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G Triadafilopoulos

Publications and source records attributed to G Triadafilopoulos.

At least 55 records · Page 3Linked to original sources
PubMed2000

Leukocytosis as a harbinger and surrogate marker of Clostridium difficile infection in hospitalized patients with diarrhea.

OBJECTIVES: Clostridium difficile is the etiological agent of antibiotic-associated diarrhea and pseudomembranous colitis and is a leading cause of nosocomial diarrhea. The objective of the study was to examine if leukocytosis could be a harbinger and surrogate marker of C. difficile infection in hospitalized patients. METHODS: We retrospectively examined the medical records of 70 hospitalized patients who presented with diarrhea of variable severity and who underwent stool examination for enteric pathogens, including C. difficile. We specifically recorded the white blood cell count and the pattern and severity of leukocytosis in two groups of patients--those who were C. difficile-positive and those who were negative. RESULTS: Leukocytosis was common in C. difficile-positive patients, compared to in C. difficile-negative patients (mean 15,800/mm3 vs 7700/mm3, p < 0.01). Review of the 35 C. difficile-positive patients revealed three patterns: Pattern A) sudden WBC increase coinciding with the onset of symptoms suggestive of C. difficile; Pattern B) unexplained leukocytosis preceding the appearance of C. difficile-related diarrhea and serving as a harbinger of the infection; and Pattern C) worsening of pre-existing leukocytosis as a surrogate marker of C. difficile infection. Treatment with metronidazole led to amelioration of symptoms and normalization of the leukocyte count in all cases. CONCLUSIONS: Infection with C. difficile should be considered in the differential diagnosis of sudden onset of leukocytosis in hospitalized patients previously or concurrently treated with antibiotics. Doing so may obviate the need for expensive and time-consuming tests for other etiologies.

Clostridioides difficile↗
PubMed2000

Bile salts induce or blunt cell proliferation in Barrett's esophagus in an acid-dependent fashion.

Barrett's esophagus (BE) results from acid and bile reflux and predisposes to cancer. We investigated the effect of bile salts, with or without acid, on cell proliferation in BE and assessed mechanism(s) involved. To mimic physiological conditions, biopsies of esophagus, BE, and duodenum were exposed to a bile salt mixture, either continuously or as a 1-h pulse, and were compared with control media without bile salts (pH 7.4) for < or =24 h. Similar experiments were also performed with acidified media (pH 3.5) combined with the bile salt mixture as a 1-h pulse. Cell proliferation was assessed by a [(3)H]thymidine incorporation assay with or without bisindolylmaleimide (BIM), a selective protein kinase C inhibitor. Bile salt pulses enhanced cell proliferation in BE without affecting cell proliferation in esophageal or duodenal epithelia. In the presence of BIM, there was complete obliteration of the bile salt-induced BE hyperproliferation. In contrast, 1-h pulses of bile salts in combination with acid significantly inhibited proliferation in BE but had no effect on esophagus or duodenum. We conclude that in BE explants, brief exposure to bile salts, in the absence of acid, increases proliferation, whereas exposure to a combination of bile salts and acid together inhibits proliferation.

Acids↗
PubMed2000

The surgical management of severe gastroparesis in heart/lung transplant recipients.

This article describes the use of gastric bypass surgery for severe gastroparesis in two lung transplant recipients. In addition to feeding intolerance, both our patients suffered from severe erosive esophagitis, transfusion-dependent upper GI hemorrhage, and recurrent aspiration pneumonia. They responded poorly to promotility agents and were eventually treated with Roux-en-Y esophagojejunostomy-one patient with subtotal gastrectomy, and one with gastric bypass without distal gastric resection. Both cases were improved by surgery. Early surgical referral may be indicated in the management of lung transplant recipients with severe symptomatic gastroparesis in whom medical management has failed. On the basis of our experience, gastric bypass with esophagojejunostomy is a worthwhile option in lung transplant recipients with severe gastroparesis.

