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Biomedical subjects

M Melis

Publications and source records attributed to M Melis.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Clinical relevance of unusual metastases from colorectal neoplasms].

BACKGROUND: The aim of the study was to evaluate the clinical relevance of isolated metastases (MII) in unusual sites (different from liver and lung), synchronous and metachronous, in patients operated on for colorectal carcinoma (CCR). METHODS: The study was performed on 655 patients who underwent surgery for CCR during the period 1985-2000. Work out for distance metastases was performed (both during preoperative evaluation and follow-up) with physical examination and other few exams (CEA, chest X-ray, abdominal US scan). Other investigations were carried out if requested by clinical features. Metastases localized in sites different from liver and lungs were considered unusual. RESULTS: Metastases in unusual sites usually are observed in patients with terminal neoplastic disease. MII was found in only 7 (1.07%) patients, all submitted to resection of the primary tumor. Sites of unusual metastases were bones (3), CNS (2), adrenal gland and anus; such lesions were easily diagnosed by clinical features or by few examinations. Curative treatment was feasible in only three patients, and actually it did improve neither survival, nor quality of life. CONCLUSIONS: Extra-abdominal MII are rare, generally they cannot be treated; therefore particular tests for early diagnosis of such lesions appear useless. Potentially curative surgery for splenic and adrenal metastases is described in the literature; anyhow these lesions are usually shown by routine investigations.

Adult↗
PubMed2000

The cyclo-oxygenase inhibitor nimesulide induces conditioned place preference in rats.

Two cyclo-oxygenase inhibitors, indomethacin and nimesulide, have been shown to potentiate morphine-induced stimulation of meso-accumbens dopamine neurons. In this study, an unbiased conditioned place preference procedure was used to evaluate whether nimesulide produces motivational effect after systemic administration in rats. These results show that nimesulide, at doses 0.1, 0.5 and 1 mg/kg, even lower than those usually applied for inflammatory conditions, induces conditioned place preference in rats, suggesting that it might possess rewarding properties in humans.

Animals↗
PubMed2000

Cyclo-oxygenase-inhibitors increase morphine effects on mesolimbic dopamine neurons.

The effect of cyclo-oxygenase inhibitors, indomethacin and nimesulide, on the action of i.v. morphine on dopamine neurons projecting to the nucleus Accumbens was studied using standard extracellular recording techniques coupled with antidromic identification in unanesthetized rats. The i.v. administration of either nimesulide (3 mg/kg) or indomethacin (3.5 mg/kg) per se did not affect the firing rate of mesolimbic dopamine cells. In contrast, the subsequent administration of morphine (0.25-2 mg/kg i.v.) potently increased the firing rate of mesolimbic dopamine neurons in cyclo-oxygenase inhibitor-pretreated rats as compared with saline-pretreated rats. The maximal enhancement of basal firing rate at the highest dose of morphine tested was 92%, 80% and 47%, for nimesulide-, indomethacin-, and saline-treated rats, respectively. Our results indicate that the effect of morphine on mesolimbic dopamine cells is potentiated by blocking cyclo-oxygenase activity and suggest that the modulation of cyclo-oxygenase pathway in dopamine cells might be involved in the cellular mechanisms of the rewarding actions of morphine.

Analysis of Variance↗
PubMed2000

Effects of gemcitabine on cell proliferation and apoptosis in non-small-cell lung cancer (NSCLC) cell lines.

