MicroRNA-320a Monitors Intestinal Disease Activity in Patients With Inflammatory Bowel Disease.

OBJECTIVES: In patients with inflammatory bowel disease (IBD), a treat-to-target treatment strategy requires tight monitoring of disease activity. Noninvasive biomarkers may help to monitor the intestinal disease activity. We demonstrated recently that peripheral microRNA (miR)-320a expression in mice follows the course of experimental colitis. The aim of this study was to evaluate the potential of miR-320a to monitor the disease activity in patients with IBD, to predict the course of disease, and to distinguish IBD from infectious colitis. METHODS: The miR-320a levels were prospectively assessed by quantitative real-time polymerase chain reaction analysis of peripheral blood samples from 40 patients with Crohn's disease (CD) and 37 patients with ulcerative colitis (UC) as well as from 19 healthy control individuals and 7 patients with infectious colitis. Disease activity was quantified by appropriate clinical disease indices and endoscopic scoring systems. RESULTS: When compared with healthy controls, miR-320a blood levels were significantly increased in patients with active CD and UC (16.1 ± 2.6 vs 2,573 ± 941; vs 434 ± 96; both P < 0.001) and patients with IBD in remission (316 ± 251 [CD] and 91 ± 29 [UC]; both P < 0.001). In patients with CD, miR-320a levels showed a strong correlation with the endoscopic disease activity (r = 0.76; P < 0.001). Similarly, in patients with UC, we detected a significantly enhanced miR-320a expression, which was highest in patients with severe endoscopic disease activity (eMayo = 0-1: 66 ± 16 vs eMayo = 2: 352 ± 102; vs eMayo = 3: 577 ± 206; both P < 0.001). Finally, miR-320a blood expression in patients with active CD and UC significantly increased compared with patients with infectious colitis (63 ± 13, P < 0.001). DISCUSSION: MiR-320a expression in peripheral blood from patients with IBD follows the clinical and endoscopic disease activities and may help to distinguish IBD from infectious colitis.

Therapeutic effects of Ginkgo biloba extract against acute ischemic colitis.

Ginkgo biloba extract (GBE) is a plant extract obtained from the leaves of G biloba tree. The aim of this study was to evaluate the clinicopathologic characteristics and therapeutic effects of GBE on ischemic colitis (IC).Forty-seven patients with IC were divided as GBE group (n = 30) and routine group (n = 17). The routine group was given routine therapy, and the GBE group was given routine therapies plus GBE intravenous injection. Clinicopathologic characteristics, endoscopy findings, serum antioxidant enzymes, and inflammatory mediators were evaluated.About 89.3% initial symptom was acute-onset abdominal cramping and abdominal pain followed with hematochezia. The lesions were mainly located in sigmoid colon (80.8%). Serum level of superoxide dismutase (SOD) in patients with IC was significantly decreased (P < .05), while methane dicarboxylic aldehyde (MDA), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) levels were significantly increased (P < .05). However, serum procalcitonin (PCT) level showed no significant change. Treatment of GBE resulted in quick remittance of abdominal pain and hematochezia, and significant attenuation of colon macroscopic and histologic damage in all patients. Furthermore, the treatment also significantly increased SOD levels, decreased MDA, TNF-α, and IL-6 levels (P < .05).Acute-onset abdominal cramping or abdominal pain followed with hematochezia was the mainly initial symptom of IC, and sigmoid and descending colons were the common vulnerable sites. GBE exerted a beneficial effect on IC with faster symptom relief and better mucosal healing, possibly through scavenging oxidative-free radicals and downregulating inflammatory mediators. GBE may be a promising candidate for protection against IC.

Ischemic colitis of the colon in streptozotocin-induced diabetic rats.

This study focuses on two inflammatory diseases, viz., "diabetes mellitus (DM)" that causes serious complications such as retinopathy, nephropathy, and neuropathy, and "ischemic colitis" which is evoked by DM. Ischemic colitis originates from the reduction in mesenteric blood flow to the colon with existence of the occlusive or non-occlusive reasons. Our study objective was to provide early diagnostic approach for ischemic colitis in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley rats were divided into four groups: (i) control use of 0.1 M citrate buffer, the solvent of streptozotocin (C), (ii). induced ischemia (I), (iii) rats subjected to 60 mg/kg STZ intraperitoneally to induce type 1 diabetes (D) (48 h after STZ injection, blood glucose levels >200 mg/dl were considered as diabetic), and (iv) diabetic rats subjected to intestinal ischemia (D+I). The third diabetic group (D) was not operated. At the end of the experimental period, rats were sacrificed, C-reactive protein (CRP) and calprotectin levels were measured in the serum and colon tissue specimens. Tissue specimens were also analyzed histologically. We found that serum and colon calprotectin levels were elevated in the D+I group compared to the D and/or I group alone, but relatively calprotectin levels increased in I as compared to C group in colon tissues. CRP levels were significantly increased with ischemic colitis in diabetes, while colon CRP levels were decreased. These results provide evidence for the existence of inflammation in the STZ-induced diabetic rats with ischemic colitis. In conclusion, our measurements of serum calprotectin levels of STZ-induced diabetic rats with ischemic colitis provide a practical approach for an early diagnosis of ischemic colitis. Furthermore, these biochemical analyses correlate well with the histopathologic findings of STZ-induced diabetic rats with ischemic colitis. Future studies would be desirable to further strengthen the role of calprotectin in the early diagnosis of ischemic colitis in diabetics clinical settings.

