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Lisa S Poritz

Publications and source records attributed to Lisa S Poritz.

11 recordsLinked to original sources
PubMed2007

Enhanced intestinal expression of the proteasome subunit low molecular mass polypeptide 2 in patients with inflammatory bowel disease.

PURPOSE: Low molecular mass polypeptide 2 is an inducible immunoproteasome subunit. The expression of low molecular mass polypeptide 2 has not been examined in the intestine of patients with inflammatory bowel disease. This study was designed to determine whether the intestinal expression of low molecular mass polypeptide 2 was enhanced in a group of patients with inflammatory bowel disease compared with a group of control patients without inflammatory bowel disease. Moreover, we examined the association between low molecular mass polypeptide 2 expression and histologic pathology in these patients. METHODS: Twenty-one patients participated in the study. These included six control subjects without inflammatory bowel disease, eight patients with ulcerative colitis, and seven patients with Crohn's disease. Intestinal low molecular mass polypeptide 2 expression was evaluated by immunohistochemistry, as well as by Western blot. Histology scores (0-40 severity scale) were determined on the same sections of intestine as those used for low molecular mass polypeptide 2 histochemistry. RESULTS: By immunohistochemistry, low molecular mass polypeptide 2 expression was significantly enhanced (P < 0.05 vs. control subjects) throughout visibly diseased areas of colon, rectum, and ileum from patients with inflammatory bowel disease. Low molecular mass polypeptide 2 expression also was increased in macroscopically normal intestine from patients with inflammatory bowel disease compared with normal tissue from control subjects. There was a significant correlation (P < 0.0001) between low molecular mass polypeptide 2 expression and histologic pathology in our patients. Western blot results confirmed that low molecular mass polypeptide 2 expression was enhanced in patients with ulcerative colitis (3.1-fold) and in patients with Crohn's disease (3.5-fold). CONCLUSIONS: Intestinal low molecular mass polypeptide 2 expression is significantly increased in inflammatory bowel disease. The association between intestinal low molecular mass polypeptide 2 expression and histologic pathology suggests that this proteasome subunit plays a role in the pathogenesis of inflammatory bowel disease.

Adult↗
PubMed2005

Modified two-stage ileal pouch-anal anastomosis: equivalent outcomes with less resource utilization.

PURPOSE: A three-stage operative approach to ileal pouch-anal anastomosis is usually undertaken in patients presenting with severe colitis. Increasingly, however, we have performed a two-stage modified ileal pouch-anal anastomosis (colectomy followed by ileal pouch-anal anastomosis without ileostomy). The present study sought to evaluate the safety, results, cost, and length of hospital stay using this modified approach compared to that of the traditional three-stage ileal pouch-anal anastomosis. METHODS: Clinical and financial data were gathered by retrospective review of patients undergoing ileal pouch-anal anastomosis at our institution since 1995. Complications were defined as any event prolonging hospitalization or requiring readmission and were included in the analysis up to six months after final surgery. Functional performance was assessed as of the last clinic visit. Data were compared with Student's t-test and chi-squared analysis. Multivariate analysis was also used to assess risk factors. RESULTS: A total of 23 patients who underwent the two-stage modified procedure and 31 patients who had the three-stage procedure were identified. The two groups were found to be statistically comparable in terms of patient age, gender, duration of illness, and preoperative hematocrit. Follow-up was shorter in the modified group because of its more recent introduction (9.7 months vs. 30.5 months mean follow-up). Ninety-five percent of patients were on immunosuppressive medication before colectomy, but all were off it before the reconstruction. clinical outcomes after ileal pouch-anal anastomosis were equivalent in terms of the number of bowel movements, prevalence of fecal incontinence, and the use of hypomotility medications. No patients with the two-stage modified procedure had anastomotic complications requiring stoma creation. One patient in the three-stage group required re-creation of a stoma after stoma closure for perianal complications suggesting Crohn's disease. Total hospital cost was significantly less in the modified group: USD $27,270 vs. $38,184 (P = 0.0119). Length of stay was also shorter in the two-stage modified group although missing absolute statistical significance (21.0 days vs. 26.0 days, P = 0.0882). CONCLUSIONS: Interval ileal pouch-anal anastomosis reconstruction without a stoma (two-stage modified procedure) after colectomy is functionally equivalent to the traditional three-stage protocol in terms of clinical outcome. However, it has the advantage of overall lower hospital costs and probably a shorter length of hospital stay.

