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Biomedical subjects

M Valentini

Publications and source records attributed to M Valentini.

At least 19 recordsLinked to original sources
PubMed1998

Lymphocyte proliferative response in brown bears: cytokine role and glucocorticoid effect.

Lymphocyte stimulation and proliferation play a pivotal role in the immune response to soluble as well as to cellular, bacterial, and viral antigens. In this study, peripheral blood mononuclear cells (PBMC), mainly composed of lymphocytes, were separated by Ficoll-Hypaque density gradient centrifugation from 50-ml jugular vein blood samples drawn from six captive and five wild-caught brown bears (Ursus arctos) (eight Apennine brown bears from the Italian population; three of undetermined origin). Stimulation of cultured bear PBMC with the two classical T lymphocyte mitogens phytohemagglutinin (PHA) and Concanavalin A (ConA) was followed by a significantly greater proliferative response than that shown by human PBMC (n = 11) (PHA: T = 4.03, d.f. = 20, P = 0.001; ConA: T = 4.25, d.f. = 20, P < 0.0005; Student's t-test, oneway ANOVA). As in humans, the PBMC proliferative response in bears was markedly (> 50%) inhibited by addition of transforming growth factor beta (TGF beta) human recombinant cytokine to the culture. Further fractionation provided a cell preparation extremely rich in peripheral blood lymphocytes (PBL) (mean +/- SD = 96.1 +/- 1.7%). Addition of interleukin 1 (IL1) or interleukin 2 (IL2) human recombinant cytokines to cultured PBL stimulated with a suboptimal concentration of mitogens resulted in a ninefold increase in the lymphocyte proliferative response. Dexamethasone (DEX, a synthetic analog of hydrocortisone) inhibited the bear PBMC proliferative response by 22.2 +/- 4.3% (mean +/- SD), compared with 46.2 +/- 6.9% and 91.8 +/- 8.1% (mean +/- SD) in humans and mice (n = 11) (Mus domesticus), respectively. Inhibition of the brown bear and human PBMC responses was markedly (> 60%) reduced by the addition of IL2. The finding that IL1 and IL2 augment and that DEX inhibits bear lymphocyte proliferative response suggests that these cytokines can be used to increase the immune response in vaccinations, and that DEX may hamper several immunologically mediated diseases.

Animals↗
PubMed1998

MLH1 and MSH2 constitutional mutations in colorectal cancer families not meeting the standard criteria for hereditary nonpolyposis colorectal cancer.

Genetic diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) may have a significant impact on the clinical management of patients and their at-risk relatives. At present, clinical criteria represent the simplest and most useful method for the identification of HNPCC families and for the selection of candidates for genetic testing. However, reports of mismatch repair (MMR) gene mutations in families not fulfilling the minimal diagnostic criteria point out the necessity to identify additional clinical parameters suggestive of genetic predisposition to colorectal cancer (CRC) related to MMR defects. We thus investigated a series of 32 Italian putative HNPCC individuals selected on the basis of one of the following criteria: 1) family history of CRC and/or other extracolonic tumors; 2) early-onset CRC; and 3) presence of multiple primary malignancies in the same individual. These patients were investigated for the presence of MLH1 and MSH2 mutations by single-strand conformation polymorphism analysis. Pathogenetic truncating mutations were identified in 4 (12.5%) cases, 3 of them involving MSH2 and 1 MLH1. In addition, 2 missense MLH1 variants of uncertain significance were observed. All pathogenetic mutations were associated with early age (<40 years) at onset and proximal CRC location. Our results support the contention that constitutional MMR mutations can also occur in individuals without the classical HNPCC pattern. Moreover, evaluation of the clinical parameters associated with MMR mutations indicates that early onset combined with CRC location in the proximal colon can be definitely considered suggestive of MMR-related hereditary CRC and should be included among the guidelines for referring patients for genetic testing.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Atrophic gastritis and intestinal metaplasia in Helicobacter pylori infection: the role of CagA status.

