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Biomedical subjects

M Cecchi

Publications and source records attributed to M Cecchi.

At least 19 recordsLinked to original sources

Use of gabexate mesylate in Italian hospitals: a multicentre observational study.

INTRODUCTION: Gabexate mesylate has been proposed as a therapeutic or prophylactic agent in a variety of diseases (e.g. disseminated intravascular coagulation, prophylaxis of pancreatic damage and acute pancreatitis), but its clinical effectiveness is still unclear. As the drug is widely used in Italy, we conducted an observational study to determine the pattern of prescription of gabexate in Italian hospitals and to assess the outcome of patients with acute pancreatitis when this treatment is given. An updated meta-analysis of the use of the drug is also presented. MATERIALS AND METHODS: From 20 May to 20 July 2001, all consecutive patients admitted to 13 Italian hospitals were enrolled. The following information was recorded from each patient: indication for the use of gabexate, total dose and duration of gabexate administration, need for surgical treatment and outcome of hospitalization (alive or dead). In the patient subgroup with acute pancreatitis, the outcome data of our observational study were compared with those reported by the randomized trials (RCTs) previously published. For this purpose, the survival data of the RCTs were summarized in an updated meta-analysis. RESULTS: A total of 170 patients were enrolled in the study. The main clinical indications were acute pancreatitis in 88 cases (52%) and prophylaxis of pancreatic damage in 62 cases (36%). At the end of the study, 80 of the 88 patients treated for acute pancreatitis (91%) were alive and eight (9%) had died. In the subgroup of patients with necrotic-haemorrhagic pancreatitis (n = 10), six died during the observation period. Our meta-analysis showed that gabexate mesylate did not improve survival in comparison with placebo. The meta-analytic odds ratio was 0.70 (95% CI: 0.45-1.09). DISCUSSION: The study described the pattern of use of gabexate mesylate in Italian hospitals and provided information on the outcome of the subgroup treated for acute pancreatitis. A meta-analysis of current data from RCTs, together with our findings, indicates that gabexate mesylate does not significantly improve survival in acute pancreatitis.

Acute Disease↗

Modulatory effects of norepinephrine in the lateral bed nucleus of the stria terminalis on behavioral and neuroendocrine responses to acute stress.

The brain noradrenergic system is activated by stress, and modulates the activity of forebrain regions involved in behavioral and neuroendocrine responses to stress, such as the lateral bed nucleus of the stria terminalis (BSTL). This region of the limbic forebrain receives dense noradrenergic innervation, and has been implicated in both anxiety and regulation of the hypothalamic-pituitary-adrenal axis. We hypothesized that stress-induced release of norepinephrine in the BSTL modulates anxiety-like behavioral responses to stress and activation of the hypothalamic-pituitary-adrenal stress axis. Using microdialysis, we showed that release of norepinephrine was increased in the BSTL of male Sprague-Dawley rats during immobilization stress. In the next experiment, we then microinjected noradrenergic antagonists into the BSTL immediately prior to acute immobilization stress to examine noradrenergic modulation of behavioral stress reactivity. Either the alpha(1)-receptor antagonist benoxathian, or a cocktail of beta(1)- and beta(2)-receptor antagonists (betaxolol+ICI 118,551) blocked the anxiety-like reduction in open-arm exploration on the elevated plus-maze, but not the reduction in social behavior induced in the social interaction test. In a third experiment, benoxathian reduced plasma levels of adrenocorticotropic hormone following stress, but beta-receptor antagonists had no effect. From these results we suggest that stress-induced norepinephrine release acts on both alpha(1)- and beta-receptors in the BSTL to facilitate anxiety-like behavioral responses on the plus-maze but not the social interaction test, and modulates hypothalamic-pituitary-adrenal axis activation via alpha(1)-receptors only. Together with previous results in which adrenergic antagonists in central amygdala attenuated behavioral responses on the social interaction test but not the plus-maze, these observations suggest the two behavioral tests measure different dimensions of stress reactivity, and that norepinephrine facilitates different components of the stress response by region- and receptor-specific mechanisms.

Acute Disease↗

Cortical acetylcholine release elicited by stimulation of histamine H1 receptors in the nucleus basalis magnocellularis: a dual-probe microdialysis study in the freely moving rat.

