Biomedical subjects
Publications and source records attributed to G Bianchi.
The Authors report a wide review of the literature on open and blunt renal traumas. All the problems related to this pathology as well as all the instrumental and laboratory tests currently available for the correct diagnosis are illustrated. Both conservative and surgical management are also discussed.
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Evaluation of estrogen (ER) and progesterone (PR) receptor content is now an important procedure in the management of breast cancer patients. Production of monoclonal antibodies to ER and PR has permitted development of an enzyme immunoassay (EIA) and immunocytochemical assay (ICA). This study compared the results of ICA and EIA to evaluate ER and PR in 197 breast cancers using the same monoclonal antibodies. The ICA results were obtained by automated computer-assisted image analysis using CAS 200. The cut-off values adopted were 15 fmol/mg protein for EIA and 10% of the positive neoplastic area of the nuclei for ICA. For statistical analysis, Spearman's correlation coefficient and chi 2 were used. There was good correlation between ICA and EIA for both ER (r = 0.714; p < 0.0001) and PR (r = 0.815; P < 0.0001). Of 197 tumors, 136 (69.04%) were ER-ICA+, and 138 (70.05%) were ER-EIA+; 111 (56.35%) were PR-ICA+, and 115 (58.38%) were PR-EIA+. Results were concordant, positive or negative with both methods, in 175 cases for ER and in 173 cases for PR. ER and PR results were only discordant in 22 and 24 cases, respectively. Concordance of results obtained by the two methods was 88.83% (P < 0.0001) for ER and 87.81% (P < 0.0001) for PR. Correlation of results obtained by EIA and ICA to determine ER and PR was good. The data obtained suggest that ICA with automated image analysis is an effective means for evaluating ER and PR content in human breast cancer, especially when, as happens ever more frequently nowadays, the tumor is too small to perform EIA or when retrospective studies are performed.
BACKGROUND: Contrasting data have so far been reported on the utility and efficacy of screening patients with cirrhosis for early detection of hepatocellular carcinoma (HCC). The goal of this study was to evaluate the efficacy of a regular ultrasonographic and laboratory follow-up for the early detection of small HCC, and to identify parameters correlated with a higher risk of developing HCC. METHODS: One hundred and sixty-four consecutive patients with liver cirrhosis living in Emilia Romagna, Italy, were enrolled in the period 1989-1991. All patients underwent clinical, biochemical, and ultrasonographic evaluations at entry and at 3- and 6-month intervals during follow-up. RESULTS: By April 1995, 34 patients had developed HCC. In 76% of the patients, ultrasonography identified HCC when it was still single and small (< 4 cm). At discriminant, logistic regression and univariate analyses, sex and the entry concentration of alkaline phosphatase, alpha-fetoprotein, gamma-glutamyl transpeptidase, and albumin were associated with a higher risk of developing HCC, whereas at multivariate analysis (Cox's model), only sex and the entry concentration of alkaline phosphatase, albumin, and alpha-fetoprotein were independently and significantly related to the appearance of HCC. CONCLUSIONS: A regular ultrasonographic follow-up, timed at 3- to 6-month intervals according to the risk of HCC development in patients with cirrhosis, allows the detection of liver carcinoma at an early stage in a high proportion of patients, possibly improving the prognosis of the disease.
The adducin heterodimer is a protein affecting the assembly of the actin-based cytoskeleton. Point mutations in rat adducin alpha (F316Y) and beta (Q529R) subunits are involved in a form of rat primary hypertension (MHS) associated with faster kidney tubular ion transport. A role for adducin in human primary hypertension has also been suggested. By studying the interaction of actin with purified normal and mutated adducin in a cell-free system and the actin assembly in rat kidney epithelial cells (NRK-52E) transfected with mutated rat adducin cDNA, we show that the adducin isoforms differentially modulate: (a) actin assembly both in a cell-free system and within transfected cells; (b) topography of alpha V integrin together with focal contact proteins; and (c) Na-K pump activity at V(max) (faster with the mutated isoforms, 1281 +/- 90 vs 841 +/- 30 nmol K/h.mg pt., P < 0.0001). This co-modulation suggests a role for adducin in the constitutive capacity of the epithelia both to transport ions and to expose adhesion molecules. These findings may also lead to the understanding of the relation between adducin polymorphism and blood pressure and to the development of new approaches to the study of hypertension-associated organ damage.
We studied the activity of plasma membrane (Ca+Mg)ATPase from erythrocytes of Milan hypertensive rat strain (MHS) and Milan low calpastatin rat strain (MLCS), that show an activity level of the specific calpain inhibitor, calpastatin, about five fold reduced in comparison with the Milan normotensive rat strain (MNS), while the protease activity level is similar. This imbalance of calpain:calpastatin ratio leads to a decrease of the erythrocyte plasma membrane (Ca+Mg)ATPase activity and to the appearance of 124 kDa fragments, which are the typical products of proteolytic calpain action on the 136 kDa (Ca+Mg)ATPase native form.
