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Biomedical subjects

O N Manousos

Publications and source records attributed to O N Manousos.

At least 19 recordsLinked to original sources

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 Crohn's 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 Crohn's disease) and from 66 matched healthy controls. RESULTS: In Crohn's 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 Crohn's 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 Crohn's disease patients (46%), 15 ulcerative colitis patients (23%) and 11 control patients (17%). Patients with active Crohn's disease had significantly higher mean lipoprotein (a) and lower apolipoprotein A-1 than patients with non-active disease. CONCLUSIONS: Our results suggest that Crohn's disease patients have different lipoprotein (a) and apolipoprotein patterns compared to ulcerative colitis patients and healthy controls. These changes in Crohn's disease patients may possibly expose them to a higher risk of thrombosis.

Adult↗

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 Crohn's 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.

Activated Protein C Resistance↗

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 Crohn's 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.

Adult↗

Appendectomy, tonsillectomy, and risk of inflammatory bowel disease: case-controlled study in Crete.

PURPOSE: Appendectomy has been suggested as a possible protective factor in ulcerative colitis and as a risk factor in Crohn's disease. Tonsillectomy has also been associated with Crohn's disease. We performed a case-controlled study to investigate these associations in a homogeneous Greek population. METHODS: One hundred thirty-four consecutive cases of ulcerative colitis and 76 cases of Crohn's disease were included in the study. For each inflammatory bowel disease patient and a corresponding healthy control subject, matched for gender, age, and educational level, a standard record on various risk factors was completed by interview. The association between disease status and risk factors was assessed by Pearson's chi-squared test and the independent contribution of each risk factor was analyzed by means of logistic regression analysis. RESULTS: Appendectomy had been performed in 11 (8.2 percent) patients with ulcerative colitis, in 18 (13.4 percent) of their matched healthy control cases, in 19 (25.0 percent) patients with Crohn's disease, and in 10 (13.2 percent) of their matched healthy control cases. Odds ratio for development of ulcerative colitis after appendectomy was 0.6 (95 percent confidence interval, 0.26-1.27). Odds ratio for Crohn's disease was 2.2 (95 percent confidence interval, 0.94-5.12). Odds ratio for development of ulcerative colitis or Crohn's disease after tonsillectomy was 0.95 (95 percent confidence interval, 0.49-1.82) and 3.29 (95 percent confidence interval, 1.29-8.37), respectively. The logistic regression analysis showed that appendectomy and tonsillectomy have no independent association with the risk of developing ulcerative colitis, whereas in Crohn's disease both appendectomy and tonsillectomy have positive associations. Well-established risk factors, such as family history and smoking status, were also verified in this study. CONCLUSIONS: This case-control study, using multivariate logistic regression analysis, showed a less pronounced association between ulcerative colitis and appendectomy than previous reports. Our data also support the conclusion that tonsillectomy is a risk factor for developing Crohn's disease.

Adult↗

Anti-cardiolipin and anti-beta2-glycoprotein I antibodies in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) frequently suffer from thromboembolic events. Anti-cardiolipin (aCL) antibodies have been shown to be associated with thrombosis. Recently, the antibodies against the anti-cardiolipin cofactor beta2-glycoprotein I (a(beta2)GPI) have been found with higher specificity for thrombosis. The presence of these antibodies was assessed in 128 patients with IBD [83 with ulcerative colitis (UC) and 45 with Crohn's disease (CD)] and 100 healthy controls (blood donors). Patients with UC and CD had a significantly higher prevalence of aCL (18.1% and 15.6%, respectively) than healthy controls (HC) (3%). Eleven IBD patients (8.6%) but no HC had a(beta2)GPI. None of the IBD patients with a history of thrombosis had aCL and only one of them (a UC patient with deep vein thrombosis of the right leg) had a high titer of IgG a(beta2)GPI. In conclusion, these data show that both aCL and a(beta2)GPI are significantly associated with IBD but further studies are needed to determine the significance of our findings.

Antibodies↗

Ulcerative colitis in Greece: clinicoepidemiological data, course, and prognostic factors in 413 consecutive patients.

