hepatic fibrosis and iron overload during common genetic or secondary liver metabolic disorders.

[Familial hypoalphalipoproteinemia. Vergani's disease]. / L'ipoalfalipoproteinemia familiare. Malattia di Vergani.

Deficiencies of lipoproteins occur as genetic disorders or may be presenting features of underlying disease. Familial high density lipoprotein (HDL), or alpha-lipoprotein, deficiency so far described includes Tangier disease, Lecithin: cholesterol acyltransferase (LCAT) deficiency, A-I Variants syndrome and Fish-eye disease. In 1981 Vergani described a familial aggregation of low HDL-cholesterol (less than 33 mg/dl) and Apo A (about 50% of normal levels) in the presence of normal VLDL and LDL-cholesterol. LCAT and lipoprotein lipase activities, both extrahepatic and hepatic, were normal. By zonal ultracentrifugation HDL2 subclass was found to be reduced. HDL apoproteins, examined by isoelectric focusing in polyacrylamide gel, were qualitatively normal. No disorders to which low levels of HDL might be secondary (e.g., overweight, cigarette smoking, nephropathy, liver disease) are present in the affected members. The underlying biochemical defect is unknown but probably involves altered synthesis or catabolism of HDL. Familial hypo-alpha-lipoproteinemia is accompanied by a high prevalence of premature myocardial infarction and sudden death. The genetic analysis of the disorder is consistent with autosomal inheritance. The criteria for the definition of familial hypo-alpha-lipoproteinemia are, therefore, as follows: 1) low HDL-cholesterol level in the presence of normal VLDL and LDL-cholesterol levels; 2) absence of diseases or factors to which hypo-alpha-lipoproteinemia might be secondary; 3) presence of a similar lipoprotein pattern in a first degree relative.

[Familial alpha lipoprotein deficiency. Tangier disease, familial hypoalphalipoproteinemia and familial deficiency of lecithin cholesterol acyltransferase deficiency]. / Il deficit familiare delle alfalipoproteine. La malattia di Tangier, l'ipoalfalipoproteinemia familiare, il deficit familiare della lecitincolesterolo aciltransferasi.

The plasma lipoproteins are a group of macromolecules all of which transport lipids, including cholesterol, triglyceride and phospholipid, and all of which have one or more protein constituents, called apoproteins. It is becoming apparent that the apoproteins play an important role in lipoprotein metabolism. Recently the so called "alpha hypothesis" has been proposed, according to which a protective role for HDL in atherosclerosis has been postulated. Three "experiments of nature", characterized by deficiencies of HDL as genetic disorders, namely Tangier disease, familial hypoalphalipoproteinemia, familial lecithin: cholesterol acetyltransferase deficiency, support the "alpha hypothesis". The first italian cases with the genetic disorders are presented.

[Bile secretion]. / La secrezione biliare

The canaliculus is the primary site for the formation of bile. Here, active secretion of bile acids creates an osmotic gradient between bile and blood, crossed passively by water and solutes. Numerous experimental data point to the existence of a canalicular bile fraction that is independent of the active transport of bile acids and related to active sodium secretion. The bile ducts are not mere conduits for the passage of bile, but can also change its volume and composition by means of both absorption and secretion. Nervous, vascular, hormonal and pharmacological factors serve to modify bile secretion. In most cases, however, their mechanism of action is virtually unknown.

[Psychological profile of the spa user. Preliminary study of motivations for spa treatment]. / Il profilo psicologico dell'utente termale. Studio preliminare delle motivazioni alla terapia termale idropinica.

The main psychological and possible psychopathological traits of the spa user are identified and classified in order to clarify motivational aspects. Two different self-assessment tests, the Middlesex Hospital Questionnaire (MHQ) and the Minnesota Multiphasic Personality Inventory (MMPI) were given, the first to 500 subjects who had undergone spa treatment cycles lasting at least 10 days and the second to a control group of 50. MHQ data showed a significant incidence of certain neurotic traits, especially phobia, obsession and somatisation in the first group. Despite their different areas of competence and survey methods, both questionnaires produced results to support the hypothesis that a particular form of neurosis may play a significant part in motivating recourse to spa treatment.

[Neurotic and depressive status related to organic pathology in patients in thermal therapy]. / Stati nevrotici e depressivi in rapporto con la patologia organica in utenti termali.

Females and males with no psychiatric history, 25-75 years old, attending thermal facilities in Boario Terme (N = 449) and in Sangemini Terme (N = 40) were administered, on the 2nd-3rd day of their admission, a questionnaire expressly conceive in order to declare conscious motivations for thermal treatments and, in addiction, the Middlesex Hospital Questionnaire (MHQ), the Zung Self Rating Scale for Depression (ZUNG-D) and the State and Trait Anxiety Inventory (STAI), in order to detect neurotic symptoms and/or anxious or depressive complaints in this kind of population. A re-test was performed after 10 days by 73 subjects, in order to verify the impact of thermal treatments on psychoneurotic profiles. Baseline data were compared with those from normal controls and psychiatric outpatients. All statistical comparisons (probands versus matched controls; test versus re-test) were analysed by means of two-tailed Student "t" test (lever of significance: p less than 0.05). In the light of the data so obtained, subjects attending thermal facilities show a typical MHQ psychoneurotic profile, more marked in females and in subjects with gastrointestinal referred somatic disease and partially responding to thermal treatments, which supports the hypothesis that a particular form of neurosis may play a significant role in motivating request of thermal therapies. The results are largely discussed.

