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Biomedical subjects

C Penna

Publications and source records attributed to C Penna.

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

Surgical management of hepatic metastases from colorectal malignancies.

Liver metastasis represents the major cause of death of patients who have been treated for colorectal adenocarcinoma. Spontaneous survival rarely exceeds two years. Surgery can offer long-term survival and resection should be considered when liver metastases can be totally resected with clear margins and when there is no non-resectable extra-hepatic disease. The choice between anatomical or wedge resection depends on the number and the location of the metastases but does not influence survival. Clamping methods limit blood loss. Operative mortality is generally less than 5%. The five-year survival rate after surgical resection varies from 20% to 45% according to several prognostic factors. The longer survival is observed in patients with fewer than four lesions, with lesions smaller than 4 cm, without extra-hepatic disease, with lesions that appeared more than two years after the resection of a stage I or II colorectal cancer and whose CEA level is normal. After resection, follow-up can detect hepatic recurrence that can be treated with repeat hepatectomy. The efficacy of systemic chemotherapy using new agents can increase the number of patients amenable to surgery. Regional therapies with cryotherapy or radiofrequency ablation can help to treat unresectable or non-totally resectable lesions and may improve survival. The effects on survival of adjuvant treatments, including pre- or postoperative systemic or postoperative intra-arterial chemotherapy, are currently under evaluation.

Adenocarcinoma↗
PubMed2001

Cytochrome P-450 metabolite of arachidonic acid mediates bradykinin-induced negative inotropic effect.

This study focused on the mechanisms of the negative inotropic response to bradykinin (BK) in isolated rat hearts perfused at constant flow. BK (100 nM) significantly reduced developed left ventricular pressure (LVP) and the maximal derivative of systolic LVP by 20-22%. The cytochrome P-450 (CYP) inhibitors 1-aminobenzotriazole (1 mM and 100 microM) or proadifen (5 microM) abolished the cardiodepression by BK, which was not affected by nitric oxide and cyclooxygenase inhibitors (35 microM NG-nitro-L-arginine methyl ester and 10 microM indomethacin, respectively). The CYP metabolite 14,15-epoxyeicosatrienoic acid (14,15-EET; 50 ng/ml) produced effects similar to those of BK in terms of the reduction in contractility. After the coronary endothelium was made dysfunctional by Triton X-100 (0.5 microl), the BK-induced negative inotropic effect was completely abolished, whereas the 14,15-EET-induced cardiodepression was not affected. In hearts with normal endothelium, after recovery from 14,15-EET effects, BK reduced developed LVP to a 35% greater extent than BK in the control. In conclusion, CYP inhibition or endothelial dysfunction prevents BK from causing cardiodepression, suggesting that, in the rat heart, endothelial CYP products mediate the negative inotropic effect of BK. One of these mediators appears to be 14,15-EET.

8,11,14-Eicosatrienoic Acid↗
PubMed2000

Role of NO and PAF in the impairment of skeletal muscle contractility induced by TNF-alpha.

The role of platelet-activating factor (PAF) and nitric oxide (NO) as mediators of the effects of tumor necrosis factor-alpha (TNF-alpha) on skeletal muscle contractility was studied in guinea pig extensor digitorum longus (EDL) muscle. TNF-alpha (5-10 ng/ml) reduced contractility at every stimulation frequency (1-200 Hz) and shifted the force-frequency relationship to the right. The role of NO and PAF as mediators of TNF-alpha was suggested by the protective effect of N(G)-nitro-L-arginine methyl ester (L-NAME; 1 mM), but not of N(G)-nitro-D-arginine methyl ester (D-NAME; 1 mM), and by the inhibitory effect of the PAF-receptor antagonist WEB-2170 (3 microM). TNF-alpha increased the production of PAF and NO. Similar to TNF-alpha, both S-nitroso-N-acetylpenicillamine (0.5-1 microM), an NO-generating compound, and PAF (10-20 nM) reduced EDL contractility. L-NAME, but not D-NAME, blocked the negative effect of PAF. Blockade of phospholipase A(2), which is required for PAF synthesis, significantly reduced the effects of TNF-alpha. WEB-2170 inhibited NO synthesis induced by TNF-alpha and PAF-stimulated NO production. These results suggest that both PAF and NO contribute to the development of the mechanical alterations induced by TNF-alpha and that NO production is downstream to the synthesis of PAF.