We evaluated the antiproliferative and the proapoptotic ability of gemcitabine in three non-small-cell lung cancer (NSCLC) cell lines. NCI-H292 (mucoepidermoid carcinoma), NCI-CorL23 (large-cell carcinoma) and NCI-Colo699 (adenocarcinoma) cells were cultured with and without 0.5, 0.05 and 0.005 microM gemcitabine for 24, 48 and 72 h, respectively. Gemcitabine exerted a stronger and earlier antiproliferative and proapoptotic effect on H292 cells than on CorL23 or Colo699 cells. Fas receptor expression was increased in all three cell lines and was higher in Colo699 than in CorL23 cells. The incubation of NSCLC with anti-Fas agonistic monoclonal antibody (CH11) induced cell apoptosis in H292 cells, demonstrating that the Fas receptor was functionally active. Finally, gemcitabine and CH-11 exerted a synergistic effect on cell apoptosis in H292 cells. This study demonstrates that gemcitabine induces apoptosis in NSCLC and that this effect might be exerted by modulating functionally active Fas expression, and these effects of gemcitabine were stronger in H292 cells than in either CorL23 or Colo699 cells.

Antigens, Neoplasm↗
PubMed2000

Different mechanisms for dopaminergic excitation induced by opiates and cannabinoids in the rat midbrain.

1. The mechanism underlying morphine and cannabinoid-induced excitation of meso-accumbens and nigro-striatal dopaminergic neurons was investigated by extracellular single unit recording techniques coupled with antidromic activation from the nucleus accumbens and striatum respectively, in unanesthetized rats. 2. The intravenous administration of cumulative doses (1-4 mg/kg) of morphine, dose-dependently increased the firing rate of dopaminergic neurons projecting to the nucleus accumbens and neostriatum, while the same doses inhibited the activity of pars reticulata neurons of the substantia nigra. Both effects were antagonized by naloxone (0.1 mg/kg i.v.) but not by the selective CB1 receptor antagonist SR 141716A (1 mg/kg i.v.). 3. The intravenous administration of cumulative doses (0.125-0.5 mg/kg) of delta9-tetrahydrocannabinol (delta9-THC) also increased the firing rate of meso-accumbens and nigro-striatal dopaminergic neurons; this effect was antagonized by SR 141716A (1 mg/kg i.v.), but not by naloxone. 4. Furthermore, nor delta9-THC up to a dose of 1 mg/kg, maximally effective in stimulating dopamine neurons, neither SR 141716A (1 mg/kg i.v.) at a dose able to reverse the stimulatory effect of delta9, THC on dopamine cells, did alter the activity of SNr neurons. 5. The results indicate that morphine and delta9-THC activate dopaminergic neurons through distinct receptor-mediated mechanisms; morphine may act by removing the inhibitory input from substantia nigra pars reticulata neurons (an effect mediated by mu-opioid receptors). Alternatively, the delta9-THC-induced excitation of dopaminergic neurons seems to be mediated by CB1 cannabinoid receptors, while neither mu-opioid receptors nor substantia nigra pars reticulata neurons are involved.

Animals↗
PubMed2000

Dissociation of haloperidol, clozapine, and olanzapine effects on electrical activity of mesocortical dopamine neurons and dopamine release in the prefrontal cortex.

The aim of the present study was to compare the effects of the typical antipsychotic haloperidol and the atypical antipsychotics clozapine and olanzapine on both extracellular dopamine (DA) levels in the medial prefrontal cortex (mPFC) as well as electrical activity of mesoprefrontal DA (mPFC-DA) neurons. Extracellular single unit recordings and microdialysis experiments were carried out in different groups of chloral hydrate anesthetised rats under identical experimental conditions. Intravenous administration of haloperidol, clozapine, and olanzapine increased the firing rate and burst activity of antidromically-identified mPFC-DA neurons; maximal increase in firing rate of approximately 140, 155, and 70 %, was produced by haloperidol, clozapine, and olanzapine at doses of 0.2, 2.5, and 1 mg/kg, i.v., respectively. Intravenous administration of the same doses increased extracellular DA levels in mPFC by 20%, 190%, and 70%, respectively. Moreover, while haloperidol and olanzapine increased extracellular levels of the deaminated DA metabolite DOPAC, by 60% and 40%, respectively, clozapine was totally ineffective. The D1 receptor antagonist SCH 23390 modified neither DA output nor neuronal firing. To determine whether the effect of the three antipsychotics on DA release might depend on a direct action on the mPFC, rats were perfused locally via inverse dialysis in the mPFC at concentrations ranging from 10(-6) to 10(-4)M. While clozapine and olanzapine increased extracellular DA concentrations by up to 400% of basal level, haloperidol was totally ineffective. The results obtained from this study indicate that the rank potency of the three antipsychotics in stimulating the firing rate of DA neurons projecting to mPFC, correlates with their affinity for D2 receptors and doses used clinically. On the other hand, their stimulating effect on DA release does not correlate with their effect on neuronal firing but depends on a direct action on the mPFC.

