Biomedical subjects

S R DeMeester

Publications and source records attributed to S R DeMeester.

36 records · Page 2Linked to original sources

PubMed1999

The extent of Barrett's esophagus depends on the status of the lower esophageal sphincter and the degree of esophageal acid exposure.

OBJECTIVE: The purpose of this study was to assess whether the extent of intestinal metaplasia is related to the severity of the gastroesophageal reflux disease. METHODS: A total of 556 consecutive patients with symptoms suggestive of foregut disease had upper gastrointestinal endoscopy with extensive biopsies from the gastroesophageal junction and the esophagus. All patients had esophageal motility and 24-hour pH monitoring. In 411 patients, cardiac-type mucosa was identified; in 147 patients, the cardiac-type mucosa showed intestinal metaplasia. They were divided into 3 groups based on the extent of intestinal metaplasia commonly seen clinically: long segments (>3 cm), short segments (<3 cm), and limited to the gastroesophageal junction. The duration of symptoms, the status of the lower esophageal sphincter, the degree of esophageal acid exposure, and the time to clear a reflux episode were assessed in each group. RESULTS: The presence of intestinal metaplasia in cardiac-type mucosa was associated with the hallmarks of gastroesophageal reflux disease. The extent of intestinal metaplasia correlated strongly with the degree of esophageal acid exposure (r = 0.711; P <.001) and inversely with the lower esophageal sphincter pressure (r = 0.351; P <.001) and length (r = 0. 259; P =.002). Patients with a long segment of intestinal metaplasia (>3 cm) had longer duration of symptoms (16 years) than those patients with a segment of intestinal metaplasia less than 3 cm (10 years; P =.048) or those patients with intestinal metaplasia limited to the gastroesophageal junction (10 years; P =.01). CONCLUSION: The extent of intestinal metaplasia, that is, Barrett's esophagus, is related to the status of the lower esophageal sphincter and the degree of esophageal acid exposure.

Adolescent↗

PubMed1999

Node status in transmural esophageal adenocarcinoma and outcome after en bloc esophagectomy.

OBJECTIVE: Adenocarcinoma has replaced squamous cell as the most common esophageal cancer in the United States. The purpose of this study was to determine the prevalence and location of lymph node metastases, the feasibility of performing an R0 resection, and disease recurrence and survival in patients with transmural adenocarcinoma of the lower esophagus and gastroesophageal junction. METHODS: Forty-four patients with transmural adenocarcinoma underwent en bloc esophagectomy with systematic thoracic and abdominal lymphadenectomy. They were followed up for a median of 23 months. RESULTS: Actuarial survival for the entire group was 26% at 5 years. The most important predictors of the likelihood of recurrent disease and 5-year survival were the presence and number of lymph node metastases and the ratio of involved to total removed nodes. Seven patients (16%) were found to have no lymph node metastases and had an 85% 5-year survival. In contrast, patients with more than 4 involved nodes or a node ratio greater than 0.1 had a high likelihood of recurrence and death. Location of involved lymph nodes did not predict the likelihood of recurrence or death. Despite all patients having transmural tumors, recurrence within the field of the en bloc resection occurred in only 1 patient (2%). CONCLUSIONS: En bloc esophagectomy in patients with transmural esophageal adenocarcinoma is required to obtain the survival benefit of an R0 resection, to adequately assess lymphatic tumor burden, and to be able to predict the likelihood of recurrence and death and thereby guide the use of postoperative adjuvant therapy.

Abdomen↗

PubMed1999

Prevalence and location of nodal metastases in distal esophageal adenocarcinoma confined to the wall: implications for therapy.