Animals↗
PubMed2000

Pattern of susceptibility to measles in Italy. Serological Study Group.

On the basis of seroprevalence and incidence data we describe the distribution of individuals susceptible and immune to measles in Italy in 1996-97. In regions where vaccination coverage was at least 70%, approximately 10% of 3-year-old children were susceptible to measles, whereas 40% were in this category in regions with lower vaccination coverage. Seroprevalence among children older than 4 years was similar for the two groups of regions; in the age group 20-39 years it was approximately 95%. During 1990-96 in the regions with lower vaccination coverage the incidence was highest among children aged 4-6 years, and the median age of cases was 7 years; in the regions with higher vaccination coverage, however, the incidence remained at around 5% for the age group 4-16 years, and the overall median age was 10 years. These data confirm the partial reduction in measles incidence in Italy, although transmission has still not been interrupted. The size and geographical distribution of the current pool of susceptible individuals can be expected to present an obstacle to measles elimination if appropriate vaccination strategies, such as catch-up campaigns, are not adopted.

Adolescent↗
PubMed1999

Role of nitric oxide and platelet-activating factor in cardiac alterations induced by tumor necrosis factor-alpha in the guinea-pig papillary muscle.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine with negative inotropic properties, is implicated in several pathophysiological events. To clarify the mechanism of action of TNF-alpha on myocardium, we investigated the possible role of platelet-activating factor (PAF) and nitric oxide (NO) as secondary mediators of the depressant effect of this cytokine. METHODS: Isometric twitches and intracellular action potentials were recorded from guinea pig papillary muscles. The effects of TNF-alpha (1-10 ng/ml) were studied in controlled conditions and after treatment with 0.5% Triton X-100, to destroy the endocardial endothelium NG-nitro-L-arginine methyl ester (L-NAME), D-NAME (1 mM) and the two different PAF-receptor antagonists WEB 2170 (3 microM) and CV 3988 (5 microM) were used to study the role of NO and PAF in cardiac depression induced by TNF-alpha. To study the role of NO in cardiac alterations induced by PAF, papillary muscles were pretreated with L-NAME or D-NAME and then challenged with PAF (0.1-1 microM). Nitrite production by papillary muscles challenged with TNF-alpha alone. TNF-alpha in the presence of WEB 2170 or CV 3988, or PAF was studied with the Greiss reagent method. PAF production by papillary muscles stimulated by TNF-alpha was studied by a bioassay method. RESULTS: TNF-alpha induced an initial, transient positive inotropic effect, then reduced the contractility and the action potential duration in a concentration-dependent manner. Treatment of papillary muscle with Triton X-100 did not modify the response to TNF-alpha, suggesting that the effect of TNF-alpha is not mediated by endocardial endothelial cells. Pretreatment with indomethacin reduced the negative effect of TNF-alpha, while propranolol abolished the initial increase of contractility. The role of PAF and NO as mediators of TNF-alpha was suggested by: (1) the protective effect of L-NAME, but not of D-NAME, on electrical and mechanical alterations; (2) the stimulatory effect of TNF-alpha on nitrite production; (3) the inhibitory effect of WEB 2170 and CV 3988, on both the electromechanical alterations and the nitrite production; (4) the synthesis of PAF induced by TNF-alpha. L-NAME blocked the negative effect of PAF and PAF enhanced nitrite production by papillary muscle. CONCLUSIONS: The present results suggest that in cardiac muscle: (1) the release of PAF triggered by TNF-alpha may account for the stimulation of NO production; (2) both PAF and NO contribute to the development of the electrical and mechanical alterations induced by TNF-alpha; (3) NO production was down-stream to the synthesis of PAF.