OBJECTIVE: Helicobacter pylori (H. pylori) is a major factor in determining the risk for development of gastric adenocarcinoma through the intermediate steps of atrophic gastritis and intestinal metaplasia. Because H. pylori infection is highly prevalent in asymptomatic populations and only a few people develop cancer, additional factors may influence the risk for development of cancer, once infection is established. Some factors may pertain to differences among bacterial strains. Because infection by H. pylori strains possessing cagA (cytotoxin-associated gene A), a gene encoding a high-molecular-weight immunodominant antigen (CagA), is associated with enhanced induction of gastritis, the aim of our study was to evaluate potential differences in the prevalence and intensity of atrophy and intestinal metaplasia between CagA-positive and CagA-negative H. pylori-infected patients. METHODS: Eighty H. pylori-infected patients among 120 consecutive dyspeptic patients referred for upper gastrointestinal endoscopy were studied. Six bioptic specimens were taken from the gastric antrum: five for histological examination, and one for urease test. The H. pylori status was determined by histology, CLO test, and serology (in a standardized ELISA) for serum IgG and IgA directed to H. pylori. The CagA status was determined by Western blotting to detect serum IgG antibodies to CagA. Gastritis was classified according to the Sydney System. A score from 0 to 3 was assigned to each of the following morphological variables: atrophy, intestinal metaplasia, and mononuclear and neutrophilic cell infiltration. The association between CagA status and histological features was assessed by means of the chi2 test for trend. RESULTS: Among the 80 H. pylori-infected patients 53 (66%) were CagA seropositive and 27 (34%) were CagA seronegative. The mean age of the two groups was similar. CagA-positive patients had significantly higher scores for atrophy (p = 0.006), intestinal metaplasia (p = 0.01), and mononuclear (p < 0.001) and polymorphonuclear (p = 0.002) cell infiltration than did CagA-negative patients. No differences in contrast, were found for H. pylori density. CONCLUSION: Infection with CagA-positive H. pylori strains is associated with an increased prevalence and intensity of antral atrophy and intestinal metaplasia, in addition to higher degrees of gastritis. Our results seem to suggest that the CagA status could be a helpful parameter to define a subgroup of H. pylori-infected patients at increased risk of developing gastric adenocarcinoma.

Adult↗
PubMed1997

Continuing on J.P. Henry's path; studies of physiology and pathophysiology of cardiopulmonary receptors in humans.

The seminal work of Henry and Gauer lead us to a) show that in healthy humans cardiopulmonary receptors (CPR) regulate renin release, b) that low renin hypertension is associated with an expanded cardiopulmonary volume. This suggested that the low renin state in hypertension may be due to excessive inhibition of renin by the CPR. In the course of these experiments we uncovered an undescribed pressor reflex which was used to investigate the effect of intermittent pressor episodes on cardiac structure in dogs. Finally, in recent years, we used unloading of CPR to show that reflex vasoconstriction causes acute insulin resistance in the human forearm.

Animals↗
PubMed1996

Palliative treatment of upper intestinal obstruction by gynecological malignancy: the usefulness of percutaneous endoscopic gastrostomy.

The usefulness of percutaneous endoscopic gastrostomy (PEG) for decompression in patients with unresolving intestinal obstruction by gynecological malignancy is examined. Between April 1993 and August 1995, 34 consecutive patients with small-bowel obstruction by gynecological cancer, heavily pretreated with surgery and chemotherapy, were admitted to our prospective study. PEG was performed in 32/34 patients (94.1%). Failure in the placing of the tube occurred in 2 patients (5.9%). Twenty-seven patients (84.4%) experienced symptomatic relief after a few days from PEG and tolerated soft and liquid foods. All of these patients were discharged from the hospital and underwent parenteral nutrition at home. The median postoperative hospital stay was 7 days (range 3-45). No major complications due to PEG placement itself occurred in our patients. Only 4 patients (12.5%) had postprocedure nausea and vomiting that was unresponsive to the conventional therapy. The use of Octreotide (0.6 mg/24 hr) obtained relief from symptoms until death. The gastrostomy remained in place for a median of 74 days (range 5-210). Relief from symptoms after PEG placement and total parenteral nutrition permitted continuation of palliative chemotherapy in 8 patients (25%). We suggest percutaneous endoscopic drainage gastrostomy technique as the procedure of choice for long-term drainage of unresolving small bowel obstruction in patient with metastatic abdominal gynecologic malignancy.

Adult↗
PubMed1996

Use of corrected QT interval in autonomic function testing: assessment of reproducibility.

