Induction of interleukin-8 expression by Helicobacter pylori infection in patients with endoscopy-negative gastroesophageal reflux disease.
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Publications and source records attributed to Dimitrios Chatzopoulos.
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PURPOSE: A prospective, nonrandomized, comparative study was carried out to investigate the levels of anti- H. pylori-specific IgG antibodies in the aqueous humor and serum of patients with primary open-angle glaucoma (POAG) and patients with exfoliation glaucoma (XFG), and to compare them with those in age-matched cataract patients. METHODS: Aqueous humor was aspirated at the beginning of glaucoma surgery from 26 eyes of 26 patients with POAG, 27 eyes of 27 patients with XFG, and at the beginning of phakoemulsification cataract surgery from 31 eyes of 31 age-matched normotensive cataract patients. Serum samples were obtained the day before surgery from all patients. Anti- H. pylori IgG concentration in the aqueous humor and serum was measured by means of an enzyme-linked immunosorbent assay. RESULTS: The mean concentration (+/- SE) of anti- H. pylori-specific IgG was significantly greater in the aqueous humor samples from patients with POAG (14.27+/-3.86 U/ml) and XFG (14.25+/-3.39 U/ml) than in those from age-matched control cataract patients (4.67+/-1.07 U/ml); ( P=0.006 and P=0.003, respectively). No difference was observed in the levels of H. pylori-specific IgG antibodies between POAG and XFG aqueous humor samples ( P=0.5). Similarly, the serum concentration of anti- H. pylori antibodies was significantly greater in patients with POAG (69.96+/-9.69 U/ml; P=0.013) and XFG (81.37+/-10.62 U/ml; P=0.002) than in the cataract controls (44.16+/-6.48 U/ml). The mean vertical cupping correlated significantly with the titer of anti- H. pylori-specific IgG in the aqueous humor in the POAG patients. CONCLUSION: H. pylori-specific IgG antibody levels are significantly increased in the aqueous humor and serum of patients with POAG and XFG. Moreover, the titer of anti- H. pylori antibody in the aqueous humor might reflect the severity of glaucomatous damage in POAG patients. These findings support a role for H. pylori infection in the pathobiology of these two common glaucomas.
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Apoptosis is critical for organ development, tissue homeostasis, the elimination of abnormal cells and the maintenance of immune homeostasis by variable regulatory mechanisms. The death of T lymphocytes following their activation involves a series of proteases (caspases), which comprise the central executioners of apoptosis. Abnormal regulation of apoptosis results in disease. T-cell resistance against apoptosis contributes to inappropriate T-cell accumulation and the perpetuation of the chronic inflammatory process in inflammatory bowel disease with potential tumourigenic effect. The use of antitumour necrosis factor-alpha, anti-interleukin-6R and anti-interleukin-12 antibodies suppresses colitis activity by induction of T-cell apoptosis, thereby having important implications for the design of effective therapeutic strategies in inflammatory bowel diseases. Contrary to international data, the incidence of cancer in Greek patients with inflammatory bowel disease appears to be low. A balance between cell proliferation (Ki-67 overexpression) and apoptosis (Bax protein overexpression) may partly explain the low incidence of cancer development in Greek inflammatory bowel disease patients.
BACKGROUND: We have documented a high prevalence of Helicobacter pylori infection in patients with glaucoma. OBJECTIVE: To evaluate the effect of H pylori eradication on the 2 most commonly used glaucoma parameters: intraocular pressure and visual field. METHODS: A total of 41 patients with glaucoma and 30 age-matched anemic controls underwent upper gastrointestinal endoscopies and gastric mucosal biopsies to detect the presence of H. pylori infection by histologic analysis and rapid urease test (CLOtest; Delta West, Draper, Utah). Saliva samples were also tested by CLOtest. Serum anti-H pylori-specific IgG was analyzed by enzyme-linked immunosorbent assay. Helicobacter pylori-positive patients received a triple eradication regimen (omeprazole, clarithromycin, and amoxicillin treatment), and all patients were observed for 2 years while remaining under the same antiglaucoma therapy. RESULTS: Helicobacter pylori was detected in 88% of glaucoma cases and in 47% of controls (P<.001). Helicobacter pylori eradication was successful in 83% of treated patients. At the 2-year clinical end point, glaucoma parameters (mean intraocular pressure and mean visual field parameters) were improved in the subgroup of patients where H. pylori eradication was successful (P<.001 for intraocular pressure; P< or =.01 for visual field parameters), but not in the other patients. CONCLUSION: Helicobacter pylori eradication may positively influence glaucoma parameters, suggesting a possible causal link between H pylori and glaucoma.
