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M J Ott

Publications and source records attributed to M J Ott.

At least 19 recordsLinked to original sources
PubMed2006

Outcomes in a series of 103 retroperitoneal sarcomas.

AIMS: To report the effect on outcome of selection in patients receiving intra-operative electron beam radiation (IOERT) and external beam radiation therapy (EBRT). METHODS: One hundred and three patients treated for primary RS were studied. Median follow-up was 27 months. Clinical presentation, tumor characteristics, and treatment methods were analyzed to determine impact on survival and recurrence and if selection was occurring. RESULTS: Mean age was 55+/-17 years. Mean tumor size was 15+/-6cm and 88 were high-grade. Complete gross tumor resection (CR) occurred in 62 patients and improved survival vs. both debulking (p=0.0005) and biopsy (p<0.0001). The 5- and 10-year survival rates were 62% and 52% for those with CR vs. 29% and 20% after incomplete resection. Among the 62 CR patients, there was selection to receive additional EBRT+/-IOERT in patients with high-grade tumors (p=0.005) and/or microscopically positive margins (p=0.011). In these high-risk patients there was a trend for IOERT to further augment survival vs. EBRT alone and to increase the time to both local and distant recurrences (p=0.036). CONCLUSIONS: Complete gross resection is the primary form of curative treatment for retroperitoneal sarcomas. Selection led to patients with high-risk tumors receiving additional radiation therapy. There appears to be a beneficial effect of IOERT plus EBRT in these high-risk patients after complete tumor resection.

Adolescent↗
PubMed2003

Availability of acupuncture in the hospitals of a major academic medical center: a pilot study.

BACKGROUND: Acupuncture is widely used by the American public, but little is known about its availability and use in academic medical settings. We performed a pilot study to compare acupuncture services provided by hospitals affiliated with a major academic teaching institution, and a parallel survey of services provided through an acupuncture school in one city in New England. METHODS: Between December 2000 and July 2001, a telephone survey was conducted of the 13 hospitals affiliated with Harvard Medical School, and the clinics affiliated with the New England School of Acupuncture. RESULTS: Acupuncture was available in 8 of the 13 hospitals. Acupuncture was provided in ambulatory clinics in all eight hospitals, but was available to inpatients in only one hospital. Six hospitals delivered acupuncture through an outpatient pain treatment service, one through a women's health center, one through an HIV clinic, and one hospital delivered acupuncture through two services; a program in the anesthesia department and a multi-disciplinary holistic program in a primary care department. In contrast, the acupuncture school clinics provided services through an on-site clinic at the school, through acupuncture departments at two community-based hospitals, and through a network of 12 satellite acupuncture-dedicated clinics operating throughout the state. CONCLUSION: Acupuncture is available on a limited basis in a majority of the teaching hospitals in this city. At the acupuncture school clinics, there are few barriers to care. Future health care studies will need to examine the role of acupuncture in diverse geographic settings and to examine its impact on quality of care, teaching and its role in research in academic centers.

Academic Medical Centers↗
PubMed2001

Long-term results of intraoperative electron beam radiotherapy for primary and recurrent retroperitoneal soft tissue sarcoma.

PURPOSE: This study assesses the long-term outcome of patients with retroperitoneal sarcoma treated by preoperative external beam radiotherapy, resection, and intraoperative electron beam radiation (IOERT). METHODS AND MATERIALS: From 1980 to 1996, 37 patients were treated with curative intent for primary or recurrent retroperitoneal soft tissue sarcoma. All patients underwent external beam radiotherapy with a median dose of 45 Gy. This was followed by laparotomy, resection, and IOERT, if feasible. Twenty patients received 10-20 Gy of IOERT with 9-15 MeV electrons. These patients were compared to a group of 17 patients receiving preoperative irradiation without IOERT. RESULTS: The 5-yr actuarial overall survival (OS), disease-free survival, local control (LC), and freedom from distant disease of all 37 patients was 50%, 38%, 59%, and 54%, respectively. After preoperative irradiation, 29 patients (78%) underwent gross total resection. For 16 patients undergoing gross total resection and IOERT, OS and LC were 74% and 83%, respectively. In contrast, these results were less satisfactory for 13 patients undergoing gross total resection without IOERT. For these patients, OS and LC were 30% and 61%, respectively. Four patients experienced treatment-related morbidity. CONCLUSIONS: In selected patients, IOERT results in excellent local control and disease-free survival with acceptable morbidity.

