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Biomedical subjects

E Colombo

Publications and source records attributed to E Colombo.

At least 37 records · Page 2Linked to original sources

[Familial variability in the clinical expression of hand-foot-mouth disease].

Aim of the paper is to describe the variability of clinical symptoms in hand, foot and mouth disease, especially among patients belonging to the same family. In spring 1999, during an epidemic of hand, foot and mouth disease, nineteen cases were observed by the authors. In eight cases also some members of the family were affected. A great variability in the clinical expression of the disease, above all among the members of the same family were observed. No cases in children below twelve months or in elderly members of the family were found. Children below three years had more stressed general symptoms, but in no case hospitalization was necessary. Hand, foot and mouth disease does not always show vesicles and aphthae in the affected areas. Clinical expression can also be lacking, but in this case diagnosis can be made easy by the presence of an epidemic or of other cases in the same family.

Child, Preschool↗

[Endometrial carcinoma: prognostic significance of cellular ploidy].

BACKGROUND: The aim of the paper is to compare ploidy status with the traditional prognostic factors (grading, myometrial invasion, cytology of peritoneal fluid and node invasion) in 118 women affected by endometrial carcinoma and treated by hysterectomy in our department in order to evaluate a relationship between these parameters. METHODS: Since January 1988 and August 1996 127 women (average age: 61) affected by endometrial carcinoma and not previously treated have been submitted to abdominal or vaginal hysterectomy. A retrospective study was carried out on 118 of these women evaluating DNA ploidy on fixed neoplastic samples through flow cytometry (Coulter Elite with Argon Laser). Aneuploidy was defined as cell population containing at the same time two or more moderate peaks in G0/G1. Histology of neoplastic tissues could evaluate grading and myometrial invasion in all cases. Cytology of peritoneal fluids and nodal state were evaluated respectively in 99 and 56 patients. The results obtained have been compared by Fisher's statistical test. RESULTS: 70.3% of evaluated neoplasias were diploid, while 29.7% were aneuploid. No statistical difference was observed comparing ploidy status with every considered parameter. CONCLUSIONS: The results obtained show that DNA ploidy doesn't seem to be positively correlated with any traditional histopathological factors. The literature about this matter is questionable. Histopathological analysis is the only prognostic factor and it is the only parameter to personalize treatment.

Endometrial Neoplasms↗

The eps15 homology (EH) domain-based interaction between eps15 and hrb connects the molecular machinery of endocytosis to that of nucleocytosolic transport.

The Eps15 homology (EH) module is a protein-protein interaction domain that establishes a network of connections involved in various aspects of endocytosis and sorting. The finding that EH-containing proteins bind to Hrb (a cellular cofactor of the Rev protein) and to the related protein Hrbl raised the possibility that the EH network might also influence the so-called Rev export pathway, which mediates nucleocytoplasmic transfer of proteins and RNAs. In this study, we demonstrate that Eps15 and Eps15R, two EH-containing proteins, synergize with Hrb and Hrbl to enhance the function of Rev in the export pathway. In addition, the EH-mediated association between Eps15 and Hrb is required for the synergistic effect. The interaction between Eps15 and Hrb occurs in the cytoplasm, thus pointing to an unexpected site of action of Hrb, and to a possible role of the Eps15-Hrb complex in regulating the stability of Rev.

Adaptor Proteins, Signal Transducing↗

Detection of normal and chimeric nucleophosmin in human cells.

In anaplastic large-cell lymphoma (ALCL), the (2;5) chromosomal translocation creates a fusion gene encoding the 80-kD NPM-ALK hybrid protein. This report describes three new monoclonal antibodies, two of which recognize, by Western blotting, the N-terminal portion of NPM present in the NPM-ALK fusion protein and also in two other NPM fusion proteins (NPM-RARalpha and NPM-MLF1). The third antibody recognizes the C-terminal portion (deleted in NPM-ALK) and reacts only with wild-type NPM. The three antibodies immunostain wild-type NPM (in paraffin-embedded normal tissue samples) in cell nuclei and in the cytoplasm of mitotic cells. Cerebral neurones, exceptionally, show diffuse cytoplasmic labeling. In contrast to normal tissues, the two antibodies against the N-terminal portion of NPM labeled the cytoplasm of neoplastic cells, in four ALK-positive ALCL, reflecting their reactivity with NPM-ALK fusion protein, whereas the antibody to the C-terminal NPM epitope labeled only cell nuclei. Immunocytochemical labeling with these antibodies can therefore confirm that an ALK-positive lymphoma expresses NPM-ALK (rather than a variant ALK-fusion protein) and may also provide evidence for chromosomal anomalies involving the NPM gene other than the classical (2;5) translocation.