OBJECTIVE: The purpose of this study was to characterize the prevalence and location of regional lymph node metastases in adenocarcinoma confined to the esophagal wall, to determine the extent of dissection required, and to investigate the applicability of nonoperative therapy. METHODS: Histologic evaluation of the resected specimens after en bloc esophagogastrectomy with mediastinal and abdominal lymphadenectomy was performed on 37 patients with adenocarcinoma confined to the esophageal wall. Follow-up was complete in all patients (median 24 months). RESULTS: Fifteen patients (41%) had intramucosal tumors. Twelve (32%) had submucosal tumors and 10 (27%) had muscular invasion. The prevalence of regional lymph node metastases (15/37 patients, 41%) increased progressively with depth of tumor invasion, with involved nodes identified in 80% of patients with muscular invasion. Lymph node metastases were also more common at distant node stations in intramuscular tumors (5/10, 50%). Actuarial survival for the entire group was 63% at 5 years. Recurrence was identified in 6 of the 37 patients (16%), with the risk of recurrence correlating with tumor depth. CONCLUSIONS: Tumor depth is a strong predictor of the probabilities of regional lymph node metastases, the likelihood of involvement of distant node groups, and the risk of recurrence. Patients with invasion of the muscular wall are at particularly high risk. En bloc esophagectomy with mediastinal and abdominal lymphadenectomy has the highest likelihood of achieving an R0 resection. The long-term survival and low recurrence rate achieved with an en bloc esophagectomy emphasizes the importance of an aggressive lymph node dissection to remove all potentially involved nodes.

Adenocarcinoma↗

PubMed1999

Occult esophageal adenocarcinoma: extent of disease and implications for effective therapy.

OBJECTIVE: The need for esophagectomy in patients with Barrett's esophagus, with no endoscopically visible lesion, and a biopsy showing high-grade dysplasia or adenocarcinoma has been questioned. Recently, endoscopic techniques to ablate the neoplastic mucosa have been encouraged. The aim of this study was to determine the extent of disease present in patients with clinically occult esophageal adenocarcinoma to define the magnitude of therapy required to achieve cure. METHODS: Thirty-three patients with high-grade dysplasia (23 patients) or adenocarcinoma (10 patients) and no endoscopically visible lesion underwent repeat endoscopy and systematic biopsy followed by esophagectomy. The surgical specimens were analyzed to determine the biopsy error rate in detecting occult adenocarcinoma. In those with cancer, the depth of wall penetration and the presence of lymph node metastases on conventional histology and immunohistochemistry staining was determined. The findings were compared with those in 12 patients (1 with high-grade dysplasia, 11 with adenocarcinoma) who had visible lesions on endoscopy. RESULTS: The biopsy error rate for detecting occult adenocarcinoma was 43%. Of 25 patients with cancer and no visible lesion, the cancer was limited to the mucosa in 22 (88%) and to the submucosa in 3 (12%). After en bloc esophagectomy, one patient without a visible lesion had a single node metastasis on conventional histology. No additional node metastases were identified on immunohistochemistry. The 5-year survival rate after esophagectomy was 90%. Patients with endoscopically visible lesions were significantly more likely to have invasion beyond the mucosa (9/12 vs. 3/25, p = 0.01) and involvement of lymph nodes (5/9 vs. 1/10, p = 0.057). CONCLUSIONS: Endoscopy with systematic biopsy cannot reliably exclude the presence of occult adenocarcinoma in Barrett's esophagus. The lack of an endoscopically visible lesion does not preclude cancer invasion beyond the muscularis mucosae, cautioning against the use of mucosal ablative procedures. The rarity of lymph node metastases in these patients encourages a more limited resection with greater emphasis on improved alimentary function (esophageal stripping with vagal nerve preservation) to provide a quality of life compatible with the excellent 5-year survival rate of 90%.

Adenocarcinoma↗

PubMed1999

The diagnosis and management of Barrett's esophagus.

