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Biomedical subjects

R Naccarato

Publications and source records attributed to R Naccarato.

At least 73 records · Page 4Linked to original sources

Activation of cytotoxic and natural killer T-cell system in patients with hepatocellular carcinoma and cirrhosis.

The immune response in liver cirrhosis and hepatocellular carcinoma is receiving renewed attention in consideration of the possible treatment with biological response modifiers. The aim of this study was to evaluate whether cirrhosis and hepatocellular carcinoma induce any modification in peripheral lymphocyte subsets. Lymphocytes were evaluated (number/percentage) in 61 patients with hepatocellular carcinoma, 35 with cirrhosis and 24 healthy controls. Using flow cytometry, 10 lymphocyte subpopulations were assayed, plus the CD4/CD8 ratio. Results demonstrated no change in the number of lymphocytes; cirrhosis and hepatocellular carcinoma patients had significantly more HLA-DR+ (p = 0.001) and CD3+/HLA-DR+ (activated T) (p = 0.002) and fewer CD3+ (mature T) (p = 0.02) cell than controls; hepatocellular carcinoma patients had significantly more CD3+/CD56+/CD16- (cytotoxic non-MHC restricted T cells) and CD25+ (IL-2 receptor positive cells). If the percentages of all cells with cytotoxic-T activity were pooled, a significant increase (p = 0.03) was seen in hepatocellular carcinoma patients. In conclusion, in contrast to previous data, hepatocellular carcinoma patients reveal an increased number of cytotoxic non-MHC restricted T cells.

Antigens, CD↗

Cysteine and serine proteases in gastric cancer.

BACKGROUND: Cysteine proteases (cathepsin B [CATB] and cathepsin L [CATL]), the serine protease urokinase-type plasminogen activator (UPA), and plasminogen activator inhibitor type-1 (PAI-1) are thought to play an important part in cancer invasion and metastasis. The aims of this study were to measure CATB, CATL, UPA, and PAI-1 in gastric cancer (GC) and normal mucosa distant from the tumor (NORM); to evaluate whether tissue levels are related to tumor stage, grade, or histotype; to assess their prognostic relevance; and to examine UPA and PAI-1 expression immunohistochemically. METHODS: Gastric cancer and NORM samples were obtained from 25 patients with gastric cancer patients undergoing surgery (17 males, 8 females; mean age, 62 years; range, 31-84 years). Antigen concentrations were measured using the enzyme-linked immunosorbent assay method. Immunohistochemistry was performed using monoclonal UPA and PAI-1 antibodies. RESULTS: Significantly higher antigen levels were found: (1) in GC vs. NORM (CATB, CATL, UPA, PAI-1) tissues; (2) in GC with versus without metastasis (CATB, CATL, UPA); (3) in poorly or moderately versus well differentiated GC; and (4) in diffuse versus intestinal-type GC (CATB, CATL). Urokinase-type plasminogen activator, PAI-1 and CATB levels had a significant prognostic impact. Cancer and stromal cells, showed immunoreactivity to anti-UPA and anti-PAI-1 antibodies. CONCLUSIONS: These results confirm the important role of CATB, CATL, UPA and PAI-1 in gastric cancer progression. Higher levels are detected in GC with metastases, poorer differentiation, and diffuse histotype, thus identifying patients with a worse prognosis.

Adenocarcinoma↗

[Ultrasound guided fine-needle aspiration biopsy in the diagnosis of hepatocellular carcinoma].