Perfusion of the nucleus basalis magnocellularis (NBM) with histamine agonists and antagonists modulates the spontaneous release of cortical acetylcholine (ACh) in freely moving rats. Perfusion of the NBM with Ringer solution containing 100 mM K+ strongly stimulated the spontaneous release of cortical ACh in freely moving rats, whereas perfusion with 1 microM tetrodotoxin reduced cortical ACh spontaneous release by more than 50%. Administration of histamine to the NBM concentration-dependently increased the spontaneous release of cortical ACh. Administration of H1 (methylhistaprodifen) but not H2 (dimaprit) or H3 (R-alpha-methylhistamine) receptor agonists to the NBM mimicked the effect of histamine. Perfusion of the NBM with either H1 (mepyramine or triprolidine) or H2 (cimetidine) receptor antagonists failed to alter ACh spontaneous release from the cortex, however, H1 but not H2 receptor antagonists antagonized the releases of cortical ACh elicited by histamine and methylhistaprodifen. Local administration of H3 receptor antagonists (clobenpropit and thioperamide) to the NBM increased the spontaneous release of ACh from the cortex; this effect was antagonized by H1 receptor antagonism. Conversely local administration of MK-801, a noncompetitive receptor antagonist of the N-methyl-D-aspartate receptor, to the NBM failed to alter ACh spontaneous release from the cortex and to antagonize ACh release elicited by histamine. This study demonstrates that activation of histamine H1 receptors in the NBM increases ACh spontaneous release from the cortex.

Acetylcholine↗

[Adenoid cystic carcinoma of the prostate. Clinical case].

The authors report an extremely rare case of adenoid cystic carcinoma of the prostate. No satisfactory clinical and pathological classification exists for this tumour, creating particular difficulties for therapeutic decisions and prognosis. Descriptions of cases with excellent survival rates are reported in the literature, to the extent that this is sometimes regarded as a low-malignancy tumour, but other reports also exist of massive diffusion of the pathology with fatal consequences. Advances in the knowledge of this tumour have enabled a number of earlier pathogenetic hypotheses to be ruled out, namely its possible derivation from ectopic salivary cells, ectopic periurethral glands or metaplastic urethral mucosa, but the origin of this carcinoma is still not certain. It is also difficult to differentiate this form from the typical adenocarcinoma and to make a prognosis for survival. In the case reported here, the final diagnosis was made on the lymph node biopsy obtained during surgery, given that a preoperative biopsy was not feasible owing to the scarcity of material available. The patient received standard hormonal therapy for prostate carcinoma.

Adenocarcinoma↗

Effects of chronic antidepressant treatments on serotonin transporter function, density, and mRNA level.

To investigate functional changes in the brain serotonin transporter (SERT) after chronic antidepressant treatment, several techniques were used to assess SERT activity, density, or its mRNA content. Rats were treated by osmotic minipump for 21 d with the selective serotonin reuptake inhibitors (SSRIs) paroxetine or sertraline, the selective norepinephrine reuptake inhibitor desipramine (DMI), or the monoamine oxidase inhibitor phenelzine. High-speed in vivo electrochemical recordings were used to assess the ability of the SSRI fluvoxamine to modulate the clearance of locally applied serotonin in the CA3 region of hippocampus in drug- or vehicle-treated rats. Fluvoxamine decreased the clearance of serotonin in rats treated with vehicle, DMI, or phenelzine but had no effect on the clearance of serotonin in SSRI-treated rats. SERT density in the CA3 region of the hippocampus of the same rats, assessed by quantitative autoradiography with tritiated cyanoimipramine ([(3)H]CN-IMI), was decreased by 80-90% in SSRI-treated rats but not in those treated with phenelzine or DMI. The serotonin content of the hippocampus was unaffected by paroxetine or sertraline treatment, ruling out neurotoxicity as a possible explanation for the SSRI-induced decrease in SERT binding and alteration in 5-HT clearance. Levels of mRNA for the SERT in the raphe nucleus were also unaltered by chronic paroxetine treatment. Based on these results, it appears that the SERT is downregulated by chronic administration of SSRIs but not other types of antidepressants; furthermore, the downregulation is not caused by decreases in SERT gene expression.

Adrenergic Uptake Inhibitors↗

Correlation between Gleason score of needle biopsy and radical prostatectomy tissue.

Gleason score has been identified as an important variable to predict disease extent and biologic behaviour of prostate cancer. However, the correlation between Gleason score of needle biopsy and surgical specimen is often poor. We studied 72 patients who underwent needle biopsy and radical prostatectomy to correlate Gleason score with PSA, clinical and pathological tumour stage. Only 47.2% of Gleason scores were identical in the biopsy and specimens, 37.5% were undergraded and 15.2% were overgraded. Correlations between clinical and pathological stage were identical in 30.5% of patients, 61.1% of patients were understaged and 8.3% overstaged. In conclusion, accuracy of clinical staging and grading of prostate cancer is low. Although the Gleason score on needle biopsy might be useful to predict the final stage and grade, correlation with surgical specimen is poor.

