Psychological factors and stress in inflammatory bowel disease.

The role of psychological distress and personality as predisposing factors for the development of inflammatory bowel disease (IBD) remains controversial. Attempts to investigate the role of psychological factors in IBD exhibited rather conflicting results. Among the studies concerning the effects of stress or depression on the course of IBD, the majority suggest that stress worsened IBD, the rest giving either negative or inconclusive results. However, application of strategies, including avoidance of coping and training patients in problem solving or emotion-oriented, could influence the course of IBD. Large controlled clinical trials are needed in order to clarify the impact of psychological interventions on the quality of life and the course of disease.

Sedation in gastrointestinal endoscopy: current issues.

Diagnostic and therapeutic endoscopy can successfully be performed by applying moderate (conscious) sedation. Moderate sedation, using midazolam and an opioid, is the standard method of sedation, although propofol is increasingly being used in many countries because the satisfaction of endoscopists with propofol sedation is greater compared with their satisfaction with conventional sedation. Moreover, the use of propofol is currently preferred for the endoscopic sedation of patients with advanced liver disease due to its short biologic half-life and, consequently, its low risk of inducing hepatic encephalopathy. In the future, propofol could become the preferred sedation agent, especially for routine colonoscopy. Midazolam is the benzodiazepine of choice because of its shorter duration of action and better pharmacokinetic profile compared with diazepam. Among opioids, pethidine and fentanyl are the most popular. A number of other substances have been tested in several clinical trials with promising results. Among them, newer opioids, such as remifentanil, enable a faster recovery. The controversy regarding the administration of sedation by an endoscopist or an experienced nurse, as well as the optimal staffing of endoscopy units, continues to be a matter of discussion. Safe sedation in special clinical circumstances, such as in the cases of obese, pregnant, and elderly individuals, as well as patients with chronic lung, renal or liver disease, requires modification of the dose of the drugs used for sedation. In the great majority of patients, sedation under the supervision of a properly trained endoscopist remains the standard practice worldwide. In this review, an overview of the current knowledge concerning sedation during digestive endoscopy will be provided based on the data in the current literature.

Crohn's disease of the small bowel, complicated by primary biliary cirrhosis, Hashimoto thyroiditis, and Raynaud's phenomenon: favorable response of all disorders to adalimumab treatment.

We describe the case of a male patient suffering from long-lasting Crohn's disease of the small bowel who developed thyroiditis Hassimoto, Raynaud's phenomenon, and primary biliary cirrhosis, during the course of the underlying bowel disease. It is not clear whether these co-morbidities appeared coincidentally, or because they share some common immunopathogenetic mechanisms. In this patient, Crohn's disease favorably responded to the treatment with an anti-TNF-α agent (adalimumab). The serum titers of antimitochondrial antibodyies and cholestatic enzymes considerably reduced during the 3-year treatment with the biologic agent. Raynaud's phenomenon, also, completely disappeared. Bearing in mind the possible involvement of TNF-α in the pathogenesis of primary biliary cirrhosis, it could be argued that the clinical and laboratory improvement of liver disease, as well as the reduction in serum titers of antimitochondrial antibodies, might be due to the anti-TNF-α action of adalimumab. We suggest that it would be worth further investigating the role of biologic agents in the treatment of patients with primary biliary cirrhosis.

Current and emerging drugs for the treatment of inflammatory bowel disease.

During the last decade a large number of biological agents against tumor necrosis factor-α (TNF-α), as well as many biochemical substances and molecules specifically for the medical treatment of patients with inflammatory bowel disease (IBD), have been developed. This enormous progress was a consequence of the significant advances in biotechnology along with the increased knowledge of the underlying pathophysiological mechanisms involved in the pathogenesis of IBD. However, conventional therapies remain the cornerstone of treatment for most patients. During recent years conventional and biologic IBD therapies have been optimized. Newer mesalazine formulations with a reduced pill size and only one dose per day demonstrate similar efficacy to older formulations. New corticosteroids retain the efficacy of older corticosteroids while exhibiting a higher safety profile. The role of antibiotics and probiotics has been further clarified. Significant progress in understanding thiopurine metabolism has improved the effective dose along with adjunctive therapies. Quite a large number of substances and therapies, including biologic agents other than TNF-α inhibitors, unfractionated or low-molecular-weight heparin, omega-3 polyunsaturated fatty acids, microbes and microbial products, leukocytapheresis, and other substances under investigation, could offer important benefits to our patients. In this paper we review the established and emerging therapeutic strategies in patients with Crohn's disease and ulcerative colitis.