The clinical course and prognosis of ulcerative colitis was studied in a group of 413 Greek patients. The study lasted for 16 years and follow-up was achieved in 95% of the patients. Both sexes were almost equally affected, mainly between the ages of 40-49. Most of the patients lived in cities and had high educational levels. Familial clustering for inflammatory bowel disease was found in 2.7% of the patients. In most of them the disease was confined to the rectosigmoid area or left bowel and was of mild to moderate severity. The disease course included exacerbations--mainly of mild to moderate severity--and remissions. Mortality was absent during first attack, and it was generally low at the completion of the study. Excluding deaths caused by colorectal cancer, most of the deaths were unrelated to the ulcerative colitis itself. Unusual combinations of ulcerative colitis with other diseases, including diseases of autoimmune origin, were noted. There were no differences between men and women in the various clinicoepidemiologic parameters or in the course of the disease. Surgery was performed in 16.7% of patients, whereas surgery at first attack was required in 0.5%. In comparison with the nonoperated group, patients who were operated on were significantly younger at the time of onset of symptoms and had significantly more extensive disease. Factors prognostic of severe attacks and colectomy were extensive disease, young age at onset, and severe recurrences. Evolution to cancer was observed in 1.45%, whereas extraintestinal cancers also appeared in 1.5%. At the completion of the follow-up period, 5.8% of the patients were dead, 16% had only one attack, 2.7% experienced continuous symptoms, whereas in 58.8% of them, the disease course included exacerbations and remissions. On the basis of the outcome of severe attacks and the more favorable short-term prognosis, it could be argued that ulcerative colitis in Greece runs a milder course compared with that of other developed countries in Western Europe and North America.

Adolescent↗

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.

Adult↗

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 GI 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 microg bolus somatostatin was followed by a continuous infusion of 250 microg/h for 3 days (100 microg and 50 microg/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 endoscopic appearance. CONCLUSIONS: This open study suggests that somatostatin is a safe and effective treatment of acute severe bleeding from portal hypertensive gastropathy.

Acute Disease↗

Treatment of hepatocellular carcinoma with octreotide: a randomised controlled study.

BACKGROUND: Standard treatment of inoperable hepatocellular carcinoma has not been established. Somatostatin has been shown to possess antimitotic activity against a variety of non-endocrine tumours. AIMS: To assess the presence of somatostatin receptors in human liver and to treat advanced hepatocellular carcinoma with the somatostatin analogue, octreotide. METHODS: Somatostatin receptors were measured in liver tissue homogenates from patients with acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Fifty eight patients with advanced hepatocellular carcinoma were randomised to receive either subcutaneous octreotide 250 micrograms twice daily, or no treatment. Groups were comparable with respect to age, sex, Okuda classification, presence of cirrhosis, and liver biochemistry and virology. RESULTS: Various amounts of somatostatin receptors were identified in liver tissue of all patients including those with hepatocellular carcinoma. Treated patients had an increased median survival (13 months versus four months, p = 0.002, log rank test) and an increased cumulative survival rate at six and 12 months (75% versus 37%, and 56% versus 13% respectively). Octreotide administration significantly reduced alpha fetoprotein levels at six months. When a multivariable Cox's proportional hazards model was fitted, variables associated with increased survival were: treatment administration, absence of cirrhosis, increased serum albumin, and small tumours. Treated patients clearly had a lower hazard (0.383) in the multivariate analysis. CONCLUSIONS: Octreotide administration significantly improves survival and is a valuable alternative in the treatment of inoperable hepatocellular carcinoma.

Acute Disease↗

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 Cox's 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 Be 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.

Aged↗

Management of varicella infection during the course of inflammatory bowel disease.

OBJECTIVE: To study the natural history and outcome of varicella infection developing in steroid treated inflammatory bowel disease. BACKGROUND: Varicella infection occurring in immunosuppressed or immunocompromised patients is a common problem with a significant mortality. Varicella infection during the course of inflammatory bowel disease has been reported in a small number of patients with at least one fatality. METHODS: Four young patients with inflammatory bowel disease who developed varicella infection while on immunosuppressive therapy, steroids, or azathioprine were studied. In each patient the infection was severe, and the three most recently treated patients received acyclovir. RESULTS: All four patients developed severe varicella infection while receiving immunosuppressive therapy for their disease. Three patients were treated with intravenous acyclovir with concomitant reduction of steroid dosage and recovered completely. One patient, treated in 1980 with antibiotics and reduction in steroids, did not receive acyclovir and also survived. CONCLUSIONS: Varicella infection is a relatively uncommon occurrence in inflammatory bowel disease. If varicella infection occurs, prompt diagnosis and treatment with acyclovir and concomitant reduction in immunosuppressive therapy (reduction in steroid dosage and discontinuation of azathioprine) should be initiated immediately to limit viremia and avoid fatal complications.

Acyclovir↗

Autoimmune hemolytic anemia and positive Coombs test associated with ulcerative colitis.