QT interval duration is influenced by the autonomic nervous system and has been proposed as an additional tool in the diagnosis of diabetic autonomic neuropathy. The study aimed to assess in normal subjects the reproducibility of QT interval duration compared with that of cardiovascular tests commonly used to explore the function of the autonomic nervous system. Fifty-nine healthy subjects (31 males, 28 females; mean age 35.1 +/- 17.7 years) performed five cardiovascular tests: deep breathing test (DBT), lying to standing test (LST), Valsalva manoeuvre (VM), postural blood pressure test (PBPT) and cough test (CT). QT interval duration was measured on an electrocardiogram (ECG) registered after a 15-min rest in the supine position. Corrected QT interval (QTc) was calculated according to Bazett's formula. The QTc interval duration for each subject was expressed as the mean of the QTc calculated by two observers. Each subject was submitted to the cardiovascular test battery and the ECG twice in 1 week. The coefficient of variation (CV) was calculated to assess the reproducibility. The observed CV values were as follows: DBT 15.8%, LST 8.0%, VM 9.5%, CT 7.2%, PBPT 176%, QTc 3.4%. Our data confirm the reproducibility of heart rate cardiovascular tests: the QTc interval is a reproducible, easily measurable parameter, which has the advantage of not requiring patient cooperation.

Adult↗
PubMed1995

Percutaneous endoscopic gastrostomy as a decompressive technique in bowel obstruction due to abdominal carcinomatosis.

BACKGROUND AND STUDY AIMS: Percutaneous endoscopic gastrostomy (PEG) is a simple method of achieving nonsurgical gastric decompression in patients suffering from metastatic abdominal tumors and upper gastrointestinal tract obstruction. The aim of this prospective study was both to evaluate the efficacy of PEG for intestinal decompression in patients with disseminated abdominal cancer and to compare two catheters with different diameters. PATIENTS AND METHODS: Over a one-year period, 22 consecutive female patients (mean age 53.7, range 29-73) were referred to us and a PEG was successfully placed in 21. In four patients with unsatisfactory endoscopic trans-illumination of the anterior abdominal wall, an ultrasound unit was used to identify an adequate site for PEG placement. RESULTS: All patients experienced substantial symptomatic relief after a few days: vomiting and nausea completely resolved, and abdominal pain persisted in one patient only. No gastrostomy-related additional morbidity was noticed. We randomly inserted a 15-French or a 20-French tube: no statistically significant difference was noticed between the two in the symptomatic relief provided. CONCLUSIONS: Our data support the hypothesis that PEG is an effective, safe, and well-tolerated method of achieving gastric decompression in cancer patients; ultrasound guidance was an interesting option in positioning a tube in difficult situations; a standard nutritional tube, namely 15 or 20 French in diameter, may be large enough to obtain excellent clinical results.

Abdominal Neoplasms↗
PubMed1995

Pantoprazole and omeprazole in the treatment of reflux oesophagitis: a European multicentre study.

BACKGROUND: Pantoprazole is a new substituted benzimidazole which inhibits gastric H+,K(+)-ATPase. METHODS: In this double-blind, multicentre study, pantoprazole 40 mg once daily was compared with omeprazole 20 mg once daily in the treatment of grade II and III (Savary-Miller) reflux oesophagitis. Endoscopy was repeated after 4 weeks of treatment, and also after 8 weeks in patients unhealed at 4 weeks. RESULTS: The primary efficacy variable was ulcer healing; after 4 weeks, 81/103 (78.6%) patients in the pantoprazole group and 83/105 (79.0%) patients in the omeprazole group had healed completely. After 8 weeks, the cumulative healing rates were 94.2% and 91.4% in the pantoprazole and omeprazole groups, respectively (P > 0.05 at 4 weeks and 8 weeks). Both groups experienced rapid relief of the key symptoms: heartburn, acid regurgitation and pain on swallowing. The time course of relief of the individual symptoms was similar in both groups after 2 and 4 weeks (P > 0.05). Both treatments were well tolerated, with only three patients withdrawing owing to adverse events. CONCLUSION: Pantoprazole has been shown to be as effective as omeprazole in the treatment of reflux oesophagitis.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

DNA flow cytometric evaluation of cell cycle distribution in ulcerative colitis: a proposed method for assessing severity of disease.