Serum procalcitonin correlates with colonoscopy findings and can guide therapeutic decisions in postoperative ischemic colitis.

BACKGROUND: Postoperative ischaemic colitis (POIC) is a life-threatening vascular gastrointestinal condition. Serum procalcitonin (PCT) levels be of value in the detection of necrosis. AIMS: To evaluate the correlation between serum PCT levels and the colonoscopic assessment of the severity of POIC. METHODS: Between January 2007 and November 2014, 150 patients with POIC and PCT data were included in the study. The main outcome measure was the correlation between serum PCT and the colonoscopy-based assessment of the severity of POIC (according to Favier's classification: stage 1/2 without multi-organ failure vs. stage 2/3 with multi-organ failure). RESULTS: Eighty-five percent of the stage 1 cases (n=22) had a serum PCT level ≤2µg/L; 63% (n=19) of the stage 2 cases with multi-organ failure had a PCT level between 4 and 8µg/L, and 70% (n=52) of the stage 3 cases had a PCT level ≥8µg/L. The PCT level was strongly correlated with the Favier stage (Spearman's rho: 0.701; p<0.0001). PCT levels were similar in stage 2 cases with multi-organ failure and in stage 3 cases (16.06µg/L vs. 7.79µg/L, respectively; p=0.35). CONCLUSION AND RELEVANCE: Serum PCT is correlated with stage 2/3 POIC requiring surgery. If PCT ≥5µg/L, surgery should be considered.

Ischemic Colitis after Cardiac Surgery: Can We Foresee the Threat?

INTRODUCTION: Ischemic colitis (IC) remains a great threat after cardiac surgery with use of extracorporeal circulation. We aimed to identify predictive risk factors and influence of early catecholamine therapy for this disease. METHODS: We prospectively collected and analyzed data of 224 patients, who underwent laparotomy due to IC after initial cardiac surgery with use of extracorporeal circulation during 2002 and 2014. For further comparability 58 patients were identified, who underwent bypass surgery, aortic valve replacement or combination of both. Age ±5 years, sex, BMI ± 5, left ventricular function, peripheral arterial disease, diabetes and urgency status were used for match-pair analysis (1:1) to compare outcome and detect predictive risk factors. Highest catecholamine doses during 1 POD were compared for possible predictive potential. RESULTS: Patients' baseline characteristics showed no significant differences. In-hospital mortality of the IC group with a mean age of 71 years (14% female) was significantly higher than the control group with a mean age of 70 (14% female) (67% vs. 16%, p<0.001). Despite significantly longer bypass time in the IC group (133 ± 68 vs. 101 ± 42, p = 0.003), cross-clamp time remained comparable (64 ± 33 vs. 56 ± 25 p = 0.150). The majority of the IC group suffered low-output syndrome (71% vs. 14%, p<0.001) leading to significant higher lactate values within first 24h after operation (55 ± 46 mg/dl vs. 31 ± 30 mg/dl, p = 0.002). Logistic regression revealed elevated lactate values to be significant predictor for colectomy during the postoperative course (HR 1.008, CI 95% 1.003-1.014, p = 0.003). However, Receiver Operating Characteristic Curve calculates a cut-off value for lactate of 22.5 mg/dl (sensitivity 73% and specificity 57%). Furthermore, multivariate analysis showed low-output syndrome (HR 4.301, CI 95% 2.108-8.776, p<0.001) and vasopressin therapy (HR 1.108, CI 95% 1.012-1.213, p = 0.027) significantly influencing necessity of laparotomy. CONCLUSION: Patients who undergo laparotomy for IC after initial cardiac surgery have a substantial in-hospital mortality risk. Early postoperative catecholamine levels do not influence the development of an IC except vasopressin. Elevated lactate remains merely a vague predictive risk factor.

Predictive Factors for Severe Outcomes in Ischemic Colitis.