Since its description in the 1950s, the definition of Barrett's esophagus has evolved from the macroscopic visualization of gastric-appearing mucosa in the esophagus to the histologic identification of goblet cells confirming the presence of intestinal metaplasia within the esophagus. The length of intestinal metaplasia necessary to be classified as Barrett's, and the relationship between intestinal metaplasia of the esophagus and that limited to the cardia are all areas currently being evaluated. However, any segment of intestinal metaplasia is capable of undergoing dysplastic change and ultimately of becoming a focus of adenocarcinoma. It is logical to expect the degree of risk for developing cancer to be proportional to the amount of intestinal metaplasia present; however, within a population, the low risk to any individual is balanced by the relative frequency of the process. Thus, given the large numbers of people in America with CIM, even a small risk of progression to cancer will result in a large number of patients with adenocarcinoma of the cardia. This is exactly what is occurring today, with the incidence of adenocarcinoma of the cardia and esophagus currently rising faster than any other cancer in the United States. A major risk factor for adenocarcinoma of the esophagus is intestinal metaplasia, which occurs as a consequence of GERD. Patients with Barrett's esophagus usually have more severe reflux disease with significant impairment of LES function and esophageal body motility compared with patients without Barrett's. Furthermore, in patients with Barrett's, the composition of the refluxed juice is different. Patients who reflux both gastric and duodenal juice have a higher prevalence of Barrett's than do those who reflux gastric juice alone. Among patients with Barrett's, a significantly greater esophageal bilirubin exposure has been demonstrated in those with dysplasia. The mechanically defective sphincter and impaired esophageal body function in many patients with Barrett's makes their disease difficult to control medically. In addition, symptoms are unreliable as a guide to successful control of reflux. The hardest symptom to control is regurgitation, and there is concern that this and continued reflux of pharmacologically altered gastric contents, particularly bile acids in their nonpolar form, may contribute to progression of Barrett's. Both medical therapy and failed antireflux surgery are associated with progression of Barrett's to dysplasia and adenocarcinoma. On the other hand, a functioning fundoplication seems to be associated with protection from progression of Barrett's. Intestinal metaplasia of the esophagus is unlikely to regress after antireflux surgery; however, intestinal metaplasia limited to the cardia is perhaps more dynamic and able to regress. Furthermore, low-grade dysplasia frequently regresses after an antireflux procedure. Antireflux surgery is safe, effective, and durable, and often can be performed using minimally invasive techniques. Thus, antireflux surgery should be strongly considered in any patient with intestinal metaplasia of the esophagus or cardia. The possibility of mucosal ablation after an antireflux repair should be considered in patients with low-grade dysplasia. Patients with Barrett's and high-grade dysplasia are at high risk for having a focus of adenocarcinoma present. Even with multiple biopsies, a degree of sampling error exists. Also, adenocarcinoma can develop within the space of several months; and if the cancer is allowed to invade into the submucosa, 50% of these patients will have lymphatic metastases, thereby negating the purpose of surveillance. Although patients with high-grade dysplasia and intramucosal adenocarcinoma on biopsy who do not have an endoscopically visible lesion are unlikely to have lymphatic metastases, 7% do have submucosal invasion. Thus, even in these very early tumors, treatment directed only at the mucosa may be inadequate. (ABSTRACT

Adenocarcinoma↗

PubMed1998

Lobectomy combined with volume reduction for patients with lung cancer and advanced emphysema.

OBJECTIVE: Early-stage lung cancer is best treated by anatomic pulmonary resection. Patients with lung cancer and severe emphysema are often denied resection or are offered only limited, nonanatomic resections when established pulmonary function criteria for lobectomy are not met. Recently, with the introduction of the volume reduction operation, selected patients with disabling emphysema have undergone excision of approximately 30% of the most destroyed lung tissue and have subsequently demonstrated subjective and objective improvement in pulmonary function. Using these principles, we elected to combine anatomic lobectomy with volume reduction in a select group of patients with both emphysema and lung cancer who would not otherwise be candidates for pulmonary resection. METHODS: Five patients with severe emphysema and suspected or proven lung cancers, who were poor candidates for anatomic lobectomy by traditional criteria but were good candidates for volume reduction, underwent lobectomy combined with volume reduction of one or more additional lobes. RESULTS: All five patients having lung volume reduction and anatomic lobectomy for early-stage primary lung cancer did well postoperatively. Furthermore, each patient has demonstrated subjective and objective improvement in respiratory function on serial postoperative studies. CONCLUSIONS: Selected patients with disabling emphysema and suitable anatomy for volume reduction, who have a lung cancer situated in destroyed lung tissue, may benefit from combined lobectomy and volume reduction. The introduction of the volume reduction operation has added a new factor in the algorithm for the evaluation and treatment of lung cancer in selected patients with advanced emphysema.