Action Potentials↗
PubMed2000

Distribution of folpet on the grape surface after treatment.

Field trials were carried out to evaluate whether folpet sprayed on grapevines penetrated the epicuticular wax and cell walls of grapes. Folpet showed poor penetration into the epicuticular wax; it was found almost totally on the surface. Despite its low solubility in water, perhaps due to the presence of adjuvants, its residues showed such a high resistance to washing that the action of rain was negligible in decreasing residues.

Chromatography, Gas↗
PubMed2000

ICAM-1 and alpha3beta1 expression by bronchial epithelial cells and their in vitro modulation by inflammatory and anti-inflammatory mediators.

BACKGROUND: Adhesion molecules are involved in inflammatory and repair processes of the bronchial epithelium. ICAM-1 is mainly involved in inflammatory reactions, whereas integrins, such as alpha3beta1, are mainly involved in repair processes. METHODS: Using bronchial biopsies from 10 asthmatics and eight controls, we first evaluated by immunohistochemistry expression of alpha3beta1 and ICAM-1 in intact and damaged epithelium. Then, using the human pulmonary epithelial cell line WI-26 VA, we studied, by flow-cytometry, the modulation of ICAM-1 and alpha3beta1 expression, and, by ELISA, the release of fibronectin by proinflammatory cytokines, such as IL-5, and anti-inflammatory cytokines, such as IL-4, TGF-beta, and EGF. RESULTS: alpha3beta1 expression was slightly higher in asthma than in controls, as well as in damaged epithelium than in undamaged epithelium. ICAM-1 expression was higher in asthma than in controls, and similarly distributed in intact or damaged epithelium. In vitro, alpha3beta1 was significantly increased by TGF-beta, EGF, and IL-4, and significantly decreased by IL-5. Fibronectin release was significantly increased by TGF-beta and IL-4, unchanged by EGF, and slightly but significantly decreased by IL-5. ICAM-1 expression was significantly decreased by TGF-beta and IL-4, unchanged by EGF, and significantly increased by IL-5. CONCLUSIONS: These differences in adhesion molecule expression and fibronectin release may be important in epithelial cell inflammation and repair.

Adolescent↗
PubMed2000

Surgical treatment of anorectal complications in Crohn's disease.

BACKGROUND: The purpose of our study was to elucidate features, surgical procedures, and long-term results in patients with anorectal complications of Crohn's disease. METHODS: Physical findings, surgical treatment, and long-term outcome were recorded prospectively for 224 patients who had anorectal complications of Crohn's disease between October 1984 and May 1999. RESULTS: Presenting complications included abscess (n = 36), fistula-in-ano (n = 51), rectovaginal fistula (n = 20), anal stenosis (n = 40), anal incontinence (n = 11), or a combination of features (n = 66). Twenty-four patients did not undergo surgical treatment; the remaining 200 patients underwent 284 procedures. Ultimately, 139 patients (62%) retained anorectal function; reasons for proctectomy in the remaining 85 patients included disease (n = 66), extensive fistular disease (n = 15), fecal incontinence (n = 2), and tight anal stenosis (n = 1). Patients with rectal disease had a significantly higher rate of proctectomy than patients with rectal sparing (77.6% vs. 13.6%, respectively, P<.0001). In the absence of rectal involvement, patients with multiple complications had a significantly higher rate of proctectomy than patients with single complications (23% vs. 10%, P<.05). CONCLUSIONS: A wide spectrum of surgical techniques is required for the management of the diverse anorectal complications of Crohn's disease. Complete healing and control of sepsis can be achieved in the majority of patients. Active rectal disease and multiple complications significantly increase the need for proctectomy.