Adult↗
PubMed2005

Intravenous cyclosporine for the treatment of severe steroid refractory ulcerative colitis: what is the cost?

PURPOSE: Intravenous cyclosporine often is used to treat patients with severe steroid refractory colitis secondary to ulcerative colitis in an attempt to avoid urgent total abdominal colectomy. The purpose of this study was to evaluate the success and cost of cyclosporine. METHODS: A retrospective, chart review of all patients from 1996 to 2002 who were treated with cyclosporine and/or had a three-stage ileal pouch-anal anastomosis for severe steroid refractory colitis at our institution was performed. Patients were divided into three groups: TAC and CyA: patients who failed cyclosporine and had urgent total abdominal colectomy on the same admission; TAC no CyA: patients who had an urgent total abdominal colectomy without cyclosporine; and CyA only: patients treated successfully with cyclosporine and discharged without surgery. A subgroup of patients who had an ileal pouch-anal anastomosis was identified from each group. Cost data were obtained from the hospital's financial records. RESULTS: Forty-one patients (25 males) were identified. Twenty-nine patients received cyclosporine for severe steroid refractory colitis. Of these, 18 (62 percent) failed and underwent total abdominal colectomy on the same admission. Eleven (38 percent) responded to the cyclosporine and were discharged. Of the 11, 4 never had surgery, 1 had a three-stage ileal pouch-anal anastomosis, 5 had a two-stage ileal pouch-anal anastomosis, and 1 had a total abdominal colectomy only. Only 14 percent of patients avoided colectomy in the long-term. Complications of cyclosporine occurred in 8 patients (28 percent), and surgical complications occurred in 12 patients. CONCLUSIONS: The highest costs, highest length of stay, and highest number of overall complications were found in the group of patients who failed intravenous cyclosporine and required colectomy during the same hospitalization.

Adult↗
PubMed2004

Surgical management of entero and colocutaneous fistulae in Crohn's disease: 17 year's experience.

BACKGROUND AND AIMS: Fistulous disease is common in Crohn's disease, and entero- and colocutaneous fistulae are particularly debilitating and difficult to manage. We present the results of surgical management of these fistulas. PATIENTS AND METHODS: Retrospective chart review of all 51 patients with Crohn's disease (56 surgical procedures) undergoing surgery for cutaneous fistulae between 1983 and 2000. RESULTS: Previous surgery for Crohn's disease had been carried out in 43 patients (84%). The fistula site was enterocutaneous in 36 patients (64%), colocutaneous in 12 (21%), and anastomotic in 8 (14%); 9 patients (16%) also had associated enteroenteric fistulas. The onset of the fistula followed abscess drainage in 15 (27%) and occurred at the site of recurrent disease in 41 (73%). Forty patients (71%) initially underwent conservative management prior to surgery; 16 (28%) underwent surgery directly. Surgical procedures were: 25 ileocolic resections, 8 stoma revisions with resection, 8 small bowel resections 7 subtotal colectomies, 4 partial colectomies, 3 proctocolectomies, and one fistula tract excision. Mean total length of stay was 18 days (postoperative 10.7 days). Six (11%) patients had eight postoperative complications. Mean follow-up was 48.6 months (range 3-187). Recurrence as defined by either clinical examination or reoperation was documented in nine fistulas (16%), with a mean time to recurrence of 27 months. CONCLUSION: Entero-and colocutaneous fistulae usually occur from a site of active disease. Surgical management with bowel resection, including the fistula, is the preferred method of treatment. Morbidity has been low and recurrence rate lower than expected.