Adult↗
PubMed1999

Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus.

The incidence of adenocarcinoma of the esophagus has been increasing in developing countries over the last three decades and probably reflects a genuine increase in the incidence of its recognized precursor lesion, Barrett's metaplasia. Despite advances in multimodality therapy, the prognosis for invasive esophageal adenocarcinoma is poor. An improved understanding of the molecular biology of this disease may allow improved diagnosis, therapy, and prognosis. We focus on recent developments in the molecular and cell biology of Barrett's metaplasia, a heterogeneous lesion affecting the transitional zone of the gastro-esophageal junction whose associated molecular alterations may vary both in nature and temporally. Early premalignant clones produce biological and genetic heterogeneity as seen by multiple p53 mutations, p16 mutations, aneuploidy, and abnormal methylation resulting in stepwise changes in differentiation, proliferation, and apoptosis, allowing disease progression under selective pressure. Abnormalities in expression of growth factors of the epidermal growth factor family and cell adhesion molecules, especially cadherin/catenin complexes, may occur early in invasion. Exploitation of these molecular events may lead to a more appropriate diagnosis and understanding of these lesions in the future.

Adenocarcinoma↗
PubMed1999

Differentiation and proliferation in Barrett's esophagus and the effects of acid suppression.

BACKGROUND & AIMS: Maintenance of normal epithelial differentiation and proliferation is an important goal in cancer chemoprevention. Because acid has a dynamic effect on cell proliferation/differentiation of Barrett's esophagus (BE) ex vivo, we investigated the relationship between differentiation, proliferation, and dysplasia in BE biopsy specimens and explored the role of normalization of intraesophageal pH in altering the BE phenotype. METHODS: Endoscopic biopsy specimens of BE (with or without dysplasia) were analyzed for (1) villin, a differentiation marker, by immunoblotting; (2) proliferating cell nuclear antigen (PCNA), a proliferation marker, by immunohistochemistry; and (3) dysplasia by histology before and after 6 months of normalization of intraesophageal pH (confirmed by 24-hour pH monitoring) with lansoprazole. RESULTS: At baseline, there was a negative correlation (r = -0.79) between villin and PCNA expression. Six months later, PCNA expression decreased and villin expression increased (P < 0.001) in 24 patients whose intraesophageal pH normalized. Fifteen patients had persistently pathological intraesophageal acid reflux and no change in villin or PCNA expression. There were no differences in the occurrence of dysplasia after 6 months in either group. CONCLUSIONS: In BE, there is an inverse relationship between villin and PCNA. In turn, dysplasia is unrelated to villin expression and well correlated with PCNA expression. Complete symptom eradication with lansoprazole does not guarantee normalization of intraesophageal pH profile in BE patients. Effective intraesophageal acid suppression favors differentiation and decreases proliferation. The intriguing possibility that acid suppression can be used to prevent dysplasia remains to be explored.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Epidemiology of NSAID induced gastrointestinal complications.

Nonsteroidal antiinflammatory drugs (NSAID) are one of the most commonly used classes of medications worldwide. It is estimated that more than 30 million people take NSAID daily. Gastrointestinal (GI) complications related to NSAID therapy are the most prevalent category of adverse drug reactions. Patients with arthritis are among the most frequent users of NSAID and are therefore particularly at risk for these side effects. To evaluate the nature of NSAID-related GI complications and to determine how their frequency can be reduced, a series of studies of such complications in patients with rheumatic disease have been carried out based on data from the Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS). This report briefly reviews the literature and presents recent findings from the ARAMIS studies, which provide an update on published information. It addresses whether GI side effects such as dyspepsia can serve as warning symptoms for life-threatening GI complications and describes the risk factors for these events. It also summarizes a study that investigated whether H2-receptor antagonists and antacids affect the development of serious GI complications. In addition, ongoing research and topics to be addressed in future studies are described.

