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Biomedical subjects

Alexander Perez

Publications and source records attributed to Alexander Perez.

11 recordsLinked to original sources

Risk factors and outcomes of pancreatitis after open heart surgery.

BACKGROUND: We sought to analyze the risk factors and natural history associated with post-cardiac surgery acute pancreatitis. METHODS: Retrospective analysis of all patients having undergone cardiac surgery at our hospital between January 1, 1992, and October 1, 2001. RESULTS: A total of 10,249 cardiac operations were performed. Thirty-nine (0.4%) patients developed postoperative pancreatitis. There was a higher incidence during the period spanning 1992 through 1996 than 1997 through 2001 (0.6% versus 0.2%, P< .05). Patients with pancreatitis had longer postoperative length of stay (51+/-5 days versus 10+/-1 days, P<.05) and a greater in-hospital mortality rate (28% versus 4%, P<.05) than patients who did not develop pancreatitis. A history of alcohol abuse, cardiac surgery performed during 1992 to 1996, increased cardiopulmonary bypass time, and increased cross-clamp time were independent risk factors for the development of pancreatitis. Multiple-organ failure was an independent predictor for death among patients with pancreatitis. CONCLUSIONS: Although the frequency of post-cardiac surgery pancreatitis is diminishing, it is still associated with significant mortality.

Acute Disease↗

Lymphangiogenesis in tissue-engineered small intestine.

BACKGROUND: Lymphangiogenesis, the formation of lymphatic vessels, has not been reported in engineered tissue. The purpose of this study was to characterize lymphangiogenesis in tissue-engineered small intestine. METHODS: Biodegradable polymer scaffolds seeded with intestinal organoid units were implanted into syngenic recipient rats. Twenty-three neointestinal grafts were harvested from adult rat recipients 1 to 8 weeks postimplantation. Cells expressing the lymphatic endothelial marker vascular endothelial growth factor receptor (VEGFR)-3 were detected immunohistochemically. The lymphangiogenic growth factor VEGF-C was quantified by enzyme-linked immunoadsorbent assay. RESULTS: Between the first and eighth weeks, neointestinal cysts increased in volume and mass. Muscular and mucosal layers increased in thickness and developed to resemble normal intestine histologically. The proportion of neointestinal VEGFR-3-positive cells increased and ultimately, tubular structures developed that resembled lymphatics architecturally, were distinct from CD34-positive blood vessels, and lacked luminal erythrocytes. CONCLUSION: Lymphangiogenesis occurs in tissue-engineered small intestine. This is the first demonstration of lymphatic vessels in an engineered tissue.

Animals↗

Effect of GLP-2 on mucosal morphology and SGLT1 expression in tissue-engineered neointestine.

Using tissue-engineering techniques, we have developed a neointestine that regenerates the structural and dynamic features of native small intestine. In this study, we tested neointestinal responsiveness to glucagon-like peptide 2 (GLP-2). Neointestinal cysts were engineered by seeding biodegradable polymers with neonatal rat intestinal organoid units. The cysts were matured and anastomosed to the native jejunum of syngeneic adult recipients. Animals were treated with GLP-2 [Gly2] (twice daily, 1 microg/g body wt) or vehicle alone (control) for 10 days. Rats were then killed, and tissues were harvested for analysis. Na+-glucose cotransporter (SGLT1) mRNA expression was assessed with Northern blotting and in situ hybridization. SGLT1 protein was localized by using immunofluorescence. GLP-2 administration resulted in 1.8- and 1.7-fold increases (P < 0.05) in neointestinal villus height and crypt depth, respectively. GLP-2 administration also resulted in a 2.4-fold increase (P < 0.01) in neomucosal SGLT1 mRNA expression. SGLT1 mRNA expression was localized to enterocytes throughout the villi, and SGLT1 protein was localized to the brush border of enterocytes along the entire length of villi from the neointestine of GLP-2-treated animals. The response of tissue-engineered neointestine to exogenous GLP-2 includes mucosal growth and enhanced SGLT1 expression. Therefore, tissue-engineering principles may help in dissecting the regulatory mechanisms mediating complex processes in the intestinal epithelium.

Animals↗

Surgical treatment of small bowel cancer: a 20-year single institution experience.

Small bowel malignancies are rare. The aims of this study were to evaluate the outcomes associated with surgical therapy for small bowel cancers and to define prognostic factors. The medical records of 96 consecutive patients with primary small bowel cancer (excluding lymphoma) treated at our institution over a 20 year period were reviewed. Survival was analyzed using the Kaplan-Meier method (mean follow-up period 57 months). Mean patient age was 56 years, and 58% of patients were male. Sixty percent of patients had an adenocarcinoma, 21% had a sarcoma, and 19% had a carcinoid tumor. The percentages of patients who underwent complete (curative) resection were 51%, 90%, and 50% for those with adenocarcinoma, sarcoma, and carcinoid tumor, respectively. For patients with adenocarcinoma who underwent curative resection, tumor (T) and node (N) stages were significant prognostic factors predicting overall survival. For patients with sarcomas who underwent curative resection, tumor grade was a significant prognostic factor predicting overall survival. The prognosis for patients with small intestinal carcinoid tumors is uniformly favorable. The prognosis for patients with sarcomas and adenocarcinomas is generally poor, although long-term survival is achieved by patients with favorable prognostic factors.

