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Biomedical subjects

J H Peters

Publications and source records attributed to J H Peters.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1998

Normal esophageal body function: a study using ambulatory esophageal manometry.

OBJECTIVE: The objective of this study was to establish normative ambulatory manometric data for contractions and contraction propagation in three levels of the esophagus. METHODS: Twenty-five healthy volunteers underwent simultaneous ambulatory 24 h manometry. Concomitant 24 h pH studies were performed to exclude the presence of increased esophageal acid exposure. Pressures were recorded over a complete circadian cycle while patients continued with their normal lifestyles including eating and sleeping. Data were analyzed with a software program that was previously modified and validated and that enables quantitation of contractions in terms of efficacy. RESULTS: The frequency of contractions was lowest during sleep, was increased when awake, and was highest during meals. Contraction amplitude increased during meals, providing a greater propulsive force for bolus transport. Similarly, the prevalence of peristaltic waves varied according to different physiologic states, ie., while eating, upright, awake, and sleeping. An increased amplitude and prevalence of peristalsis resulted in an increase in manometric efficacy during meals. CONCLUSIONS: This study provides normative data for ambulatory manometry for comparison when studying patients with disease.

Adult↗
PubMed1998

In-vitro differentiation of mature dendritic cells from human blood monocytes.

Representing the most potent antigen-presenting cells, dendritic cells (DC) can now be generated from human blood monocytes. We recently presented a novel protocol employing GM-CSF, IL-4, and IFN-gamma to differentiate monocyte-derived DC in vitro. Here, such cells are characterized in detail. Cells in culture exhibited both dendritic and veiled morphologies, the former being adherent and the latter suspended. Phenotypically, they were CD1a-/dim, CD11a+, CD11b++, CD11c+, CD14dim/-, CD16a-/dim, CD18+, CD32dim/-, CD33+, CD40+, CD45R0+, CD50+, CD54+, CD64-/dim, CD68+, CD71+, CD80dim, CD86+/++, MHC class I++/ , HLA-DR++/ , HLA-DP+, and HLA-DQ+. The DC stimulated a strong allogeneic T-cell response, and further evidence for their autologous antigen-specific stimulation is discussed. Although resembling a mature CD11c+ CD45R0+ blood DC subset identified earlier, their differentiation in the presence of the Th1 and Th2 cytokines IFN-gamma and IL-4 indicates that these DC may conform to mature mucosal DC.

Animals↗
PubMed1997

Apoptosis in the small intestinal allograft of the rat.

BACKGROUND: Necrosis and apoptosis are different cell death mechanisms. Necrosis is a pathological process that occurs after destruction of the cell membrane. Apoptosis is a DNA-dependent cell death mechanism, which occurs under physiological and pathological conditions. Although necrosis is a well-defined phenomenon in an acute graft rejection, the occurrence and relevance of apoptosis during this process is largely unknown. METHODS: The enterocyte apoptosis rates in allografted (n=24) and isografted (n=24) small intestines of the rat were compared using the in situ end-labeling technique. RESULTS: In situ end-labeling showed a dramatically increased number of apoptotic enterocytes in allografted small intestines, whereas increased labeling could not be observed in isogeneic small intestinal grafts. CONCLUSIONS: We suggest that graft rejection-associated apoptosis, in addition to necrosis, plays an important role in the course of organ failure, and that the degree of apoptosis represents another reliable indicator for the diagnosis and prognosis of transplant rejection.

Animals↗
PubMed1997

Nissen fundoplication prevents shortening of the sphincter during gastric distention.