OBJECTIVES: To estimate the frequency of autoimmune hemolytic anemia and Coombs positivity without overt hemolysis in ulcerative colitis, to determine possible subsets of patients with ulcerative colitis susceptible to this complication, and to assess the efficacy of the applied therapeutic modalities. METHODS: Three hundred and two patients with ulcerative colitis treated at the University Hospital of Heraklion, Crete, over a 6-yr period were included. Within this group, a subgroup of 152 patients were studied prospectively for the presence of a positive direct Coombs test. RESULTS: Autoimmune hemolytic anemia was diagnosed in five of 302 patients with ulcerative colitis (1.7%). One more patient developed Coombs-positive hemolytic anemia, attributed to sulfasalazine. A positive Coombs test without evidence of hemolysis was found in three of 152 patients (2%). The mean age of all Coombs-positive patients was 50.5 yr, and there was a definitive male preponderance (male: female, 2:1). Autoimmune hemolytic anemia occurred during active colitis in all cases. The mean time between the onset of colitis and the diagnosis of autoimmune hemolytic anemia was 17 months. Three of five patients with autoimmune hemolytic anemia (60%) and seven of nine of all Coombs-positive patients (77.7%) had total colitis. All patients with autoimmune hemolytic anemia were treated initially with large doses of corticosteroids. Three of five (60%) had good hematological responses. One patient responded to the addition of azathioprine, and one underwent splenectomy and proctocolectomy. CONCLUSIONS: In this study, the frequency with which autoimmune hemolytic anemia was associated with ulcerative colitis was higher than in previous reports. The complication occurred early in the course of colitis and was related to activity and extent of the disease. In contrast to others studies, we found a preponderance of males. Although corticosteroids and/or immunosuppressive therapy was successful in most of our cases, one patient required surgery.

Adolescent↗

A prospective epidemiologic study of Crohn's disease in Heraklion, Crete. Incidence over a 5-year period.

BACKGROUND: There has been an impression from published work that Crohn's disease is less common in southern than in northern Europe. A low incidence of Crohn's disease has been observed in Greece, but conclusive data are still lacking. METHOD: A 5-year prospective and population-based epidemiologic study of Crohn's disease was carried out in a well-defined area of Crete. RESULTS: The mean annual incidence of the disease for the years 1990-94 was 3.0 per 10(5) inhabitants. During the study period the incidence increased from 1.9/10(5) in 1990 to 3.8/10(5) in 1994. The male to female ratio was 2.4:1. The age group 25-34 years had the highest age-adjusted incidence (6.3/10(5)). The incidence of Crohn's disease was also found to be higher in smokers, in urban areas, and in people with high educational level. CONCLUSION: Crohn's disease is common in Heraklion, Crete. The findings of the study are discussed in relation to those of other European countries.

Adult↗

Ulcerative colitis is as common in Crete as in northern Europe: a 5-year prospective study.

OBJECTIVE: To study the incidence of ulcerative colitis and to analyse the pattern of the disease in the prefecture of Heraklion, Crete. PARTICIPANTS: The population at risk comprised 263,670 inhabitants in the prefecture of Heraklion (2641 km2). The two regional hospitals, five health centres, 109 private family doctors and 145 specialists participated in the study. METHODS: A prospective and population-based epidemiological study of ulcerative colitis over five years from 1990 to the end of 1994. RESULTS: Overall, 117 patients with ulcerative colitis (75 males and 42 females) were newly diagnosed during the study period. The mean annual incidence of the disease for the years 1990-1994 was 8.9 per 10(5) inhabitants (95% CI 7.2-10.4). The male to female ratio was 1.8:1. There were no significant difference between the age-specific incidences of the age groups. The majority (51.3%) of the patients were exsmokers and one-third had never smoked. A family history of first-degree relatives positive for inflammatory bowel disease was obtained in 9.6% of our patients. CONCLUSION: Ulcerative colitis is common in Crete; its incidence is as high as in Northern Europe.

Adolescent↗

Ulcerative colitis in Greece. Epidemiologic and clinical data.

Epidemiologic and clinical observations were made in 217 cases of ulcerative colitis between 1977 and 1983 in Evangelismos Hospital, Athens, Greece. The disease affected both sexes equally. The peak incidence occurred between 21 and 30 years of age. A second peak concerning only men was observed in the 6th decade of life. Urban and highly educated sections of the population were more often affected. Severe attacks were seen in only 3.4% of the patients at onset of the disease. Surgical treatment (colectomy) was applied to one in every seven patients either for a severe attack or on suspicion of cancer or debilitating symptoms.

Adult↗

Ulcerative colitis in Greece: course and prognostic factors.

The clinical course and prognosis of ulcerative colitis were studied in a group of 205 Greek patients. The study lasted for 6 years and follow-up was achieved in 98% of the patients. In most patients the disease was confined to the left bowel and it was of mild or moderate severity. Mortality was absent during the first attack and low at completion of the study while the cumulative colectomy rate was 14%. Bad prognostic factors leading to severe attacks and colectomy were: extensive disease, young age at onset and continuous symptoms. Compared to highly developed countries, the disease in Greece seems to run a milder course as can be judged by the better outcome of severe attacks and the more favorable short-term prognosis.

Adult↗