Adolescent↗
PubMed2001

The effect of surgery and grade on outcome of gastrointestinal stromal tumors.

HYPOTHESIS: Gastrointestinal stromal tumors (GIST) are aggressive, rare, and difficult-to-cure gastrointestinal tumors. We believe that the clinical behavior of these tumors can be predicted by reproducible prognostic factors. DESIGN AND SETTING: A retrospective review of all patients (N = 70) with GIST treated at a tertiary care center from 1973 to 1998. PATIENTS: Adequate data for evaluation were available for 69 patients. Male-female distribution was 40:29. Median age was 60 years. Median follow-up duration was 38 months. MAIN OUTCOME MEASURES: Tumor grade, stage, and histologic subtype at presentation; effect of grade, surgery and adjuvant therapy on recurrence, salvage, and survival. RESULTS: Tumor distribution included 61% in the upper, 23% in the middle, and 16% in the lower digestive tract, with a median tumor size of 7.9 cm (range, 1.8-25 cm). Tumors with more than 1 mitosis per 10 high-power fields constituted 57% of neoplasia in the series. Distant disease at initial visit occurred in 49% of patients. Complete gross resection occurred in 59% of patients. After complete resection, the 5-year survival rate was 42%, compared with 9% after incomplete resection (hazard ratio = 0.27, P<.001). Neither radiation nor chemotherapy demonstrated any significant benefit. Among 39 patients who were disease free after complete resection, 2% developed lymph node recurrence, 25% developed local recurrence, and 33% developed distant recurrences (54% liver, 20% peritoneum). By multivariate analysis the risk of local and/or distant metastases was significantly increased for tumors with more than 1 mitosis and size larger than 5 cm (P<.05). Multivariate analysis in all 69 patients revealed that incomplete resection, age greater than 50 years, non-smooth muscle histological feature, tumor with more than 1 mitosis, and tumor size larger than 5 cm significantly decreased survival. CONCLUSION: Complete gross surgical resection is presently the only means of cure for GIST. Tumors with more than 1 mitosis and a size larger than 5 cm have an especially poor prognosis, with decreased survival, and increased local and/or distant recurrence.

Adolescent↗
PubMed2001

Intraoperative radiation therapy for locally advanced recurrent rectal or rectosigmoid cancer.

BACKGROUND AND PURPOSE: To update and summarize the experience at the Massachusetts General Hospital of a treatment program of high-dose preoperative irradiation, surgical re-resection, and intraoperative radiation therapy (IORT) as a salvage treatment for patients with recurrent rectal or rectosigmoid carcinoma. PATIENTS AND METHODS: From June 1978 to February 1997, the records of 69 patients with locally recurrent rectal carcinomas or rectosigmoid carcinomas without metastases referred for consideration of IORT were reviewed. Forty-nine patients received IORT and local control and disease-free survival curves were calculated using the actuarial method of Kaplan-Meier. RESULTS: The 5-year overall survival, local control and disease-free survival rates of 49 patients receiving IORT were 27, 35, and 20%, respectively. Thirty-four patients who underwent a macroscopic complete resection had a significantly better 5-year overall survival than the remaining 15 patients with gross residual disease (33 vs. 13%, P=0.05, log rank). For those patients, local control and disease-free survival rates were 46 and 27%, respectively. Patients with a microscopic complete resection had a superior 5-year overall survival than partially resected patients (40 vs. 14%, P=0.0001, log rank). Chemotherapy had no significant influence on overall or disease-free survival. CONCLUSION: The current analysis shows the importance of a microscopic complete resection in a multi-modality approach with IORT for survival and local control. Salvage is rare for patients undergoing subtotal resection.