OBJECTIVE: To determine the dynamic effects of a Nissen fundoplication on a volume-stressed lower esophageal sphincter (LES). DESIGN: Before and after experimental study in 10 baboons. SETTING: University animal research unit. INTERVENTIONS: Continuous manometric evaluation of the esophagus, cardia, and stomach during distention of the stomach with water. Slow motorized pull-through of the LES after each successive intragastric increment of 50 mL of water. Tests were performed again after a Nissen fundoplication. MAIN OUTCOME MEASURES: Lower esophageal sphincter length and frequency of common cavity episodes after each volume increment. The pressure and intragastric volume at the yield point are defined as the point of permanent loss of the gastroesophageal pressure gradient. RESULTS: Gastric distention of the stomach with water resulted in a progressive decrease in LES length and competency. The median +/- interquartile range LES length decreased by 1.5 +/- 0.3 mm for every 1-mm Hg increase in gastric pressure before fundoplication and by 0.2 +/- 0.1 mm after fundoplication (P < .02). With gastric distention there was an indirect correlation between the degree of LES length and the frequency of reflux episodes (r = -0.70). This correlation was abolished by a Nissen fundoplication (r = -0.31). The median +/- interquartile range frequency of common cavity episodes (2.19 +/- 2.05 episodes per minute) before fundoplication decreased significantly (P < .001) to 0 +/- 0.59 episodes per minute after fundoplication. The median +/- interquartile range yield pressure (13 +/- 9 mm Hg) and yield volume (825 +/- 855 mL) were significantly (P < .01) improved after Nissen fundoplication to 39 +/- 36 mm Hg and 1250 +/- 750 mL, respectively. CONCLUSION: By preventing sphincter shortening, a Nissen fundoplication improves competency of the LES to progressive degrees of gastric distention.

Animals↗
PubMed1997

A new intraluminal antigastroesophageal reflux procedure in baboons.

BACKGROUND: A new endoscopic intraluminal procedure (valvuloplasty) was designed to provide a simple, easy approach to the cardia and to correct and augment any mechanical deficiencies present. The feasibility, durability, and efficacy of this procedure was tested in 13 baboons. METHODS: The valvuloplasty consisted of an intussusception of the gastroesophageal junction into the stomach to create a nipple-type valve. The configuration of the valve was maintained with eight staples and stability was aided by an intramural injection of sodium morrhuate. Gastrointestinal endoscopy and esophageal manometry were performed before and after the procedure. Competency was determined as the intragastric pressure (yield pressure) and volume (yield volume) needed to result in equalization of gastric and esophageal pressure while distending the stomach with water. Comparisons were made with a group of normal baboons (n = 10). RESULTS: All baboons had a normal eating pattern with none showing any evidence of vomiting or regurgitation. Endoscopic circumferential integrity of the valves was 86% at 6 months. The median lower esophageal sphincter length in the valvuloplasty group was significantly (p < 0.01) increased after the procedure from 21 mm to 30 mm. The median yield pressure (22.1 mm Hg) and yield volume (1,525 ml) of the valvuloplasty group was significantly (p < 0.01) greater than the controls (14 mm Hg and 859 ml). CONCLUSIONS: The valvuloplasty is simple, safe, and durable. It augments mechanical function of the cardia and improves competency.

Animals↗
PubMed1997

Isolated upright gastroesophageal reflux is not a contraindication for antireflux surgery.

BACKGROUND: Patients with gastroesophageal reflux disease who reflux only in the upright position are thought to have a less severe abnormality. Controversy exists over whether these patients should be considered candidates for antireflux surgery. METHODS: A total of 224 consecutive patients with increased esophageal acid exposure on 24-hour pH monitoring were classified as having upright (n = 54), supine (n = 72), or bipositional (n = 98) reflux and were evaluated by manometry and endoscopy. Of these, 116 patients had a laparoscopic Nissen fundoplication. Their clinical outcome at a median of 12 months (range 4 to 44 months) was compared. RESULTS: Patients with upright reflux had a lower prevalence of a structurally defective lower esophageal sphincter, fewer hiatal hernias, and less esophageal injury when compared to those with bipositional reflux (p < 0.005). Excellent (asymptomatic) or good outcome (minor symptoms not requiring acid suppression therapy) was achieved in 86% of the patients with upright reflux, 90% of those with supine reflux, and 89% of those with bipositional reflux. CONCLUSIONS: Patients with upright reflux have less complicated, earlier disease and have results equivalent to those patients with supine and bipositional reflux after antireflux surgery.

Adolescent↗
PubMed1997

Composition and concentration of bile acid reflux into the esophagus of patients with gastroesophageal reflux disease.