NK cells are present mostly in blood and spleen but under certain pathological and physiological conditions rapidly accumulate at extrahematic sites. The present study investigates the responsiveness of NK cells to C-C chemokines and the mechanisms of emigration from the bloodstream. MCP-1 induced migration across polycarbonate filters of IL-2-activated NK cells, whereas it was a weak attractant for unstimulated cells. The related chemokines MCP-2 and MCP-3 were also active. IL-2-activated NK cells showed specific binding sites for labeled MCP-1, and cell migration was inhibited by both cholera and Bordetella pertussis toxins. In agreement with functional assays the expression of mRNA specific for MCP-1 receptors was detectable only in IL-2-activated NK cells. The ability of NK cells to respond to MCP-1 and related chemokines may be one important determinant of NK cell emigration and recruitment in tissues.
The frequency of gross cystic breast disease in premenopausal women and its possible association with increased breast cancer risk emphasises the importance of investigations relating to breast cyst fluid composition. In order to contribute to a better analysis of this medium, we have measured the presence of prostate-specific antigen immuno-reactivity in sixty-four human breast cyst fluids. Data analyses show that 35% of samples presented a level of this antigen < 0.05 micrograms/L, whereas 42 out of 64 cysts show a significant increase in the mean value of metabolically active apocrine cysts when compared to flattened cysts (p < 0.01). We report the first evidence that breast epithelium of gross cysts produces, secretes, and accumulates large amounts of prostate-specific antigen, a glycoprotein produced by prostatic tissue but recently detected in breast tumours, normal tissues, and during pregnancy. The production and intracystic accumulation of this serine protease in biosynthetically active apocrine type cyst can play a feasible role in the natural history gross cystic breast disease as well as in the mechanism of cyst formation, enlargement, and transformation.
Recent experimental evidence has suggested that peripheral benzodiazepine receptors (PBR) may play a role in epilepsy and antiepileptic drug action. Since PBR are also present in circulating lymphocytes, and may interact with anticonvulsant drugs, this study was designed to look for possible modifications of these receptors and their endogenous ligand diazepam binding inhibitor (DBI) in the lymphocytes of epileptic patients treated with various drugs. PBR levels were 50% to 80% higher in patients treated with carbamazepine, phenobarbital and valproic acid than in controls and untreated epileptics. DBI levels were significantly increased in the lymphocytes of untreated patients, and showed only a slight further increase after anticonvulsant therapy. The possibility that PBR and DBI modifications in the lymphocytes of epileptic patients may be linked to the immunological alterations reported in these patients and/or may represent possible markers of neurochemical modifications in the central nervous system is discussed.
Calpains, calcium activated neutral proteases (CANP), and calpastatin (CAST), their specific inhibitor, are involved in the proteolysis of amyloid precursor protein (APP), which is thought to be abnormal in Alzheimer's disease (AD). We studied the CANP/CAST system in erythrocytes of 14 clinically probable AD patients, 11 young and 14 old controls. CANP and CAST activities in the control subjects significantly correlated with increasing age; old controls showed a significant increase in CANP and CAST activities compared to young controls. Values of CANP and CAST activities in AD patients were similar to those of young controls. The physiological gage-related increase in proteolysis seems to be lost in AD patients, and this could play a role in the pathogenesis of the disease. However, due to the overlap of results between patients and controls, we could not reliably differentiate the healthy from the disease state on the basis of erythrocytic CANP/CAST activity.
PURPOSE: The Carotid Atherosclerosis Italian Ultrasound Study (CAIUS) was performed to test the effects of lipid lowering on the progression of carotid intima-media thickness (IMT) in 305 asymptomatic patients from a Mediterranean country. PATIENTS AND METHODS: Eligibility included hypercholesterolemia (baseline means: low-density lipoprotein [LDL] = 4.68 mmol/L, high-density lipoprotein [HDL] = 1.37 mmol/L), and at least one 1.3 < IMT < 3.5 mm in the carotid arteries. Patients (mean age 55 years, 53% male) were assigned to pravastatin (40 mg/day, n = 151) or placebo (n not equal to 154). Ultrasound imaging was used to quantify IMT at baseline, and semiannually thereafter for up to 3 years. The mean of the 12 maximum IMTs (MMaxIMT), was calculated for each patient visit, and used to determine each patient's longitudinal progression slope. The intention-to-treat group difference in the MMaxIMT progression was chosen a priori as the primary end point. RESULTS: Five serious cardiovascular events (1 fatal myocardial infarction), and 7 drop-outs for cancer were registered. In the pravastatin group, LDL decreased -0.22 after 3 months versus -0.01 in the placebo group, and remained substantially unchanged afterward (-0.23 versus +0.01 at 36 months, respectively). Progression of the MMaxIMT was 0.009 +/- 0.0027 versus -0.0043 +/- 0.0028 mm/year (mean +/- SE, P < 0.0007) in the placebo and pravastatin groups, respectively. IMT progression slopes diverged after 6 months of treatment. CONCLUSIONS: Pravastatin stops the progression of carotid IMT in asymptomatic, moderately hypercholesterolemic men and women. This finding extends the beneficial effects of cholesterol lowering to the primary prevention of atherosclerosis in a population with relatively low cardiovascular event rates, and suggests that this benefit is mediated by specific morphological effects on early stages of plaque development.