Animals↗

Management of Helicobacter pylori-related gastrointestinal diseases by general practitioners in Italy.

AIMS: To investigate the diagnostic approach to and management of Helicobacter pylori infection at primary care level in Italy 2 years after the Maastricht consensus report. METHODS: A total of 100 randomly selected general practitioners (GPs) answered a 12-item multiple-choice questionnaire, personally delivered and collected by non-medical staff. RESULTS: In 25% of cases, GPs preferred a prompt referral of dyspeptic patients to the specialist. The favourite diagnostic test for H. pylori infection was gastroscopy with biopsies (55%), followed by standard and office-based serology (24% and 18%, respectively), and 13C urea breath test (5%). H. pylori-eradication was prescribed in patients with peptic ulcer, reflux oesophagitis and functional dyspepsia by 64%, 43% and 66% of GPs, respectively. Only 7% of GPs adopted a test-and-treat approach. Proton pump inhibitor-based triple therapies were used by almost all physicians. In peptic ulcer disease, most of GPs re-tested patients in order to confirm H. pylori eradication (50% by gastroscopy with biopsies and 30% by serology only 2 months after therapy). CONCLUSIONS: Uncertainty seems to persist among Italian GPs concerning the indications for H. pylori treatment, the use of diagnostic tests, and patient follow-up. In contrast, no doubts exist regarding the first choice eradication regimens. This survey suggests that further efforts should be made to spread scientific knowledge and guidelines on H. pylori diagnosis and management in primary care in Italy.

Anti-Bacterial Agents↗

Antioxidant drugs combined with alpha-interferon in chronic hepatitis C not responsive to alpha-interferon alone: a randomized, multicentre study.

OBJECTIVE: After non-response to the initial course of therapy, retreatment with alpha-interferon is not effective. The aim of this study was to ascertain whether the administration of N-acetyl cysteine and vitamin E could increase the response rate to retreatment with alpha-interferon. DESIGN: Prospective, multicentre clinical trial. SETTING: Twelve hospitals in Lombardy, Italy. PARTICIPANTS: 120 consecutive patients affected by biopsy-proven chronic hepatitis C who had been non-responders to a previous course of alpha-interferon, administered at the dosage of 3-6 million units (MU) three times a week (tiw) for 6 months. INTERVENTIONS: The patients were randomly assigned to one of two groups of treatment: group A, natural interferon-alphaN3, 6 or 9 MU tiw, when the body weight was < 60 kg or > or = 60 kg, respectively; group B, the same dosage of natural interferon-alphaN3 in association with oral administration of N-acetyl cysteine 1200 mg/day and vitamin E 600 mg/day. The period of treatment was 6 months in both groups. RESULTS: Neither end-therapy biochemical response nor sustained biochemical response rates were improved by the combination treatment, and in no case was clearance of the virus from serum observed. CONCLUSIONS: In this randomized study carried out on 120 patients with chronic hepatitis C not responsive to alpha-interferon, oral supplementation with N-acetyl cysteine and vitamin E did not improve the poor efficacy of retreatment with alpha-interferon alone.

Acetylcysteine↗

Interferon alfa treatment of HCV RNA carriers with persistently normal transaminase levels: a pilot randomized controlled study.