This retrospective study was undertaken to evaluate the diagnostic usefulness of 244 sonographically guided fine- needle aspiration biopsy in 226 patients with ultrasonographically suspected hepatic malignant lesions. A final diagnosis of malignancy was established in 166 cases (73%) (145 hepatocellular carcinoma, 21 metastasis); benign lesions were aspirated in 60 cases (27%). The diagnostic sensitivity of this technique was 93%, with 100% specificity. When both cytology and microhistology were obtained, the positive correlation of the two techniques was 80% In the series of 244 fine-needle aspiration biopsy the authors had only one acute complication. They report one case of needle tract tumor seeding after biopsy. These results confirm the usefulness of sonographically guided fine-needle aspiration biopsy in diagnosing malignant hepatic tumors. The procedure is simple, safe, free of important side effects. The authors believe that ultrasound guided fine-needle aspiration biopsy represents the first choice of invasive technique in the assessment of hepatic focal benign lesions and malignant tumours.

Adult↗

[Role and behavior of cathepsin B and cathepsin L in gastric cancer].

Cathepsin B and cathepsin L--cysteine proteinases--may play an important role in cancer invasion and metastasis. The authors determined tissue antigen concentrations of cathepsins, using the ELISA method, in 25 patients with gastric cancer (17 males, 8 females, mean age 62, range 31-84). They evaluated the possible relationship that these proteinases may have with the presence of metastases, differentiation and histotype. Significantly higher cathepsin B and cathepsin L antigen levels were found: 1. in gastric cancer tissues vs. normal tissues distant from tumors (CATB: p < 0.05, CATL: p < 0.005); 2. in diffuse vs. intestinal type cancers (p < 0.05); 3. in patients with poorly vs. well-differentiated cancers (p < 0.05); in gastric cancers with vs. without metastasis (p < 0.05). Their results confirm that cathepsin B and L play an important role in gastric cancer invasion and metastasis. Considering the significantly higher cathepsins detected in cancers with metastasis, a poor differentiation and of diffuse histotype, these proteinases could be useful for identification gastric cancer patients with a poor prognosis.

Adult↗

[Local transcatheter arterial chemoembolization in the palliative treatment of inoperable hepatocellular carcinoma].

Hepatocellular carcinoma is a tumor with high mortality. Adequate oncological therapy is essential to modify the poor prognosis. Transcatheter arterial chemoembolisation has been proposed as a useful and well-tolerated treatment for unresectable carcinoma. In the study 51 patients with unresectable carcinoma (mean age 61.6, range 45-81, Child-Pugh A = 34 patients, Child-B = 13, Child-C = 4; Okuda I = 33 patients, Okuda II = 18) underwent chemoembolisation. A total of 122 procedure were performed, with a median number of 2.4 (range 1-6) per patient. One and two year survivals are 91% and 74% respectively (Child-A: 100% and 82%; Child-B: 100% and 63%; Child-C 0% at 1 year). The difference among the 3 groups is statistically significant (p = 0.001). Median overall survival is 20 months, with 22, 20 and 6 month in Child-A, B and C patients respectively (p = 0.006). Commonly reported side effects and biochemical changes included: fever, pain and increased serum amylase, transaminase levels. One patient developed a liver abscess and died of liver failure. In addition, in 18 patients (35%) mild to severe changes in glucose metabolism were also observed. Mild hyperglycemia was observed in 14 patients, with severe derangement in 4 patients (8%). It is suggested that careful evaluation of glucose metabolism is advisable in patients being considered for chemoembolisation. Their results confirm the usefulness of chemoembolisation in Child-A and B patients with unresectable hepatocellular carcinoma.

Aged↗

Functional and morphological changes in small bowel of Crohn's disease patients. Influence of site of disease.

Morphological and functional changes were examined in the upper jejunum and terminal ileum of 18 patients suffering from Crohn's disease. Intestinal permeability, biochemical determination of enzymatic activities, and morphologic evaluation of the severity of the lesions were evaluated. Ulcerative colitis and irritable bowel syndrome patients served as controls. We found abnormal lactulose-mannitol tests in all patients with active Crohn's disease. Permeability changes correlated with increased crypt cell proliferation, as indicated by thymidine kinase activity. A significant reduction in brush border enzyme activities was seen in the terminal ileum, but no significant change was observed in the unaffected upper jejunum. The number of mast cells was increased in the diseased ileum. We conclude that the site of inflammation and the healing capacity of the epithelium are important in determining functional and biochemical abnormalities in active Crohn's disease. Changes may be dependent on the type and number of immune cells involved in the inflammatory process.