Adenocarcinoma↗
PubMed1999

Outcome of patients with melanoma and histologically negative sentinel lymph nodes.

HYPOTHESIS: Patients with melanoma and histologically negative sentinel lymph nodes identified by lymphatic mapping have a very good prognosis. DESIGN: Cohort study with follow-up information obtained from medical records and telephone interviews. SETTING AND PATIENTS: Of all patients with cutaneous melanoma who underwent intraoperative sentinel lymph node mapping between November 15, 1993, and April 18, 1997, at the Massachusetts General Hospital, Boston, 89 were found to have no evidence of melanoma in their sentinel nodes. Forty-six lesions (51%) were on an extremity and 44 (49%) were of axial location. The median tumor thickness was 1.8 mm (range, 0.36-12.0 mm) and 11 tumors (12%) were ulcerated. INTERVENTIONS: Patients underwent intraoperative sentinel lymph node mapping with lymphazurin and radiolabeled sulfur colloid. Sentinel lymph nodes were analyzed by standard hematoxylin-eosin staining. Only 2 patients received adjuvant therapy following wide excision of the primary lesion. MAIN OUTCOME MEASURES: Site of initial recurrence and time to initial recurrence. RESULTS: The median follow-up for all patients was 23 months (range, 2-54 months). Eleven patients (12%) developed melanoma recurrences, and 78 (88%) patients remain disease free. Regional lymph nodes were the initial site of recurrence in 7 (8%) of 89 patients, and 7 (7%) of 106 mapped basins. Four patients had recurrence without involvement of regional lymph nodes: 2 with distant metastases and 2 with in transit metastases. The median time to recurrence was 12 months (range, 2-35 months). Sentinel lymph nodes were reanalyzed using serial sections and immunoperoxidase stains in 7 patients with recurrence and metastatic melanoma was identified in 3 (43%). CONCLUSIONS: The risk for melanoma recurrence is relatively low in patients with histologically negative sentinel nodes identified by lymphatic mapping. Longer follow-up will improve our understanding of the prognostic value of this procedure.

Adult↗
PubMed1999

Multimodality management of Merkel cell carcinoma.

HYPOTHESIS: Merkel cell carcinoma is a rare dermal neuroendocrine carcinoma whose optimal treatment and prognostic factors are poorly defined. We hypothesize that high-risk patients with Merkel cell carcinoma are best treated with multimodality therapy. DESIGN: A retrospective review of all patients (N = 33) with Merkel cell carcinoma treated at the Massachusetts General Hospital from January 1, 1980, to August 24,1997. Median follow-up time was 37 months (range, 6-157 months). PATIENTS: Adequate data for evaluation were available for 31 patients. Male to female distribution was 14 men and 17 women, with a median patient age of 68 years. MAIN OUTCOME MEASURE: Stage at presentation; factors associated with recurrence; and the effects of surgery, radiation therapy (XRT), and chemotherapy on recurrence, salvage, and survival rates. RESULTS: There were 12 extremity, 11 head and neck, and 8 truncal tumors. There were 22 isolated primary tumors, 8 with additional clinically positive lymph nodes, and 1 with distant disease. Therapy was local excision with or without XRT in 19 patients, local resection and lymphadenectomy with or without XRT in 8 patients, and XRT alone in 4 patients with head and neck tumors. Fifteen patients developed recurrences (7 local, 8 nodal, and 10 distant). Median time to recurrence was 8 months (range, 3-48 months). There were 7 tumor-related deaths, 6 of which were associated with truncal lesions (P<.001). No locoregional recurrences occurred in patients with margins of resection of 2 cm or greater or adequate XRT. A multivariate analysis selected truncal location (P = .005) and nodal disease (P = .05) as predictors of mortality. Remission was possible in 5 patients with locoregional and 2 patients with distant recurrences. CONCLUSIONS: Merkel cell carcinoma is an aggressive dermal cancer with frequent nodal metastases; truncal tumors have the worst prognosis. Locoregional recurrence correlates with inadequate margins and lack of XRT, but remission is possible with multimodality therapy.