The assessment of disease severity in ulcerative colitis depends mainly on subjective variables, and an objective method of assessing mucosal inflammation is needed. Determination of the synthetic phase of the cell cycle is an accurate expression of inflammatory activity in the colonic mucosa. The aim of the study was to find out if the proliferative index or the synthetic phase (S phase) of the colonic mucosa of patients with ulcerative colitis, as evaluated by DNA flow cytometry, is a reliable and reproducible marker of disease activity. Sixty consecutive patients with ulcerative colitis of different degrees of activity were entered into the study and submitted to colonoscopy plus multiple rectal biopsies. Disease severity was defined for each patient by means of a clinical, endoscopic, and histological score. Flow cytometry was used to calculate the proliferative index and the S phase of the cell cycle. A statistically significant correlation (p < 0.001) was found between all indices of severity. It is suggested that flow cytometric evaluation of the cell cycle in the rectal mucosa may be an efficient method of assessing severity of disease and efficacy of medical treatment in ulcerative colitis.

Adult↗
PubMed1995

Nonsteroidal antiinflammatory drugs for cancer pain: comparison between misoprostol and ranitidine in prevention of upper gastrointestinal damage.

PURPOSE: The prophylactic strategy of nonsteroidal antiinflammatory drug (NSAID)-induced upper gastrointestinal (UGI) damage has largely been studied in arthritic patients, but not in cancer patients. The efficacy of misoprostol and ranitidine in the prevention of gastroduodenal damage in patients taking diclofenac for their cancer pain has been compared in this study. PATIENTS AND METHODS: Patients who needed high-dose (200 to 300 mg/d) diclofenac for cancer pain and without mucosal lesions at baseline gastroduodenal endoscopy were randomized to receive misoprostol (200 micrograms twice daily; M group) or ranitidine (150 mg twice daily; R group). UGI endoscopy was repeated after 4 weeks. RESULTS: Twenty-three patients treated with misoprostol and 26 treated with ranitidine concluded the study. The M group showed a significantly (P < .02) lower incidence of gastroduodenal lesions (two patients; 8.7%) than the R group (10 patients; 38.5%). Gastric ulcers occurred in one (4%) misoprostol-treated patient and in six (23%) ranitidine-treated patients. Six of seven patients with ulcers were asymptomatic. Seventy-one percent and 86% of ulcers occurred in patients older than 60 years and in those who received greater than 3.1 mg/kg of diclofenac, respectively. CONCLUSION: Misoprostol was significantly more effective than ranitidine in the prevention of gastroduodenal lesions in cancer patients receiving diclofenac.

Adult↗
PubMed1995

Gastroduodenal involvement in staging of nodal non-Hodgkin lymphomas: a clinical and endoscopic prospective study of 235 patients.

OBJECTIVES: The gastrointestinal tract is often the site of involvement of non-Hodgkin lymphomas (NHL). The aim of this endoscopic prospective study was to verify the prevalence of the gastroduodenal involvement in patients in staging for NHL and to assess its impact on the choice of therapeutic strategies. METHODS: Two hundred and thirty-five consecutive patients were included in the study. Upper gastrointestinal endoscopy was performed, and biopsy samples were taken on every mucosal lesion and on macroscopically illness-free duodenal and gastric mucosa. The samples were submitted to histological examination, and the clinical stage of NHL was reevaluated. RESULTS: Sixty-one of the 235 patients exhibited histological involvement of gastric (40), duodenal (7), or both (14) mucosae. Endoscopic lesions were recorded in 51 patients, but the involved mucosa appeared macroscopically normal in 10 patients (16.3%). In 13 patients, the gastroduodenal involvement modified the clinical stage from I and II to III, indicating a different therapeutic approach. No difference was detected in the frequency of gastrointestinal involvement among the high, intermediate, and low grades of lymphoma malignancies. Thirty-five positive patients underwent a further endoscopic examination after the chemotherapy treatment. Although clinical remission was expected in all cases, 42.8% of them subsequently exhibited NHL. CONCLUSIONS: Upper digestive endoscopy plus biopsy sampling plays a necessary diagnostic role, not only when major clinical signs (hemorrhage) are present, but also in earlier stages of NHL (I and II), when a reevaluation of the therapeutic strategy may be indicated. In stages III and IV of illness, it may also prove useful in evaluating the efficacy of chemotherapy.

Biopsy↗
PubMed1994

The blockage of the human transferrin receptor by a monoclonal antibody, EA.3, induces growth inhibition in leukemia cell lines.

