Orestes N. Manousos

Resistance to activated protein C and low levels of free protein S in Greek patients with inflammatory bowel disease

OBJECTIVE:Patients with inflammatory bowel disease (IBD) frequently suffer from thromboembolic events. A recently identified mechanism for thrombophilia, the poor anticoagulant response to activated protein C, has been suggested as one of the leading risk factors for thrombosis. The aim of this study was to evaluate the frequency of thrombophilic abnormalities, including activated protein C-resistance (APCR), in Greek patients with ulcerative colitis (UC) and Crohns disease (CD).METHODS:Forty-eight patients with UC, 36 with CD, and 61 matched healthy controls (HC) were studied. Cases with presence of lupus anticoagulant, use of anticoagulants or heparin, and pregnancy were excluded. Disease activity in CD was evaluated by use of the Crohns Disease Activity Index (CDAI) score and in UC by the Truelove-Witts grading system. Plasma levels of protein C, free protein S, antithrombin III (AT-III), activated protein C resistance (APCR), and fibrinogen were determined in IBD patients, as well as in HC. All the cases and controls with abnormal APCR were further studied by genetic testing for the factor V Leiden mutation.RESULTS:Mean fibrinogen levels in UC and CD patients were significantly elevated (p < 0.0001), compared with HC. The mean values of free protein S, as well as mean APCR, were significantly lower in UC and CD patients than in the HC (p < 0.0001). Seven (five UC and two CD) of 84 IBD patients (8.3%) and three of the HC (4.9%) had the factor V Leiden mutation. No significant difference was observed for the other thrombophilic parameters. Fibrinogen levels and profound free protein S deficiency were found related to disease activity.CONCLUSIONS:Thrombophilic defects are common in Greek patients with IBD and they could interfere either in the disease manifestation or in the thrombotic complications.

Somatostatin for acute severe bleeding from portal hypertensive gastropathy

Objectives To investigate the effect of somatostatin in acute severe bleeding from portal hypertensive gastropathy in 26 cirrhotic patients. Methods All patients with signs of acute gastrointestinal bleeding and an upper Gl endoscopy (during the first 24 h) indicating overt bleeding from portal hypertensive gastropathy were included in the study. Somatostatin (or the synthetic tetradecapeptide, octreotide) was administered in all cases. Eleven patients received somatostatin and 15 patients received octreotide. An initial injection of 250 μg bolus somatostatin was followed by a continuous infusion of 250 μg/h for 3 days (100 μg and 50 μg/h for octreotide). Results Somatostatin arrested bleeding in all 26 patients and in 23 there was no hospital relapse. In the remaining three patients the bleeding recurred each time somatostatin infusion was discontinued and arrested again on reinstitution of treatment In two there was a control of haemorrhage, while the third required a total gastrectomy after repeated episodes. The rebleeding rate in our study is much lower compared to untreated patients of other series. There were no differences between the somatostatin and octreotide group. There were no significant side effects. Gastroscopy at the end of the therapy showed improvement of the endoscopie appearance. Conclusions This open study suggests that somatostatin is a safe and effective treatment of acute severe bleeding from portal hypertensive gastropathy.

Elevated thrombopoietin serum levels in patients with inflammatory bowel disease

OBJECTIVES:Elevated platelet count is a well recognized marker of inflammatory bowel disease (IBD) activity. Thrombopoietin (TPO) is a critical cytokine in the physiological regulation of thrombopoiesis. The aim of this study was to investigate the serum levels of endogenous TPO in patients with IBD, the relationship between platelet counts and TPO levels, and the correlation of TPO with the clinical characteristics of the patients.METHODS:TPO levels in 40 patients with Crohns disease (CD), 63 patients with ulcerative colitis (UC), and in 42 healthy blood donors were assessed by ELISA. Platelet and white blood cell counts as well as C-reactive protein, and erythrocyte sedimentation rate were measured.RESULTS:TPO levels were significantly elevated in patients with CD (mean 124.3 ± SD 58.0 pg/ml, p < 0.0001) and in patients with UC (mean 152.2 ± SD 142.3 pg/ml, p < 0.0001), compared to controls (mean 53.4 ± SD 45.7 pg/ml). TPO levels remained significantly elevated in remission (mean 144.7 ± SD 131.1 pg/ml, p < 0.0001 compared to controls). Platelets were significantly elevated only in active CD, being normal in inactive disease as well as in all patients with UC. There was no significant correlation between TPO levels and various clinical characteristics of patients with IBD. No significant correlation was found between TPO levels and either platelet counts or white blood cell counts, erythrocyte sedimentation rate, and C-reactive protein.CONCLUSIONS:TPO levels are increased in IBD, irrespective of disease activity, platelet counts, and clinical characteristics of the patients. These observations indicate that TPO, apart from being a platelet producer, might have additional functions, probably related to the procoagulant state of IBD.

Increased levels of lipoprotein (a) in Crohn's disease: a relation to thrombosis?

