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Biomedical subjects

C U Casciani

Publications and source records attributed to C U Casciani.

At least 55 records · Page 3Linked to original sources
PubMed1999

Local expression of cytokines in human colorectal carcinoma: evidence of specific interleukin-6 gene expression.

The expression of cytokine mRNAs in tumor tissue, normal mucosa, and peripheral blood mononuclear cells (PBMCs) was studied in 12 patients with colorectal cancer undergoing surgical resection, to characterize local immune conditions. mRNA transcripts for interleukin (IL)-1 beta, IL-2, IL-2-R(p55), IL-4, IL-5, IL-6, and IL-10 were detected using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. IL-6 mRNA was expressed in tumor tissue in 83% of the cases but only in one case in normal mucosa (p < 0.001); serum levels of IL-6 did not show any correlation with IL-6 mRNA; IL-1 beta transcripts were present in all tumor tissue samples; no IL-4 expression was detected; IL-2 mRNA was only present in two tumors; IL-2R(p55) mRNA was found in 58% of tumors but not in normal mucosae (p = 0.005). The expression of IL-10 suggests that it does not play a central role in colorectal cancer immunosuppression, and cytokine expression in PBMCs indicates a different and independent activation. This study suggests a pattern of expression of inflammatory cytokines in the tumor microenvironment, probably produced by infiltrating immune cells. The absence of the specific immune-activating cytokines, IL-2 and IL-4, could indicate an impairment of the anticancer immune response; IL-2R results confirm the dysregulation of the IL-2/IL-2R activation pathway. These findings may lead to a better understanding of the role of cytokines and especially IL-6 at the tumor site and hence their importance in developing an effective immunotherapy.

Aged↗
PubMed1999

Activation of 5-lipoxygenase and related cell membrane lipoperoxidation in hemodialysis patients.

Lipid peroxidation was shown at the membrane level in peripheral blood cells of patients hemodialyzed on cuprophan dialyzers, and was mainly attributable to the generation of conjugated hydroperoxides in the lipid bilayer. The oxidative index (i.e., the A234/205 ratio) of membrane lipids was 3.2-fold higher in hemodialysis patients than in healthy control subjects, and also the level of leukotriene B4 was significantly increased (up to 1.7-fold over control). Both membrane peroxidation and release of leukotriene B4 were linked to upregulation of 5-lipoxygenase activity (up to 2.4-fold over control) and expression at the protein level (up to 1.9-fold). Vitamin E, the most important lipophilic antioxidant, prevented both membrane peroxidation and release of leukotriene B4 by inhibiting 5-lipoxygenase activity without affecting enzyme expression. Similar results were observed in patients hemodialyzed on polymethylmetacrylate membranes, but in this case the activation of 5-lipoxygenase was less pronounced. The use of a purified 5-lipoxygenase demonstrated that vitamin E was a reversible inhibitor of enzyme activity (IC50 = 35 +/- 4 microM), further characterized as noncompetitive (Ki = 30 +/- 3 microM). Taken together, the results reported here shed some light on the mechanism responsible for the oxidative damage in hemodialysis. Moreover, the beneficial effect of vitamin E described here may have relevance for the therapy of patients with kidney disease.

Arachidonate 5-Lipoxygenase↗
PubMed1999

[The endorectal repair of rectovaginal fistulae].

BACKGROUND: Twenty-one patients who had simple rectovaginal fistulas were treated at the Surgical Department of "Tor Vergata" University from 1992 to 1996 all of whom were at the first approach. METHODS: The fistulas were treated with complete excision of the external tract and primary closure of the internal opening with advancement of a rectal mucosal flap, distal to the origin fistulas opening. The vaginal side is left open for drainage. RESULTS: Eighteen of the twenty-one patients had good results; three patients required reoperation for recurrences; all of them had satisfactory results. CONCLUSIONS: The advancement flap technique was very useful for simple rectovaginal fistulas with any sphincter damage, and it is very well tolerated by patients.

Adult↗
PubMed1999

Red blood cell membrane lipid peroxidation and resistance to erythropoietin therapy in hemodialysis patients.