Adult↗
PubMed2004

Stat6(null phenotype) human lymphocytes exhibit increased apoptosis.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with altered apoptosis and increased levels of Th1 cytokines (IL-12, TNF-alpha, and IFN-gamma). These proinflammatory events may result from dysfunctional IL-4/Stat6 signal transduction that normally promotes Th2 lymphocyte differentiation and consequential down-regulation of the immune response. The goal of the present study was to measure apoptosis, levels of relevant cytokines, and the effects of cytokine manipulation on apoptosis in cell lines derived from IBD patients that express dysfunctional Stat6 (Stat6(null phenotype)) and wild-type Stat6 (Stat6(high phenotype)). MATERIALS AND METHODS: Lymphocytes with Stat6(null phenotype) (n = 5) or wild-type (n = 5) status were cultured with and without the addition of exogenous cytokines or neutralizing antibodies (IL-12, TNF-alpha, and IFN-gamma). Apoptosis was determined by flow cytometry using Annexin V-PE dual staining. Cytokine levels were determined by ELISA. RESULTS: Stat6(null phenotype) cells exhibited increased apoptosis compared with wild-type cell lines (13.3% +/- 2.9 versus 4.5% +/- 0.4, P < 0.0001). Four of five Stat6(null phenotype) cell lines expressed 5- to 10-fold elevations in IL-12 and IFN-gamma. Addition of exogenous cytokines or neutralizing antibodies had no effect on apoptosis. CONCLUSIONS: Apoptotic cell death is elevated in Stat6(null phenotype) cell lines suggesting a role for Stat6 in apoptosis regulation, a previously unrecognized observation. Increased levels of IL-12 and IFN-gamma were found in the Stat6(null phenotype) cell lines; however, the apoptosis observed is not the consequence of increased IL-12, IFN-gamma, or TNF-alpha. Stat6(null phenotype) cell lines exhibit variably increased levels of these Th1 cytokines, consistent with their human source, and may be a valid source for investigations into IBD pathophysiology.

Antibodies↗
PubMed2004

Tumor necrosis factor alpha disrupts tight junction assembly.

BACKGROUND: We have previously shown an increase in intestinal permeability and a corresponding decrease in the expression of tight junction (TJ) proteins in the in testines of patients with Crohn's disease (CD). Tumor necrosis factor-alpha (TNFalpha) has been implicated in the inflammatory process of CD and its suppression has therapeutic benefit. ZO-1, occludin, and the claudins are key proteins in the TJ. HYPOTHESIS: TNFalpha disrupts the TJ. METHODS: MDCK cells were incubated with TNFalpha (0-100 ng/ml) for 5 days. Qualitative evaluation of the TJ was done with monoclonal antibody to ZO-1 detected by an immunofluorescence. Duplicate cells were lysed and ZO-1, occludin, and claudin-1 amount determined by western blot. RESULTS: Immunofluorescent staining of MDCK cells for ZO-1 showed TJ structural disruption with increasing amount of TNFalpha characterized by fragmented staining of ZO-1. There were no significant differences in quantitation of ZO-1 or occludin in the MDCK cells for all TNFalpha concentrations. There was a significant decrease in the amount of claudin-1 with increasing concentration of TNFalpha. CONCLUSIONS: (1) MDCK TJs are qualitatively disrupted by TNFalpha. (2) This disruption is not because of a decrease in cell number, lack of cell layer confluency, or a decrease in the amount of ZO-1 or occludin. (3) The amount of claudin-1 present in the cell is decreased with increasing amounts of TNFalpha suggesting that the lack of claudin-1 may cause a relocation of ZO-1 away from the TJ. (4) This rearrangement may play a role in the increased intestinal permeability seen in CD and other diseases.

Animals↗
PubMed2004

Human B lymphoblast cell lines defective of Stat6 signaling produce high levels of proinflammatory cytokines IL-12, TNFalpha and IFNgamma.