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Etiopathogenesis of mucosal inflammation in inflammatory bowel disease remains a complex and enigmatic field; various factors (genetic, environmental and microbial) trigger an event that activates intestinal immune and nonimmune systems culminating in inflammation and tissue injury. Specifically, both innate and adaptive immune systems seem to play important roles in the pathophysiology of this disease. Cyclosporine A represents a macrolide immune modulator with primary inhibitory effects on T helper lymphocyte production of interleukin-2, and other cytokines leading to altered T-lymphocyte and B-lymphocyte function. The diversity of its therapeutic outcome reported in inflammatory bowel disease may be due to the intricate immuno-pathogenic profile of the disease and the variety of the applied dose-dependent courses of therapy. Cyclosporine A exerts additional actions on other components of the inflammatory infiltrate, including neutrophils and mast cells, thereby appearing to be a multi-dynamic therapeutic approach, although with potential drawbacks, that may be applied alone or combined with other immunomodulatory agents in inflammatory bowel disease patients. Because cyclosporine A induces apoptosis of T-lymphocytes responsible for perpetuation of the chronic inflammatory process in the disease with potential tumorigenic effect, it may exert a further inhibitory effect on cancer development in inflammatory bowel disease patients, and can be combined with other relative agents, such as rapamycin, which also promotes T-lymphocyte apoptosis. Therefore, recently established multifactorial action of cyclosporine A in relation to the pathogenesis of the disease can open new horizons for prospective, controlled trials in large cohorts, aiming to emphasize cyclosporine A's potential.
The process of apoptosis plays a crucial role in several physiological as well as pathophysiological processes, and is a fundamental mechanism for the deletion of unwanted, senescent, or damaged cells. Defects in the apoptotic mechanisms or, even more, disturbances of the equilibrium between cellular replication, growth, differentiation and apoptosis favor the growth of preneoplastic and tumoral lesions in the liver. Clinical and molecular medical analyses have yielded a considerable amount of information about liver oncogenesis. Studies on transgenic models of hepatocarcinogenesis have allowed a meticulous examination of the roles of apoptosis, tumor suppressors, DNA repair processes and other events in the clonal expansion and accumulation of genetic lesions. During initiation, there is rapid proliferation and a high amount of apoptosis, whereas in the promotion stage, there is decreased cell death and increased cell proliferation. Accumulating evidence suggests a defective apoptotic process in human hepatocellular carcinoma. Moreover, a range of prognostic factors related to apoptosis might be used in the early assessment of the progress of hepatocarcinogenesis as well as in hepatocellular carcinoma recurrence. Lastly, many potential therapeutic strategies, that induce the apoptotic process in various ways, can be applied to the hepatocellular carcinoma management.
BACKGROUND/AIMS: Primary and metastatic liver tumors are the most common malignancies that resist conventional chemotherapy and radiotherapy. Several immunotherapies have been attempted for cancer treatment on the basis of stimulating host immune response to tumors and recent development of combined targeting locoregional immunochemotherapy reported with promising results. However, the efficacy of this therapeutic modality is not yet widely established. METHODOLOGY: We reviewed the medical literature for publications dealing with the value of locoregional immunochemotherapy in patients with primary or metastatic liver tumors. RESULTS: We found that 5 and 7 studies have been controlled and inadequately controlled, respectively. Among 131 patients with primary liver cancer, 40 were treated with combined locoregional immunochemotherapy, and 20 with systemic immunochemotherapy, and 71 with systemic chemotherapy served as two control groups. Complete or partial response was observed in 32 out of 40 (80%) patients who received combined locoregional therapy, and in 10 out of 20 (50%) systemic immunochemotherapy controls (P = 0.03). Survival was three times higher in the patients who received combined locoregional therapy compared with systemic chemotherapy controls (18 vs. 5.6 months). Recurrence of tumor was higher in systemic immunochemotherapy controls (P = 0.003). Among 286 patients with metastatic liver disease, 180 patients were treated with combined locoregional immunochemotherapy and 106 patients with systemic immunochemotherapy. Response (complete or partial) was observed in 65 out of 98 (66.3%) patients who received combined therapy, and in 4 out of 26 (15.4%) controls (P < = 0.001). Survival was two-fold higher in the patients treated with combined therapy (21 vs. 10.5 months). Tumor recurrence was higher in the systemic immunochemotherapy controls (P < = 0.001). CONCLUSIONS: The observational studies indicate a plausible therapeutic rationale for the introduction of locoregional immunotherapy in patients with primary and metastatic liver disease.