BACKGROUND: Reflux of duodenal contents into the esophagus of patients with gastroesophageal reflux disease has been suggested by pH and bilirubin monitoring but is rarely directly measured. A portable device has been developed and was used to collect and quantitate material refluxed into the esophagus under ambulatory conditions during a prolonged time period. The objective of this study was to use this device to quantitate the composition and concentration of bile acids refluxed into the esophagus of patients with gastroesophageal reflux disease. METHODS: Esophageal aspiration was performed on 43 normal subjects and 37 patients with reflux disease during a 17-hour period. Aspiration was performed through a modified 16F Salem sump tube, positioned 5 cm above the lower esophageal sphincter and connected to a portable, battery powered pump that aspirated continuously at 100 mm Hg pressure. Validation studies showed that minimal amounts of saliva and swallowed liquids were aspirated and that gastric pressure was not altered. Postprandial, upright, and supine collections were performed. Total bile acids were assayed by a standard enzymatic assay; specific conjugated bile acids were analyzed by high-performance liquid chromatography. RESULTS: There was no difference in the total aspiration volume between normal volunteers and patients with gastroesophageal reflux disease, although patients tended to have a higher volume in the supine and postprandial periods. Bile acids could be detected in 58% of normal subjects and 86% of patients (p < 0.003). The mean concentration of bile salt exposure (micromole per liter) was higher in patients during the postprandial and supine periods. The mean bile acid reflux rate (micromole per hour) during all three aspiration periods was significantly higher in patients. On a molar basis the composition of the bile acids was 60% glycocholic acid, 16% glycodeoxycholic acid, and 15% glycochenodeoxycholic acid. Taurocholic, taurodeoxycholic, taurochenodeoxycholic, and glycolithocholic acid constituted the remaining 10%. CONCLUSIONS: Patients with reflux disease have an increased concentration of bile acids in their esophageal aspirates. Most of the exposure occurs during the postprandial and supine periods. A variety of bile acids were detected, most of which were in their glycine conjugated form.

Adult↗
PubMed1997

Esophageal replacement for end-stage benign esophageal disease.

The fact that esophageal resection and foregut reconstruction for benign disease can be performed with only a 2% mortality and minimal morbidity is encouraging news to patients who are crippled by the various manifestations of end-stage disease. The continuation of slow, anxious, and socially restricted alimentation or the maintenance of nutrition by enteral or parenteral means is unnecessary. The patient should be referred to a unit skilled in evaluating foregut function, performing esophageal replacement surgery, and caring for patients in the perioperative period. In our experience, the colon, when available, is the preferred conduit for esophageal replacement over the long term. Even though some subtle preoperative symptoms of foregut dysfunction may persist after surgery, the overall outcome is generally judged to be satisfactory. Indeed, patients can re-enter society and live a normal and fulfilled life after remedial surgery. Prolonged attempts at medical management of patients with severe derangements of esophageal structure and function are not warranted. Long-term esophageal replacement for severe end-stage benign disease can be accomplished with low mortality, a high degree of success, and a marked improvement in the quality of alimentation. Reconstruction restores the pleasure of eating and is viewed by the patient to be highly successful.

Colon↗
PubMed1997

The surgical management of Barrett's esophagus.

Barrett's esophagus is an increasing health concern in most Western countries. The diagnosis is usually made during investigation of patients with symptoms of gastroesophageal reflux disease. The appropriate antireflux procedure, performed in properly selected patients, provides long-term symptomatic relief in 80% to 90% of patients. The effect of reliable and complete control of gastroesophageal reflux on the natural history of Barrett's metaplasia once it has developed and on its prevention in symptomatic patients who have not yet developed Barrett's changes is one of the most important areas of study over the next decade.

Barrett Esophagus↗
PubMed1997

Enrichment and characterization of dendritic cells from rat renal mesangium.