Aged↗

PubMed1998

The impact of an antireflux procedure on intestinal metaplasia of the cardia.

OBJECTIVE: The aim of this study was to determine whether antireflux surgery is more effective in producing loss of intestinal metaplasia located only at the gastroesophageal junction than it has been in patients with intestinal metaplasia extending up into the distal esophagus. SUMMARY BACKGROUND DATA: Biopsies of a normal appearing gastroesophageal junction will demonstrate cardiac mucosa containing goblet cells--the hallmark of intestinal metaplasia--in 10% to 15% of patients who are evaluated for symptoms of gastroesophageal reflux. The incidence of adenocarcinoma of the esophagus and cardia is rising faster than any other cancer in America, and most of these cancers are found adjacent to areas of intestinal metaplasia. Antireflux surgery in patients with Barrett's esophagus may provide protection from progression to dysplasia and cancer; however, it does not reliably cause regression of the intestinal metaplasia. Less is known about the potential for intestinal metaplasia limited to the cardia (CIM) to regress. METHODS: Sixty patients with intestinal metaplasia of the esophagus or cardia had antireflux surgery. Patients in the intestinal (CIM) group (n = 15) had no endoscopically visible segment of columnar epithelium. Patients in the Barrett's group (n = 45) had columnar epithelium visible within the esophagus. Median follow-up was 25 months in each group. RESULTS: Postoperative biopsies showed complete loss of intestinal metaplasia in 73% of the patients with CIM compared with 4.4% of the patients with Barrett's. Low-grade dysplasia, present in 10 patients preoperatively, regressed in 7 patients (70%). No patient progressed to high-grade dysplasia or cancer. CONCLUSIONS: Loss of intestinal metaplasia after antireflux surgery is rare in patients with Barrett's, but occurred in most patients with CIM. This suggests that cardiac epithelium is dynamic and that microscopic areas of intestinal metaplasia are able to regress much more frequently than longer, visible segments of intestinal metaplasia.

Adult↗

PubMed1998

Pharyngeal swallowing disorders: selection for and outcome after myotomy.

OBJECTIVE: To develop selection criteria based on the mechanical properties of pharyngoesophageal swallowing that indicate when patients with pharyngeal dysphagia will benefit from a myotomy. SUMMARY BACKGROUND DATA: The pathophysiology of pharyngoesophageal swallowing disorders is complex. The disorder is of interest to several medical specialists (gastroenterologists, otorhinolaryngologists, general and thoracic surgeons), which contributes to confusion about the entity. The management is compounded because it is most frequently seen in the elderly, is often associated with generalized neuromuscular disease, and occurs with a high prevalence of concomitant disease. The selection of patients for myotomy is difficult and of major importance to the quality of life of the affected patients. METHOD: One hundred seven patients without a Zenker diverticulum but with pharyngeal dysphagia underwent a detailed manometric assessment of the upper esophageal sphincter (UES). Cricopharyngeal opening was identified by the presence of a subatmospheric pressure drop before bolus arrival. Impaired pharyngoesophageal segment compliance resulting in a resistance to pharyngoesophageal flow was determined by measuring the intrabolus pressure generated by a 5-ml liquid bolus. RESULTS: Thirty-one of 107 patients underwent a myotomy (29%). Both impaired sphincter opening and increased intrabolus pressure predicted a good outcome. CONCLUSION: Myotomy is beneficial in patients with pharyngeal swallowing disorders and manometric evidence of defective sphincter opening and increased intrabolus pressure.

Adult↗

PubMed1997

Management of Barrett's esophagus free of dysplasia.