Action Potentials↗
PubMed1999

The effects of ischemic preconditioning on resting coronary flow and reactive hyperemia: involvement of A1 adenosine receptors.

During the myocardial protection induced by ischemic preconditioning a reduction in myocardial metabolism occurs due to activation of the A1 adenosine receptors. This study investigates whether preconditioning changes both resting coronary flow and the magnitude of coronary reactive hyperemia and whether A1 adenosine receptors are involved in the observed changes. Experiments were performed in 14 goats (30-50 kg body weight). After the animals were anesthetized with ketamine, an electromagnetic flow-probe was used to record blood flow in the left circumflex coronary artery. Distal to the probe, an occluder was placed to produce ischemic preconditioning and reactive hyperemia. Preconditioning was obtained with two periods of 2.5 min of coronary occlusion separated from each other by 5 min of reperfusion. Coronary reactive hyperemia was obtained with 15 s of occlusion of the artery before and after preconditioning. In a group of goats before preconditioning 0.2 mg kg(-1) of 8-cyclopentyl-dipropylxanthine (CPX), an A1 adenosine receptor blocker, were given intravenously. In all animals ischemic preconditioning did not alter resting coronary flow, but, in the absence of A1 adenosine receptor blockade, reduced the reactive hyperemic response. The total hyperemic flow and the excess/debt flow ratio were reduced by about 25% and 30% respectively. The A1 adenosine receptor blockade "per se" did not cause any change in the resting flow and in the parameters of the reactive hyperemia. Unlike what observed in the absence of blockade, after CPX ischemic preconditioning was unable to reduce total hyperemic flow and the excess/debt flow ratio. The results suggest that ischemic preconditioning reduces the coronary hyperemic response by decreasing the myocardial metabolism through the activation of the A1 adenosine receptors.

Adenosine Triphosphate↗
PubMed1999

Restorative proctocolectomy for distal ulcerative colitis.

BACKGROUND: Chronic distal colitis may cause troublesome symptoms and alter quality of life. When medical treatment fails to control symptoms, patients and doctors are often reluctant to consider surgical resection because of the relatively small portion of the large bowel affected by the disease. AIM: To assess the outcome of restorative proctocolectomy (RP) in patients with distal colitis who required surgery for chronic debilitating symptoms and failed medical management. PATIENTS/METHODS: From 1986 to 1996, of 263 patients receiving RP for ulcerative colitis, 27 (16 men) were operated on for distal ulcerative colitis limited to the rectum and sigmoid colon. Bowel function and quality of life were compared before and one year after RP. RESULTS: The mean (SD) duration of ulcerative colitis was 11 (6) years. RP was performed at a mean age of 46 (10) years. All the pouches were J-shaped, and a diverting loop ileostomy was always performed. Mean (SD) hospital stay was 25 (10) days. Seven complications occurred in six patients. Previously unknown severe dysplasia was discovered on the colectomy specimen in two patients. After RP there was a significant decrease in mean (SD) daytime stool frequency (8.2 (4) v 4.7 (2), p<0.05), night-time stool frequency (2 (2) v 1 (1), p = 0.05), and the number of patients with urgency to defecate (26/27 v 1/27, p<0.001). Sex life was improved in eight patients, social life in 26, and professional life in eight. Twenty six patients were satisfied with the results, and 25 wished that they had received surgery earlier in the course of their disease. CONCLUSION: RP can improve bowel function and quality of life in patients with disabling chronic symptoms of distal ulcerative colitis.

Adult↗
PubMed1999

[Established data and practical recommendations concerning pre- and postoperative chemotherapy of rectal cancer].