Dendritic cells (DC) initiate primary immune reactions and are distributed throughout most tissues. The most potent DC population of the kidney has long been suggested to reside within the glomerular mesangium. Using LEW.1A rats, we enriched and characterized such low-density cells. Mesangial DC generally exhibited round to oval cell bodies and cytoplasmic veils. Phenotypically, these cells were 100% OX-6++, 45% OX-42++, 35% ED1low, 10% OX-62low, and negative for ED2 and alpha-naphtylbutyrate esterase. Introducing a new monoclonal antibody, R3, which stains a subset of splenic DC, we showed strong antigen expression on 60% of mesangial DC. Correlating cell populations were detected immunohistochemically. Functionally, mesangial DC potently stimulated allogeneic mixed leucocyte reactions, but did not phagocytose opsonized Escherichia coli. In addition to their striking phenotypic similarity with autologous splenic DC, mesangial DC exhibited 88% of the allostimulatory activity of splenic DC. Calculation indicated approximately two mesangial DC per glomerulum. We suggest that these cells comprise different maturation-dependent subsets. The OX-62 integrin especially appears to be expressed only on mature mesangial DC, which may correlate to lymphoid veiled cells or interdigitating DC. An employment of mesangial DC in experimental models of acute allograft rejection or glomerulonephritis is discussed.

Animals↗
PubMed1997

A human in vitro granuloma model using heat killed Candida albicans cells immobilized on plastic culture wells.

A new model for studying the initial events of granuloma formation in vitro is presented using heat killed Candida albicans immobilized on the surface of plastic culture wells. Human monocytes were induced to accumulate and to proliferate, forming multinucleated giant cells (MGC) and epitheloid cells within 4 days of culture. Tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta and IL-6 were detected in culture supernatants. These monokines, and additionally macrophage colony stimulating factor (M-CSF), were also detected immunocytochemically. The granuloma formation was inhibited by Dexamethasone (Dex), Pentoxifylline (POF), or interferon-gamma (IFN-gamma) in a dose-dependent manner. Antibodies to M-CSF reduced the granuloma formation to a great extent with a striking reduction of monocyte proliferation. Using antibodies to TNF-alpha the authors found a complete inhibition of the granuloma including MGC formation and monocyte proliferation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1997

Inflammation and specialized intestinal metaplasia of cardiac mucosa is a manifestation of gastroesophageal reflux disease.

OBJECTIVE: The purpose of the study was to test the hypothesis that cardiac mucosa, carditis, and specialized intestinal metaplasia at an endoscopically normal-appearing cardia are manifestations of gastroesophageal reflux disease. SUMMARY BACKGROUND DATA: In the absence of esophageal mucosal injury, the diagnosis of gastroesophageal reflux disease currently rests on 24-hour pH monitoring. Histologic examination of the esophagus is not useful. The recent identification of specialized intestinal metaplasia at the cardia, along with the observation that it occurs in inflamed cardiac mucosa, led the authors to focus on the type and condition of the mucosa at the gastroesophageal junction and its relation to gastroesophageal reflux disease. METHODS: Three hundred thirty-four consecutive patients with symptoms of foregut disease, no evidence of columnar-lined esophagus, and no history of gastric or esophageal surgery were evaluated by 1) endoscopic biopsies above, at, and below the gastroesophageal junction; 2) esophageal motility; and 3) 24-hour esophageal pH monitoring. The patients were divided into groups depending on the histologic presence of cardiac epithelium with and without inflammation or associated intestinal metaplasia. Markers of gastroesophageal reflux disease were compared between groups (i.e., lower esophageal sphincter characteristics, esophageal acid exposure, the presence of endoscopic erosive esophagitis, and hiatal hernia). RESULTS: When cardiac epithelium was found, it was inflamed in 96% of the patients. The presence of cardiac epithelium and carditis was associated with deterioration of lower esophageal sphincter characteristics and increased esophageal acid exposure. Esophagitis occurred more commonly in patients with carditis whose sphincter, on manometry, was structurally defective. Specialized intestinal metaplasia at the cardia was only seen in inflamed cardiac mucosa, and its prevalence increased both with increasing acid exposure and with the presence of esophagitis. CONCLUSION: The findings of cardiac mucosa, carditis, and intestinal metaplasia in an endoscopically normal-appearing gastroesophageal junction are histologic indicators of gastroesophageal reflux disease. These findings may be among the earliest signs of gastroesophageal reflux and contribute to the authors understanding of the pathophysiology of the disease process.

