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Biomedical subjects

C Penna

Publications and source records attributed to C Penna.

At least 55 records · Page 3Linked to original sources

Surgical treatment of severe duodenal polyposis in familial adenomatous polyposis.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) are at risk for adenomas and cancers in the duodenum but the ideal management of duodenal polyposis remains uncertain. METHODS: The outcome of surgical resection was analysed in 18 patients with FAP who had severe duodenal polyposis. RESULTS: Duodenotomy and clearance of duodenal adenomas was performed seven times in six patients. There were two duodenal leaks and, after a mean follow-up of 53 (range 36-72) months, duodenal adenomas recurred in all patients and five had severe polyposis. Pancreatoduodenectomy was performed in seven patients with severe duodenal polyposis. Histology of the specimens revealed two unsuspected duodenal carcinomas at an early stage. After a mean follow-up of 42 months all patients were alive and well, and there was no case of jejunal polyposis. Pancreatoduodenectomy was attempted in five patients with duodenal cancer and only one survived more than 4 years. CONCLUSION: Surgical excision of duodenal adenomas should be discussed before carcinoma occurs. Surgical polypectomy fails to guarantee a polyp-free duodenum and carries a risk of postoperative complications whereas pancreatoduodenectomy eliminates the risk of duodenal cancer with an acceptable morbidity rate. Pancreatoduodenectomy could be offered to some patients with large or multiple villous duodenal adenomas repeatedly showing severe dysplasia.

Adenoma↗

Differential effects of paclitaxel and derivatives on guinea pig isolated heart and papillary muscle.

Paclitaxel (Taxol) is an anticancer agent with clinical activity against various human cancer types. Paclitaxel blocks cell division by stabilizing microtubules, a mechanism that also underlies its major side effects (neutropenia and neurotoxicity). Paclitaxel can also alter cardiac function, and to elucidate the mechanism of this activity, we tested the mechanical and electrical effects of paclitaxel and a series of analogs (docetaxel, taxol B, taxol C and N-methyltaxol C; 5-20 microM) on two different cardiac preparations, the isolated coronary perfused heart and the papillary muscle of the guinea pig. Paclitaxel and N-methyltaxol C induced conduction arrhythmias and reduced coronary flow and left ventricular systolic pressure in the isolated heart, whereas the other taxol derivatives tested had no significant effect. Moreover, paclitaxel blocked the vasodilator effect of bradykinin in the isolated heart. Paclitaxel and N-methyltaxol C produced a positive inotropic effect in papillary muscle, without alterations in the action potential. In the latter preparation, no significant variations were observed after treatment with the other taxol derivatives. The in vitro cardiodepressant and arrhythmogenic activity of paclitaxel is similar to that reported after its clinical administration and might be due to coronary vasoconstriction. The precise role of microtubules as modulators of intracellular calcium in cardiac and smooth muscle cells is at present unclear, because docetaxel and other taxol analogs, though they exhibited similar activity on tubulin, lacked cardiac effects.

Action Potentials↗

Femorodistal bypass using cryopreserved venous allografts for limb salvage.

Critical ischemia due to extensive femoropopliteal occlusive disease often leads to amputation in patients in whom an autologous vein is unavailable for reconstruction. The purpose of this nonrandomized prospective study is to evaluate the usefulness of cryopreserved venous allografts (CPVA) as an arterial substitute in these cases. Between October 1990 and March 1993, long bypass to a tibial or a foot artery using a CPVA was performed in 25 consecutive patients with ulcerations or gangrene. There were 19 women and six men with a mean age of 72 years (range: 51-90). The indication for allograft reconstruction was absence (17 cases) or unsuitability (eight cases) of an autologous vein graft. Greater saphenous vein allografts were harvested from multiple organ donors and frozen at -80 degrees C with 12% dimethylsulfoxide (DMSO). Sixteen patients had undergone one or more previous unsuccessful limb salvage attempts. The plantar arch was absent or incomplete in 16 patients (64%). Patients were followed up prospectively for a mean of 21 months (range: 3-32). One patient died early (32 days) and three patients died late with patent bypasses. Cumulative survival rate was 77% at 1 year and 72% at 2 years. Cumulative secondary patency rate (Kaplan-Meier) was 88% at 1 months, 72% at 6 months, and 52% at 1 year. The cumulative limb salvage rate was 78% at 2 years. When an autologous vein is unavailable, long bypass using a CPVA is a simple, quick, minimally traumatic, economical, and effective method to achieve limb salvage in patients with severe distal arterial occlusive disease. However, CPVA causes immunoreaction and there is a risk of proximal postanastomotic stenosis. Doppler ultrasound surveillance of a subcutaneous graft allows accurate assessment and repair of the abnormalities with no increase in mortality or morbidity.

Aged↗

[Colorectal cavernous hemangiomatosis treated by total coloproctectomy and ileo-anal anastomosis].