Based on Stat6 gene knockout animal models, the Stat6 signaling pathway has been suggested to play a role in carcinogenesis and Th1/Th2 cytokine balance. Using a semiquantitative EMSA assay and EBV-transformed human B lymphoblast cell lines, we have previously identified three Stat6 activational phenotypes, termed as Stat6high, Stat6low, and Stat6null. A genetic mechanism has been proposed which determines the IL-4-induced activation of the human Stat6 signaling. With respect to the contribution of variant phenotypes to human disease, we further hypothesize that the Stat6null phenotype may result from a partial defect in Stat6 signaling which resembles Stat6 knockout animals in several functional aspects. The characterization of the human Stat6null phenotype stably displayed by the EBV-B cell lines is easily assailable and possesses important implications with respect to Th1/Th2 cytokine imbalance in diseases such as cancer development/metastasis and inflammatory diseases. In this study, we have extended our investigation to the downstream regulatory consequences associated with these Stat6 phenotypes. Production of three important proinflammatory cytokines, IL-12, TNFalpha and IFNgamma was examined in spontaneous EBV-B cell culture using ELISA methodology. Individual cell lines defined as Stat6null produced significantly higher levels of IL-12, TNFalpha and IFNgamma on day 4 in spontaneous culture in comparison with cell lines characterized as Stat6high and Stat6low. These observations of the human Stat6null phenotype, together with those accruing from Stat6 knockout mouse model studies, suggest that the Stat6 signaling pathway may play a role in maintaining the Th1/Th2 cytokine balance by directly and indirectly down-regulating the production of proinflammatory cytokines, a regulatory process which appears to go awry in inflammatory diseases. Moreover, observations from signal transduction studies in our human B lymphocyte model may be compatible with those in the chosen mouse B lymphocyte for establishing signaling networks by the Alliance for Cellular Signaling (AfCS).

Animals↗
PubMed2003

Surgical management of ulcerative colitis in the presence of primary sclerosing cholangitis.

INTRODUCTION: The surgical management of ulcerative colitis in the patient with primary sclerosing cholangitis is controversial. METHODS: This study was designed as a retrospective chart review of all patients with primary sclerosing cholangitis who were surgically treated for ulcerative colitis. RESULTS: Sixteen patients with primary sclerosing cholangitis and ulcerative colitis were identified. The indication for ulcerative colitis surgery was dysplasia in 7 patients (44 percent), cancer in 2 (13 percent), intractability in 4 (25 percent), and unknown in 1. Final colon pathology demonstrated cancer in three patients and dysplasia in four. Two patients had biliary cancer discovered at the time of orthotopic liver transplantation. Thirteen patients were known to have primary sclerosing cholangitis when they underwent surgery for ulcerative colitis; two patients with severe primary sclerosing cholangitis underwent simultaneous orthotopic liver transplantation/total abdominal colectomy and did well with subsequent ileal pouch reconstruction. Two patients had orthotopic liver transplantation first and then ileal pouch-anal anastomosis (1 patient) or total abdominal colectomy (1 patient) and did well. Seven patients had well-controlled primary sclerosing cholangitis on medication and underwent ileal pouch-anal anastomosis or total abdominal proctocolectomy without significant hepatic compromise. One patient with moderate primary sclerosing cholangitis underwent ileorectal anastomosis and had severe liver failure postoperatively but survived. Another patient with worsening primary sclerosing cholangitis after total abdominal colectomy has since developed persistent bleeding from peristomal varices. CONCLUSIONS: The overall cancer/premalignant lesion rate was high (50 percent in this study) in patients with primary sclerosing cholangitis and ulcerative colitis. Complications associated with the surgical management of ulcerative colitis are largely dictated by the degree of liver disease present at the time of surgery. Patients with significant primary sclerosing cholangitis that requires colectomy can undergo simultaneous orthotopic liver transplantation/total abdominal colectomy and then be candidates for subsequent ileal pouch-anal anastomosis reconstruction once liver function has improved. Patients with well-controlled primary sclerosing cholangitis can undergo ileal pouch-anal anastomosis surgery safely.

Adult↗
PubMed2002

Remicade does not abolish the need for surgery in fistulizing Crohn's disease.

