Biomedical subjects
Publications and source records attributed to L Barbara.
The natural history of asymptomatic gallstones, according to the best published studies, indicates that seventy per cent of the patients remain symptom-free. Nonetheless there are no clinical or morphological findings which can predict the occurrence of symptoms on a individual basis.
Studies suggest that cell proliferation abnormalities of the colorectal mucosa are associated with risk of neoplasia, and most cancers of the large bowel are thought to arise from adenomas. The results of other studies suggest that vitamins A, C, and E have chemopreventive efficacy against colon cancer in animal models. This study evaluates the effect of dietary vitamin supplementation on cell kinetics in uninvolved rectal mucosa in patients with colorectal adenomas. Twenty patients with colorectal adenomas were given vitamins A, C, and E for 6 months after complete polypectomy, and 21 patients with adenomas received placebo. In each patient, six biopsy specimens were taken from normal-appearing rectal mucosa before treatment and after 3 and 6 months of treatment and were incubated with tritiated thymidine ([3H]thymidine), and the [3H]thymidine-labeled cells were counted by use of autoradiography. Two parameters of cell proliferation were evaluated: 1) the ratio of the number of labeled cells to the total number of cells (thymidine labeling index) and 2) the ratio of the number of labeled cells in the upper 40% of the crypt to the total number of labeled cells in the crypt (phi h). The latter index reflects abnormal expansion of the proliferative compartment and is thought to be an intermediate biomarker of cancer risk. In patients receiving vitamins, phi h decreased progressively from baseline values, with increasing statistical significance (P less than .05 after 3 months, P less than .01 after 6 months). There was a statistically significant decrease in the thymidine labeling index in the 40% of the crypt near the mucosal surface, but the variation in the overall labeling index was not statistically significant. In the placebo group, we observed no statistically significant change in cell kinetics. These findings suggest that vitamin A, C, and E supplementation is effective in reducing abnormalities in cell kinetics that may indicate a precancerous condition. Before larger trials on chemoprevention of colorectal adenoma recurrence are conducted, additional studies are needed (a) to validate that cell kinetics is an intermediate biomarker, (b) to determine active agents, optimal dosage, and the relative efficacy of agents given alone and in combination, and (c) to test toxicity.
We assessed the correlation between the positivity for serum IgM antibody to hepatitis C virus and the activity of liver disease in patients with chronic hepatitis C virus infection. Serum samples were taken from 10 antibody to hepatitis C virus-positive asymptomatic patients with normal serum ALT levels, from 14 untreated patients with clinically and histologically proven chronic hepatitis C and from 26 patients with clinically and histologically proven chronic hepatitis C assigned to receive recombinant interferon alpha-2a (6 million IU three times a week for 6 mo). Each serum specimen was tested for IgM antibody to hepatitis C virus-associated C100-3 antigen by enzyme-linked immunosorbent assay. Patients were observed for at least 12 mo. All 10 patients with normal ALT values tested negative for IgM antibody to hepatitis C virus. In contrast, 33 of 40 (82%) patients with chronic hepatitis C had IgM antibody to hepatitis C virus, and a positive correlation was seen between the ALT level and the level of IgM antibody to hepatitis C virus (r = 0.803, p less than 0.001). During interferon treatment, ALT levels declined into the normal range in 18 of 26 treated patients (69%) and remained normal after stopping treatment in 8 patients (31%). In untreated patients, in treated patients who did not respond to interferon treatment and in responder patients who relapsed, no significant changes in IgM antibody to hepatitis C virus levels were seen during the study period. In contrast, IgM antibody to hepatitis C virus became undetectable by the end of interferon treatment in seven of eight patients with a sustained response.(ABSTRACT TRUNCATED AT 250 WORDS)