A diffuse cavernous hemangioma of the colon and rectum was made in a 20-year-old man. Treatment consisted of total colectomy with ileorectostomy. A proctectomy was mandatory four years later because of massive rectal bleeding. A sphincter-saving operation was possible and bowel continuity was restored with an ileal "J" pouch-anal anastomosis. Cavernous hemangioma generally affects the rectosigmoid and colo-anal sleeve anastomosis is the treatment of choice. When cavernous hemangioma affects the colon and rectum or when the colon has been removed for an other reason, an ileo-anal anastomosis, although technically difficult, can be performed in order to prevent recurrent bleeding while preserving continence and allowing acceptable bowel function.

Adult↗

[Hemorrhagic ascites disclosing massive Fasciola hepatica infection].

Multi-organ infection with Fasciola hepatica is uncommon. We report a case of severe infection with Fasciola hepatica as a cause of liver and peritoneum injuries with hemorrhagic ascites as well as pulmonary, pericardial, splenic and portal system injuries in a 37-year old man who was a native of Green Cape. The patient was in poor general health, had a major inflammatory syndrome, and polyclonal hypergammaglobulinemia (90 g/L). The diagnosis was confirmed by positive distomatosis serology and the presence of eggs of Fasciola hepatica in the histological samples of the liver and peritoneum. After treatment with praziquantel then triclabendazole, the global outcome was favorable.

Adult↗

Pulmonary metastases neutralization and tumor rejection by in vivo administration of beta glucan and bispecific antibody.

Bispecific antibody (BsAb) with specificity for tumor cell surface antigen and the CD3 molecule on T cells can redirect activated T cells to lyse tumor cells. Since the ex vivo expansion and activation of T cells is impractical and ineffective for treating established tumors, we tested whether the immune stimulant beta glucan could in situ-activate T cells, which could secondarily be retargeted with BsAbs to lyse tumor cells. To test for tumor neutralization, C3H/HeN mice were injected i.v. with Cl-62 melanoma cells and immediately treated with i.p. beta glucan and/or anti-CD3 (500A2) x anti-p97 (96.5) F(ab')2 BsAb i.v. Pulmonary metastases were counted 14 days later. To test for tumor rejection and survival in a solid tumor model, mice were injected s.c. and i.p. with Cl-62 cells and 7 days later administered beta glucan i.p. and/or F(ab')2 BsAb i.v. In the neutralization model, there was a significant reduction in the number of metastases in the beta glucan + BsAb group, as compared with controls, and with beta glucan alone. In the established tumor model, beta glucan + BsAb reduced the incidence of s.c. tumors as compared with control, with BsAb alone and with beta glucan alone. It also prolonged survival of tumor-bearing mice compared with control, BsAb alone and beta glucan alone. We conclude that T cells can be activated in vivo by beta glucan and retargeted with F(ab')2 BsAb.

Adjuvants, Immunologic↗

Pouch-related fistula following restorative proctocolectomy.

Prognostic factors and outcome of pouch-related fistula were analysed from a series of 21 patients, 20 of whom had an ileal J pouch manually anastomosed to the dentate line following mucosectomy. Fistula occurred more often after pouch formation for ulcerative colitis than for familial adenomatous polyposis. In 6 patients the fistula occurred more than 5 months after closure of the diverting loop ileostomy. The origin of the leak was the anastomosis in 14 patients, the vertical staple line in two and the end of the efferent limb in five. Nine forms of treatment were utilized and these were successful in 11 patients and unsuccessful in ten including three pouch excisions. Adverse prognostic factors were late fistula, the presence of an enterocutaneous or a pouch-vaginal fistula track, and diagnosed or suspected Crohn's disease. Resolution of the fistula followed none of six diverting loop ileostomies performed alone, three of 33 attempted drainage procedures, four of ten direct closures, and four of five repeat ileal pouch-anal anastomoses. It is concluded that an aggressive therapeutic approach using repeat ileal pouch-anal anastomosis increases the success rate.

Adenomatous Polyposis Coli↗

Effects of yew alkaloids and related compounds on guinea-pig isolated perfused heart and papillary muscle.

The mechanical and electrical effects of selected yew alkaloids were studied on two different cardiac preparations: the isolated coronary perfused heart and the isolated papillary muscle of the guinea-pig. In the isolated heart, the Winterstein acid type alkaloids 1, 2 and 3 induced electrical and mechanical effects similar to those reported after yew intoxication (negative inotropic effect, block of atrio-ventricular conduction), but the coronary flow was unchanged. Taxine B (1), the most potent compound of this group, reduced cardiac contractility and the maximum rate of depolarisation of the action potential in the isolated papillary muscle, acting as a class I antiarrhythmic drug. In the isolated heart, the cinnamates 4 and 5, corresponding to the degradation products of 1 and 3, exerted arrhythmogenic effect due to a reduction of coronary flow. No alterations in electrical and contractile activities were in fact recorded after perfusion of the isolated papillary muscle with 4. Taxine A (6) and the taxane alcohol 7, corresponding to the terpenoid core of 3 had no significant cardiac effect. Our results suggest that the poisonous properties of the yew tree are probably due to the combined activity of alkaloids of the Winterstein acid type and their corresponding cinnamtes, which can reduce both the excitability and the coronary flow of the heart.