In patients with differentiated thyroid carcinoma (DTC) who after thyroidectomy underwent radioiodine-131 ((131)I) treatment for the ablation of the thyroid remnant, isolation period is considered as the period of time needed for patients' radiation dose rates to be reduced below specific adopted dose rate release limits. The aim of our study was to determine mathematical equations for the prediction of the isolation period in these patients and of their discharge from special isolation rooms in nuclear medicine departments. In order, to predict the duration of the isolation period, we studied twenty-eight patients with DTC and total thyroidectomy having no metastases, who underwent (131)I ablation treatment for a minimal residual thyroid remnant. The administered (131)I activity was 5.22 +/- 0.68 GBq, ranging from 3.66 to 6.21 GBq. Dose rates, as mean +/- SD, at a distance of 1 m from the patients were 277 +/- 44 microSv/h, immediately after (131)I administration, 72 +/- 18 microSv/h at 24 h and 23 +/- 9 microSv/h at 48 h. Whole body (131)I retention was 0.261 +/- 0.05 (range 0.168-0.385) at 24 h and 0.082 +/- 0.03 (range 0.041-0.149) at 48 h, calculated as the ratio of dose rate at 24 h and 48 h versus the initial dose rate after (131)I administration. Isolation period was calculated by a mono-exponential fitting in dose rate decay data according specific dose rate release limits. For a dose rate release limit of 30 microSv/h at 1 m, isolation period was 42.7+/-7.2 h (range 31.2-56.6 h). Seventy-five percent of the patients satisfied this limit within 48 h and 25% between 48 h and 72 h. This isolation period was positively correlated with the whole body (131)I retention and the dose rates at 24 h and 48 h, but not always with the administered activity or the initial dose rate, measured immediately after (131)I administration. On the contrary, a strong negative correlation was found between patients' isolation period and dose rate release limits between 3 and 60 microSv/h at 1 m. This study indicates that isolation period is variable but can be predicted by multiple formulas, since it depends strongly on the adopted dose rate release limits, (131)I dose rates and whole body retention at 24 h and 48 h after (131)I treatment. For a dose rate release limit of 30 microSv/h at 1 m, isolation period is sufficient for 72 h for all of our patients, while 75% of them had dose rates below that limit within 48 h.
Gastric cancer not located in the cardia still remains the second most common cancer worldwide, whereas adenocarcinoma of the cardia and gastroesophageal junction has been rapidly rising over the past two decades. Gastric cancer can be subdivided into two distinct pathologic entities, diffuse and intestinal, that have different epidemiologic and prognostic features. Various genetic and environmental factors play important roles in gastric carcinogenesis; both lead to either abnormal genes overexpression or inappropriate expression of normal genes, whose products confer the malignant phenotype. Advances have been made in the genetic changes mostly of the intestinal type; its development is probably a multistep process, as has been well described in colon cancer pathogenesis, whereas it remains tentative whether the diffuse type of malignancy follows an analogous progression. The most common genetic abnormalities in gastric cancer tend to be loss of heterozygosity of tumor suppressor genes, particularly of p53 or "Adenomatous Polyposis Coli" gene. The latter leads to gastric oncogenesis through changes related to E-cadherin-catenin complex, which plays a critical role in the maintenance of normal tissue architecture. Mutation of any of its components results in loss of cell-cell adhesion, thereby contributing to neoplasia. E-cadherin/CDH1 gene germline mutations have been recognized in families with an inherited predisposition to gastric cancer of the diffuse type. Amplification and/or overexpression of putative trophic factors have also been observed in gastric cancer. Finally, Helicobacter pylori (H. pylori) infection is also involved in gastric carcinogenesis through various mechanisms, thereby necessitating H. pylori eradication in patients with gastric cancer.