Barrett's esophagus is a condition in which intestinal metaplasia replaces a portion of the normal squamous epithelium lining the distal esophagus. It occurs as a consequence of chronic gastroesophageal reflux. Patients with Barrett's often have both lower esophageal sphincter dysfunction and impaired esophageal body motility, and therefore tend to have relatively severe reflux. In addition, it is likely that the composition of refluxed material is important in patients with Barrett's. There is increasing evidence that Barrett's and complications of Barrett's are related to duodenogastric rather than pure gastric reflux. By allowing continued duodenogastric reflux, acid suppression therapy may promote the development of Barrett's. On the other hand, a functioning fundoplication abolishes reflux, ends repetitive injury to the esophageal mucosa, and is associated with a decreased incidence of disease progression in patients with Barrett's compared with medical therapy. Barrett's is a premalignant condition, and all patients should undergo routine endoscopic surveillance. Patients with adenocarcinoma detected while on surveillance present at an earlier stage and have better survival than patients who present outside a surveillance program. In the future, mucosal ablation techniques may allow removal of the metaplastic epithelium and eliminate the risk of malignancy.

Adenocarcinoma↗

PubMed1996

Attenuation of rat lung isograft reperfusion injury with a combination of anti-ICAM-1 and anti-beta2 integrin monoclonal antibodies.

Four different combinations of monoclonal antibodies against rat ICAM-1, CD-11a, and CD-18 were utilized to determine the relative importance of LFA-1, Mac-1, and ICAM-1 in a rat model of severe lung allograft reperfusion injury. Negative control animals were given phosphate buffered saline (the carrier solution for the antibodies), while positive control animals were rendered neutropenic by the administration of a polyclonal mouse IgG. Antibodies were given with the donor lung flush, prior to left lung graft reperfusion, or both. Isolated graft function was determined 24 hr after implantation by arterial blood gas (ABG), and after sacrifice the native and transplanted lungs underwent bronchoalveolar lavage for alveolar protein quantitation, cell count and differential, and myeloperoxidase assay. Additionally, whole lung homogenates were assayed for myeloperoxidase activity. We found that the combination of anti-ICAM-1 (1 mg/kg) added to the donor lung flush, and anti-CD11a, anti-CD18, and anti-ICAM-1 (2 mg/kg i.v. of each) given to the recipient prior to reperfusion, resulted in significantly improved lung graft pAO2 by ABG, and decreased alveolar protein, cell count, and myeloperoxidase activity compared with control animals. Improvement was less than that seen in the neutropenic recipients, however. We conclude that LFA-1, Mac-1, and ICAM-1 are all important adhesion molecules in lung allograft reperfusion injury--yet even with antibody blockade of all three there are additional mechanisms allowing for neutrophil influx into the lungs.

Animals↗

PubMed1996

Inhaled nitric oxide improves lung allograft function after prolonged storage.

Morbidity caused by early allograft dysfunction, manifested by a progressive increase in pulmonary vascular resistance and a decrease in oxygenation, remains a serious problem in lung transplantation. Inhalation of nitric oxide, an essential homeostatic molecule, has been shown to have beneficial effects on a variety of acute lung injuries. The purpose of the present study was to investigate the effect of inhaled nitric oxide on posttransplant function of canine left lung allografts. Fourteen dogs underwent left lung allotransplantation. Donors received systemic heparin and prostaglandin E1 followed by pulmonary artery flush with modified Euro-Collins solution. Donor left lungs were stored for 18 hours at 1 degree C and subsequently implanted. Immediately after reperfusion, the contralateral right main pulmonary artery and bronchus were ligated. The chest was closed and recipients turned to the supine position for the 6-hour assessment period. Hemodynamic and arterial and venous blood gas analyses were made at 15-minute intervals at an inspired oxygen fraction of 1.0 and 5 cm of water positive end-expiratory pressure. Animals were killed at the end of the assessment. Allograft myeloperoxidase activity assays and wet/dry weight ratios were done. In group I (n = 5), nitric oxide gas was administered continuously at concentrations of 60 to 70 ppm before reperfusion and throughout the 6-hour assessment period. In group II (n = 5), nitric oxide administration was initiated at the same concentration after reperfusion injury had developed. Group III animals (n = 4) received no nitric oxide. Significant improvement in gas exchange was apparent in group I. At the end of the 6-hour assessment period, mean arterial oxygen tension was 253.8 +/- 44.7 mm Hg and 114.9 +/- 25.5 mm Hg in groups I and III, respectively (p < 0.05). Group II animals had no improvement in oxygenation with nitric oxide. Systemic hemodynamics were unaffected by nitric oxide. However, an immediate decrease in pulmonary vascular resistance was noted. Group I myeloperoxidase activity was significantly lower than that in control group III (0.24 +/- 0.06 versus 0.36 +/- 0.04 units, respectively; p < 0.05).