Most patients with serum hepatitis C virus (HCV) RNA and persistently normal alanine transaminase (ALT) levels show histological features of mild to moderately active chronic hepatitis. Some cirrhosis has also been reported. To assess whether interferon (IFN) treatment led to long-term HCV suppression in these patients, 31 previously untreated patients (15 men, 16 women; mean age, 44 years) with serum HCV RNA, persistently normal ALT levels on at least four consecutive occasions 2 months apart, and histological features of chronic hepatitis (21 mild activity, 10 moderate activity) were randomized to receive 1FN-alpha-2a, 3 MU three times a week for 6 months (n = 16), or no treatment (n = 15). All patients were followed up for at least 6 months after treatment ended. HCV RNA was tested by nested reverse-transcription polymerase chain reaction (RT-PCR) using 5'-untranslated region complementary primers, quantified by branched-DNA assay, and typed by nested RT-PCR testing for the HCV core region. Treated and untreated patients had similar epidemiological, virological, and histological characteristics. At the end of treatment, serum HCV RNA was still detected in 15 patients (94%) and 14 controls (93%). ALT levels flared up in 10 patients receiving IFN (62%) and in 1 control (62% vs. 7%; P < .005, chi2 test). In conclusion, 6 months' treatment with IFN-alpha-2a did not eradicate HCV RNA from serum in carriers with persistently normal ALT levels but caused ALT flare-ups in two thirds of them. Until more is known about the natural history of HCV RNA carriers with normal ALT levels, these patients should not be treated with IFN.

Adult↗

Comparison of omeprazole and lansoprazole in short-term triple therapy for Helicobacter pylori infection.

BACKGROUND: Effective anti-Helicobacter pylori therapies with few side-effects are needed. AIM: To study the effectiveness of short-term triple therapy with amoxycillin, clarithromycin and either omeprazole or lansoprazole for eradication and healing of peptic ulcers. METHODS: Patients with gastric or duodenal ulcers received amoxycillin (1 g b.d.), clarithromycin (500 mg b.d.) and lansoprazole (30 mg b.d.) (LAC) or omeprazole (20 mg b.d.) (OAC) for 7 days. Endoscopic examinations were performed before treatment and at least 4 weeks after completion of therapy. H. pylori status was confirmed by rapid urease test and histological examination (Giemsa stain) from gastric biopsies taken from both the antrum and the body. RESULTS: A total of 356 patients were randomized in this single-blind study. On a per protocol basis, H. pylori was eradicated in 134 of 170 patients (79%) in the lansoprazole group and in 105 of 146 (72%) in the omeprazole group (P = 0.189); and in intention-to-treat analysis 72% and 62%, respectively (P = 0.043). Healing of the ulcers was obtained in 166 of 186 (98%), and in 139 of 146 patients (95%), respectively (P = 0.357). Side-effects occurred in two patients in the LAC group and in six in the OAC group B (four stopped therapy). CONCLUSIONS: This study has shown that the two regimens are highly effective in healing duodenal ulcers and are well tolerated. Neither treatment achieves the ideal cure rate for H. pylori. Lansoprazole does not appear to have a significant advantage over omeprazole either in ulcer healing or in H. pylori eradication.

2-Pyridinylmethylsulfinylbenzimidazoles↗

The promyelocytic leukemia gene product (PML) forms stable complexes with the retinoblastoma protein.

PML is a nuclear protein with growth-suppressive properties originally identified in the context of the PML-retinoic acid receptor alpha (RAR alpha) fusion protein of acute promyelocytic leukemia. PML localizes within distinct nuclear structures, called nuclear bodies, which are disrupted by the expression of PML-RAR alpha. We report that PML colocalizes with the nonphosphorylated fraction of the retinoblastoma protein (pRB) within nuclear bodies and that pRB is delocalized by PML-RAR alpha expression. Both PML and PML-RAR alpha form complexes with the nonphosphorylated form of pRB in vivo, and they interact with the pocket region of pRB. The regions of PML and PML-RAR alpha involved in pRB binding differ; in fact, the B boxes and the C-terminal region of PML, the latter of which is not present in PML-RAR alpha, are essential for the formation of stable complexes with pRB. Functionally, PML abolishes activation of glucocorticoid receptor-regulated transcription by pRB, whereas PML-RAR alpha further increases it. Our results suggest that PML may be part of transcription-regulatory complexes and that the oncogenic potential of the PML-RAR alpha protein may derive from the alteration of PML-regulated transcription.