Adult↗

Iron storage, lipid peroxidation and glutathione turnover in chronic anti-HCV positive hepatitis.

BACKGROUND/AIMS: Little is known about the pathogenesis of liver damage related to hepatitis C virus. The presence of steatosis or increased ferritin levels, and preliminary data on the relevance of iron as a prognostic factor prompted us to ascertain whether hepatitis C virus-related liver damage might be mediated by iron accumulation. METHODS: We evaluated the degree of hepatic inflammation and steatosis, serum ferritin, transferrin saturation and iron levels, tissue iron concentrations and iron index, liver glutathione and malondialdehyde in 33 males and 20 females with chronic hepatitis C virus- or hepatitis B virus-related hepatitis (42 + 11). We also considered six patients with both alcohol abuse and hepatitis C virus, four males with chronic alcoholic liver disease and four males with genetic hemochromatosis, giving a total of 67. All diagnoses were histologically confirmed. Patients with cirrhosis were excluded. RESULTS: Our data show that: 1. Steatosis is more frequent in hepatitis C virus and hepatitis C virus+alcohol abuse patients; 2. In males, serum ferritin and tissue iron are significantly higher in hepatitis C virus- than in hepatitis B virus-positive patients (p < 0.01 and 0.05); transferrin saturation is higher (p < 0.05) in hepatitis C virus-positive than in hepatitis B virus-positive patients only when males and females are considered together; 3. Serum ferritin and transferrin saturation only correlate with liver iron (r = 0.833 and r = 0.695, respectively, p = 0.00001); tissue iron is significantly higher in hepatitis C virus- than in hepatitis B virus-positive patients (p < 0.05); 4. In patients with chronic hepatitis, serum ferritin is a better marker of liver iron storage than transferrin saturation, both in males and in females; 5. Hepatitis C virus-positive patients have higher malondialdehyde levels and activation of turnover of glutathione, probably in response to free-radical-mediated liver damage. Females have lower liver iron levels but similar trends. CONCLUSIONS: These findings suggest that hepatitis C virus-related liver damage is characterized by increased iron storage (possibly induced by the virus) which elicits a free-radical-mediated peroxidation, with consequent steatosis and activation of glutathione turnover.

Adult↗

Persistence of anti-HBs antibodies in health care personnel vaccinated with plasma-derived hepatitis B vaccine and response to recombinant DNA HB booster vaccine.

Long-term persistence of specific antibodies after primary immunization against HBV infection has been reported. In this study, we evaluated the persistence of anti-HBs in vaccinees 6 years after primary immunization and the response to a booster dose using a recombinant DNA yeast-derived HB vaccine. An 85.4% seroprotection rate was observed after 6 years with a significantly higher seroprotective rate in those subjects who received four doses of vaccine primary immunization as compared with those who received three doses (93.9% versus 67.2%, p < 0.001). One month after receiving the booster dose, 98.6% of the subjects had an anamnestic type of response. The GMTs were found to decrease progressively with increasing age. The antibody levels after booster dose were higher than those attained at the end of primary immunization and reflected the trend seen before the administration of the booster. These results are consistent with the existence of an effective immunological memory in HB vaccine responders. Subjects who received four doses during primary immunization were better seroprotected and had a higher seroprotection rate after the booster dose.

Adolescent↗

Determinants for the development of chronic atrophic gastritis and intestinal metaplasia in the stomach.