Adolescent↗
PubMed1997

Expression of fibronectin splicing variants in organ transplantation: a differential pattern between rat cardiac allografts and isografts.

Allograft rejection is associated with infiltration of inflammatory cells and deposition of extracellular matrix proteins. The extent to which diversity in the extracellular matrix regulates inflammatory cell function in transplants remains unclear. One group of extracellular matrix proteins, termed fibronectins (FNs), exhibits inherent diversity as a consequence of alternative splicing in three segments: EIIIA, EIIIB, or V. Although the EIIIA segment has documented functions in mesenchymal cell differentiation, neither this segment nor the EIIIB segment have been tested for effects specific to leukocyte functions. By contrast, the V region can include the CS-1 segment to which leukocytes may adhere through alpha 4 beta 1 integrins. In this study, we demonstrate that EIIIA+, EIIIB+, and V+ FN variants are synthesized, primarily by macrophages in distinct temporal and spatial patterns in two rat cardiac transplant models: either with antigenic challenge, allografts, or without challenge, isografts. The ratio of EIIIA inclusion into FN increases by day 1 in allografts and isografts and remains high until allografts are rejected (approximately 7 days) but falls to normal levels in tolerated isografts (day 6). EIIIB+ FN ratios in allografts peak later than do EIIIA+ FNs (day 4). EIIIB+ FN ratios remain relatively low in isografts. Interestingly, EIIIA+ and EIIIB+ FNs are deposited prominently in the myocardium of rejecting allografts in close association with infiltrating leukocytes, and FN expression and deposition are prominent at sites of infarction. By contrast, these FNs are largely restricted to the epicardium and to a lesser degree in the immediately adjacent myocardium in isografts. CS-1+ FNs increase in allografts and isografts at 3 hours after transplantation but are particularly prominent in allografts 1 to 3 days before rejection. Our data suggest that FN splicing variants have a differential role in the effector functions of leukocytes in allografts and isografts and provide a foundation for testing their function on leukocytes and a rationale for FN-based therapeutics to modulate allograft rejection in transplant recipients.

Alternative Splicing↗
PubMed1997

The origin of P-selectin as a circulating plasma protein.

P-selectin is a 140 kD protein found in the alpha-granules of platelets and the Weibel-Palade bodies of endothelial cells. On cell activation it is expressed on the cell surface and also secreted into plasma. Whether the circulating soluble P-selectin (sP-selectin) originates from platelets, endothelial cells, or both, is not known. We studied the level of sP-selectin in diseases with different platelet counts, with or without evidence of endothelial cell activation. Endothelial cell activation was confirmed by the detection of sE-selectin and ED1-fibronectin. A significant positive correlation between platelet count and sP-selectin concentration was observed in healthy controls, and in patients with thrombocytopenia due to bone marrow aplasia, or with thrombocytosis (r = 0.85; n = 47; p < 0.001). In patients with idiopathic thrombocytopenic purpura (ITP) the sP-selectin concentration was 110 +/- 39 ng/ml (n = 10), compared to 122 +/- 38 ng/ml in healthy controls (n = 26). However, their mean platelet count was lower (58 x 10(9)/l versus 241 x 10(9)/l in the control group). Accordingly, the levels of sP-selectin expressed per platelet increased to significantly higher levels (2.0 +/- 1.2 versus 0.6 +/- 0.2 fg/platelet in the control group; p < 0.0001). This suggests increased platelet turnover in patients with ITP. High levels of sP-selectin were found in patients with sepsis (398 +/- 203 ng/ml; n = 15) and with thrombotic thrombocytopenic purpura (TTP; 436 +/- 162 ng/ml; n = 12). Compared with patients with ITP, the concentration of sP-selectin per platelet was higher in patients with sepsis (4.8 +/- 4.3 fg/platelet; p < 0.005) or TTP (17.1 +/- 9.5 fg/platelet; p < 0.001). Endothelial cells are very likely to be the source in these patients and the presence of endothelial cell activation was confirmed by increased levels of circulating E-selectin and ED1-fibronectin. This study suggests that platelets are the major source of circulating sP-selectin in healthy individuals. Endothelial cell activation is associated with an increased sP-selectin concentration per platelet.

Adult↗