PURPOSE: Tumor necrosis factor antagonist therapy in the form of infliximab has been shown to promote significant healing in fistulizing Crohn's disease and therefore is often considered as a possible alternative to surgery. Our aim was to evaluate the role of infliximab in supplanting surgery for fistulizing Crohn's disease. METHODS: We performed a retrospective chart review of all adult patients who received infliximab for fistulizing Crohn's disease at one institution between September 1998 and October 2000. RESULTS: Twenty-six patients (14 male; mean age, 38 years; range, 19-80 years) received a mean of three (range, one to six) doses of infliximab (5 mg/kg) with the intent to cure fistulizing Crohn's disease. Nine patients (35 percent) had perianal, 6 (23 percent) enterocutaneous, 3 (12 percent) rectovaginal, 4 (15 percent) peristomal, and 4 (15 percent) intra-abdominal fistulas. Nineteen (73 percent) of the patients had had prior surgery for Crohn' s disease. Six patients (23 percent) had a complete response to infliximab with fistula closure, 12 (46 percent) had a partial response, and 8 (31 percent) had no response to infliximab. Fourteen (54 percent) patients still required surgery for their fistulizing Crohn's disease after infliximab therapy (10 bowel resections, 4 perianal procedures), whereas half (6/12) of the patients treated with infliximab who still had open fistulas after treatment declined surgical intervention. Five of six patients with fistula closure on infliximab had perianal or rectovaginal fistulas. None of the patients with either enterocutaneous or peristomal fistulas were healed with infliximab. CONCLUSIONS: Although it was associated with a 61 percent complete or partial response rate, infliximab therapy did not supplant the need for surgical intervention in the majority of our patients with fistulizing Crohn's disease. Seventy-three percent of the patients either required surgery or still had open fistulas after infliximab therapy. Infliximab was much more effective in treating perianal disease than abdominal enterocutaneous disease.

Adult↗
PubMedDate not supplied

Factors affecting surgical risk in elderly patients with inflammatory bowel disease.

The operative treatment of elderly patients with inflammatory bowel disease (IBD) has often been avoided in favor of medical management because of a perceived increase in surgical risk. This study sought to define the following in the elderly IBD patient population: (1) the risk of surgical management and (2) those factors affecting risk. Thirty patients with IBD, aged 60 years or more, who were surgically managed by a single surgeon over a 10-year period, were retrospectively matched to 75 patients with IBD who were less than 60 years of age; patients were matched according to sex, date of surgery, and type of surgery performed. Regression analysis using generalized estimating equation methodology to account for the matched clusters of patients was performed to evaluate the effect of age group on the complication rate, operating room time, and length of hospital stay. Presence of comorbid conditions, surgical indications, prior surgery for IBD, and the use of immunosuppressive medications were studied in multivariate models, adjusting for age group. By means of univariate analysis, the odds of complications in elderly IBD patients were shown to be statistically higher than the odds seen in younger patients (47% vs. 20%, P = 0.01). Also observed in the elderly group were a longer length of hospital stay (11.5 days vs. 7.1 days, P = 0.001) and longer operating room time (249 minutes vs. 212 minutes, P = 0.02). Multivariate analysis revealed that the effect of age remained statistically significant, even when adjusted for potential confounding variables such as comorbidity, medications, date of diagnosis of IBD, and indications for surgery. The complication outcome was significantly associated with the surgical indication, with obstruction, fistula, and bleeding having increased odds of complications as compared with other indications (odds ratio = 1.7 vs. 4.2 vs. 7.2, respectively, P = 0.02). The length of hospital stay similarly was significantly associated with the surgical indication (fistula, 10.5 days vs. bleeding, 9.8 days vs. obstruction, 7.4 days vs. other, 9.3 days; P = 0.04) and a history of prior surgery. A significant interaction for length of hospital stay was present between age group and prior surgery status (with prior surgery: old, 18 days vs. young, 6.4 days, P = 0.0001; without prior surgery: old, 9.5 days vs. young 7.3 days, P = 0.10). Elderly patients with IBD have an increased rate of postoperative complications along with an increased length of hospital stay and increased operating room time. This effect of age persists when adjusted for comorbidity and immunosuppressive therapy. Complications are most dependent on surgical indications, with obstruction being the least and bleeding the worst predictive factors. The longest hospital stay is associated with patients who require surgery for fistulous disease and patients who have undergone previous surgery. The fact that the higher complication rate seen in older patients with IBD is associated with disease-defined surgical indications suggests that IBD in elderly patients may be more aggressive than what is observed in younger individuals.

Adolescent↗