We analyzed the growth pattern of tumor masses and the survival of 39 asymptomatic Italian patients with a total of 59 small (less than or equal to 5 cm in diameter) hepatocellular carcinomas arising from cirrhosis. The total length of the observation period ranged from 90 to 962 days, with an average of 364 +/- 229 (mean +/- S.D.). Doubling time ranged from 27.2 to 605.6 days (mean +/- S.D., 204.2 +/- 135; median = 171.6 days). Three different growth patterns were recognized: (a) tumors with no or very slow initial growth pattern (doubling time greater than 200 days), 10 cases (37%); (b) tumors with declining growth rate over time, 9 cases (33.4%); and (c) tumors with almost constant growth rate, 8 cases (29.6%). Using the stepwise discriminant analysis, we found a score based on albumin, alcohol intake, number of nodules, echo pattern and histological type that allowed a correct prediction of short doubling time (less than or equal to 150 days) in 55.6%, medium doubling time (151 to 300 days) in 60% and long doubling time (greater than 300 days) in 100% of cases. The estimated survival rate of the 39 patients, calculated by the Kaplan-Meier method was 81% at 1 yr, 55.7% at 2 yr and 21% at 3 yr. Stepwise discriminant analysis showed that a score based on sex, HBsAg status, alcohol consumption, ascites, gamma-glutamyltranspeptidase, prothrombin time, Child-Pugh class and all the sonographical parameters could predict 2-yr survival in 100% of cases. We conclude that great variability of growth patterns exists among and within small hepatocellular carcinomas. Prediction of subsequent growth rate is unreliable in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)
Measurements of epithelial cell proliferation in the mucosa of the gastrointestinal tract pointed out the existence of cell kinetic abnormalities which can be involved in the first steps of carcinogenesis. In particular, an increase in the cell proliferation rate and an abnormal distribution of proliferating cells were found both in animals exposed to carcinogens and in human subjects at high risk of gastrointestinal cancer. In some diseases which predispose to cancer (i.e., chronic atropic gastritis, hereditary gastrointestinal cancer, sporadic colorectal neoplasia, chronic ulcerative colitis) we observed an expansion of the proliferative compartment even when the mucosa was not affected by morphological abnormalities. This proliferative feature seems to be associated with the presence of defects in cell differentiation. The abnormality is well detected by the histological examination of the proliferative pattern using microautoradiography after incorporation of tritiated thymidine, or using immunohistochemistry after bromodeoxyuridine uptake. The literature, and our own results, indicate that the search for abnormalities of epithelial cell proliferation can be useful in studying the earliest mechanisms leading to gastrointestinal cancer, in detecting subjects at high cancer risk, and for pilot chemoprevention studies using these abnormalities as intermediate biomarkers of gastrointestinal cancer risk.
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A quantitative polymerase chain reaction (PCR) assay for hepatitis C viral RNA (HCV-RNA) was used to monitor viraemia levels in six patients at multiple time points before, during, and after interferon therapy for chronic non-A, non-B hepatitis (NANBH). Prior to therapy, serum HCV-RNA was detected in all patients at approximately 10(4)-10(5) HCV genomes/ml. HCV viraemia became undetectable within 1 month of commencing interferon in three of the five patients whose alanine aminotransferase (ALT) levels decreased to normal on therapy. In the remaining two responder patients, viraemia levels declined more slowly, becoming undetectable after a period of several months. Recurrence of viraemia during therapy was observed in two cases. The one patient whose serum ALT levels remained elevated throughout therapy showed no decline in viraemia. On stopping interferon after a 6 months course, HCV genome titres climbed rapidly in all patients, reaching higher levels than had been observed prior to therapy. Biochemical relapse occurred within 7 months of ending interferon treatment in all but one of the patients who demonstrated this viraemia "rebound" phenomenon.
Histological signs of chronic active hepatitis were found in 11/41 (27%) patients with chronic alcoholic liver disease. All these 11 patients tested positive for antibodies to HCV and no other causes of chronic hepatitis were found.
Villus atrophy in celiac sprue determines not only a great reduction of the intestinal absorptive surface, but also destroys the underlying microcirculation which depends on the small artery of the villus and the rich network of capillaries. This may result in a significant shortening of the mesenteric vascular bed. We describe three cases of celiac sprue in which duplex Doppler ultrasound flowmetry revealed a high blood flow velocity in the superior mesenteric vein during the acute stage of the disease. A gluten withdrawal diet produced in all cases a restoration of the normal thickness of the mucosa, together with a significant decrease of blood flow velocity in the superior mesenteric vein.