Administration, Inhalation↗

PubMed1995

Effect of ischemic injury on subsequent rat lung allograft rejection.

BACKGROUND: It has been suggested that the frequency and severity of allograft rejection may be related to the degree of allograft ischemia. The purpose of this study was to determine whether ischemic insult correlates with lung allograft rejection. METHODS: Forty-eight left lung transplants were performed from Lewis donor rats into F344 recipient rats. Allografts were divided into two groups based on the degree of ischemic insult. Transplantation was performed immediately (group 1, minimum injury) or after 18 hours of cold (1 degree C) preservation (group 2, severe injury). Allografts were evaluated radiographically based on aeration scores (0 = opaque to 6 = normal). Animals were randomly sacrificed on days 7, 14, or 21 for histologic and immunohistochemical evaluation of rejection. RESULTS: On postoperative day 3, significantly lower aeration score was demonstrated in group 2 (3.69 +/- 1.71) compared to group 1 (5.0 +/- 1.09) (p < 0.05) as a result of the difference in reperfusion injury. However, by day 7 and thereafter, there was no significant difference. Histologic rejection was present by day 7 and peaked at day 14 with no significant difference between groups. There was also no difference in CD4+, CD8+ infiltrating lymphocyte population or expression of class II major histocompatibility complex antigen on bronchial epithelium. CONCLUSIONS: We conclude that ischemic injury in rat lung allograft does not correlate with the onset or severity of rejection.

Animals↗

PubMed1995

Inhibition of inducible nitric oxide synthase ameliorates rat lung allograft rejection.

Recently, the inducible isoform of nitric oxide synthase has been shown to be an important immunomodulation molecule in allograft rejection. We have observed the production of nitric oxide during rejection and the effect of nitric oxide synthase inhibition on allograft rejection in a rat lung transplant model. Rat left lung allotransplants were performed in two strain combinations: brown Norway-to-F344 (major histocompatibility complex incompatible); and Lewis-to-F344 (minor loci incompatible) as severe and mild rejection models respectively. Syngeneic F344-to-F344 transplants were performed as a negative control. Nitric oxide production during rejection was determined by measuring the recipient's serum nitrite/nitrate levels as a stable end product of nitric oxide. The progression of rejection was evaluated radiographically and the grade of rejection was determined histologically. After operation, recipients of allotransplantation were randomly divided into two groups and received either aminoguanidine (200 mg/kg, intraperitoneal every 6 hours), a potent inducible nitric oxide synthase inhibitor, or normal saline treatment. The levels of serum nitrite and nitrate in recipients increased in the early phase of rejection in both allotransplant combinations. However, in the terminal phase of rejection, the serum nitrite/nitrate level decreased significantly compared with the peak level in the brown Norway-to-F344 recipients. The serum nitrite/nitrate levels in the syngeneic transplant recipients were normal during the entire observation period. In aminoguanidine-treated animals, serum nitrite/nitrate levels remained normal in both allograft combinations. Significant suppression of rejection in aminoguanidine-treated recipients was observed histologically and radiographically in comparison with untreated recipients in the brown Norway-to-F344 combinations. In the Lewis-to-F344 combination, aminoguanidine treatment significantly ameliorated histologic rejection but did not affect radiologic appearance. We therefore conclude nitric oxide is produced during early allograft rejection and may prove to be a marker and mediator of early rejection. The inhibition of inducible nitric oxide synthase results in significant reduction in rat lung allograft rejection.

