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M Ingrosso

Publications and source records attributed to M Ingrosso.

At least 19 recordsLinked to original sources
PubMed2001

Oral tacrolimus long-term therapy in patients with Crohn's disease and steroid resistance.

AIM: To report the results of a prospective, open-label, uncontrolled study in 13 patients affected by Crohn's disease with resistance to steroids. METHODS: The patients were treated long-term with oral tacrolimus, aiming to both resolve acute attacks and maintain remission. Tacrolimus was administered at the dose of 0.1--0.2 mg.day/kg and adjusted in order to achieve levels of 5--10 ng/mL; only mesalazine was continued concomitantly. Steroids and total parenteral nutrition were tapered when appropriate. RESULTS: Median treatment was 27.3 months. Only one patient dropped out due to adverse events. Crohn's disease activity index score significantly decreased after 6 months in 11 patients; for 1 year in nine of them, and 7 years in two of them. The inflammatory bowel disease life-quality questionnaire score significantly increased over the same periods. A marked drop in hospitalizations was recorded. In three out of six patients complete closure of fistulas occurred. Tacrolimus allowed total parenteral nutrition to be withdrawn in three out of five patients. Supplementation with low-dose steroids was required in five patients. Two patients underwent surgery. CONCLUSIONS: Tacrolimus therapy appears to be associated with both short- and long-term benefits, and may represent a therapeutic option in Crohn's disease when conventional therapies fail. This study encourages its use in controlled trials.

Administration, Oral↗
PubMed2000

Response

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Journal Article↗
PubMed2000

Age-related clinical severity at diagnosis in 1705 patients with ulcerative colitis: a study by GISC (Italian Colon-Rectum Study Group).

Clinical-endoscopic parameters of UC presentation were studied in 1705 out-patients, observed consecutively in 17 Italian gastroenterology centers (males 60.2%; average age at diagnosis 38.5 +/- 16.4 years), and were subdivided arbitrarily into quartile age groups at diagnosis (0-25, 26-35, 36-50, >50). A significantly greater prevalence in males, increasing with age, was shown at diagnosis (P = 0.0002), which seems to correlate with the condition of being an ex-smoker, most frequently found in males. The greater frequency of exsmokers could also, in part, justify the second peak of incidence in old age. Greater colitis extent, greater clinical activity, and greater use of steroids as the first therapeutic step are shown to prevail among younger patients and among women (P = 0.02 and P = 0.019, respectively). The same is observed for symptoms mainly representing clinical severity such as diarrhea, fever, and weight loss (P = 0.004; P = 0.006; P = 0.009, respectively). This study confirms the UC risk factor represented by the condition of being an ex-smoker and shows a greater severity of illness on diagnosis in younger patients.

Adult↗
PubMed2000

Oral tacrolimus (FK 506) in Crohn's disease complicated by fistulae of the perineum.

We describe the cases of two patients with Crohn's disease affected by severe perineal fistulae resistant to conventional therapies, successfully treated with FK 506, a new immunomodulatory drug. It is well absorbed from diseased bowel and preliminary experiences have indicated its short-term use in complicated Crohn's disease. The first patient was a 24-year-old male with perineal fistula and severe skin ulceration (8 cm of external opening diameter). He had undergone colectomy and ileostomy because of severe pancolitis refractory to medical treatment and had been treated with azathioprine and metronidazole. Two months after starting FK 506, a dramatic improvement made further surgical operation unnecessary. Local and general benefit was observed during the following 26 months, until FK 506 was withdrawn. The second patient was a 28-year-old male with a diagnosis of ulcerative pancolitis changed to Crohn's disease two months after the onset of a perineal fistula, recurring despite drainage procedures, steroid therapy, and total parenteral nutrition. FK 506 was administered for two months with a complete healing of fistula. Successively, it was stopped and corticosteroids (associated to enteral nutrition) were given because of recurrent rectal bleeding. Our experience encourages the use of oral FK 506 in complicated Crohn's disease and suggests the possibility of a long-term primary therapy other than the use as a "bridge" to other treatments.

Administration, Oral↗
PubMed1998

STK11 mutations in Peutz-Jeghers syndrome and sporadic colon cancer.