Rectal treatment with enemas, foams, and suppositories is the most efficient method of delivering an adequate quantity of locally active drugs to the distal colon. In a pilot study carried out by colonoscopy in four patients, it was observed that 4 g 5-ASA in 20 ml foam spread up or beyond the splenic flexure and more extensively than 2 g 5-ASA in 10 ml foam. Therefore we have undertaken a study in order to compare by scintigraphy the colonic distribution of 4 g 5-ASA foam versus 4 g 5-ASA in 100 ml liquid enemas in 10 patients with ulcerative colitis using a crossover randomized design. Both preparations were labeled with 100 MBq [99mTc]sulfur colloid before administration. Anterior scans were taken at intervals for 4 hr. Activity, expressed as a percentage of total radioactivity, was measured in the rectum, sigmoid, descending, transverse, and ascending colon. Six patients had the same extent of spread with the two formulations; in three patients with foam and in one patient with enema a greater spread was observed. The foam reached the upper limit of disease in all cases, while enema failed in two cases. The maximum spread with foam was observed within 30 min in nine of 10 patients compared with seven of 10 after enema. Compared to enema, foam distributes more uniformly and seems to persist longer in the descending and sigmoid colon. The 5-ASA colonic foam shows some more favorable characteristics than enema for the local treatment of left-sided ulcerative colitis.
Treatment of Crohn's disease (CD) in clinical remission is still a debated issue. Previous studies have shown a high risk of relapse for patients with CD in clinical remission (CDAI less than 150) but with some abnormally high laboratory parameters as well as a possible beneficial role of low-dosage steroid treatment in this group of patients. Furthermore, good results have been reported on the efficacy of 5-aminosalicylic acid (5-ASA) in moderately active CD. In our study we verified the efficacy of a slow-release oral 5-ASA preparation in preventing relapses in a group of patients in clinical remission but with raised laboratory parameters. Forty-four patients were randomized in a double-blind manner to receive either 5-ASA (2 g/day) or placebo for four months. Location of disease and previous steroid treatment were similar in both groups. One patient in the 5-ASA group discontinued the drug because of uterine bleeding. During the study period, 13 of 22 placebo-treated patients and 11 of 21 5-ASA-treated patients relapsed (corrected chi square = NS). Considering the location of disease, three of 10 patients in the 5-ASA group and six of nine patients in the placebo group with ileal CD relapsed (therapeutic gain with 5-ASA: 36.6%; 95% allowance for error from -6% to 79.2%). Moreover, in seven patients with ileal CD who remained in remission, we found a statistically significant decrease in alpha 1 acid glycoprotein and C-reactive protein from the second month of the study.(ABSTRACT TRUNCATED AT 250 WORDS)
In this study, we investigated the hypothesis that increased opioid activity may be involved in the development of hyperinsulinemia in women with obesity and abdominal body fat distribution. Two groups of nine obese body (body mass index [BMI], 30 to 40 kg/m2) women with abdominal (A-ob) (waist to hip ratio [WHR] greater than 0.85) or gluteo-femoral (F-ob) (WHR greater than or equal to 0.80) fat distribution were examined and compared with eight normal-weight controls. Basal beta-endorphin levels were higher in the A-ob group than in the other groups. Each woman underwent two oral glucose tolerance tests (OGTT, 75 g glucose). A bolus of naloxone (0.8 mg) followed by a constant infusion of naloxone (0.04 mg/kg/h) or saline was also administered during the glucose challenge in random order, and blood samples for glucose, insulin, and C-peptide were collected at regular times after glucose administration. No difference was observed in basal or stimulated glucose concentrations between the three groups, nor between the saline or naloxone study. However, basal and stimulated insulin levels were significantly higher in obese women (particularly in the A-ob group) than in controls. Naloxone administration, however, did not significantly modify insulin and C-peptide glucose-stimulated concentrations in controls and in the F-ob group, whereas it significantly reduced (by approximately 47%) insulin levels in the A-ob group. Partial correlation coefficients showed a significant negative correlation between percent variation of glucose-stimulated insulin incremental areas during the naloxone study and the WHR in all women considered together (r = .544, P less than .025).(ABSTRACT TRUNCATED AT 250 WORDS)