Aged↗
PubMed1999

Surgical management of phyllodes tumors.

HYPOTHESIS: Although phyllodes tumors have minimal metastatic potential, we hypothesized that they have a proclivity for local recurrence and should be excised with a wide margin. We reviewed the clinical and radiological appearance of phyllodes tumors and analyzed the role of surgical treatment in their management. DESIGN: Medical records, imaging studies, pathology reports, and interventions were reviewed. SETTING: A large tertiary care teaching hospital. PATIENTS: Between 1980 and 1997, 40 patients with phyllodes tumors were identified through the tumor registry at the Massachusetts General Hospital, Boston. MAIN OUTCOME MEASURES: Surgical resection margins, rates of local recurrence, incidence of distant metastases, and survival. RESULTS: All 40 patients were female, with a mean age of 41 years. Each patient had a palpable mass or a mammographic finding that was indistinguishable from a fibroadenoma on examination. Tumor size ranged from 5 mm to 28 cm. Local recurrence correlated with excision margins (P<.05), but not with tumor grade or size. Local recurrence occurred in 5 patients, each of whom had positive margins or margins less than 1 cm after excision. After reexcision with a 1-cm margin, these individuals remained free of recurrence. One patient developed metastatic disease after total mastectomy and died after chemotherapy. CONCLUSIONS: Phyllodes tumors mimic fibroadenomas and are often excised with close margins. Primary excision or reexcision with a 1-cm margin is recommended. Mastectomy is indicated for patients with large lesions. Lymph node metastases are unusual and occur secondary to necrotic tumor. Chemotherapy is based on guidelines for the treatment of sarcomas, not breast adenocarcinoma.

Adolescent↗
PubMed1999

Prognosis and survival in patients with gastrointestinal tract carcinoid tumors.

OBJECTIVE: To determine the impact of clinical presentation variables on the management and survival of patients with gastrointestinal (GI) tract carcinoid tumors. METHODS: A 20-year (1975-1995) retrospective analysis of 150 patients with GI tract carcinoid tumors at the Massachusetts General Hospital was conducted. Median follow-up was 66 months (range 1-378). Survival estimates for prognostic factors were calculated using Kaplan-Meier product limit estimators, with death from carcinoid as the outcome. Univariate analyses for each factor were obtained using a log-rank test, and multivariate survival analysis was performed. RESULTS: All but two patients underwent surgical intervention with the intent to cure (90%) or debulk the tumor (9%). Mean age at presentation was 55 +/- 18 years (range 11-90). There was a slight female/male predominance (80:70). Symptoms were nonspecific; the most common were abdominal pain (40%), nausea and vomiting (29%), weight loss (19%), and GI blood loss (15%). Incidental carcinoids, discovered at the time of another procedure, occurred in 40% of patients and were noted at multiple sites throughout the GI tract. The distribution of tumors was ileojejunum (37%), appendix (31 %), colon (13%), rectum (12%), stomach (4%), duodenum (1.3%), and Meckel's diverticulum (1.3%). Of the 27 patients with documented liver metastases, carcinoid syndrome developed in only 13 patients (48%), manifested by watery diarrhea (100%), upper body flushing (70%), asthma (38%), and tricuspid regurgitation (23%). All 13 patients with carcinoid syndrome had elevated levels of 5-HIAA, but the absolute levels did not correlate with the severity of symptoms. An additional 11 patients, 3 without liver metastases, had elevated levels of 5-HIAA without any evidence of carcinoid syndrome. Multicentric carcinoid tumors occurred in 15 patients (10%), and all but one of these tumors were centered around the ileocecal valve. There was no difference in the incidence of liver metastases between solitary (18%) and multicentric carcinoids (20%). Synchronous noncarcinoid tumors were present in 33 patients (22%), and metachronous tumors developed in an additional 14 patients (10%) in follow-up. Age and tumor size, depth, and location were significant predictors of metastases. By multivariate analysis, age > or = 50 years, metastases, and male gender were statistically significant predictors of death. CONCLUSIONS: Gastrointestinal tract carcinoid tumors have a nonspecific clinical presentation, except in the case of the carcinoid syndrome. Surgical resection is the treatment of choice for improving survival. Surgically treated patients with carcinoid tumor have an overall favorable 83% 5-year survival rate.