Objective Lipoprotein (a) is recognized as a risk factor for arterial and venous thrombosis, a property that might be related to its structural similarity to plasminogen. Since patients with inflammatory bowel disease frequently suffer from thromboembolic events, we studied the role of lipoprotein (a) in conjunction with lipids and apolipoproteins in Greek patients with ulcerative colitis and Crohns disease. Methods Lipoprotein (a), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein A-1 and apolipoprotein B-100 were determined in sera from 129 consecutive fasting Greek patients with inflammatory bowel disease (66 with ulcerative colitis and 63 with Crohns disease) and from 66 matched healthy controls. Results In Crohns disease patients, the mean serum lipoprotein (a) level was significantly higher than in control patients (41.2 mg/dl vs 22.9 mg/dl;P = 0.005). Mean apolipoprotein A-1 and apolipoprotein B-100 levels were significantly lower in Crohns disease patients than in the controls. In ulcerative colitis patients the mean levels of lipoprotein (a) and apolipoprotein A-1 were not significantly different to the controls, but the levels of apolipoprotein B-100 were significantly lower. Raised levels of lipoprotein (a) of > 30 mg/dl were found in 29 Crohns disease patients (46%), 15 ulcerative colitis patients (23%) and 11 control patients (17%). Patients with active Crohns disease had significantly higher mean lipoprotein (a) and lower apolipoprotein A-1 than patients with non-active disease. Conclusions Our results suggest that Crohns disease patients have different lipoprotein (a) and apolipoprotein patterns compared to ulcerative colitis patients and healthy controls. These changes in Crohns disease patients may possibly expose them to a higher risk of thrombosis.

Association between ulcerative colitis and systemic lupus erythematosus: report of two cases.

Background Common aetiopathogenic factors may explain the association of ulcerative colitis with autoimmune disorders such as systemic lupus erythematosus. Patients We report two cases of ulcerative colitis associated with idiopathic systemic lupus erythematosus: one patient who developed ulcerative colitis 11 years after having been diagnosed as a case of systemic lupus erythematosus and one case of simultaneous appearance of the two diseases. The lupus clinical manifestations were in neither case correlated with the treatment of ulcerative colitis. Conclusion The association between ulcerative colitis and systemic lupus erythematosus is rare. Although a chance occurrence cannot be excluded it is possible that both conditions share some genetic or immunological defects.

Natural history of advanced hepatocellular carcinoma in Crete. Association with hepatitis C virus.

Objective: To investigate the clinical characteristics of advanced hepatocellular carcinoma (HCC) in Crete and to analyse the natural course of the untreated disease. Participants: Seventy‐three patients (62 men) were enrolled in a prospective 4‐year study. Clinical and virological parameters were recorded. Diagnosis was based on either ultrasound guided liver biopsy or a pathognomonic increase in alpha‐fetoprotein plus compatible imaging. Methods: Statistical analysis was performed using histograms, contingency tables and one‐way analyses of variance to analyse the characteristics of the disease. For survival analysis Kaplan‐Meier survival curves and Coxs proportional hazards models were constructed. Results: HCC in Crete is a mostly male disease (7:1 male:female ratio) and unlike in mainland Greece, it is mostly a hepatitis C virus (HCV)‐related disease (54% HCV positive as opposed to only 13% in mainland Greece). Prognosis was associated with Okuda classification (Okuda stage III patients have a relative risk of dying that is seven to nine times higher than for Okuda stage I), the presence or absence of hepatitis B e antigen (HBeAg) and antibody to hepatitis B core antigen (anti‐HBc). By contrast the presence of anti‐HCV was not associated with a worse prognosis. A unit increase of albumin concentration was associated with an 11% decrease in the hazard rate. Conclusion: In general, Crete, despite the extremely similar population to the rest of Greece, resembles more closely the situation in Spain or Italy rather than mainland Greece.

Validation and results of a questionnaire for functional bowel disease in out-patients.

BackgroundThe aim was to evaluate and validate a bowel disease questionnaire in patients attending an out-patient gastroenterology clinic in Greece.MethodsThis was a prospective study. Diagnosis was based on detailed clinical and laboratory evaluation. The questionnaire was tested on a pilot group of patients. Interviewer-administration technique was used. One-hundred-and-forty consecutive patients attending the out-patient clinic for the first time and fifty healthy controls selected randomly participated in the study. Reliability (kappa statistics) and validity of the questionnaire were tested. We used logistic regression models and binary recursive partitioning for assessing distinguishing ability among irritable bowel syndrome (IBS), functional dyspepsia and organic disease patients.ResultsMean time for questionnaire completion was 18 min. In test-retest procedure a good agreement was obtained (kappa statistics 0.82). There were 55 patients diagnosed as having IBS, 18 with functional dyspepsia (Rome I criteria), 38 with organic disease. Location of pain was a significant distinguishing factor, patients with functional dyspepsia having no lower abdominal pain (p < 0.001). Significant factors distinguishing between IBS and functional dyspepsia were relief of pain by either antacids or defecation (19% vs 71% and 66% vs 0% respectively). Awakening from pain at night was also a factor distinguishing between IBS and organic disease groups (26% vs 61%, p < 0.01).ConclusionsThis questionnaire for functional bowel disease is a valid and reliable instrument that can distinguish satisfactorily between organic and functional disease in an out-patient setting.

Granulomatous appendicitis: a clinical and epidemiological study in Crete

Objective: The aims of our study were: to provide an estimate of the incidence of epithelioid granulomas of the appendix in Greece; to investigate the relationship between granulomatous appendicitis and Crohns disease, and to estimate long-term prognosis. Methods: All pathology reports of patients who underwent appendicectomy from 1986–1991 in the prefecture of Heraklion were reviewed. In the cases with epithelioid granulomas of the appendix, the clinical, histological and laboratory features, as well as the clinical course, were recorded. Results: Four cases with epithelioid granulomas of the appendix, with no known cause, were identified. Postoperative investigation of the alimentary tract in two of the patients was negative. Follow-up of the four patients for 1.5–5 years (median 3.0 years) showed that all had been free of gastrointestinal symptoms since the operation. Conclusion: Patients with epithelioid granulomas of the appendix have an excellent long-term prognosis and in most cases, granulomatous appendicitis seems to be unrelated to Crohns disease.