BACKGROUND/AIMS: An impaired methionine degradation along the transsulfuration pathway has been widely described in cirrhosis. Evidence has been provided that methionine can also be degraded via a transamination pathway, leading to formation of methanethiol and its metabolites, protein-S-SCH3 (a mixed disulphide of blood proteins and methanethiol), alpha-ketomethylthiobutyrate and X-S-SCH3 (a mixed disulphide of a thiol with an unknown component X and methanethiol). This pathway seems to be of little importance in normal subjects, even after methionine loading, but its role in the presence of an acquired transsulfuration defect has never been tested. METHODS: We measured the plasma concentration of methanethiol metabolites in six normal subjects and 11 patients with cirrhosis receiving a primed-continuous infusion of L-methionine, at rates able to increase plasma methionine to levels approximately 20 times basal concentrations. RESULTS: Before methionine infusion, the sum of transamination metabolites was similar in the two groups (0.29 +/- SD 0.07 mumol/l in controls and 0.45 +/- SD 0.22 in patients with cirrhosis). During methionine infusion and after the end of infusion, there was a progressive increase of transamination metabolites, which reached values approximately 10 times basal concentrations, with no difference between groups. CONCLUSIONS: We conclude that transamination cannot represent a quantitatively important exit for excess methionine in subjects with cirrhosis, in the presence of an acquired block along the transsulfuration pathway.
Human primary hypertension is a polygenic disease; its phenotypic expression is modulated by the environment. Though the kidney can play a major role in the initiation and maintainance of hypertension, many questions remain open. Kidney cross-transplantation demonstrated that hypertension can be transplanted with the kidney in all strains of genetically hypertensive rats where such experiments have been carried out. Data consistent with those in rats were also obtained in humans. Many abnormalities in kidney function and ion transport were described in hypertensive rats and humans, but the logical sequence from genetic-molecular to cellular abnormality that causes hypertension via modification of kidney function is difficult to prove. We established this sequence in Milan hypertensive rats using a variety of experimental techniques (isolated kidney and renal cell function, cell membrane ion transport, cross-immunization with membrane proteins, molecular biology, genetic crosses and manipulation). Such studies led to the identification of a polymorphism in the cytoskeletal protein adducin. This polymorphism seems involved in blood pressure regulation both in rats and humans. Preliminary results suggest that adducin polymorphism affects kidney function by modulating the overall capacity of tubular epithelial cells to transport ions modifying the assembly of actin cytoskeleton.
Zinc deficiency is common in cirrhosis and has been involved in the altered nitrogen metabolism. In this study, we measured the effects of zinc supplementation on the dynamics of amino acid-derived urea synthesis in cirrhosis with mild or latent encephalopathy. The hepatic conversion of amino acids into urea was studied in eight patients with advanced cirrhosis under controlled conditions of substrate availability (continuous alanine infusion), before and after 3-month oral zinc sulfate supplementation (600 mg/d). Eight more patients, matched for hepatocellular failure and encephalopathy, served as controls. Plasma zinc levels were reduced in all patients and returned to normal after oral zinc. The alanine-stimulated urea nitrogen synthesis rate in relation to alpha-amino-N concentration--the functional hepatic nitrogen clearance--increased by 25% after zinc supplementation, i.e., more urea was produced at any alpha-amino-N concentration. Basal and alanine-induced glucagon decreased by 50%, and the ammonia response to alanine decreased by 30%. Psychometric tests improved, as did routine and dynamic liver function tests and the Child-Pugh score. Also, the plasma concentration of lipid peroxides was reduced by zinc. No significant changes were observed in the control group. Our data indicate that long-term oral zinc speeds up the kinetics of urea formation from amino acids and ammonia. Changes in the hormonal drive and/or the antioxidant activity of zinc might be involved in the general improvement in liver function, whereas the beneficial effects on encephalopathy might stem from decreased ammonia.