Cell Division↗

Evaluation of regional left ventricular wall motion with color kinesis: comparison with two-dimensional echocardiography in patients after acute myocardial infarction.

BACKGROUND: Color kinesis (CK) is a new echocardiographic technique for the assessment of left ventricular (LV) wall motion based on acoustic quantification. Using integrated backscatter data, this technique identifies the pixel value transitions from blood to myocardial tissue throughout systole and tracks endocardial motion in real time. The color-encoded images, built on a frame-by-frame basis by adding one color at a time, provide an integrated display of the timing and amplitude of endocardial motion in a single end-systolic frame. Recent studies have shown that CK is a promising clinical tool for quantitative assessment of regional LV function. OBJECTIVES: The aim of this study was to evaluate the feasibility and accuracy of CK in identifying the regional wall-motion abnormalities diagnosed by conventional two-dimensional (2-D) echocardiography in patients after acute myocardial infarction (AMI). METHODS: The end-systolic color overlays were analyzed using a method to quantify the regional timing and amplitude of endocardial systolic excursion (ESE) based on the count of the numbers of colors. At this point, the total duration (ESE timing) and distance (ESE amplitude) of endocardial excursion from end-diastolic to end-systolic color-frame was calculated in each segment. In 54 patients after AMI, we compared the feasibility and ability of CK superimposed on 2-D superimposed on 2-D superimposed on 2-D echocardiographic images and visual 2-D echo analysis to evaluate the endocardial border excursion in parasternal short-axis (SAX) and apical four-(AP4CH) and two-(AP2CH) chamber views. In 20 normal subjects, the end-systolic color overlays were used to evaluate the variability of the measurements of ESE timing (msec) and amplitude (cm) and to define the reference values. Image quality was considered adequate if at least 12 of 16 segments could be evaluated for systolic function by conventional visual 2-D echo. Among 54 patients, 35 with adequate studies were selected to determine the accuracy of quantitative analysis of CK images in identifying regional wall-motion abnormalities. RESULTS: The SAX view was obtained in 36 of 54 patients; of the possible 216 segments, 210 (97%) were adequately visualized by 2-D echocardiography and 207 (96%) by CK. Apical views were obtained in 50 patients (93%); of the possible 300 segments, 93% were visualized by 2-D echocardiography and 90% by CK in the AP4CH view and 94% and 92%, respectively, were visualized by the two methods in the AP2CH view. In normal subjects, measurements of ESE timing and amplitude were found to be consistent and the mean values were 346 msec (range 280-360) and 0.99 cm (range 0.72-1.26) respectively. In the 35 selected patients, 2-D echocardiography identified 355 normokinetic segments in which ESE timing and amplitude were similar to the reference values. In 83 hypokinetic segments and 108 akinetic segments, ESE timing and amplitude were significantly inferior to values of normokinetic segments (p < 0.001). An ESE timing below the reference values of 280 msec identified all of the 191 asynergic segments (sensitivity and specificity = 100%) and an ESE amplitude of less than 0.70 cm identified 188 asynergic segments (sensitivity = 98% and specificity = 99%). CONCLUSIONS: CK showed good feasibility and diagnostic accuracy in identifying regional wall motion abnormalities in patients with acute myocardial infarction. The model used in our study for the quantitative analysis of color kinesis images, which provided easy and feasible indices of timing and amplitude of endocardial excursion, enabled fast and objective evaluation of LV regional wall motion.

Acute Disease↗

Comparative analysis of antibody and cell-mediated autoimmunity to transaldolase and myelin basic protein in patients with multiple sclerosis.