This study aimed to identify the factors associated with the development of gastric precancerous changes, in a prospective series of patients undergoing endoscopy. Risk factors and associated mucosal changes were evaluated in 134 endoscoped patients affected by chronic non-atrophic (n = 76) or atrophic gastritis (CAG) (n = 32), with or without intestinal metaplasia (IM), or lacking any major histological changes (n = 26). The following variables were taken into account: age, alcohol consumption, smoking habit, vitamin C intake (using a questionnaire), gastric juice vitamin C (HPLC on gastric juice samples obtained at endoscopy), H. pylori infection, gastric mucosa malondialdehyde (MDA; a measure of free radical production) and extent of CAG in gastric biopsies (only for IM). Tissue MDA levels were significantly higher, and vitamin C levels significantly lower in CAG and IM patients (P = 0.01). Multiple regression analysis showed significant correlations for: CAG vs age (P < 0.02), MDA (< 0.02) and gastric vitamin C (< 0.05); IM vs age (P < 0.0005), CAG (< 0.0005) and MDA (< 0.001). Using stepwise discrimination analysis, the independent variables included in the model were: for CAG, age (P < 0.003), MDA (< 0.05), gastric juice vitamin C (< 0.05); for IM, CAG (P < 0.0005), age (< 0.001), MDA (< 0.03) and vitamin C intake (< 0.05). H. pylori was not included. The major determinants for CAG and IM were age, free radical production (as measured by MDA), vitamin C (for CAG) and vitamin C intake and CAG (for IM).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Association between inflammatory bowel disease and sarcoidosis. Report of two cases and review of the literature.

BACKGROUND: Common etiopathogenic factors may explain the association of systemic sarcoidosis with inflammatory bowel disease. METHODS: We report two cases of such an association: one of sarcoidosis that developed 2 years after proctocolectomy for ulcerative colitis and one of sarcoidosis and Crohn's colitis. Factors like increased cellular immunity or circulating immunocomplexes or autoantibodies may have a role. Exogenous agents or familiarity may also be involved. CONCLUSIONS: It is postulated that the association between sarcoidosis and inflammatory bowel disease (both ulcerative colitis and Crohn's disease) does not occur by chance alone and that the two conditions may share some genetic or immunologic alterations. The two diseases, however, follow an independent clinical course.

Adult↗

Hepatocellular carcinoma in alcoholic cirrhosis: is sex hormone imbalance a pathogenetic factor?

OBJECTIVE: A sex hormone imbalance has been reported in patients with hepatocellular carcinoma (HCC). We investigated the serum levels of eight sex hormones in patients with alcohol-related and non-alcohol-related cirrhosis and HCC. METHODS: Luteinizing hormone, follicle-stimulating hormone, estradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone and sex hormone binding globulin were assayed in 81 patients with cirrhosis (59 men, 22 women) and 97 with HCC and cirrhosis (82 men, 15 women). Hepatitis B or hepatitis C virus infection was present in 58% of patients with cirrhosis and 69% of patients with HCC. Alcohol abuse was the aetiopathogenetic factor in the remaining patients. RESULTS: In men, mean testosterone levels were at the lower limit of the normal range for both patients with HCC and for controls with cirrhosis. Mean estradiol levels were increased both in patients with HCC and in those with cirrhosis, but patients with alcohol-related HCC had higher estradiol levels (P = 0.0002). An index of sex hormone imbalance, the estradiol to testosterone ratio (ETR), was calculated. The ETR was significantly higher in patients with alcohol-related HCC (P = 0.0002). Multiple regression analysis showed that the ETR correlated best with patients' diagnosis (P < 0.05). In women, the ETR was significantly lower in patients with HCC than in controls with cirrhosis. CONCLUSIONS: Men with alcohol-related HCC are characterized by an oestrogen and androgen imbalance and have a higher ETR than patients with other types of liver damage. Since sex hormones modulate hepatocellular proliferation, our data suggest that a sex hormone imbalance plays a role in hepatocarcinogenesis in patients with alcohol-related cirrhosis.

Adult↗

Cognitive assessment in primary biliary cirrhosis: a case-control study.