Animals↗

PubMed1994

Pentoxifylline reduces lung allograft reperfusion injury.

Early graft dysfunction remains a significant problem in clinical lung transplantation. Pentoxifylline, a methylxanthine derivative, has been shown to have various beneficial effects on neutrophil-induced lung injury. We investigated effects of pentoxifylline on early posttransplantation lung function in a canine allograft model. Ten dogs underwent left lung allotransplantation. Donor lungs were flushed with modified Euro-Collins solution (50 mL/kg) and stored in an inflated state for 18 hours at 1 degrees C. In five experiments (group I), pentoxifylline was added to the flush and storage solutions (200 mg/L) at the time of harvest. The recipient animals received pentoxifylline (20 mg/kg intravenously) before reperfusion followed by pentoxifylline (0.1 mg.kg-1.min-1 intravenously) during the 6-hour posttransplantation assessment period. In group II, donors and recipients received no pentoxifylline. To evaluate only allograft function, the right main pulmonary artery and bronchus were ligated immediately after implantation. For 6 hours thereafter hemodynamics and gas exchange were assessed at 15-minute intervals while the animal was ventilated at an inspired oxygen fraction of 1.0. After 1 hour of assessment there was a significant difference in gas exchange between the groups, which persisted until the end of the study. By the end of the 6-hour assessment, the mean arterial oxygen tension was 236.7 mm Hg for group I versus 101.1 mm Hg for group II (p < 0.01), and the alveolar-arterial oxygen difference was 443.1 mm Hg versus 562.2 mm Hg (p < 0.015). Hemodynamics were not different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

The bimodal expression of tumor necrosis factor-alpha in association with rat lung reimplantation and allograft rejection.

Lung transplantation has become a therapeutic option for a number of end-stage pulmonary disorders. Lung transplant recipients experience more complications due to acute and chronic allograft rejection as compared to recipients of other solid organs. We postulated that the generation of TNF-alpha plays a significant role in the pathogenesis of acute lung allograft rejection. To test our hypothesis, we used a RT1-incompatible rat lung allograft model and demonstrated the time course, cellular source(s), and major compartment(s) of TNF production during the course of lung allograft rejection. This model allowed for immunogenetic standardization and reproducibility of lung allograft rejection across disparate major histocompatibility barriers. TNF production was characterized at the whole animal, organ, cellular, and molecular levels, and was found to be compartmentalized and expressed in a bimodal fashion from the lung allograft during lung allograft reimplantation and maximal rejection. Lung allograft rejection was significantly attenuated in animals pretreated with neutralizing TNF antisera as compared to animals receiving control sera. These findings may provide interesting insight into the use of novel and specific therapeutic intervention(s) during periods of acute lung allograft rejection.

Animals↗

PubMedDate not supplied

Suppression of gastric acid secretion in patients with gastroesophageal reflux disease results in gastric bacterial overgrowth and deconjugation of bile acids.

The aim of this study was to test the hypothesis that gastric bacterial overgrowth is a side effect of acid suppression therapy in patients with gastroesophageal reflux disease (GERD) and that the bacteria-contaminated gastric milieu is responsible for an increased amount of deconjugated bile acids. Thirty patients with GERD who were treated with 40 mg of omeprazole for at least 3 months and 10 patients with GERD who were off medication for at least 2 weeks were studied. At the time of upper endoscopy, 10 ml of gastric fluid was aspirated and analyzed for bacterial growth and bile acids. Bacterial overgrowth was defined by the presence of more than 1000 bacteria/ml. Bile acids were quantified via high-performance liquid chromatography. Eleven of the 30 patients taking omeprazole had bacterial overgrowth compared to one of the 10 control patients. The median pH in the bacteria-positive patients was 5.3 compared to 2.6 in those who were free of bacteria and 3.5 in the control patients who were off medication. Bacterial overgrowth only occurred when the pH was >3.8. The ratio of conjugated to unconjugated bile acids changed from 4:1 in the patients without bacterial overgrowth to 1:3 in those with bacterial growth greater than 1000/ml. Proton pump inhibitor therapy in patients with GERD results in a high prevalence of gastric bacterial overgrowth. The presence of bacterial overgrowth markedly increases the concentration of unconjugated bile acids. These findings may have implications in the pathophysiology of gastroesophageal mucosal injury.