Antibody and T cell-mediated immune responses to oligodendroglial autoantigens transaldolase (TAL) and myelin basic protein (MBP) were examined in patients with multiple sclerosis (MS). Immunohistochemical studies of postmortem brain sections revealed decreased staining by MBP- and TAL-specific antibodies in MS plaques, indicating a concurrent loss of these antigens from demyelination sites. By Western blot high titer antibodies to human recombinant TAL were found in 29/94 sera and 16/23 cerebrospinal fluid samples from MS patients. Antibodies to MBP were undetectable in sera or cerebrospinal fluid of these MS patients. Proliferative responses to human recombinant TAL (stimulation index [SI] = 2.47+/-0.3) were significantly increased in comparison to MBP in 25 patients with MS (SI = 1.37+/-0.1; P < 0.01). After a 7-d stimulation of PBL, utilization of any of 24 different T cell receptor Vbeta gene segments in response to MBP was increased less than twofold in the two control donors and six MS patients investigated. In response to TAL-H, while skewing of individual Vbeta genes was also less than twofold in healthy controls, usage of specific Vbeta gene segments was differentially increased ranging from 2.5 to 65.9-fold in patients with MS. The results suggest that TAL may be a more potent immunogen than MBP in MS.

Adult↗

Arteritis following intra-arterial chemotherapy for liver tumors.

Primary and metastatic tumors of the liver can be treated successfully with transcatheter chemoembolization (TACE) during selective arterial catheterism. Arteritis is a possible referred side effect which can lead to tortuosity of the arteries, stenosis and occlusion of vessels. In our hospitals 117 consecutive patients were treated with TACE from January 1990 to December 1992; 61 patients were affected by hepatocellular carcinoma (HCC) and 56 were affected by metastases from colorectal carcinoma. Each patient received from 1 to 4 treatments at monthly intervals using epirubicin/Lipiodol ultrafluid (E/LUF) or a mixture of epirubicin and mitomicin C (MC)/LUF and followed by gelatine sponge injection in the hepatic artery. Selective angiography performed 30-62 days after the first chemoembolization showed artery stenosis in 7 patients and thrombosis in 2 cases related to toxic arteritis due to chemoembolization. Reports about arteritis during TACE treatments are discussed.

Aged↗

Randomized study comparing omeprazole plus amoxycillin versus omeprazole plus clarithromycin for eradication of Helicobacter pylori.

BACKGROUND: Dual therapy with omeprazole plus amoxycillin or with omeprazole plus clarithromycin has been proposed for eradication of Helicobacter pylori. The main problem is the great variability in the rate of eradication. METHODS: A group of 287 consecutive patients with active peptic ulcers and H. pylori infections were admitted to a prospective, randomized, multicentre study, to be given omeprazole 20 mg b.d. plus either amoxycillin 1 g b.d. or clarithromycin 500 mg t.d.s. for 2 weeks. Cure was defined as the absence of H. pylori infection, 4-6 weeks after completing anti-microbial therapy, assessed by urease activity and histology of antral and body gastric biopsies. RESULTS: The bacteria were eradicated in 68/143 patients (48%) treated with amoxycillin and omeprazole and 70/144 patients (49%) treated with clarithromycin and omeprazole (intention-to-treat analysis). The ulcers were healed in 118/127 patients (93%) treated with amoxycillin and in 115/123 (94%) of those treated with clarithromycin. Undesirable effects were rare with both treatments. CONCLUSIONS: Combined treatment with omeprazole plus either amoxycillin or clarithromycin produced a high percentage of short-term healing of ulcers and was well tolerated, but is not useful as first-line anti-Helicobacter pylori treatment.

Adolescent↗

Glutathione levels and sensitivity to apoptosis are regulated by changes in transaldolase expression.