There is increasing interest for the use of surrogate end points in the evaluation of treatments in patients with liver disease, but adequate validation is seldom available. This study aimed to describe the different course of galactose elimination capacity in patients with alcoholic cirrhosis who continued to drink or abstained from alcohol consumption during follow-up, and to validate changes in galactose elimination as a surrogate end point for death from liver-related causes. Forty-five patients with alcoholic cirrhosis (22 who continued drinking throughout the study period, and 23 who stopped drinking and were abstinent throughout the study period) were retrospectively selected among patients who had galactose elimination capacity measured at 6-month intervals. During follow-up 10 drinkers and 3 abstainers died of liver-related causes (P = .025). Abstainers showed a transient improvement in galactose elimination capacity, followed by a decrease. Continuous drinkers showed a reduction from the beginning. According to Cox's regression analyses, persistent alcohol abuse and galactose elimination capacity were separately related to the risk of death, but, when a time-dependent model was fitted containing galactose elimination capacity and persistent alcohol abuse, only the former remained significant. This implies that variations in the risk of death occurring as a consequence of abstinence from alcohol consumption may be predicted from changes in galactose elimination capacity, and that the mechanisms through which abstinence influences survival are strictly linked to the mechanisms responsible for the changes in the test. Because of the strict association of decrease in galactose elimination capacity and short survival, as proved in several series, this observation represents adherence to the criteria requested for adequacy of a surrogate end point. In conclusion, in alcoholic cirrhosis the decrease in galactose elimination capacity is an adequate surrogate end point for death from liver-related causes, which is worth testing in other conditions and in response to other treatments.
Propionyl-L-carnitine (PLC) was shown to improve global cardiac function in pressure overload hypertrophy by acting directly on muscle mechanics. We investigated whether PLC can effectively ameliorate papillary muscle mechanics in a volume overload (VO) model. We induced VO by constructing an aortocaval anastomosis in adult Wistar rats. Three experimental groups were studied: sham-operated controls and untreated and PLC-treated VO animals. Isometric function of right and left papillary muscle was studied 16-18 weeks later. PLC was administered in the drinking water at the dose of 180 mg/kg for the last 2 weeks before experiment. One-way analysis of variance (ANOVA) showed that in right papillary muscles from the untreated VO group the time course of the isometric contraction was significantly prolonged [time-to-peak tension (TPT, ms +/- SEM) from 126 +/- 4.9 to 156 +/- 7.1; time from peak tension to 30% relaxation (TRel) from 133 +/- 11.9 to 196 +/- 13.9; n = 11 and 8, respectively], and peak rates of contraction and relaxation normalized over developed tension were significantly decreased in comparison with sham [from (s-1 +/- SEM) 12.9 +/- 0.5 to 10.8 +/- 0.6, and from 7.2 +/- 0.6 to 5.2 +/- 0.4, respectively]. These parameters in the PLC VO group did not differ from sham (TPT, 140 +/- 5.7; TRel, 158 +/- 14.4; +dF/df/DT, 12.2 +/- 0.6; -dF/df/DT, 6.5 +/- 0.5; n = 8). Function of left papillary muscle was not modified by either VO or PLC treatment. Total carnitine levels in either ventricle free walls were unchanged by VO. PLC significantly increased total carnitine content of left ventricle free wall (from 5.4 +/- 0.28 to 7.0 +/- 0.50). The contraction changes observed in the right papillary muscle are likely to depend on the pressure overload occurring in the right chamber; moreover, they are unrelated to tissue carnitine depletion. PLC improved the altered right papillary muscle mechanics without exerting any apparent effect on the functionally normal left papillary muscle. PLC activity is independent of carnitine stores, but may presumably be ascribed to its anaplerotic properties.
PURPOSE: To evaluate screening with three-dimensional (3D) phase-contrast magnetic resonance (MR) angiography with a phased-array multicoil to detect renal artery stenosis. MATERIALS AND METHODS: Fifty consecutive patients suspected of having renovascular disease were prospectively examined with 3D phase-contrast MR imaging with a phased-array multicoil. Findings were correlated with those at intra-arterial digital subtraction angiography (DSA) as the standard of reference for grade of stenosis. RESULTS: MR angiography depicted 101 of 103 renal arteries depicted at intraarterial DSA; the two missed arteries were an accessory artery outside the imaging volume and an artery with a stent. At intraarterial DSA, a stenosis was found in 31 of 101 arteries. On the basis of findings at 3D phase-contrast MR angiography, the presence of any degree of stenosis was correctly depicted in 29 of 31 cases and the absence of stenosis was correctly depicted in 66 of 70 cases (accuracy, 94%; sensitivity, 94%; negative predictive value, 97%). Overall accuracy was 97% for correct depiction of severe renal artery stenosis (> 50%). CONCLUSION: 3D phase-contrast MR angiography with a phased-array multicoil was an accurate noninvasive screening technique in patients with suspected renal artery stenosis.