Antacids↗
PubMed1998

Hot water swallows improve symptoms and accelerate esophageal clearance in esophageal motility disorders.

Cold liquid ingestion may precipitate episodes of dysphagia and chest pain in patients with spastic esophageal motility disorders. The effect of hot liquids on esophageal symptoms, esophageal peristalsis, and clearance and any potential therapeutic benefit in such patients has not been examined. Using esophageal scintigraphy and manometry, we have investigated the effects of hot water swallows on dysphagia, chest pain, and esophageal motility and clearance in patients with esophageal motility disorders. We studied 48 men and women with intermittent dysphagia to both solids and liquids, chest pain, and/or regurgitation. All patients underwent upper endoscopy, barium swallow, and esophageal manometry using standard techniques. Esophageal scintigraphy assessed esophageal transit time (ETT) and retrograde intraesophageal movement of bolus at baseline (22 degrees C) and after hot (60 degrees C) water swallows. Esophageal manometry assessed the amplitude and duration of esophageal contractions in response to baseline and hot water swallows. Patients were followed clinically for as long as 6 months to assess symptomatic response. We found that baseline esophageal scintigraphy revealed a mean ETT of 48.5 seconds; after hot water swallow, mean ETT was 27.8 seconds (p < 0.001). The number of secondary peaks at baseline was 3.5; after hot water swallow, it was 2.1 (p < 0.001). Baseline esophageal manometry showed a mean esophageal body contraction amplitude of 188 mm Hg (mean duration, 11.8 seconds) in response to wet swallows and 125 mm Hg (mean duration, 5.7 seconds) with hot water swallows (p < 0.001). Clinically, 28 (58%) of 48 patients noted significant (>50%) improvement of their symptoms and have been ingesting hot water or other hot liquids regularly with their meals. We conclude that hot water accelerates esophageal clearance, decreases the amplitude and duration of esophageal body contractions, and improves symptoms in patients with esophageal motility disorders. Because of its safety and simplicity, it may have an important role in the management of these chronic conditions.

Deglutition↗
PubMed1998

Complete elimination of reflux symptoms does not guarantee normalization of intraesophageal acid reflux in patients with Barrett's esophagus.

OBJECTIVE: Normalization of intraesophageal acid exposure is increasingly recognized as a desired goal in the management of Barrett's esophagus. In this prospective trial, we studied patients with Barrett's esophagus by 24-h intraesophageal pH monitoring after having completely eliminated their reflux symptoms with lansoprazole, to determine whether they had achieved normalization of intraesophageal pH. METHODS: Thirty patients with Barrett's esophagus, all of whom had presented with reflux symptoms, were treated with lansoprazole (15-30 mg/day) until they were asymptomatic. Twenty-four-hour ambulatory pH monitoring was performed while they were receiving lansoprazole and were asymptomatic. RESULTS: Twelve patients (40%) showed persistent bipositional, pathologic acid reflux while on therapy, with a mean DeMeester score of 52.8 (95% CI: 33.8-71.8); the remaining 18 (60%) exhibited normalization of intraesophageal acid exposure with a score of 4.4 (95% CI: 2.3-6.6,p < 0.001). This inadequate control of intraesophageal pH is most likely due to incomplete gastric acid suppression induced by the drug and is associated with a variable acid (distal > proximal) exposure within the esophagus. The two groups were not different in regard to their symptom frequency and severity before therapy, amount of lansoprazole dosage required to eliminate symptoms, length of Barrett's metaplasia, presence of hiatal hernia, lower esophageal sphincter resting tone and length, or esophageal peristaltic function. CONCLUSION: Complete symptom eradication with lansoprazole (15-30 mg daily) in patients with Barrett's esophagus does not guarantee normalization of intraesophageal pH profile. If the goal of therapy in such patients is to achieve complete intraesophageal acid suppression, 24-h ambulatory esophageal pH monitoring should be performed to titrate therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Altered sodium-hydrogen exchange activity is a mechanism for acid-induced hyperproliferation in Barrett's esophagus.