The present study was undertaken because we could not find references related to the minimal radiation doses emitted from patients treated with (90)Y-silicate colloid ((90)Y-SC) for radiosynectomy (RS). Radiation doses from 16 patients treated with about 181+/-13 MBq (90)Y-SC for RS of knee synovitis were estimated by dose rate measurements performed within 10 min after the (90)Y-SC injection with a calibrated survey dose ratemeter at 0.5 m, 1 m and 2 m distances from the treated joint. The mean dose rate values from the patients after bg subtraction were 0.6+/-0.4 microSv/h at 0.5 m, 0.1+/-0.1 microSv/h at 1 m and 0.1 +/- 0.0 microSv/h at 2 m distance. Dose rates at a distance of 0.5 m were significantly correlated (P<0.02) with the patient's weight but not with the height or the injected activity. The assumed estimated maximum whole body doses from a treated patient were 55 microSv for persons living with the patient, 2.9-3.4 microSv for the nursing staff, 0.2-1.8 microSv for the therapist physician and 0.3-0.6 microSv for the technologist, involved in the whole procedure. The above values were lower than those published with the same methodology for alternative RS radiopharmaceuticals for knee synovitis like dysprosium-165 ferric hydroxide macroaggregate ((165)Dy-FHMA) or holmium-166 ((166)Ho-FHMA), as estimated with their typical injected activities. In conclusion our results demonstrate that in (90)Y-SC knee synovectomy, the whole body radiation doses to medical and non medical personnel were as expected well below the maximum annual dose limits for the public and professionals exposed to radiation.
A case of left knee synovitis scintigraphic imaging is presented in a 66-year-old patient with bilateral knee osteoarthritis and a right knee Baker's cyst, who had undergone a 74 MBq (99m)Tc-pertechnetate intra-articular injection in the right knee. The findings in this case were compared with the intravenously injected methylene disphosphonate technetium-99m ((99m)Tc-MDP) scintigraphic findings and could be interpreted as the result of (99m)Tc-pertechenate through blood communication from the right to the left knee. This case implies that (99m)Tc-pertechnetate may be useful in imaging the synovitis in multiple arthroses even up to 60 min after its administration, instead of the 5 min imaging after the injection of (99m)Tc-MDP.
We describe the case of a 37-year-old male patient suffering from papillary carcinoma of the thyroid gland with pulmonary metastases who after total thyroidectomy on 29/07/1998 was submitted to three treatments with high doses of (131)I and studied as to the whole body clearance of (131)I by measuring the dose rate of (131)I. The patient was referred to us for total ablation of post surgery remnant of thyroid tissue on 19/09/1998. Due to lymphadenic metastases and high Tg values: 450 ng/ml, he was purposely given therapeutically a high dose of 5146 MBq (131)I. On the whole body post-operative scintiscan that followed, a diffuse uptake of (131)I in the lungs and in the thyroid remnant was found. The patient was given 7307 MBq (131)I after 7 months and 5154 MBq of (131)I after another 10 months, because Tg was increased. Whole body scintiscan after the third treatment as mentioned above, showed poor uptake of (131)I in the thyroid gland area and in the lungs. No side effects were noticed, Tg fell to 4.5-7 ng/ml and the patient was in good condition with no abnormal findings on the X-rays or CT of the thorax. After iodine administration whole body measurements of the dose rate of the clearance of (131)I measured by an ionization chamber at a distance of 2 m from the thorax, were performed. For the first treatment effective half-lives of (131)I of the patient, as measured for the two components of the clearance curve, were 4.4 h and 16.8 h respectively. For the second and third treatment clearance curve had only one component and effective half-lives were 22.5 h and 11 h respectively. Remaining activity of (131)I at 48 h was for the first, second and third treatment: 13.3% (685 MBq), 22.8% (1670 MBq) and 4.2% (222 MBq) respectively. We do not know any similar case in the literature with whole body measurements of (131)I clearance in patients undergoing repeated (131)I treatment as above, especially with diffuse pulmonary uptake of (131)I indicating metastatic lesions after the first treatment of (131)I post total thyroidectomy. The interest of the above case also lies on the fact that there were three successive treatments with (131)I and three whole body (131)I measurements. Clearance rate indicated the need for additional treatment and the treatment followed was successful.