Adenocarcinoma↗

Work hours reform: perceptions and desires of contemporary surgical residents.

BACKGROUND: New Accreditation Council for Graduate Medical Education (ACGME) requirements on resident duty hours are scheduled to undergo nationwide implementation in July 2003. General surgery residents, because of their long duty hours, are likely to be among those most affected by changes imposed to comply with the ACGME requirements. There are few contemporary data on their attitudes toward work hours reform. STUDY DESIGN: The study entailed a region-wide survey of residents enrolled in general surgery residencies in New England to characterize the perceptions and desires of surgical residents on the issue of work hours reform. RESULTS: Respondents reported working a mean of 105 +/- 0.7 hours per week, considerably more than the 80-hour limit stipulated by the ACGME. Of the respondents, 81% reported that sleep deprivation had negatively affected their work. A strong majority of respondents believe that work hours reform would improve their quality of life but less than one half expect it to have a positive impact on patient care. A greater percentage of senior residents than junior residents (p < 0.05) have negative perceptions of work hour limitations, particularly with respect to consequences for patient care. Other findings suggest that residents who have actually experienced work hour restrictions are less positive about such restrictions than these residents who had not yet experienced them. CONCLUSIONS: Changes imposed by residency programs to comply with work hour requirements might have detrimental effects on senior residents and patient care. The impact of such changes should be carefully monitored as the ACGME requirements are implemented.

Accreditation↗

Angiogenesis in tissue-engineered small intestine.

Tissue-engineered intestine offers promise as a potential novel therapy for short bowel syndrome. In this study we characterized the microvasculature and angiogenic growth factor profile of the engineered intestine. Twenty-three tissue-engineered small intestinal grafts were harvested from Lewis rat recipients 1 to 8 weeks after implantation. Architectural similarity to native bowel obtained from juvenile rats was assessed with hematoxylin and eosin-stained sections. Capillary density, measured after immunohistochemical staining for CD34, was expressed as number of capillaries per 1000 nuclei. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) tissue levels were measured by ELISA and normalized to total protein. Over the 8-week period cysts increased in volume (0.5 cm(3) at week 1 versus 12.6 cm(3) at week 8) and mass (1.30 +/- 0.29 versus 9.74 +/- 0.3 g; mean +/- SEM). Muscular and mucosal layers increased in thickness, but capillary density remained constant (82.95 +/- 4.81 capillaries per 1000 nuclei). The VEGF level was significantly higher in juvenile rat bowel than in engineered cyst (147.6 +/- 23.9 versus 42.3 +/- 3.4 pg/mg; p < 0.001). Tissue bFGF levels were also higher (315 +/- 65.48 versus 162.3 +/- 15.09 pg/mg; p < 0.05). The mechanism driving angiogenesis differs in engineered intestine and in normal bowel. VEGF and bFGF delivery may prove useful for bioengineering of intestine.

Aging↗

Tissue-engineered small intestine: ontogeny of the immune system.

BACKGROUND: Using tissue-engineering techniques, we have developed a that regenerates structural and transporter properties of native jejunum. The purpose of this study was to characterize the mucosal immune system of the engineered neointestine. We hypothesized that the neointestinal mucosa is capable of developing a mature immunocyte population and that exposure to luminal stimuli is critical to this development. METHODS: Neointestinal cysts were engineered by implanting polymer-organoid constructs into syngeneic adult recipients. Neointestine (cysts left nonanastomosed [NA] and cysts anastomosed to native bowel [AN]) and native jejunum were harvested serially (3-56 weeks postoperatively). Immune cell subsets were characterized by the immunohistochemical detection of cell-specific antigens (T cells [CD3], B cells [CD32], NK cells [CD56], and macrophages [CD68]) combined with computer-based morphometry. RESULTS: Intraepithelial and lamina propria immunocyte population densities and subset distributions were identical in AN cysts harvested 20 weeks postoperatively and in native jejunum. Mucosal immunocyte population densities were lower in AN cysts harvested 10 weeks postoperatively and only rudimentary in NA cysts, even those harvested 20 weeks postoperatively. CONCLUSIONS: These results suggest that tissue-engineered intestine has the capacity to develop a mucosal immune system with an immunocyte population similar to that of native small intestine. The development of this immune system is a function of both exposure to luminal stimuli and the duration of this exposure. Tissue-engineered intestine offers promise as a new therapeutic approach for patients who have intestinal insufficiency.

Anastomosis, Surgical↗

Glucagon-like peptide 2 enhances intestinal epithelial restitution.