Acid produces a dynamic effect on the cell phenotype of Barrett's esophagus (BE) ex vivo. An acid pulse induces hyperproliferation, whereas continuous acid exposure promotes differentiation. To examine the mechanism for acid pulse-induced hyperproliferation, we studied the Na+/H+ exchanger (NHE), which plays a role in the control of intracellular pH and cell proliferation. NHE was inhibited pharmacologically in endoscopic BE biopsies using amiloride analogs. Cell proliferation was assessed after pulsed or continuous acid exposure using tritiated thymidine incorporation assays and immunohistochemical analysis of proliferating cell nuclear antigen expression. The NHE-dependent intracellular pH response to an acid pulse was examined by pH-sensitive microfluorimetry using a Barrett's adenocarcinoma cell line TE7. NHE inhibition significantly reduced the hyperproliferative acid-pulse effect. Furthermore, the acid-pulse activation of NHE occurred via increased transporter activity (22Na uptake) without any change in NHE-1 protein levels. Inhibition of protein kinase C (PKC), an NHE activator, also reduced the hyperproliferative response. The response of TE7 cells to an acid pulse was similar to that of BE biopsies in terms of cell proliferation and NHE and PKC dependence. Acid-pulse exposure of TE7 cells resulted in intracellular acidification followed by reneutralization to an intracellular pH greater than preacidosis values. We conclude that NHE may mediate the hyperproliferative response of BE to an acid pulse via changes in intracellular pH.

Amiloride↗
PubMed1998

Bowel dysfunction in postmenopausal women.

BACKGROUND/AIMS: The perimenopausal and postmenopausal states are frequently accompanied by a variety of symptoms of hormonal imbalance. Although vasomotor, vaginal and genitourinary symptoms prevail, gastrointestinal complaints such as abdominal bloating may occur. In this study, we investigated the nature and prevalence of gastrointestinal and irritable bowel syndrome (IBS)-type complaints in women going through their climacteric and postmenopausal periods. PATIENTS/METHODS: 228 women (170 postmenopausal and 58 premenopausal) who presented for evaluation at a primary care practice limited to women's health were evaluated prospectively by a previously validated gastrointestinal symptoms questionnaire designed to evaluate symptoms suggestive of IBS. At the time of their participation in the study, none of these women was presenting for evaluation of abdominal or genitourinary symptoms. RESULTS: Thirty-eight percent of postmenopausal women reported altered bowel function, in contrast to 14% of premenopausal ones (p < 0.001). Despite this, the two groups did not differ in regards to the occurrence of abdominal pain, diarrhea or constipation, suggestive of IBS. The prevalence of IBS-type complaints peaked to 36% during the climacteric period (40-49 years). Laxative usage (9.4% prevalence), gaseousness/excessive flatulence (48% prevalence) and heart-burn/acid regurgitation (34% prevalence) were also more common among postmenopausal women. Estrogen use did not affect gastrointestinal symptoms in any of the two groups. CONCLUSIONS: Although the possible role of aging on symptom perception-regardless of hormonal status-cannot be ruled out, these results suggest that peri- and postmenopausal women have a high prevalence of altered bowel function and IBS-like gastrointestinal complaints that should be carefully assessed. If the diagnosis of IBS is confirmed, appropriate treatment may improve patients' symptoms, although this approach requires further study.

Abdominal Pain↗
PubMed1998

Oesophageal mucosal diseases in the elderly.