Abscess↗
PubMed2000

Side-to-side isoperistaltic strictureplasty in extensive Crohn's disease: a prospective longitudinal study.

OBJECTIVE: To report on the results of a prospective longitudinal study of a new bowel-sparing procedure (side-to-side isoperistaltic strictureplasty [SSIS]) in patients with extensive Crohn's disease. METHODS: Between January 1992 and April 1999, the authors operated on 469 consecutive patients for Crohn's disease of the small bowel. Seventy-one patients (15.1%) underwent at least one strictureplasty; of these, 21 (4.5%; 12 men, 9 women; mean age 39) underwent an SSIS. The long-term changes occurring in the SSIS were studied radiographically, endoscopically, and histopathologically. RESULTS: The indication for surgical intervention was symptomatic partial intestinal obstruction in each of the 21 patients. Fourteen SSISs were constructed in the jejunum, four in the ileum, and three with ileum overlapping colon. The average length of the SSIS was 24 cm. Performance of an SSIS instead of a resection resulted in preservation of an average of 17% of small bowel length. One patient suffered a postoperative gastrointestinal hemorrhage. All patients were discharged on oral feedings after a mean of 8 days. In all cases, SSIS resulted in resolution of the preoperative symptoms. With follow-up extending to 7.5 years in 20 patients (one patient died of unrelated causes), radiographic, endoscopic, and histopathologic examination of the SSIS suggests regression of previously active Crohn's disease. CONCLUSIONS: SSIS is a safe and effective procedure in patients with extensive Crohn's disease. The authors' results provide radiographic, endoscopic, and histopathologic evidence that active Crohn's disease regresses at the site of the SSIS.

Adult↗
PubMed2000

Benign tumors of heterotopic tissue in the thyroid gland: a report of two cases of lipomatous lesions.

A report of two cases, concerning heterotopic nests of fat cells in the thyroid gland, is presented here together with a review of lipomatous lesions in the literature. Both cases involved patients who presented with goiter; one had Grave's disease and the other had adenomatous hyperplasia. The fat cells were principally located in the subcapsular areas and scattered among the follicles. The distribution of the immunohistochemical staining, and the morphologic characteristics of the adipose tissue, suggested a probable origin of the fat cells from inclusion nests during embryogenesis of the thyroid gland.

Adipocytes↗
PubMed1999

Clozapine potently stimulates mesocortical dopamine neurons.

The effects of clozapine on dopamine neurons projecting to the medial-prefrontal cortex, nuclei accumbens and caudatus were compared. Clozapine (1.25 mg/kg i.v.) maximally stimulated the firing rate and burst activity of dopamine neurons projecting to the medialprefrontal cortex. Much higher doses (5 and 10 mg/kg i.v.) were needed to stimulate mesoaccumbens and nigrostriatal dopamine neurons. The results suggest that the activation of mesocortical dopamine neurons is responsible for clozapine-induced dopamine release in the prefrontal cortex.

Animals↗
PubMed1999

Lasting reduction in mesolimbic dopamine neuronal activity after morphine withdrawal.