Adjuvant chemotherapy appears to be active in stage II-III rectal cancers; the NSAPB R01 trial demonstrated a survival advantage for patients receiving chemotherapy using the MOF protocol and 3 meta-analyses are in favor of the efficacy of adjuvant chemotherapy in rectal cancer. Three randomized trials have also demonstrated that combinations of radiation and chemotherapy are superior to surgery alone or adjuvant radiotherapy and demonstrated the major role of systemic chemotherapy combined with radiotherapy. However this efficacy of adjuvant chemotherapy alone or combined with radiation therapy is still debated and specific trials must be conducted to test the value of chemotherapy using more active regimens than those previously tested and taking into account the quality of surgery and radiotherapy; such trials are in progress, especially the trial conducted by the EORTC and the FFCD. The efficacy of neoadjuvant chemotherapy has never been clearly demonstrated, although a combination of radiotherapy and chemotherapy as first-line treatment for locally advanced rectal cancer and in the case of synchronous metastasis seems to facilitate surgical resection. It is a reasonable and tolerable approach with manageable toxicity which gives substantial results in 2/3 of patients. This strategy also allows better selection of patients likely to benefit from surgical resection of their primary tumor and in some cases of their synchronous metastases. However, the efficacy of perioperative treatments should not decrease the quality of the surgical resection and especially mesorectal excision as well as the need for high quality pathological examination which must be very thorough with analysis of a sufficient number of lymph nodes. The efficacy of combined treatment in advanced rectal cancers is a major argument in favor of the multidisciplinary coordination required for optimal treatment of patients with rectal cancer.

Antineoplastic Agents↗
PubMed1998

Modulation of guinea-pig cardiac L-type calcium current by nitric oxide synthase inhibitors.

1. Electrophysiological (whole-cell clamp) techniques were used to study the effect of NO synthase (NOS) inhibitors on guinea-pig ventricular calcium current (ICa), and biochemical measurements (Western blot and citrulline synthesis) were made to investigate the possible mechanisms of action. 2. The two NOS inhibitors, NG-monomethyl-L-arginine (L-NMMA, 1 mM) and NG-nitro-L-arginine (L-NNA, 1 mM), induced a rapid increase in ICa when applied to the external solution. D-NMMA (1 mM), the stereoisomer of L-NMMA, which has no effect on NOS, did not enhance ICa. 3. Western blot experiments gave no indication of the presence of inducible NOS protein (iNOS) in our cell preparation, neither immediately after dissociation nor after more than 24 h. Statistically, there was no significant difference between electrophysiological experiments performed on freshly dissociated cells and experiments performed the next day. Moreover cells prepared and kept in the presence of dexamethasone (3 microM), to inhibit the expression of iNOS, gave the same response to L-NMMA as control cells. 4. The stimulatory effect of L-NMMA (1 mM) on basal ICa was reversed by competition with higher doses (5 mM) of externally applied L-arginine, the natural substrate of NOS. The effect of L-NMMA was also eliminated by L-arginine in the patch pipette solution. 5. Intracellular perfusion with GDP beta S (0.5 mM), which stabilizes the G-proteins in the inactive state, did not affect the L-NMMA-induced stimulation of ICa. 6. Carbachol (1 microM) reduced the ICa previously stimulated by L-NMMA, and intracellular cGMP (10 microM) prevented L-NMMA enhancement. 7. Simultaneous treatment with L-NMMA and isoprenaline (1 microM) induced a non-cumulative enhancement of ICa that could not be reversed by carbachol (1 microM). 8. NO synthesis, measured by the formation of [3H]citrulline from L-[3H]arginine during a 15 min incubation, showed a relatively high basal NO production, which was inhibited by L-NMMA but not affected by carbachol. 9. These results suggest that inhibitors of NOS are able to modulate the basal ventricular ICa in the absence of a receptor-mediated pathway, and that NO might be required for the muscarinic reduction of ICa under isoprenaline stimulation, even if NO production is not directly controlled by the muscarinic pathway.

Animals↗