Gastric Outlet Obstruction due to Cytomegalovirus Infection in an Immunocompromised Patient.

A case of gastric outlet obstruction accompanied by diffuse gastritis and gastric ulcer due to cytomegalovirus infection is presented. The patient, a woman aged 67 years with a long history of rheumatoid arthritis under immunosuppressive treatment (methotrexate), was admitted to our department complaining mostly of abdominal pain located in the epigastrium and the right abdomen. Upper gastrointestinal endoscopy revealed the presence of gastritis accompanied by ulcer in the prepyloric area and gastric outlet obstruction due to cytomegalovirus infection which was confirmed histologically. The patient responded well - although after many weeks - to specific treatment with antiviral treatment (ganciclovir). It is concluded that gastric outlet obstruction caused by cytomegalovirus infection can be observed in immunocompromised patients. The clinician must search for possible cytomegalovirus infection in all immunocompromised patients presenting with a clinical picture of gastric outlet obstruction by obtaining enough biopsies and by asking the histopathologist to specifically stain the specimen for the presence of cytomegalovirus, especially if infection by Helicobacter pylori is not present.

Favorable response to subcutaneous administration of infliximab in rats with experimental colitis.

AIM: To investigate the influence of infliximab (Remicade) on experimental colitis produced by 2,4,6,trinitrobenzene sulfonic acid (TNBS) in rats. METHODS: Thirty-six Wistar rats were allocated into four groups (three groups of six animals each and a fourth of 12 animals). Six more healthy animals served as normal controls (Group 5). Group 1: colitis was induced by intracolonic installation of 25 mg of TNBS dissolved in 0.25 mL of 50% ethanol and infliximab was subcutaneously administered at a dose of 5 mg/kg BW; Group 2: colitis was induced and infliximab was subcutaneously administered at a dose of 10 mg/kg BW; Group 3: colitis was induced and infliximab was subcutaneously administered at a dose of 15 mg/kg BW; Group 4: colitis was induced without treatment with infliximab. Infliximab was administered on d 2-6. On the 7(th) d, all animals were killed. The colon was fixed in 10% buffered formalin and examined by light microscopy for the presence and activity of colitis and the extent of tissue damage. Tumor necrosis factor-alpha (TNF-alpha) and malondialdehyde (MDA) were also measured. RESULTS: Significant differences concerning the presence of reparable lesions and the extent of bowel mucosa without active inflammation in all groups of animals treated with infliximab compared with controls were found. Significant reduction of the tissue levels of TNF-alpha in all groups of treated animals as compared with the untreated ones was found (0.47+/-0.44, 1.09+/-0.86, 0.43+/-0.31 vs 18.73+/-10.53 respectively). Significant reduction in the tissue levels of MDA was noticed in group 1 as compared to group 4, as well as between groups 2 and 4. CONCLUSION: Subcutaneous administration of infliximab reduces the inflammatory activity as well as tissue TNF-alpha and MDA levels in chemical colitis in rats. Infliximab at a dose of 5 mg/kg BW achieves better histological results and produces higher reduction of the levels of TNF-alpha than at a dose of 10 mg/kg BW. Infliximab at a dose of 5 mg/kg BW produces higher reduction of tissue MDA levels than at a dose of 15 mg/kg BW.

Increased fasting serum levels of growth hormone and gastrin in patients with gastric and large bowel cancer.

BACKGROUND: Growth hormone (GH), Insulin-like growth factor-I (somatomedine, IGF-I) and gastrin seem to play a significant role in cell proliferation in mammalian and rat cells. The role of these factors in the etiology of gastric and large bowel cancer has not been completely elucidated. The aim of this study was to concurrently estimate the levels of GH, IGF-I and gastrin in a group of patients with gastric and colorectal cancer and to compare the results with those of a group of normal controls. PATIENTS AND METHODS: In 33 consecutive patients with gastric (16 patients) and large bowel (17 patients) cancer, the serum levels of GH, IGF-I and gastrin were measured by radioimmunoassay. Fifty-four normal people were served as controls. RESULTS: Significantly higher levels of serum GH (3.16 +/- 3.12 ng/ml in gastric cancer patients vs. 3.01 +/- 2.91 ng/ml in colorectal cancer patients vs. 0.69 +/- 1.60 ng/ml in normal controls, adjusted P<0.001) and gastrin (98.2 +/- 87.9 pg/ml in gastric cancer patients vs. 95.3 +/- 85.4 pg/ml in colorectal cancer patients, vs. 47.5 +/- 32.4 pg/ml in normal controls, adjusted P<0.035 and <0.05 respectively) were found in both groups of patients compared with normal controls. The levels of IGF-I in patients with gastric and colorectal cancer although higher compared to normal controls did not reach statistical significance. (98.2 +/- 87.9 pg/ml vs. 95.3 +/- 85.4 vs. 47.5 +/- 32.4 respectively) (adjusted P=0.070). CONCLUSION: It is concluded that in patients with gastric and colorectal cancer a significant increase of serum GH and gastrin can be found. This increase is likely to play a role in gastric and colorectal carcinogenesis.