Transaldolase (TAL) is a key enzyme of the reversible nonoxidative branch of the pentose phosphate pathway (PPP) that is responsible for the generation of NADPH to maintain glutathione at a reduced state (GSH) and, thus, to protect cellular integrity from reactive oxygen intermediates (ROIs). Formation of ROIs have been implicated in certain types of apoptotic cell death. To evaluate the role of TAL in this process, Jurkat human T cells were permanently transfected with TAL expression vectors oriented in the sense or antisense direction. Overexpression of TAL resulted in a decrease in glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities and NADPH and GSH levels and rendered these cells highly susceptible to apoptosis induced by serum deprivation, hydrogen peroxide, nitric oxide, tumor necrosis factor-alpha, and anti-Fas monoclonal antibody. In addition, reduced levels of TAL resulted in increased glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities and increased GSH levels with inhibition of apoptosis in all five model systems. The effect of TAL expression on susceptibility to apoptosis through regulating the PPP and GSH production is consistent with an involvement of ROIs in each pathway tested. Production of ROIs in Fas-mediated cell death was further substantiated by measurement of intracellular ROI production with oxidation-sensitive fluorescent probes, by the protective effects of GSH precursor, N-acetyl cysteine, free radical spin traps 5,5-dimethyl-1-pyrroline-1-oxide and 3,3,5,5-tetramethyl-1-pyrroline-1-oxide, the antioxidants desferrioxamine, nordihydroguaiaretic acid, and Amytal, and by the enhancing effects of GSH depletion with buthionine sulfoximine. The results provide definitive evidence that TAL has a role in regulating the balance between the two branches of PPP and its overall output as measured by GSH production and thus influences sensitivity to cell death signals.

Apoptosis↗

Comparison of two lansoprazole-antibiotic combinations (amoxycillin or classical triple therapy) for treatment of H. pylori infection in duodenal ulcer patients.

AIM: To compare the eradicating capacity of two different antibiotic-lansoprazole combinations (amoxycillin vs. standard triple therapy) with that of lansoprazole alone in Helicobacter pylori-positive duodenal ulcer patients. METHODS: Ninety-six out-patients with H. pylori-positive duodenal ulcer were randomly assigned to receive one of the following three antiulcer regimens: (1) lansoprazole 30 mg b.d. for 4 weeks plus amoxycillin 1 g t.d.s. during the last 2 weeks; or (2) lansoprazole 30 mg once daily for 4 weeks plus classical triple therapy (tripotassium dicitratobismuthate 240 mg b.d., amoxycillin 1 g t.d.s. and tinidazole 500 mg b.d.) for the last 2 weeks; or (3) lansoprazole 30 mg once daily for 4 weeks. Endoscopy was repeated at the end of treatment and 1 month later. A rapid urease test and histology were used to determine H. pylori status. RESULTS: Duodenal ulcer healing rates at 4 weeks were 96% after both lansoprazole with amoxycillin, and lansoprazole with triple therapy, and 97% after lansoprazole alone. Eradication of H. pylori was significantly better with lansoprazole with triple therapy than with either lansoprazole with amoxycillin or lansoprazole alone (90% vs. 55% vs. 3%, respectively). CONCLUSION: Classical triple therapy combined with lansoprazole is significantly more effective than the lansoprazole with amoxycillin combination for the eradication of H. pylori in duodenal ulcer patients pre-treated with lansoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Helicobacter pylori serology in chronic gastritis with antral atrophy and negative histology for Helicobacter-like organisms.

It has been suggested that there may be a correlation between Helicobacter pylori (Hp) infection and precancerous lesions of the stomach. However, histological evaluation of bacterial colonization in chronic atrophic gastritis shows a relatively low prevalence of the microorganism, which does not support the hypothesis. The aim of our study was to investigate the Hp serology in 95 patients with chronic gastritis with antral atrophy, with (27 cases) and without (68 cases) intestinal metaplasia, and without Helicobacter-like organisms in antral and corpus biopsy specimens. For all subjects, serum anti-Hp immunoglobulin IgG was identified by a fluorescent immunoenzymatic method (Helori-test; Eurospital), and mucosal atrophy and activity were graded histologically (Sydney System score). The serum Hp-antibody status documented the presence of current bacterial infections in 64 of 95 (67.4%) patients and previous infections in another 17 subjects. In only 14.7% of cases was there no evidence of current or previous infection. These subjects had less severe mucosal atrophy and lower inflammatory scores. In addition, there were no cases of intestinal metaplasia in such subjects. The high prevalence of Hp infection confirms the primary role of the microorganism in the pathogenesis of chronic gastritis with antral atrophy, although the bacterium is no longer present in the advanced stages of such disease. The histological evaluation of Hp colonization following the criteria of the Sydney System appears from our study to underestimate the true prevalence of the infection in the stomach when there is mucosal atrophy.

Adult↗