A potential tumor suppressor gene, STK11 , encoding a serine threonine kinase, has recently been identified on chromosome 19p13. Germ-line mutations of this gene have been found in patients with Peutz-Jeghers syndrome (PJS). To further investigate the relevance of STK11 mutations in PJS, we analyzed its coding sequence in nine patients and identified two deletions and three missense mutations. Because intestinal carcinomas have been observed to develop in association with PJS, we analyzed tumors from 71 patients for allelic deletions (loss of heterozygosity) and STK11 gene mutations, to elucidate the etiological role of STK11 gene in sporadic colorectal cancer. Loss of heterozygosity, evaluated using the microsatellite D19S886, was observed in 10 of 52 informative cases. No somatic mutations were detected except for a missense alteration in one tumor. Our data indicate the heterogeneity of PJS and the infrequent involvement of the STK11 gene in colorectal cancer.

AMP-Activated Protein Kinase Kinases↗
PubMed1998

Hepatobiliary alterations in patients with inflammatory bowel disease: a multicenter study. Caprilli & Gruppo Italiano Studio Colon-Retto.

BACKGROUND AND METHODS: Four hundred and eighty-four patients with inflammatory bowel disease underwent clinical examination, ultrasonography, and biochemical liver function tests, to estimate the prevalence of hepatobiliary alterations. The patient group included patients without a history of liver disease. Controls were recruited from patients with functional symptoms. RESULTS: More patients with ulcerative colitis than controls had liver steatosis and increased alkaline phosphatase levels. Factors increasing the probability of liver damage were long-standing disease, the presence of moderate/severe disease activity, and treatment with steroids and mesalazine. A significant association was found between biliary disease and long-standing colitis and also therapy with steroids and mesalazine. Alkaline phosphatase and aminotransferase levels were significantly higher in Crohn's disease patients than in controls. Hepatic and biliary damage was found more commonly in the 1st year after diagnosis. CONCLUSIONS: The monitoring of hepatobiliary function is suggested for patients with inflammatory bowel disease, even in the absence of symptoms and history.

Adolescent↗
PubMed1998

Risk of inflammatory bowel disease attributable to smoking, oral contraception and breastfeeding in Italy: a nationwide case-control study. Cooperative Investigators of the Italian Group for the Study of the Colon and the Rectum (GISC).

BACKGROUND: Using data from a case-control study carried out in Italy 1989-1992, we estimated the odds ratios (OR) and the population attributable risks (AR) for inflammatory bowel diseases (IBD) in relation to smoking, oral contraception and breastfeeding in infancy. METHODS: The study focused on 819 cases of IBD (594 ulcerative colitis: UC; 225 Crohn's disease: CD) originating from populations resident in 10 Italian areas, and age-sex matched paired controls. RESULTS: Compared with non-smokers, former smokers were at increased risk of UC (OR = 3.0; 95% confidence interval [CI]: 2.1-4.3), whereas current smokers were at increased risk of CD (OR = 1.7; 95% CI: 1.1-2.6). Females who reported use of oral contraceptives for at least one month before onset of symptoms had a higher risk of CD (OR = 3.4; 95% CI: 1.0-11.9), whereas no significant risk was observed for UC. Lack of breastfeeding was associated with an increased risk of UC (OR = 1.5; 95% CI: 1.1-2.1) and CD (OR = 1.9; 95% CI: 1.1-3.3). Being a 'former smoker' was the factor with the highest attributable risk of UC both in males (AR = 28%; 95% CI: 20-35 %) and in females (AR = 12%; 95% CI: 5-18%). Smoking was the factor with the highest attributable risk for CD in males (AR = 31%; 95% CI: 11-50%). Lack of breastfeeding accounted for the highest proportion of CD in females (AR = 11%; 95% CI: 1-22%). Oral contraceptive use accounted for 7% of cases of UC and for 11% of cases of CD. CONCLUSIONS: Taken together, the considered factors were responsible for a proportion of IBD ranging from 26% (CD females) to 36% (CD males). It is concluded that other environmental and genetic factors may be involved in the aetiology of IBD.

Adolescent↗
PubMed1997

Effect of Helicobacter pylori eradication on gastric epithelial proliferation. Relationship with ras oncogene p21 expression.