[Study of the motivations for balneotherapy. Considerations on the needs of thermal baths users]. / Studio delle motivazioni alla terapia idropinica. Considerazioni sui bisogni dell'utente termale.

After a brief reminder of the dual therapeutic aspect (biological and psychological) of spa treatment, the results are presented of a series of psychological reaction tests (McFarland's Psychosomatic Inventory, the Middlesex Hospital Questionnaire, the Rorschach test) given to a randomized sample of 106 patients together with semistructured interviews conducted by two different psychiatrists. The results show substantial agreement between the motivations volunteered verbally and those revealed by the tests and may be summed up as affective rigidity, impoverished emotional life and difficulty in handling body-related anxieties. It is therefore suggested that it would be useful to create a psychosocial spa centre able to provide global treatment adapted to the specific needs of individual users.

[Behavior of total lipids, cholesterol, lipoproteins and apolipoprotein A in the blood of subjects with acute hepatitis and chronic hepatopathy]. / Comportamento dei lipidi totali, del colesterolo, delle lipoproteine e dell'apolipoproteina A nel siero di soggetti con epatite acuta ed epatopatia cronica.

Serum total lipids, lipoprotein cholesterol, apolipoprotein A (Apo A) and liver function parameters have been investigated in patients with acute viral hepatitis and chronic liver disease. Hypertriglyceridaemia, absence of alpha and pre beta bands on the lipoprotein electrophoresis pattern, low level of Apo A, presence of abnormal lipoproteins (beta-VLDL and beta2-LP) were observed in the early phase of acute hepatitis. A positive correlation was found between Apo A and triglyceride bile acids, log total bilirubin, log SGPT. Lipoprotein abnormalities are probably due to low lecitin-cholesterol aciltransferasi activity. The reappearance of alpha lipoprotein and the increase of Apo A are sensitive indices of improvement of liver function. In chronic liver disease the levels of cholesterol and Apo A correlate with changes in the hepatocellular function.

[Controlled clinical trial of 2-mercapto-propionyl-glycine in chronic hepatopathies]. / Sperimentazione clinica controllata della 2-mercapto-propionil-glicina nelle epatopatie croniche

A controlled clinical trial comparing 2-Mercapto-Priopionyl-Glycine (2-MPG) plus B12 vitamin with B12 vitamin alone in chronic liver disease has been conducted in seven hospitals in Italy. Patients were divided into two groups on the basis of liver histology; group I included 26 patients showing histological evidence for chronic persistent hepatitis (C.P.H.) (according to De Groote et al.) whereas group II consisted of 54 patients with chronic aggressive hepatitis (C.A.H.) or compensated liver cirrhosis. Patients of each group were randomly allocated to 2-MPG plus B12 vitamin, or to placebo plus B12 vitamin, in a double-blind way. The drug (or placebo) was diluted in 500 ml of 10% Levulose, and administered intravenously; 1000 gamma of B12 vitamin were added to each bottle. Patients in the 2-MPG group received 2.5 gms of the drug daily; the treatment lasted for 30 days. The following parameters were checked in all patients on admission, and repeated at the end of treatment: Serum bilirubin, serum Cholesterol, A.P., BSP retention, Prothrombin time, S-GOT, S-GPT, Gamma-GT, Total serum Protein, serum electrophoresis, Immunoglobulins. Patients given 2-MPG showed significant decreases of serum transaminases, and improvement of BSP retention.

[Double-blind polycentric study of the action of S-adenosylmethionine in hepatic cirrhosis]. / Studio policentrico in doppio cieco sull'azione della solfoadenosilmetionina nella cirrosi epatica

Two comparable groups of patients with hepatic cirrhosis of different genesis in a compensation phase have been treated for 30 days with S-adenosylmethionine and vitamine B-12 (28 cases) or with vitamine B-12 alone (25 cases). The drugs were given by slow intravenous route at the daily dose of 150 mg of SAMe and 2000 gamma of vit. B-12 or of 2000 gamma of vit. B-12 alone, in two adminstrations. An evaluation of the results was carried out mostly on the laboratory data testing the liver function. Only the group of patients who had received SAMe showed significant modifications of all the parameters considered. This is confirming SAMe ability to restore hepatocyte activity bringing also to normal the protein synthesis.

Geometry of liver system functioning: from a helix to a trajectory on curved space.

Autoisodiasostasis of the liver, i.e., its self-maintenance without change over the course of time, is characterized by a bistable equilibrium between two extreme states called homopoiesis (during which the liver system repairs its worn structures and replicates its cells) and homoerhesis (during which it satisfies the needs of the body). Retinol binding protein traffic within the hepatocyte, made visible by means of immunohistology, has been used as a prototype for studying the competition processes and dynamics of autoisodiasostasis. An account is given of the oscillation of autoisodiasostasis between homopoiesis and homeorhesis through intermediate phases. The phase cycle of autoisodiasostasis is illustrated in the form of bi-dimensional and tri-dimensional diagrams. The temporal behaviour of the systems is represented as a helix trajectory obtained by projecting homopoiesis-homeorhesis phase cycles onto a time series. A unified topological representation of the uncoupled but combined processes of competition and autoisodiasostasis is proposed.