Carcinoid Tumor↗
PubMed1998

Histopathology of the liver in children with chronic hepatitis C viral infection.

Although the epidemiology, natural history, and pathological aspects of chronic hepatitis C are well-defined in the adult population, little is known about the characteristics of chronic hepatitis C infection in children. Reports on the histological features and progression of hepatitis C in children are scarce, and consist primarily of multicenter studies in Japanese and European children. Given the geographic variations in viral genotype and the association of pathology with genotype, whether the Japanese and European studies can be extended to the North American populations is unclear. We report the histopathology of the liver in 40 children with chronic hepatitis C infection treated in a single North American institution. The children included 19 males and 21 females ranging in age from 2.0 to 18.6 years at the time of liver biopsy (mean +/- SD: 11.4 +/- 4.3 years). Our findings indicate that the characteristic histopathological lesions of chronic hepatitis C infection, including sinusoidal lymphocytosis, steatosis, portal lymphoid aggregates/follicles, and bile duct epithelial damage, occur with approximately the same frequencies in children as have been reported in adults. Necroinflammatory activity was generally mild. Portal fibrosis was present in 78% of the specimens, including fibrous portal expansion (26%), bridging fibrosis (22%), bridging fibrosis with architectural distortion (22%), and cirrhosis (8%). Centrilobular pericellular fibrosis, which has not been previously reported in the context of chronic hepatitis C infection in adults or children, was also a prominent feature in our series, occurring with a similar frequency as steatosis or portal lymphoid aggregates/follicles. Our data suggest that in spite of mild histological necroinflammatory activity in general, the stage of fibrosis in children can be severe in spite of relatively short duration of infection.

Adolescent↗
PubMed1998

Interferon-alpha treatment of chronic hepatitis C virus infection in children.

OBJECTIVES: To determine the safety and efficacy of interferon-alpha therapy of chronic hepatitis C virus (HCV) infection in children. STUDY DESIGN: This was an open-labeled prospective trial of interferon-alpha-2a (IFN-alpha) in children with evidence of HCV infection for at least 6 months. Twenty-three children were enrolled and treated with IFN-alpha at a dosage of 3 million units/m2 three times weekly. Beginning in 1995 patients defined as complete or partial responders after 6 months were offered an additional 6 months of treatment. Endpoints were alanine aminotransferase normalization and loss of hepatitis C viral ribonucleic acid from serum. Responders were compared with nonresponders for age, gender, duration of infection, pretreatment alanine aminotransferase and hepatitis C viral ribonucleic acid levels, saturation of serum iron-binding capacity, histologic score of chronic hepatitis and viral genotype. Statistical methods used for these comparisons included the Kruskal-Wallis test, the Mann-Whitney two-sample test and the Fisher exact test. RESULTS: Of the 21 children who completed at least 6 months of treatment, 4 (19%) had complete response, 8 (38%) had partial response and 9 (43%) had no response. Three of the 4 complete responders had prolonged treatment; in 2 the response was maintained. One responder relapsed but responded to a second, longer course of treatment. Four of the 8 partial responders had prolonged therapy and 3 of them became complete responders. One child who was originally a nonresponder lost HCV RNA within the first year after therapy. Thus eventually 7 (33%) of 21 patients were complete responders. After at least 12 months of follow-up on most of these children, no relapses have been observed. No differences in any of the variables tested could be demonstrated between responders and nonresponders, but small sample size limits power. IFN-alpha was discontinued in only one child because of side effects, and temporary dosage adjustments were needed in 4 children. CONCLUSIONS: IFN-alpha is of some efficacy in the treatment of chronic HCV infection in children. Complete or partial responders at 6 months should undergo prolonged treatment.