OBJECTIVES: Primary biliary cirrhosis (PBC) patients frequently complain of fatigue and loss of memory. The aim of this study was to evaluate the mental performance and the neuropsychological assessment in patients with PBC. METHODS: A case-control study was performed that included 36 PBC patients (34 female, two male, mean age 55 yrs, 11 with stage II, 16 with stage III, and nine with stage IV disease) and 36 sex and age-matched controls with rheumatoid arthritis. A preliminary routine neurological examination failed to show any abnormality in each patient, including signs of encephalopathy. A battery of neuropsychological tests was administered to each subject, including: the Global Deterioration Scale; the Mini Mental State Examination; Buschke test; Gatterer's test; the Wechsler Memory Scale; the Blessed-Roth memory test; and the Clifton Assessment Schedule. RESULTS: The overall score for each test was not statistically different in PBC patients compared with rheumatoid arthritis patients, except for the Global Deterioration Scale and the Clifton Assessment Schedule; the performance was significantly poorer for these measures in PBC patients compared with rheumatoid arthritis patients. In both groups no correlation was found between the score of each test and age and/or duration of the disease. However, in the PBC group the score of BR was negatively correlated with the histological stage (p < 0.0025). CONCLUSION: The global mental status is not altered in PBC, but early changes in orientation and in personal memory are present in cirrhotic stage.

Adult↗

The role of urokinase-type plasminogen activator and its inhibitor PAI-1 in gastric cancer.

BACKGROUND: It has been proposed that the serine protease urokinase-type plasminogen activator (UPA) and its inhibitor type-1 (PAI-1) may play an important part in cancer spread and metastasis. AIMS OF THE STUDY: 1. To determine the UPA, PAI-1 antigen levels in gastric cancer (GC) and in normal gastric mucosa far from the tumor (NORM). 2. To evaluate changes related to the presence of metastasis, tumor differentiation (grading) and histotype. PATIENTS AND METHODS: Samples of tumor and of normal mucosa were obtained from 25 GC patients undergoing surgery (17 males, 8 females, mean age 62, range 31-84). Antigen concentrations were measured using the ELISA method. RESULTS: Significantly higher UPA and PAI-1 antigen levels were found: 1. in GC vs. NORM tissue; 2. in patients with poorly and moderately differentiated GC vs. well-differentiated GC. UPA was significantly higher in GC with vs. without metastasis. PAI-1 was also higher, though not significantly so, in GC with metastasis than in GC without metastasis. CONCLUSION: Our results confirm that the serine protease UPA and its inhibitor PAI-1 play an important role in GC progression. Considering the higher protease levels detected in GC with metastases and poorer differentiation, UPA and PAI-1 might be useful for identifying gastric cancer patients with a poor prognosis.

Adult↗

Fine-needle biopsy in focal liver lesions: the usefulness of a screening programme and the role of cytology and microhistology.

We evaluated the diagnostic usefulness of 244 ultrasound-guided fine-needle biopsies (FNB) in 226 patients with suspected liver malignancies. A malignancy was detected in 166 cases (73%) -145 hepatocellular carcinomas (HCC), 21 metastases; benign lesions were aspirated in 60 cases (27%). The sensitivity of FNB was 93%, with 100% specificity. In the FNB false-negative cirrhotic nodules, a final diagnosis of HCC was reached on repeating the biopsy 1-8 months later. When both cytological and microhistological examinations were performed, the positive correlation between the two techniques was 80%, with a slightly higher sensitivity for microhistology (93%). The malignancies diagnosed were potentially resectable in 26% of cases. We experienced 1 acute complication of FNB and 1 case of needle tract tumour seeding. These results confirm that FNB is useful in diagnosing malignant liver tumours. We believe that US-guided FNB is the first-choice invasive technique for assessing focal benign lesions and malignant tumors in the liver.

Adult↗

Effect of infusing branched-chain amino acid during incremental exercise with reduced muscle glycogen content.