BACKGROUND: Glucagon-like peptide 2 (GLP-2) is a potent intestinotrophic peptide that enhances recovery following intestinal injury. We tested the hypothesis that GLP-2 acutely enhances intestinal epithelial restitution. MATERIAL AND METHODS: Rat jejunal segments were mounted in Ussing chambers. HCl (10 mM) was applied to the mucosal surfaces for 10 min to induce injury. Tissues were then lavaged with modified Ringer's solution and maintained in the chambers for an additional 3 h. Tissues were treated with 10 microM GLP-2 or vehicle alone (control). Electrical parameters were recorded, and tissues were salvaged for morphometric analysis. RESULTS: GLP-2-treated tissues exhibited a significantly greater recovery of potential difference and resistance (P < 0.05) than did controls. Morphometric analysis revealed that columnar cells covered a greater percentage of the epithelial surface in GLP-2-treated tissues than in controls (P < 0.05). CONCLUSIONS: These results suggest that GLP-2 acutely enhances intestinal epithelial restitution following acid-induced injury. This novel biological action of GLP-2 may contribute to its therapeutic effect in models of intestinal disease.

Animals↗

Is severity of necrotizing pancreatitis increased in extended necrosis and infected necrosis?

INTRODUCTION: We previously reported that organ failure occurs in 50% of patients with necrotizing pancreatitis, that extended pancreatic necrosis (greater than 50% necrosis) is not associated with an increased prevalence of organ failure or infected necrosis, and that the prevalence of organ failure is similar in sterile necrosis and infected necrosis. AIMS To analyze these relations in a larger group of patients and to evaluate other factors that might have prognostic significance. METHODOLOGY: We reviewed 1,110 consecutive cases of acute pancreatitis between January 1, 1995, and January 1, 2000. Necrosis was documented by contrast-enhanced CT. A value less than 0.05 was considered significant. RESULTS: Ninety-nine patients (9%) had necrotizing pancreatitis; 52% had organ failure. Patients with extended pancreatic necrosis did not have increased prevalence of organ failure or infected necrosis but did have an increased need for intubation and an increased mortality rate associated with multiple organ failure. Patients with infected necrosis did not have an increased prevalence of organ failure but did have a marginally increased prevalence of multiple organ failure and increased need for intubation. Overall mortality was 14% and was markedly increased among patients with organ failure at admission (47%) and among patients who had multiple organ failure during the hospitalization (49%). CONCLUSION: Although severity of necrotizing pancreatitis was somewhat increased in extended pancreatic necrosis and infected necrosis, mortality was more strongly linked to organ failure at admission and multiple organ failure during hospitalization.

Female↗

Benign nonampullary duodenal neoplasms.

Benign duodenal neoplasms (BDNs) are uncommon, and their optimal management remains undefined. We analyzed all cases of BDN treated at our institution during a 10-year period (January 1990 through January 2000). Data are expressed as median (range). Sixty-two patients were treated for BDNs. The results of histologic examination of their lesions were as follows: 36 adenomas, eight Brunner's gland tumors, 10 inflammatory polyps, two hamartomas, and six others. Forty-seven patients were treated nonoperatively, and 15 patients underwent surgery. Lesion characteristics leading to surgical intervention included large polyp diameter and submucosal penetration detected on endoscopic ultrasound imaging. There were no treatment-related deaths. Major morbidity occurred in 2% of patients who underwent endoscopic resection and in 33% of patients who underwent surgery (P = 0.002). Among patients treated for adenomas, seven (19.4%) had a recurrence at a median of 12 (4 to 48) months. Most BDNs can be managed with minimal morbidity using endoscopic techniques. Systematic follow-up of patients treated for adenomas is required.

Adenoma↗

Glucagon-like peptide 2 is an endogenous mediator of postresection intestinal adaptation.

BACKGROUND: After massive small bowel resection, the remnant intestine undergoes compensatory adaptation. We tested the hypothesis that glucagon-like peptide-2 (GLP-2) is an endogenous mediator of postresection intestinal adaptation. METHODS: Rats were allocated to 1 of 4 groups: groups 1 and 2 rats underwent mid-small bowel transection and reanastomosis; groups 3 and 4 rats underwent 75% mid-small bowel resection and reanastomosis. Groups 2 and 4 rats were administered 1.8 mg of antirat GLP-2 antibody twice daily beginning immediately after the surgical procedure; groups 1 and 3 rats were administered rabbit serum (control). Ileal specimens were harvested on postoperative day 7. RESULTS: Ileal mucosa from group 3 animals displayed morphologic and proliferative indices of adaptation. Each of these indices of adaptation was inhibited by GLP-2 immunoneutralization (group 4). Morphologic and proliferative parameters in the ileum from animals that had undergone transection with reanastomosis were unaffected by GLP-2 immunoneutralization. CONCLUSIONS: These results suggest that GLP-2 is an endogenous mediator of postresection intestinal adaptation.

Adaptation, Physiological↗