Diseases of the oesophageal mucosa are particularly prevalent in the elderly population and may present with various symptoms, such as heartburn, dysphagia or chest pain. Recent technological advances, such as endoscopy, ambulatory pH monitoring and radiological imaging, have allowed for a more accurate diagnosis and assessment of disease severity. Depending on the leading presenting symptom, empirical medical therapy or stepwise diagnostic tests may be used. Elderly patients with mild reflux symptoms respond well to over-the-counter antacids, acid suppressants or prescription prokinetic drugs. Those with more severe gastrooesophageal reflux disease and Barrett's oesophagus benefit from powerful acid suppressive therapy to relieve symptoms, heal the mucosal damage and prevent complications. Long term, cost-effective pharmacological therapies are constantly being defined. Because of the widespread utilisation of medications in the elderly, drug-induced oesophageal injury should always be considered and prevented. An increasing number of immunocompromised elderly patients are diagnosed and successfully treated for infectious oesophagitis. Overall, for most elderly patients, when the diagnosis is made correctly, modern medical and/or surgical treatments yield maximal therapeutic benefit and improve quality of life.

Aged↗
PubMed1997

Serum 13C-bicarbonate assay for the diagnosis of gastric Helicobacter pylori infection and response to treatment.

BACKGROUND & AIMS: Current serological tests for Helicobacter pylori (HP) infection are not useful in assessing active infection or eradication. The feasibility, sensitivity, and specificity of serum 13C-bicarbonate (13C-HCO3) measurement in determining gastric HP before and after eradication by antibiotics were investigated. METHODS: Twenty-seven symptomatic patients underwent endoscopy, biopsy, and CLOtest. Patients then consumed a 13C-urea-rich meal; serum was collected before and 1 hour after meal ingestion for quantitative determination of 13C by mass spectrometry. Postprandial fractional elevation of 13C (delta 13C-HCO3) was correlated with endoscopy, histology, and CLOtest at baseline and at 4 and 8 weeks after therapy. RESULTS: delta 13C-HCO3 +/- SEM was 17.02 +/- 2.94 in HP-positive patients and 2.77 +/- 044 in HP-negative patients (P < 0.0001). In HP-positive patients who responded to therapy, the mean change was initially 20.5 +/- 3.1, 3.2 +/- 0.9 1 month after therapy, and 2.8 +/- 0.4 2 months after therapy (P < 0.001). The overall sensitivity of this method was 90.6% (95% confidence interval, 74.9-98.0), and its specificity was 85.7% (95% confidence interval, 42.1%-99.6%). delta 13C-HCO3 correlated positively with the degree of histological gastritis and the number of HP organisms. CONCLUSIONS: Serum 13C-HCO3 analysis is a novel, simple, and noninvasive method for diagnosis and assessment of eradication of HP infection.

Amoxicillin↗
PubMed1997

Esophageal manifestations of rheumatic disorders.

This study was performed to review information on functional and anatomic esophageal manifestations in patients with rheumatic disorders and to outline their pathogenesis, diagnosis, and treatment in light of the current medical, endoscopic, and surgical advances. A MEDLINE search of English-language articles published between 1985 and 1995, reviews of the bibliographies of textbooks, and a manual search of the reference lists of relevant articles formed the data sources, all combined with our own clinical experience. Primary research and review articles addressing the pathogenesis, diagnosis, treatment, prognosis, and complications of esophageal disease occurring in a rheumatic context were selected, with emphasis on recently developed medical, endoscopic, and surgical methods for diagnosis and management. Study design and quality were assessed, with particular attention paid to methods and aims. Relevant data on frequency, clinical presentation, and relationship to underlying rheumatic disorder, prognosis, and clinical management were analyzed. Esophageal manifestations are common in patients with rheumatic diseases and range in nature and severity from functional myopathic or neuropathic esophageal dysmotility to extrinsic lumenal compression and esophageal mucosal damage from gastroesophageal acid reflux or opportunistic infection. The primary symptoms of heartburn, dysphagia, odynophagia, chest pain, and bleeding may be directly related to the underlying rheumatic disease or may be the unwanted effects of therapy with nonsteroidal antiinflammatory drugs, immunosuppressants, or disease-modifying agents. Easily over-looked in the context of a multisystemic disease, these esophageal symptoms may be amenable to simple treatments, but frequently require a thorough assessment by modern, sophisticated diagnostic tools. In many instances, functional and structural involvement of the esophagus in patients with rheumatic disorders requires a high index of suspicion for an early diagnosis, correct assessment, intensive surveillance, and aggressive therapy to avoid end-organ damage and decline in quality of life. Significant recent advances in the understanding of esophageal pathophysiology, the development of diagnostic techniques, progress in diagnostic and therapeutic endoscopy, and minimally invasive surgery allow early detection and effective long-term therapy for esophageal dysfunction associated with rheumatic diseases.