BACKGROUND: Impaired changes in gastric epithelium proliferation have been described in Helicobacter pylori infection, and a progressive increase of proliferating cells has been shown with the progression of mucosal lesions. AIMS: Purpose of this investigation was to study the effect of eradication on bacterium-induced proliferative changes, evaluated by the proliferating cell nuclear antigen labelling index (PCNA LI) and its relationship to the ras oncoprotein p21, involved in early events of gastric carcinogenesis. PATIENTS AND METHODS: This retrospective study was performed, before and after therapy, in five different groups of patients with progressive stages of Helicobacter pylori damage (N: normality; HG: histological gastritis with normal endoscopy; EHG: histological gastritis with endoscopic chronic erosions; CIM: complete intestinal metaplasia; IIM: incomplete intestinal metaplasia). RESULTS: Six months after eradication, a normalization of PCNA LI was observed in the areas of gastritis, but not in those of intestinal metaplasia, which showed on unchanged type. Moreover, immunohistochemical membrane expression of ras oncoprotein p21 was only associated to intestinal metaplasia. The protein was also expressed in the cytoplasm in 3 patients with incomplete type. CONCLUSIONS: These results suggest that the development of intestinal metaplasia may be associated with an alteration in the control of gastric epithelium proliferation and could represent an initial stage in gastric carcinogenesis. Nevertheless, further genetic changes are necessary for a complete progression to neoplastic disease. A long-term follow-up on extension, type, proliferative situation and oncoprotein expression in areas of intestinal metaplasia may be helpful to explain whether the present data provide new information on the mechanism of Helicobacter pylori induced gastric carcinogenesis.

Adult↗
PubMed1996

Proliferative activity of gastric epithelium in progressive stages of Helicobacter pylori infection.

Helicobacter pylori (HP) infection is the main etiopathogenetic agent responsible for inflammatory and ulcerative changes in gastroduodenal mucosa and the basis for both intestinal and diffuse types of gastric carcinoma. In this latter case, intestinal metaplasia is the intermediary between gastritis and cancer. In this study we describe the proliferative activity of gastric epithelium in the progressive stages of HP infection. The expression of proliferating cell nuclear antigen (PCNA), which has proven to be a reliable method for this evaluation, was used as a marker. The study was performed on endoscopic biopsies of the gastric antrum of 40 patients, who were divided into five groups, eight in each group: normal histology and endoscopy, HP-; histological HP+ gastritis with normal endoscopy; histological HP+ gastritis with endoscopic evidence of chronic erosions; complete and incomplete intestinal metaplasia in a HP+ stomach. PCNA was detected by immunohistochemistry and expressed as labeling index, ie, percentage of positive nuclei either in the whole or upper third of foveolae. Our data show a progressive increase of epithelial proliferation in the successive stages of HP infection ranging from gastritis alone to the development of incomplete intestinal metaplasia, a well-known precancerous condition. The proliferative pattern tended to expand towards the upper foveolar third, which in normal conditions does not represent a site of epithelial renewal. These alterations may be related to the development of neoplastic transformations of gastric epithelium. It is well known that genetic mutations are facilitated in proliferating cells. Therefore, our results indicate that the high epithelial turnover, expressed by PCNA LI, may be an indicator of increased risk of neoplastic changes in long-standing untreated HP+ chronic gastritis.

Adult↗
PubMed1989

Effect of cimetidine, ranitidine, famotidine and omeprazole on hepatocyte proliferation in vitro.