In our program to produce monoclonal antibodies against hemopoietic functional antigens we have obtained an hybridoma cell line EA.3 reacting with human transferrin receptor. This monoclonal antibody is an IgM that displays "in vitro" antiproliferative activity against leukemic cells due to its competition with transferrin on the receptor. Cell cytotoxicity was demonstrated either with the blockage of BrdU incorporation in HL-60 cells and with leukemic CFU inhibition. In contrast, K562 cells were insensitive to the blockage of the transferrin receptor induced by this MAb.

Antibodies, Monoclonal↗
PubMed1994

Inhibition of NK binding to K562 cells induced by MAb saturation of adhesion molecules on target membrane.

Cell to cell interaction play a major role in the induction of a immune response. NK cells represent a special lymphoid subset which displays its cytotoxic function without the engagement of MHC system. In order to investigate the role of different adhesion molecules in the mechanism of binding of the NK cell to the classic tumor target K562 cell, we have employed different unclustered mAbs of the Adhesion session (5th "CD" Workshop, Boston 1993) mostly of the CAM (cell adhesion molecule) subpanel. After their reactivity characterization both on lymphocytes and K562 cells, those that demonstrate reactivity against the tumor target were tested in the binding assay. The target was pretreated with the monoclonal in order to block a possible reacting molecule for the effector. Then, after the incubation of lymphocytes with PE-labelled anti CD16 mAb, their ability to bind to the target was tested in flow. While the majority of the mAbs did not induce any significant change in the binding capacity of the NK subset, few of them did, and precisely anti-CD58 (LFA-3) and anti-CD54 (ICAM-1) which showed different level of inhibition, particularly drastic with S002, S083 and S100. Other mAbs, such as the S011 (anti-CD59), due to the presence of the PI-linked glycoprotein recognized on both target and effector membranes, and to its capacity to stimulate NK activity, produced a total binding of the NK population. The coincubation of targets with anti-CD54 and anti-CD58 allowed to reduce at the lowest level this function. This data seem to support the hypothesis of specific surface molecules involved in the binding process of the NK cell, after recognition of the target.

Antibodies, Monoclonal↗
PubMed1993

Effect of short- and long-term treatment with omeprazole on cell cycle distribution in the gastric mucosa. Results of a flow cytometric study.

Omeprazole may exert an effect on gastric mucosal proliferation by inhibiting gastric acid secretion and increasing serum gastrin levels. It may also influence the kinetics of endocrine cells and the oxyntic mucosa. The aim of the present study was to evaluate the cell cycle in different gastric compartments following short- (1 month) and long-term (6 months) administration of two different dosages of omeprazole by means of a flow cytometric method. We also determined serum gastrin levels at the same time. No differences in cell cycle distribution of the antrum, body, and fundus were found in the two different dosage groups after 1 month of therapy, considering the synthetic phase (S-phase) of the cell cycle. A statistically significant increase in S-phase was reported after long-term therapy in the mucosa of the fundus and body of the stomach in both groups. Gastrin levels showed no clear correlation with cell cycle distribution variables. We postulate a proliferative adaptation of the oxyntic mucosa to long-term drug administration not mediated by gastrin influence.

Adult↗
PubMed1993

Changes in autonomic nervous function over a 5-year period in non-insulin-dependent diabetic patients.

One hundred and eight non-insulin-dependent diabetic patients who had been tested for autonomic dysfunction in 1984/85 were re-evaluated 5 years later. Autonomic function was assessed by means of four cardiovascular tests (heart rate variation during deep breathing and standing, and blood pressure variation after standing and sustained handgrip). Eighteen subjects were lost to follow-up; in the 90 patients who completed the study, both the deep breathing and the handgrip test significantly worsened (respectively from 13.7 +/- 7.8 to 11.6 +/- 6.3 beats min-1 p < 0.01, and from 16.9 +/- 8.2 to 12.7 +/- 7.1 mmHg, p < 0.001), whereas both the 30:15 ratio and the variation of blood pressure on standing did not change. The impairment of a comprehensive evaluation score (from 2.5 +/- 1.7 to 3.0 +/- 1.5; p < 0.05) also confirmed the gradual deterioration of autonomic function over the study period.

Autonomic Nervous System↗