The activity of mesolimbic dopaminergic neurons was investigated in rats at various times after a chronic regimen of morphine, which produced, upon suspension, a marked somatic withdrawal syndrome. Single-cell extracellular recording techniques, coupled with antidromic identification from the nucleus accumbens, were used to monitor neuronal activity while behavioural observations allowed quantification of the somatic signs of morphine withdrawal. Temporal correlation of electrophysiological indices, such as firing rate and burst firing, with scores obtained through behavioural assessments proved negative, in that somatic signs were pronounced at 24 h after suspension of treatment and then subsided to control values at 72 h after the last morphine injection. In contrast, the firing rate and burst firing of mesolimbic dopaminergic neurons were found to be reduced at 1, 3 and 7 days after morphine withdrawal. After 14 drug-free days, electrophysiological analysis revealed an apparent normalization of various parameters. However, at this time, intravenous administration of morphine produced an increment of electrical activity which was significantly higher than that obtained in control (saline treated) rats. Further, administration of the opiate antagonist naltrexone, administered without prior morphine, at 3, 7 and 14 days after the last morphine administration, failed to alter dopaminergic neuronal activity. The results indicate: (i) that the activity of mesolimbic dopaminergic neurons remains reduced well after somatic signs of withdrawal have disappeared; (ii) after 14 days of withdrawal, the augmented magnitude of the electrophysiological response to exogenous morphine suggests an increased sensitivity of opiate receptors; and (iii) the lack of relationship between dopaminergic activity and somatic signs of withdrawal corroborates the notion that dopaminergic activity in the mesolimbic system does not participate in the neurobiological mechanisms responsible for somatic withdrawal. The present results may be relevant to the phenomenon of drug addiction in humans and consequent relapse after drug-free periods.

Analgesics, Opioid↗
PubMed1999

Interleukin-8 induces lymphocyte chemotaxis into the pleural space. Role of pleural macrophages.

The pleural space is a potential compartment between the lung and chest wall that becomes filled with fluid and inflammatory cells in a number of respiratory diseases. In an attempt to understand one aspect of the inflammatory process in the pleural space, we compared the responses in three different diseases (congestive heart failure [CHF], tuberculosis [TB], and cancer). Large concentrations of interleukin-8 (IL-8) were detected in cancer and TB effusions, but not in CHF. Surprisingly, the concentration of IL-8 correlated best with lymphocyte recruitment and not with neutrophil recruitment. Pleural fluid from cancer and TB patients was chemotactic for lymphocytes, and this activity was partly blocked by an anti-IL-8 antibody in cancer and completely blocked in TB. To determine whether there was the potential for a chemotactic gradient into the pleural space, pleural effusion cells were analyzed for the expression of IL-8. Cells in the effusions of cancer patients expressed IL-8, whereas IL-8 could not be detected from the cells of TB and CHF effusions. To explore the possible role of pleural macrophages in the regulation of IL-8, pleural effusion cells were treated with culture supernatants from stimulated pleural macrophages. Stimulated pleural macrophages were able to induce expression of messenger RNA (mRNA) for IL-8 and IL-8 protein production, and this activity was abrogated by blocking tumor necrosis factor-alpha. These findings suggest that soluble IL-8 is an important factor for the recruitment of lymphocytes into the pleural space, and that this cytokine is produced by both pleural structural and cancer cells after their activation by macrophage-derived, cytokine-mediated signals.

Adult↗
PubMed1999

Phenotypic and functional characterization of normal rat pleural macrophages in comparison with autologous peritoneal and alveolar macrophages.