BACKGROUND: Chronic hemolysis, inadequate production of erythropoietin (EPO) or an impaired response of erythroid stem cells to EPO are the main factors of anemia in end-stage renal disease (ESRD) patients. Oxidative damage of red blood cell (RBC) membrane is a well-established cause of chronic hemolysis in hemodialysis (HD) patients. Administration of high-dose recombinant human EPO (rHuEPO) fails to correct anemia in 5 to 10% HD patients although all established factors of resistance to rHuEPO therapy have been previously ruled out or corrected. PATIENTS AND METHODS: We investigated the degree of RBC membrane oxidative damage in 9 HD patients who failed to respond to maximal rHuEPO administration (more than 200 UI/Kg weekly for 4 months consecutively, group A), compared to 10 patients who showed a good response to standard rHuEPO therapy (group B) and to 10 patients who needed no treatment (group C). RBC malondialdehyde (MDA) was assumed as the index of oxidative stress in erythrocyte membrane. RESULTS: No significant difference in erythrocyte MCV and MCHC, iron status, parathyroid function, aluminum and dialysis-related blood loss was observed between patients of group A, B and C. RBC MDA, reticulocyte count, plasma-free hemoglobin (fhb) and serum lactate dehydrogenase (LDH) were significantly higher while plasma haptoglobin was significantly lower in patients of group A compared to patients of groups B and C. Moreover, a significant inverse relationship was observed between RBC MDA and either plasma hemoglobin, RBC count and hematocrit when all patients were evaluated together. CONCLUSION: In conclusion, increased oxidative damage of RBC membrane is often detectable in HD patients who fail to respond to rHuEPO administration even in the absence of all established factors of resistance to EPO. Peripheral response to rHuEPO may be normal in these patients and persistent anemia may be related to enhanced hemolysis due to oxidative stress. Oxidative damage itself may therefore be considered a factor of resistance to EPO.

Anemia↗
PubMed1998

Novel clinical approaches in monoclonal antibody-based management in colorectal cancer patients: radioimmunoguided surgery and antigen augmentation.

Surgery, the most effective treatment for colon and rectal cancer, is based on empirical knowledge of the patterns of tumor spread, gross findings at laparotomy, and histologic confirmation of tumor-free margins. In spite of the many technical improvements in surgery, there has not been a significant change in cure rates for colon and rectal cancers. In fact, one-half of affected patients will not survive 5 years. It is in this arena of treatment for primary colon and rectal cancer patients that radioimmunoguided surgery (RIGS) technology may provide the most benefit. RIGS is an intraoperative procedure for detection of carcinoma lesions that are targeted with a radiolabeled monoclonal antibody (MAb) to provide the surgeon with immediate intraoperative definition of tumor margins and identification of occult disease. To optimize this technique, our studies were designed to increase tumor uptake by higher affinity CC-49 (a second-generation MAb) and to increase tumor antigen expression using biological response modifiers (BRMs). The ability of BRMs, such as interferons (IFNs), to enhance the expression of tumor-associated antigens, may play an important role in an adjuvant setting for MAb-based treatment. Preclinical and clinical data provided evidence for the use of IFN as an adjuvant to enhance MAb-targeting of human carcinoma lesions. A combination protocol with IFN and RIGS is ongoing at our institution.

Antibodies, Monoclonal↗
PubMed1998

Hepatic steatosis: a specific sign of hepatitis C reinfection after liver transplantation.

Hepatitis C virus (HCV) infection is one of the major causes leading to orthotopic liver transplantation (OLT) worldwide. Although viral infection persists in almost all patients, the pathology of recurrent HCV infection after OLT is not well characterized. To address this issue, we compared the pathological findings of 28 patients who underwent transplantation for HCV-related cirrhosis (group A, aged 47 +/- 15 years; 23 men, 5 women) with those of 21 patients who underwent transplantation for nonviral indications (group B, aged 45 +/- 21 years; 13 men, 8 women) during the first year after transplantation. Patients from group A were assessed for serum HCV RNA by 5' untranslated region nested polymerase chain reaction before and 1 year after OLT. Patients underwent protocol liver biopsies 3 months and 1 year after transplantation. Group A patients more frequently had histological evidence of hepatic steatosis than group B patients, both at 3 months (P = .003) and 1 year (P = .003) after OLT. Fibrosis and portal inflammation were statistically more frequent in group A 1 year after transplantation. The sensitivity of steatosis in detecting histological disease recurrence was 100% at 3 months and 94% at 1 year; the specificity was 40% and 60%, respectively. Conversely, steatosis was 100% specific in detecting viral recurrence, with a sensitivity of 89%. The 1-year actuarial incidence of abnormal transaminase levels was 52% in group A and 13% in group B (P = .05). No biochemical or histological differences between patients infected with genotype 1b and patients with other HCV genotypes were found. Hepatic steatosis is a specific sign of viral recurrence after liver transplantation and a less specific sign of disease recurrence. HCV-infected liver transplant recipients often develop abnormal transaminase levels and liver fibrosis 1 year after OLT; these features are unrelated to HCV genotypes.

Adult↗
PubMed1998

Immunosuppression without prednisone after liver transplantion is safe and associated with normal early graft function: preliminary results of a randomized study.