Serum gastrin levels in patients with inflammatory bowel disease.

The aim of this study was to estimate the levels of serum gastrin in a group of patients with either ulcerative colitis or Crohn's disease and to compare the results with those of a group of normal controls. In 108 consecutive patients with IBD (66 with ulcerative colitis, 32 with Crohn's disease and 10 with indetermined colitis) serum levels of gastrin were measured by radioimmunoassay. One hundred and eight normal people were served as controls. The levels of serum gastrin were significantly elevated in patients with Crohn's disease compared to normal controls (74.4 +/- 43.9 pg/ml vs. 47.5 +/- 32.4 pg/ml, P<0.05), irrespectively of the activity of the disease. On the contrary, patients with ulcerative colitis exhibited no significant differences compared to normal controls. Differences between Crohn's disease and ulcerative colitis patients were statistically significant (P<0.001). The rate of infection by Helicobacter pylori in patients with inflammatory bowel disease was statistically significantly lower as compared with normal controls (31.7% vs. 55.1%, P<0.001). It is concluded that patients with active or inactive Crohn's disease have increased levels of serum gastrin. This may have implications concerning the high incidence of upper GI lesions found in patients with Crohn's disease despite the very low incidence of Helicobacter pylori infection.

Relation between Helicobacter pylori infection, thyroid hormone levels and cardiovascular risk factors on blood donors.

The aim of this study was to assess the relationship between Helicobacter pylori (Hp) infection, serum thyroid hormone levels and certain cardiovascular risk factors in normal volunteers. In 110 blood donors (85 men, 25 women, aged 35.6 +/- 9.76) the serum levels of IgG antibodies against Hp were estimated using a sensitive immunoassay. Serum estimation of T3, T4, TSH, FT3, FT4, thyroid (microsomial) autoantibodies, C-Reactive-Protein, a1-acid-glycoprotein, vitamin B12, folic acid, cholesterol, triglycerides, total lipids, HDL, LDL, and antibodies against hepatitis A, was also carried-out. In all subjects a number of clinicoepidemiological parameters including body mass index, smoking habits, educational level, number of siblings and presence of symptoms from the digestive system were carefully recorded. Statistical analyses were performed using the SPSS statistical package. Helicobacter pylori infection was found in 54 subjects (49.1%). On univariate analysis, significant differences between subjects positive and negative for Helicobacter pylori infection were found for FreeT3 (3.11 +/- 0.5 pmol/ vs. 3.42 +/- 0.8 pmol/l, P=0.025), FreeT4 (1.04 +/- 0.2 ng/dl vs. 1.17 +/- 0.3 ng/dl, P=0.025), and thyroid autoanti bodies (23.65 +/- 24 vs. 14.97 +/- 8, P=0.018). Significant differences were also found for Cholesterol (207.8 +/- 39 mg/dl vs. 193.3 +/- 40 md/dl, P=0.05), LDL (133.2 +/- 32 mg/dl vs. 119.6 +/- 40 mg/dl, P=0.05) and folic acid (7.66 +/- 3.7 ng/ml vs. 6.39 +/- 2.5 ng/ml, P=0.038). A significantly positive correlation of Hp infection with age and number of siblings and a negative one with educational level were noticed. No differences concerning the levels of acute phase proteins, vitamin B12, antibodies against hepatitis A, body mass index, and smoking habits were found. On logistic regression analysis, significant differences remained only for thyroid autoantibodies (Odds ratio for titer ?30: 7.8, P=0.012), age (Odds Ratio for those aged >40 years vs those aged <40 years: 3.8, P=0.022) and educational level (Odds ratio for elementary 8.7 and moderate 5.1 vs higher education, P=0.003 and P=0.011 respectively). It is concluded that a relationship exist between Hp infection and the presence of high titers of thyroid autoantibodies in blood donors. There are no indications of the existence of a relationship between Hp infection with thyroid hormone levels, lipid concentrations and other cardiovascular risk factors.