Pleural mononuclear phagocytes (PleMP) were isolated from normal rats by pleural lavage and compared with autologous peritoneal (PerMP) and bronchoalveolar mononuclear phagocytes (BAMP) isolated by peritoneal and bronchoalveolar lavage, respectively. The phagocytic activity of PleMP, PerMP, and BAMP, evaluated by testing their ability to ingest latex beads, was lower for PleMP and PerMP than for BAMP. The phenotype of PleMP, PerMP, and BAMP was characterized by immunocytochemical staining with a panel of monoclonal antibodies (mAbs). As expected, PleMP, PerMP, and BAMP did not react with OX19, OX33, ED5, MOM/3F12/F2, and anticytokeratin mAbs, specific for T lymphocytes, B lymphocytes, dendritic cells, granulocytes, and epithelial/mesothelial cells, respectively. Moreover, PleMP and PerMP populations were highly enriched with OX6-, OX42-, ED7-, and ED8-positive MP, whereas BAMP population was enriched with ED1- and ED9-positive cells. To test the ability of PleMP, PerMP, and BAMP to function as accessory cells (AC), mitomycin C-treated MP were used as stimulatory cells in mixed leukocyte reaction experiments, using allogeneic T cells as responders. 3HdTR incorporation by T cells was assessed as an index of AC function. PleMP and PerMP were more potent AC than BAMP. Moreover, when cultured together with autologous pulmonary interstitial dendritic cells, PleMP and PerMP exerted a more potent ability to stimulate T-cell proliferation than did BAMP. To investigate the capacity of MP to function as bactericidal and fungicidal cells, we tested their ability to kill Escherichia coli and Cryptococcus neoformans, respectively. PleMP and PerMP were less potent bactericidal and fungicidal cells than BAMP. The results of this study demonstrate that PleMP isolated from normal rat pleural space are functionally and phenotypically different from BAMP but similar to PerMP, and suggest that these cells might play an important role in cell-mediated immune reactions in the pleural space.

Animals↗
PubMed1999

[Angiodysplasia of the duodenum with arteriovenous shunts, sub-serosal prevalence and interstitial elastosis; peritonitis and rupture of sub-serous dysplasic vessels and hemoperitoneum. Description of a case and review of the literature].

We present a case report of a 74 year old man, affected by angiodysplasia of the duodenum, which developed in peritonitis and hemoperitoneum. After undergoing two surgical interventions, it is 14 days since he died. First of all, the importance of this case is due to the extreme rarity of the angiodysplasia of the duodenum, specially when it becomes worse in peritonitis and hemoperitoneum, this case having been described only one time till now, then the localization mainly sub-serousal and lastly the presence of a component, characterized by an elastotic nature, disposed in islets and interstitial widespread also among the glands, which we have first described in literature.

Aged↗
PubMed1999

Expression of bcl-2, c-erbB-2, p53, and p21 (waf1-cip1) protein in thyroid carcinomas.

The study was carried out on 53 patients who had thyroid cancer with various degree of differentiation. We studied the expression of bcl-2, a-erbB-2, p53, and p21 ras protein. The protein encoded by bCL-2 proto-oncogene is implicated in the prolongation of cell survival by blocking programmed cell death, i.e. apoptosis. The role of p53 and bcl-2 genes in the regulation of apoptosis has important implications in oncogenesis. Wild-type p53 is thought to promote apoptosis, whilst mutant p53 has a similar effect on apoptosis as bcl-2 that is inhibition of programmed cell kinase activity. C-erb-2 protein overexpression is currently being evaluated as a potential risk factor in breast cancer patients? The ras gene family codes for a 21 kD protein (p21), which binds guanine nucleotides and possesses GTPase activity. Through this mechanism, the ras p21 protein participates in the control of cell proliferation, possibly as a signal transducer from cell surface receptors to the nucleus. Activation of ras genes has been implicated in neoplastic transformation of cells. The aim of our study is to evaluate the expression of these markers in thyroid carcinomas. All immunohistochemical study was performed in paraffin-embedded tissues pathology specimen. Any well differentiated tumor in our study was positive for bcl-2 protein. C-erb-2 immunostaining was present in tumor samples in 60% of cases. In most cases, specific membrane staining as well as a weak cytoplasmic positivity of tumor cells were seen. Immunoreactivity for p53 was positive only in 10% of cases. By immunostaining, p21 protein was expressed in 55% of the 53 tumors tested, with different degree of expression. Only some poorly differentiated tumours were positive for bcl-2, furthermore all markers tested were strongly positive in these tumours. In conclusion, our results indicate that bcl-2, c-erbB-2, p53, and p21 ras protein are differently expressed in thyroid carcinomas in relation to the degree of aggressiveness and differentiation.

Adenocarcinoma, Follicular↗