To establish the sensitivity and specificity of the mean portal flow velocity in the diagnosis of portal hypertension, a population of 304 consecutive cirrhotic patients, in whom 246 abdominal Doppler examinations were performed, was prospectively analysed between June 1988 and December 1990. To avoid equipment-related variability only examinations performed using the same equipment were considered. Further inclusion criteria were the absence of portal vein thrombosis or reversed flow in the portal vessels and the absence of spontaneous, ultrasonographically detectable, portosystemic shunts. The parameter evaluated was mean portal flow velocity calculated directly from the Doppler trace by specific, operator-independent, software. 123 patients satisfied the inclusion criteria. As a control group 60 healthy age- and sex-matched subjects were examined. Mean portal flow velocity was significantly lower in cirrhotic patients than healthy subjects (13.0 +/- 3.2 cm/s vs. 19.6 +/- 2.6 cm/s; p < 0.001). There was also a decrease in mean portal flow velocity in cirrhotics in each Child-Pugh category (13.8 +/- 2.8 cm/s in Child-Pugh A class; 12.1 +/- 3.5 cm/s in Child-Pugh B class and 11.0 +/- 2.4 cm/s in Child-Pugh C class) with a statistically significant difference between each Child-Pugh category and healthy subjects (p < 0.001), between Child-Pugh A and B (p < 0.01) and between Child-Pugh A and C (p < 0.005). The sensitivity and specificity of mean portal flow velocity in the detection of portal hypertension was then analyzed with the receiver operating characteristic curve.(ABSTRACT TRUNCATED AT 250 WORDS)
Using endoscopic ultrasonography (EUS) a large part of the portal venous system can be visualized. In 40 patients with portal hypertension (PH) and in 48 control subjects EUS displayed the azygos, splenic, mesenteric and portal veins in both groups. However, esophageal and gastric varices, peri- esophageal and peri-gastric collateral veins and submucosal gastric venules were displayed only in patients with PH. EUS was inferior to endoscopy for detecting and grading esophageal varices (p less than 0.0005), but superior in the detection of varices in the fundus of the stomach (p less than 0.0005). EUS cannot be considered a reliable method for the study of esophageal varices: it has an overall sensitivity of 50%, does not permit flow measurements, and does not provide information that could be used to estimate the risk of bleeding. EUS has been demonstrated to be superior to endoscopy in the diagnosis of gastric varices. This finding is extremely important for the optimal selection of treatment of patients with portal hypertension. EUS can detect portal hypertensive gastropathy; thus inflammatory gastritis can be more easily distinguished from congestive gastropathy and therapeutic decisions are strongly influenced.
The influence of a very-low-calorie diet (VLCD) on lipid pattern is controversial. To evaluate the long-term effect of semistarvation on lipid patterns, a group of severely obese patients [aged 37 +/- 12 y, body mass index (BMI) 40.0 +/- 0.9] underwent a VLCD for 8 wk. Total cholesterol (TC), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C), triglycerides (TGs), apolipoproteins A1 (apo A1) and B (apo B) were analyzed every week. TC (6.07 +/- 0.23 vs 5.53 +/- 0.25 mmol/L, P less than 0.0008), HDL-C (mmol/L 1.26 +/- 0.06 vs 1.04 +/- 0.05 mmol/L, P less than 0.0001), TGs (1.46 +/- 0.19 vs 1.06 +/- 0.10 mmol/L, P less than 0.0008), and apo A1 (1.57 +/- 0.06 vs 1.32 +/- 0.06 g/L, P less than 0.0002) decreased, whereas LDL-C and apo B showed a biphasic behavior: they significantly fell during the first 3 wk, but during the last weeks returned to their initial values.
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This study aimed to compare fasting and postprandial gastrointestinal motor patterns in patients with ulcer and non-ulcer dyspepsia. Forty five subjects were studied: 10 with uncomplicated gastric ulcer, eight with uncomplicated duodenal ulcer, 18 with chronic idiopathic dyspepsia, and nine healthy asymptomatic controls. Gastrointestinal fasting and postprandial motor patterns were recorded using a low compliance perfusion technique. The interdigestive antral cumulative motility index, computed for 30 minutes before the appearance of duodenal activity fronts, and the number of activity fronts with an antral component were significantly less in patients with ulcers and those with non-ulcer dyspepsia compared with asymptomatic controls. The patient groups also had a reduced antral motor response to a solid-liquid test meal compared with healthy controls. Intestinal motor abnormalities (bursts of non-propagated phasic pressure activity and discrete clustered contractions) were recorded in a minority of patients, all with associated irritable bowel symptoms. In conclusion, antral hypomotility is a frequent but nonspecific motor abnormality in dyspepsia; abnormal motor patterns of the small bowel are less frequent and seem to be confined to patients with concomitant irritable bowel syndrome.