Esophageal Diseases↗
PubMed1997

Src activation in malignant and premalignant epithelia of Barrett's esophagus.

BACKGROUND & AIMS: The neoplastic progression of Barrett's esophagus (BE) may involve genomic instability, inactivation of tumor suppressor genes, or activation of oncogenes. Because activation of Src tyrosine kinase occurs in malignant and premalignant epithelia of the colon, the aim of this study was to determine whether BE is associated with changes in Src expression and activity. METHODS: Src expression and in vitro protein-tyrosine kinase activity in endoscopic tissue samples of BE and esophageal adenocarcinoma were measured and compared with expression and activity in normal esophagus and duodenum from the same patient. Src phosphorylation was assessed by immunoblotting using antiphosphotyrosine antibodies and two-dimensional tryptic phosphopeptide mapping. RESULTS: Src-specific activity was 3-4 fold higher in BE and 6-fold higher in esophageal adenocarcinoma than in control tissues. Different regions of BE from the same patient showed heterogeneity in Src activity compared with the uniform Src activity observed in different regions of normal esophagus and duodenum. In all tissues, Src kinase activity and protein were associated preferentially with the Triton X-100-soluble rather than-insoluble fraction. Immunoblotting and two-dimensional tryptic phosphopeptide mapping showed dephosphorylation of Src at Tyr527 in BE. CONCLUSIONS: Src is activated in BE, in part, because of dephosphorylation of Tyr527. Src activation and its heterogeneous expression occur before development of dysplasia or carcinoma in BE.

Adenocarcinoma↗
PubMed1997

Acid modulation of HT29 cell growth and differentiation. An in vitro model for Barrett's esophagus.

Cell proliferation and differentiation are influenced by environmental factors, including the extracellular pH. We recently showed, using an ex vivo organ culture system of human mucosal Barrett's esophageal biopsies, that acid has a highly variable effect on cell proliferation and differentiation depending on the pattern of acid exposure. Study of the mechanisms underlying these dynamic effects of acid on this premalignant intestinal-like epithelium is hampered by lack of an immortalized cell line. We therefore investigated the effect of acid exposure on the human colonic carcinoma cell line HT29, chosen because of its intestinal cell derivation and its ability to differentiate in vitro. HT29 cells exposed to pH 5 medium either continuously (up to 3 weeks), or as a short (1 hour) pulse, were compared with cells cultured at pH 7.4. Villin expression was induced only by long term acid exposure, and correlated with the development of differentiated polarized cells that contain a brush border and microvillus inclusions. Chronic acid exposure arrested cell proliferation, whereas a 1 hour acid-pulse enhanced cell proliferation, as determined by [3H]thymidine incorporation assays and proliferating cell nuclear antigen expression. Serum starvation attenuated the hyperproliferative effect of an acid-pulse. In addition, the doubling time of at least the first cell cycle after an acid-pulse was shortened. The Na/H exchanger is likely to play a role since the hyperproliferative acid-induced response was blocked by amiloride; and the activity of the exchanger was increased at acidic pH as determined by 22Na uptake. These results support a role for extracellular pH on cell proliferation and differentiation of HT29 cells. Furthermore, these findings parallel the dynamic effects of acid on Barrett's esophagus, and suggest that HT29 cells could serve as an in vitro model for studying the mechanism of acid modulation in Barrett's esophagus.

Barrett Esophagus↗