Alkaloids↗

Locoregional chemotherapy for adjuvant treatment of colorectal adenocarcinoma.

Adjuvant chemotherapy with 5-fluorouracil (5-FU) and levamisole administered intravenously for 1 year has proved to be effective after curative surgical resection of Dukes' stage C colon carcinomas. Locoregional chemotherapy aims at delivering drugs directly into the abdominal cavity or the liver using either intraperitoneal or intraportal route of administration. Theoretically, these routes of administration have several advantages. The drugs can be delivered at a high dose concentration to the most common site of recurrence (i.e. peritoneum and liver) with decreased systemic toxicity. This article reviews the present status of intraportal and intraperitoneal chemotherapy as adjuvant postoperative treatment for colorectal carcinoma with special attention to the results of prospective randomised trials. Some positive results confirm that both route of administration represent promising methods for adjuvant chemotherapy. However, currently there are insufficient data on which to make a clear-cut conclusion on real benefits. New trials are currently in progress to test new modalities using different drugs or different drug combinations, using both locoregional and systemic treatments, and may prove to be more effective than systemic chemotherapy alone in the adjuvant treatment of colorectal cancers.

Adenocarcinoma↗

Pouchitis after ileal pouch-anal anastomosis for ulcerative colitis occurs with increased frequency in patients with associated primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC), present in 5% of patients with ulcerative colitis, may be associated with pouchitis after ileal pouch-anal anastomosis. The cumulative frequency of pouchitis in patients with and without PSC who underwent ileal pouch-anal anastomosis for ulcerative colitis was determined. A total of 1097 patients who had an ileal pouch-anal anastomosis for ulcerative colitis, 54 with associated PSC, were studied. Pouchitis was defined by clinical criteria in all patients and by clinical, endoscopic, and histological criteria in 83% of PSC patients and 85% of their matched controls. PSC was defined by clinical, radiological, and pathological findings. One or more episodes of pouchitis occurred in 32% of patients without PSC and 63% of patients with PSC. The cumulative risk of pouchitis at one, two, five, and 10 years after ileal pouch-anal anastomosis was 15.5%, 22.5%, 36%, and 45.5% for the patients without PSC and 22%, 43%, 61%, and 79% for the patients with PSC. In the PSC group, the risk of pouchitis was not related to the severity of liver disease. In conclusion, the strong correlation between PSC and pouchitis suggest a common link in their pathogenesis.

Adolescent↗

Solitary fibrous tumor of the adrenal gland.

Solitary fibrous tumors are rare neoplasms, most commonly involving the pleura, recently described in various other locations. We report a solitary fibrous tumor of the right adrenal gland in a 42-year-old woman, discovered incidentally during abdominopelvic ultrasonographic examination. Pathologic and immunohistologic features of the tumor were identical to those of other solitary fibrous tumors. Three-quarters of this unencapsulated infiltrating tumoral mass presented foci of hemorrhage and were made of small, round, epithelioid-like cells that expressed the CD34 antigen more weakly than do the typical spindle cells usually observed in solitary fibrous tumors. Despite hemorrhage and poor limitation, the tumor behaved in a innocuous manner; the mass remaining unchanged for more than 5 years before the patient agreed to surgical intervention, which was recommended because of a sudden enlargement of the mass.

Adrenal Gland Neoplasms↗

Bifunctional antibody retargeting in vivo-activated T lymphocytes: simplifying clinical application.

For antitumor x anti-CD3 bifunctional antibody (BFA) therapy to be clinically relevant in solid tumors, activated lymphocytes must be present within tumors. Toward that end, three uniquely different in vivo activation approaches were investigated in a p97 human antigen expressing syngeneic murine melanoma model. beta-Glucan (200 micrograms), staphylococcal enterotoxin B (SEB) (50 micrograms), and F(ab')2 BFA (10 micrograms) were tested for their ability to activate lymphocytes, neutralize pulmonary metastases, and treat established tumors. Systemic activation, measured as the ability of splenocytes to lyse tumor cells in vitro in the presence of BFA, was enhanced by the in vivo administration of SEB but not by beta-glucan or F(ab')2 BFA. Despite lacking a systemic effect, F(ab')2 BFA increased both direct and BFA-mediated cytotoxicity in fresh tumor infiltrating lymphocytes. beta-Glucan did not increase systemic or intratumor T cell activation. However, it significantly enhanced the ability of splenocytes to lyse NK-sensitive YAC-1 cells. When tested in a pulmonary metastases model, all three forms of immune modulation combined with F(ab')2 BFA significantly reduced the number of metastases. BFA were more effective at tumor neutralization when combined with SEB compared with adoptively transferred, in vitro-activated splenocytes. These studies demonstrate that immune modulators when combined with F(ab')2 BFA can provide effective antitumor therapy. Several clinical obstacles may be overcome by the application of these reagents.

Animals↗