Prednisone has been commonly considered the mainstay of immunosuppressive therapy after liver transplantation. Recent data suggest that prednisone withdrawal late after transplant reduces complications without affecting graft function. We report here the preliminary results of an open-label, randomized study aimed at investigating whether prednisone therapy can be completely avoided during the first 3 months after transplantation. Twenty-seven consecutive patients were randomized to receive double (group A: cyclosporine and azathioprine) or triple (group B: prednisone, cyclosporine, and azathioprine) immunosuppressive therapy after liver transplantation. Six patients died within the first 3 weeks in each group and were excluded from the calculations. The present results refer to 10 patients in group A and 11 in group B. The actuarial 1-year survival did not differ between the two groups (90.9% vs 88.8%). There were no differences with respect to infectious complications or episodes of histological acute graft rejections. Only one severe acute rejection occurred in group A and two in group B. During the first month after transplant, liver and kidney functions tended to be better in the group of patients treated without prednisone, although there were no differences in the mean cyclosporine blood levels. These data, though preliminary, indicate that early immunosuppression without the use of prednisone is safe and tends to be associated with improved liver and renal functions compared to conventional triple therapy.

Adult↗
PubMed1998

The significance of an increase in soluble interleukin-2 receptor level in colorectal cancer and its biological regulating role in the physiological switching of the immune response cytokine network from TH1 to TH2 and back.

Current research has still not clarified the biological role of soluble interleukin(IL)-2 receptor (sIL-2R) and the significance of its increase in the serum of colon cancer patients compared to healthy subjects. To address these questions at the immunological level in a group of patients and healthy subjects, we determined the sIL-2R level in the serum and its release from peripheral blood mononuclear cells (PBMC) as a function of tumour necrosis factor (TNF) alpha, IL-1 alpha, IL-1 beta, IL-2, interferon (IFN) gamma, IL-4, IL-6 and IL-10 levels in the serum and PBMC production; and PBMC proliferative responses to IL-2, IL-4 and anti-CD3 monoclonal antibody (CD3), variously combined. The level of sIL-2R in patients' serum was higher than in healthy subjects and correlated with the stage of advancement. Moreover, while in healthy subjects the serum level of sIL-2R was not significantly correlated with other parameters, in patients it was positively related to IL-4, IL-6 and IL-10 serum levels, PBMC IL-4 production and to the PBMC proliferative response to CD3 and CD3 + IL-2; it was negatively correlated to IL-2 serum level and IL-1 beta PBMC release. A negative connection between IFN gamma serum level and the PBMC production of sIL-2R was also found. This suggests that the increase of sIL-2R in the serum of patients, compared to healthy subjects, is involved in the inappropriate expansion of the T helper (TH2) suppressive immune response, which we previously reported. The multivariate statistical method supported the above suggestions and we also found that, in healthy subjects, the up- and down-regulation of sIL-2R in the serum within the physiological ranges seems to have a regulating role in the relationships between TNF alpha, IFN gamma and IL-4, IL-6, contributing to the operation of the cytokine network between TH1 and TH2 cells. However, in patients compared to healthy subjects the increased sIL-2R serum level seems to direct the immune response towards a suppressive type, which may be due to an alteration in the above-mentioned physiological regulating role.

Adult↗
PubMed1998

Rhomboid flap procedure for pilonidal sinus: results from 67 cases.

Sixty-seven patients with chronic pilonidal sinuses were treated by excision and rhomboid flap transposition (RFT). Primary healing was obtained in all patients except two who developed a seroma and one who had a partial dehiscence of the surgical wound due to a hematoma, which necessitated drainage through the margin of the flap. The average stay was 5.3 days (range 1-16). All patients returned to normal activities within 2 weeks of surgery. No late recurrence occurred after a mean follow-up of 74.4 months (range 8-137).

Adolescent↗
PubMed1998

Plasmapheresis in severe forms of myasthenia gravis.

In this study we introduce a new combination treatment of plasma exchange (PE) and high daily doses of prednisone for severe forms of myasthenia gravis (MG). The clinical efficacy of the combined therapy has been tested in 18 patients suffering from severe forms of MG. The protocol included 5 sessions of PE, performed in a range of 15 days, 1 session every 3 days, with concurrent administration of oral prednisone (1 mg/kg of body weight), starting at the first session of PE and given daily for at least 3 months. At the end of the entire cycle of PE, almost complete recovery (more than 90% of the initial clinical score) was obtained in 8 of 18 patients while an improvement between 60 and 90% of the initial score was achieved in 9 of 18 patients. An early improvement was noted 24 h after the beginning of plasmapheresis in 11 of 18 patients. No recurrence of symptoms was reported after 36 months of follow-up for 17 patients. The administration of steroid therapy was never followed by an early exacerbation of myasthenic symptoms as reported when it is administered in the absence of concomitant PE. According to our results, we can conclude that high doses of oral prednisone therapy in simultaneous association with PE lead to successful control of severe forms of MG, significantly superior to the therapeutic strategies until now adopted and reported in literature.

Administration, Oral↗