The aim of this study was to investigate whether, when muscle glycogen is reduced, a pre-exercise infusion of branched-chain amino acids (BCAA) modifies exercise performance or the metabolic and respiratory responses to incremental exercise. Six moderately trained volunteers took part in the following protocol on two occasions. On day 1, at 9 a.m. in the postabsorptive state, they performed a graded incremental exercise (increases of 35 W every 4 min) to exhaustion (Ex-1). A meal of 1,000 kcal (4,200 kJ; 60% protein, 40% fat) was consumed at 12 p.m. No food was then allowed until the end of the experiment (20-21 h later). A 90-min period of exercise at alternating high and moderate intensities, designed to deplete muscle glycogen, was performed between 6 p.m. and 7.30 p.m. The morning after (day 2), the subjects randomly received either a mixed solution of BCAA (260 mg x kg-1 x h-1 for 70 min), or saline. They then repeated the graded incremental exercise to exhaustion (Ex-2). Metabolic and respiratory measurements suggested a muscle glycogen-depleted state had been achieved. No significant differences were observed in total work performed, maximal oxygen uptake or plasma ammonia, alanine, and blood pyruvate concentrations in the two treatments. After BCAA infusion, higher blood lactate concentrations were observed at maximal power output in comparison with those during saline [BCAA 4.97 (SEM 0.41) mmol x l-1, Saline 3.88 (SEM 0.47) mmol x l-1, P < 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Different response to ursodeoxycholic acid (UDCA) in primary biliary cirrhosis according to severity of disease.

To evaluate the effect of ursodeoxycholic acid (UDCA) treatment according to the severity of primary biliary cirrhosis, a long-term prospective open trial in 54 consecutive PBC patients, 19 with histological stage I-II, 24 stage III, and 11 stage IV was carried out. UDCA was administered at a dosage of 250 mg twice a day. Clinical and biochemical assessment (AST, ALT, alkaline phosphatase, GGT, bilirubin) were done initially and every six months. Serum hyaluronate (HY) and type III procollagen amino propeptide (PIIIP) were also evaluated, as they are considered markers of fibrosis and prognosis. All patients were followed-up for at least two years (24-36 months); results were analyzed at 24 months after treatment. The composite pruritus score failed to show significant changes during UDCA treatment, while intensity score demonstrated a significant reduction from the 6th month. Patients with histological stage I-II disease had a significant decrease of liver enzymes (AST, ALT, alkaline phosphatase, GGT) after six months and maintained the levels up to 24 months. The patients with histological stage III disease showed a significant decrease of AST, ALT, alkaline phosphatase (but not GGT) up to month 18; subsequently AST and ALT serum levels increased, reaching values comparable to baseline by 24 months. In patients with histological stage IV disease no significant change in liver enzymes was observed during the follow-up. HY and PIIIP serum levels failed to show significant changes during UDCA treatment in the three groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholestyramine Resin↗

Pepsin concentration in gastroduodenal biopsy homogenates in chronic ulcer disease.

A modification of Berstad's spectrophotometric method was tested and proved capable of detecting pepsin concentrations in mucosal perendoscopic biopsy homogenates. The relationship between this parameter and pepsin in gastric juice and pepsinogen group I in serum and in biopsy homogenates was analyzed. From the biochemical point of view, the assay was found sufficiently accurate. Mucosal pepsinogen group I, but not mucosal pepsin, concentration was found higher in gastric and duodenal ulcer patients than in controls. Patients with corpus-fundic gastric ulcer showed significantly lower mucosal pepsin and mucosal pepsinogen group (PG) I. Aging and smoking did not influence either parameter but male duodenal ulcer subjects presented higher mucosal pepsinogen group I concentration. The lack of any relationship between serum and mucosal PG I and between pepsin in gastric juice and in mucosa raises a question, at least in methodological terms, about the validity of using serum pepsinogen group I and pepsin as indicators of peptic output.

Adult↗