Anti-Ulcer Agents↗

PubMedDate not supplied

Telomerase reverse transcriptase expression is increased early in the Barrett's metaplasia, dysplasia, adenocarcinoma sequence.

Barrett's esophagus is a multistage polyclonal disease that is associated with the development of adenocarcinoma of the esophagus and esophagogastric junction. Telomerase activation is associated with cellular immortality and carcinogenesis, and increased expression of the telomerase reverse transcriptase catalytic subunit (hTERT) has been used for the early detection of malignant diseases. To identify biomarkers associated with each stage of the Barrett's process, relative mRNA expression levels of hTERT were measured using a quantitative reverse transcription-polymerase chain reaction method (ABI 7700 Sequence Detector (TaqMan system) in Barrett's intestinal metaplasia (n = 14), Barrett's dysplasia (n = 10), Barrett's adenocarcinoma (n = 14), and matching normal squamous esophagus tissues (n = 32). hTERT expression was significantly increased at all stages of Barrett's esophagus, including the intestinal metaplasia stage, compared to normal tissues from patients without cancer (intestinal metaplasia vs. normal esophagus, P <0.0001; dysplasia, P = 0.001; adenocarcinoma, P = 0.007; all Mann-Whitney U test ). hTERT expression levels were significantly higher in adenocarcinoma tissues than in intestinal metaplasia tissues (P = 0.003), and were higher in dysplasia compared with intestinal metaplasia tissues (P = 0.056). hTERT levels were also significantly higher in histologically normal squamous esophagus tissues from cancer patients than in normal esophagus tissues from patients with no cancer (P = 0.013). Very high expression levels ([hTERT x 100: beta-actin] >20) were found only in patients with cancer. These findings suggest that telomerase activation is an important early event in the development of Barrett's esophagus and esophageal adenocarcinoma, that very high telomerase levels may be a clinically useful biomarker for the detection of occult adenocarcinoma, and that a widespread cancer "field" effect is present in the esophagus of patients with Barrett's cancer.

Adenocarcinoma↗

PubMedDate not supplied

Multivariate analysis of factors predicting outcome after laparoscopic Nissen fundoplication.

Laparoscopic Nissen fundoplication has been applied with increasing frequency in the treatment of gastroesophageal reflux disease. The aim of this study was to determine the variables that predict outcome of laparoscopic Nissen fundoplication. A multivariate analysis was performed on data from 199 consecutive patients undergoing laparoscopic Nissen fundoplication. Variables included age, sex, body mass index, primary symptoms, clinical response to acid suppression therapy, erosive esophagitis, 24-hour esophageal pH score, and the percentage of time the esophageal pH was less than 4 on 24-hour pH monitoring, lower esophageal sphincter competence, status of the esophageal body motility, hiatal hernia, carditis, intestinal metaplasia of cardiac epithelium limited to the gastroesophageal junction, and Barrett's esophagus of any length. Clinical outcome was obtained from all patients at a median follow-up of 15 months (range 6 to 74 months) after surgery. One hundred seventy-three patients had an excellent or good outcome (87%) and 26 had a fair or poor outcome. Three factors were significantly predictive of a successful outcome: an abnormal 24-hour pH score (odds ratio = 5.4; 95% confidence interval [CI] = 1. 9-15.3), a typical primary symptom (odds ratio = 5.1; 95% CI = 1. 9-13.6), and a clinical response to acid suppression therapy (odds ratio = 3.3; 95% CI = 1.3-8.7). We conclude that 24-hour pH monitoring provides the strongest outcome predictor of laparoscopic Nissen fundoplication and that outcome is based more on the correct identification of the disease than on its severity.

Adolescent↗