Aged↗

The origin, effects and control of air pollution in laboratories used for human embryo culture.

Testing shows that most laboratories conducting human gamete and embryo culture have air quality and sources of contamination that exceed the levels measured in homes, businesses and schools. The sources of these contaminants have been shown to be either from activities outside the laboratory, or emitted from materials used in the facility, such as compressed gas, cleaning and sterilizing agents, plastic and stored materials. Both the laboratory structure and the air handling systems may affect the air composition. The significance of these findings is being validated by the accumulation of field case studies and now by assay procedures. Products given off by road sealant were shown to have accumulated in one of the examined laboratories, adjacent to a large re-surfaced parking area. Aldehydes such as acrolein, hexanal, decanal, pentanal and others were detected at elevated concentrations that were statistically significant. Since it is not appropriate to add potentially suspect chemicals to human embryos, we used a mouse-model to study the effect of acrolein. The growth of mouse embryos was significantly affected after acrolein was added at different concentrations to the culture environment. The physiological effect was noted at concentrations in the low ppm range. The testing end-point of embryo death must still be considered to be a crude basis for evaluating toxicological effects, since it involves addition of compounds to culture media and unprotected growth until the blastocyst stage. The findings may, however, support observations of decreased pregnancy rate following exposure of human embryos to aldehydes or other adverse conditions. With proper engineering and material selection, it is possible to reduce such contamination. The usefulness of this approach for controlling aldehydes has been demonstrated by decreasing levels in the laboratory to below those of the outside air.

Acrolein↗

Serotonergic modulation of acetylcholine release from cortex of freely moving rats.

The modulation of acetylcholine (ACh) release by 5-HT3 receptor activation was studied using in vivo microdialysis. Spontaneous and K+-stimulated ACh release were measured in frontoparietal cortex and hippocampus of freely moving rats. Two consecutive exposures to high K+ produced ACh release of similar magnitude. In the cortex, serotonin (5-HT) failed to alter spontaneous ACh release, but caused a concentration-dependent decrease of K+-evoked ACh release. Phenylbiguanide (PBG) and m-chlorophenylbiguanide, two selective 5-HT3 agonists, mimicked the 5-HT responses, but 8-hydroxy-2-(di-n-propylamino)tetralin, a selective 5-HT1A agonist, was without effect. However, PBG failed to modify K+-evoked ACh release from the hippocampus. Systemic and local administration of a highly selective 5-HT3 antagonist, tropisetron ((3-alpha-tropanyl)1H-indole-carboxylic acid ester) blocked the effect of both 5-HT and PBG. The inhibition of ACh release by PBG was sensitive to tetrodotoxin. These observations provide direct evidence that, in rat cortex, 5-HT modulates in-vivo release of ACh through activation of 5-HT3 receptors.

Acetylcholine↗

[Prostatic endoprosthesis in the treatment of prostatic obstruction: preliminary experience with the new Trestle model].

The urethral stent is a relatively new treatment modality for benign prostatic hypertrophy ostruction. Although the ultimate prostatic endoprosthesis has yet to be developed, various stents have been produced and investigated with good results. We review the several currently available stents and we report the preliminary clinical experience with a new device (Trestle).

Catheterization↗

Painless treatment of hydrocele: EMLA cream anaesthesia and fibrin adhesive sclerotherapy.

Sclerotherapy for hydroceles was performed in 18 patients. Cutaneous anaesthesia was induced with an anaesthetic cream (lidocaine and prilocaine, EMLA cream) and a fibrin sealant (Tissucol) was injected into the sac after fluid aspiration. Patients experienced no pain during needle insertion and sclerosant procedure; 2 recurrences were observed during follow-up. EMLA cream anaesthesia and fibrin adhesive sclerotherapy represent a useful alternative to surgical treatment of hydroceles.

Aged↗

Bladder replacement with modified Studer pouch using absorbable staples.

The use of absorbable staples may allow to reduce the operating time of orthotopic bladder replacement. We report our experience in 14 patients with a modification of the Studer technique using absorbable PolyGIA instruments. The technique has been shown to be simple and quick to perform (time for pouch creation 15-40 minutes, mean 16 minutes) with no significant intraoperative difficulties. Urodynamic data and continence are satisfactory and seem comparable to different procedures and not related to staples' use. The main question remains if the reduced operating time equalizes the high cost of staple devices.

Absorption↗