Adolescent↗
PubMed1998

Therapeutic touch. Nurturing the nurse leader.

As a complementary modality, therapeutic touch is gaining increasing recognition. Not only are nurses incorporating therapeutic touch into their daily patient care, but patients also are requesting this healing modality. Nurse leaders also use this nursing intervention to weave their vision of healing into their managerial role.

Clinical Nursing Research↗
PubMed1996

Gretchen's crisis.

Explore the source record for details and available documents.

Acute Disease↗
PubMed1996

Gastric and esophageal intraepithelial lymphocytes in pediatric celiac disease.

Celiac disease (CD) is associated with marked mononuclear cell inflammation in the small intestinal mucosa. This study was performed to evaluate analogous changes in the gastric and esophageal mucosa of pediatric patients with CD, with emphasis on epithelial lymphocytosis. We evaluated intraepithelial lymphocytes (IELs) in 23 gastric (no.IELs/100 epithelial cells) and 14 esophageal mucosal biopsy specimens (IELs/hpf) from 23 pediatric cases of CD and 10 nonceliac matched controls. Four patients had postgluten withdrawal biopsy specimens reviewed, and one of these had further postgluten challenge biopsy specimens evaluated as well. Gastric specimens from the CD cases showed a significantly increased IEL count (20.5 +/- 14.4; range, 4-50) compared to controls (3.4 +/- 1.9; range, 1-8; p < 0.001), which also correlated directly with the histologic severity of the small intestinal disease as assessed by the degree of villous shortening. Sixteen (69.5%) of 23 gastric specimens showed > 8 IELs, which was the highest value obtained in control specimens. The four posttreatment specimens showed a significant reduction in the gastric IEL counts from a mean of 19.8 to 3.5 IELs/100 epithelial cells (p < 0.001). The single case that had a further postgluten challenge biopsy showed a return to the pregluten withdrawal IEL count. However, the degree of gastric intraepithelial lymphocytosis did not correlate with any of the clinical data, such as age, gender, presenting symptoms, or serum antibody levels (antigliadin, antireticulin, or antiendomysium). Furthermore, no differences were observed in the IEL count in CD esophageal specimens (5.3 +/- 2.6; range, 2-10) compared to controls (5.2 +/- 1.5; range, 3-8; p = 0.935). These findings suggest that an immune-mediated lymphocytic response linked to gluten occurs in the gastric epithelium, similar to that seen in the small intestine of pediatric patients with CD. Therefore, gastric intraepithelial lymphocytosis may represent a concurrent manifestation of CD rather than a separate entity in the pediatric population.

Biopsy↗
PubMed1995

Postoperative abdominal complications in cardiopulmonary bypass patients: a case-controlled study.

Intraabdominal complications (IAC) after cardiopulmonary bypass often are difficult to diagnose and are associated with high mortality (13% to 67%). From 1984 to 1991 we retrospectively analyzed 53 patients undergoing cardiopulmonary bypass for coronary artery bypass grafting, valve reconstruction, or arch reconstruction who experienced 55 episodes of IAC and compared them with matched control patients (matched for operation, age, and sex). The overall incidence of IAC was 0.65%. Univariate analysis identified the following preoperative variables as significantly (p < 0.05) increasing the risk of IAC: history of congestive heart failure, chronic renal failure, and more than three medical problems. A history of congestive heart failure was the most powerful predictor by multivariate analysis (p = 0.045). Early postcardiopulmonary bypass complications were increased significantly in IAC patients. These included acute renal failure (p < 0.0001), cerebrovascular accidents (p < 0.03), and lower extremity ischemia (p < 0.05). Twenty-eight of 38 laparotomies performed were diagnostic. However, analysis of 58 combined clinical, radiologic, and laboratory tests failed to identify which predicted the diagnostic utility of a laparotomy. Fifteen of the 53 IAC patients (28%) survived: 8 patients had had a therapeutic laparotomy, 1 patient underwent a nondiagnostic laparotomy, and 6 patients were managed nonoperatively. Multivariate analysis identified ventilator dependence (p = 0.004) and acute renal failure with creatinine level greater than 1.9 mg/dL (p = 0.011) as the most powerful predictors of mortality regardless of intervention. These data suggest a profile of cardiac surgical patients at risk for IAC as well as those patients who are most likely to benefit from timely intervention.