Recently reports have indicated that both cimetidine and ranitidine delay cell proliferation in rats following 70% partial hepatectomy and result in an increased mortality following this procedure. The present study was designed to determine whether three H2 blocking agents (cimetidine, ranitidine, famotidine) and a new, powerful antisecretory drug (omeprazole) specifically influence hepatocyte proliferation in primary culture. Hepatocytes were isolated from livers of normal male rats by the standard collagenase perfusion technique. Hepatic DNA synthesis and percent of labelled nuclei were determined after 48 h incubation. Hepatocytes in culture were incubated with the H2 blocking agents and omeprazole or with different concentrations of serum obtained from sham-operated or 70% hepatectomized rats treated or not with the same agents. Rats were injected intraperitoneally at 8:00 a.m. on two consecutive days. In hepatectomized rats, the first dose was injected at 8:00 a.m. immediately after surgery, the second, 24 h later. The serum of sham-operated or 70% hepatectomized rats that did not receive drugs served as control. No changes in DNA synthesis, percentage of labelled nuclei and transaminase were detected when the agents were added to the hepatocytes in culture at concentrations within the effective pharmacological dosage and 30 times higher. Similarly, no changes in these parameters were obtained when different concentrations of serum obtained from sham-operated rats treated with H2 blocking agents or omeprazole were added to the basal culture medium. However, a significant inhibition of DNA synthesis and of percentage of labelled nuclei was observed when hepatocytes were incubated in the presence of serum from 70% hepatectomized rats that had been treated with cimetidine or with ranitidine. The serum of 70% hepatectomized rats treated with famotidine and omeprazole had no effect on hepatocyte proliferation in vitro. No effect on transaminase was found in these conditions.

Animals↗
PubMed1986

Circadian rhythm of hepatic cytosolic and nuclear estrogen and androgen receptors.

Mammalian liver is a sex steroid-responsive tissue. The effects of these hormones presumably are mediated by hepatic estrogen receptors (ER) and androgen receptors (AR). Serum levels of sex hormones display circadian rhythms. Further, estrogens and androgens are commonly administered; administration of these agents is associated frequently with liver disease. Therefore, we investigated whether the cytosolic and nuclear sex steroid receptors also display a similar circadian rhythm, and whether variations occurred in the distribution of receptors between cytosolic and nuclear compartments. Animals were killed every 4 h from midnight till the following midnight; cytosolic and nuclear levels of both ER and AR were measured. Cytosolic ER reached a maximum level at 4 AM, and a minimum at 8 PM and midnight of both days. Nuclear ER was highest at 8 AM and lowest at 4 PM and 8 PM, a pattern which parallels variations in serum estradiol levels. Cytosolic AR was highest at 8 PM and lowest at midnight and 4 AM. Nuclear AR was highest at 4 AM and lowest at 4 PM and 8 PM. The highest level of nuclear AR does not correspond to the maximum serum testosterone level, which occurred at 4 PM. The total hepatic content of both ER and AR was not constant over the 24-h period, but varied considerably with time of day. These studies suggest that both ER and AR show a distinct circadian rhythm in subcellular compartmentalization, and that total hepatic content of ER and AR varies significantly during a 24-h period.

Androgens↗
PubMed1986

Sex hormone-related functions in regenerating male rat liver.

Sex hormone receptors were quantitated in normal male rat liver and in regenerating liver at several different times after partial (70%) hepatectomy. Both estrogen and androgen receptor content were altered dramatically by partial hepatectomy. Total hepatic content and nuclear retention of estrogen receptors increased, with the zenith evident 2 days after partial hepatectomy, corresponding to the zenith of mitotic index. Serum estradiol increased after 1 day, and reached a maximum at 3 days after surgery. In contrast, total and nuclear androgen receptor content demonstrated a massive decline at 1, 2, and 3 days after resection. Serum testosterone displayed a parallel decline. In addition, hepatic content of two androgen-responsive proteins was reduced to 15% and 13% of normal values during this period. The activity of these various proteins during regeneration of male rat liver is comparable to that observed in the liver of normal female rats. Taken together, these results indicate that partial hepatectomy induces a feminization of certain sexually dimorphic aspects of liver function in male rats. Furthermore, these data provide evidence that estrogens, but not androgens, may have an important role in the process of liver regeneration.

Androgens↗
PubMed1985

[Behavior of the pressure of the lower esophageal sphincter after intravenous administration of domperidone in normal subjects].

Manometric studies on the action of domperidone 10 mg and 20 mg i.v. on the lower esophageal sphincter pressure (LESP) have been carried on ten healthy volunteers. Domperidone inhibits dopamine receptors and results in an increase of LESP. A dose of 10 mg produces a significant increase in LESP which is rapid and prolonged for thirty minutes; a dose of 20 mg is less efficient. The stimulatory effect of domperidone on LESP suggests an important role for endogenous dopamine as an inhibitory neuromodulator of LES pressure. The use of domperidone in therapy for reflux esophagitis is suggested.

Adult↗