Abdomen↗
PubMed1995

Shear stress-conditioned, endothelial cell-seeded vascular grafts: improved cell adherence in response to in vitro shear stress.

BACKGROUND: Prosthetic vascular grafts with adherent endothelial cell monolayers may prove useful for small-caliber vessel bypass. However, endothelial cells adhere poorly to prosthetic graft material, and they are stripped when exposed to in vivo shear stress. This study sought to determine whether in vitro shear stress conditioning improves endothelial cell adhesion and decreases thrombogenicity of endothelial cell-seeded grafts. METHODS: The lumens of 1.5 mm (inside diameter) spun polyurethane polymer vascular grafts were seeded with bovine aortic endothelial cells and cultured in vitro for 6 days with or without continuous laminar shear stress, first at 1 to 2 dynes/cm2 for 3 days, then at approximately 25 dynes/cm2 for 3 days. Grafts preconditioned by shear stress and the static control grafts were then exposed to arterial shear stress at 25 dynes/cm2 for 25 seconds. The number of dislodged cells was counted, and the grafts were examined by light and scanning electron microscopy. Whole blood clotting time in the grafts was also determined. RESULTS: Exposure of grafts to acute shear stress dislodged 1.35 x 10(6) +/- 0.44 x 10(6) cells from static grafts compared with 1.05 x 10(4) +/- 0.16 x 10(4) cells from grafts preconditioned by shear stress. By light and electron microscopy an intact endothelial monolayer was observed to cover the lumen of shear stress-conditioned grafts, whereas few cells remained on the luminal surface of grafts not previously exposed to shear stress. The clotting time in shear stress-conditioned grafts was significantly prolonged in relation to grafts not exposed to shear stress. CONCLUSIONS: These findings show that endothelial cell adhesion and retention on vascular grafts in vitro is markedly enhanced by preconditioning the seeded endothelial cell monolayer with long-term shear stress. Consequently, vascular grafts containing shear stress-conditioned endothelial monolayers are less thrombogenic in vitro than small-caliber vascular grafts without intact endothelial cell monolayers.

Animals↗
PubMed1995

Adhesion and differentiation of endothelial cells by exposure to chronic shear stress: a vascular graft model.

Long-term patency of artificial vascular grafts for hemodialysis access and for bypass or interposition in small caliber arteries is limited due to neointimal hyperplasia and associated graft thrombosis. Given the anticoagulant and vasodilatory properties of endothelial cells, these problems could be partially overcome if grafts were seeded with an adherent monolayer of differentiated endothelial cells, prior to implantation. Endothelial cells in vivo are highly adherent and can resist disruption by hemodynamic shear stress at levels that far exceed physiological conditions. Endothelial cells in vivo also are highly differentiated, with an organized cytoskeleton, Weibel-Palade bodies, and basal stress fibers with focal adhesion plaques. In cell culture, endothelial cells rapidly lose many of their differentiated features, and endothelial cells on artificial surfaces, like vascular graft material, are not sufficiently adherent or differentiated to resist physiologic shear stress. We find that endothelial cells exposed to chronic shear stress in vitro, applied in a stepwise fashion over several days, are induced to become tightly adherent to the substratum and exhibit more differentiated features. Thus, pre-conditioning of endothelial cells seeded on vascular grafts with stepwise shear stress in vitro could be used to improve endothelial cell retention and differentiation for subsequent in vivo use.

Animals↗