BACKGROUND/AIMS: Ischemic colitis includes a wide clinical spectrum ranging from mild to severe forms. This study aimed to determine the factors that are related to the occurrence of severe ischemic colitis. METHODS: This multicenter study was conducted retrospectively in Korea. The patients were divided into mild and severe groups. This study surveyed clinical characteristics, blood tests, endoscopic findings, and imaging studies. RESULTS: In the comparison of comorbidities, the severe group had a higher ratio of chronic kidney disease than the mild group (p=0.001). In the blood test, the severe group had a reduced number of platelets (p=0.018) and a higher C-reactive protein value (p=0.001). The severe group had a higher ratio of involvement of the right colon (p=0.026). The Eastern Cooperative Oncology Group (ECOG) performance status score of the patients showed that the severe group had higher scores than the mild group (p=0.003). A multivariate analysis showed that chronic kidney disease and high ECOG performance status scores were significant risk factors. CONCLUSIONS: If patients diagnosed with ischemic colitis are also treated for chronic kidney disease or have poor performance status, more attention and early intervention are necessary.

Serum value of procalcitonin as a marker of intestinal damages: type, extension, and prognosis.

BACKGROUND: Ischemic and necrotic damages are complications of digestive diseases and require emergency management. Nevertheless, the decision to surgically manage could be delayed because of no sufficiently preoperative accurate marker of ischemia diagnosis, extension, and prognosis. METHODS: The aim of this study was to assess the predictive value of serum procalcitonin (PCT) levels for diagnosing intestinal necrotic damages, their extension, and their prognosis in patients with ischemic disease including ischemic colitis and mesenteric infarction by a gray zone approach. Between January 2007 to June 2014, 128 patients with ischemic colitis and mesenteric infarction (codes K55.0 and K51.9) were operated, for whom data on PCT were available. We perform a retrospective, multicenter review of their medical records. Patients were divided into subgroups: ischemia (ID group) versus necrosis (ND group); the extension [focal (FD) vs. extended (ED)] and the vital status [deceased (D) vs. alive (A)]. RESULTS: PCT levels were higher in the ND (n = 94; p = 0.009); ED (n = 100; p = 0.02); and D (n = 70; p = 0.0003) groups. With a gray zone approach, the predictive thresholds were (i) for necrosis 2.473 ng/mL, (ii) for extension 3.884 ng/mL, and (iii) for mortality 7.87 ng/mL. CONCLUSION: In our population, PCT could be used as a marker of necrosis; especially in case of extended damages and reflects the patient's prognosis.

Clinical Characteristics of Ischemic Colitis in Elderly Patients.

BACKGROUND/AIMS: The aim of this study was to retrospectively analyze the endoscopy findings, clinical symptoms, signs and biochemical data of elderly patients with ischemic colitis (IC). METHODOLOGy: A retrospective study of 58 patients diagnosed with IC in the endoscopy center of Jinan Central Hospital from October 2008 to October 2013 was carried out. The patients were divided into two groups based on the age: elderly group (≥ 65 years) versus young group (< 65 years). Symptoms, signs, biochemical data, endoscopic findings and the length of hospitalization were compared. RESULTS: Of the 58 patients with IC (43 women and 15 men), the median age was 72.5 years (range 30-84 years), and 70.69% (41/58) were over the age of 65 years. Compared with the young group, the elderly group had a less frequent hyperactive bowel sounds, a higher baseline levels of C-reactive protein(CRP) and a longer average periods of hospitalization. CONCLUSION: Clinical characteristics of IC in the elderly were similar to those in the young group. CRP may be involved in the development of IC in the elderly patients. By considering the basic dieases combined with CRP levels, it is possible to more effectively predict and prevent the development of IC.

Predictive Factors for Severe Outcomes in Ischemic Colitis

BACKGROUND/AIMS: Ischemic colitis includes a wide clinical spectrum ranging from mild to severe forms. This study aimed to determine the factors that are related to the occurrence of severe ischemic colitis. METHODS: This multicenter study was conducted retrospectively in Korea. The patients were divided into mild and severe groups. This study surveyed clinical characteristics, blood tests, endoscopic findings, and imaging studies. RESULTS: In the comparison of comorbidities, the severe group had a higher ratio of chronic kidney disease than the mild group (p=0.001). In the blood test, the severe group had a reduced number of platelets (p=0.018) and a higher C-reactive protein value (p=0.001). The severe group had a higher ratio of involvement of the right colon (p=0.026). The Eastern Cooperative Oncology Group (ECOG) performance status score of the patients showed that the severe group had higher scores than the mild group (p=0.003). A multivariate analysis showed that chronic kidney disease and high ECOG performance status scores were significant risk factors. CONCLUSIONS: If patients diagnosed with ischemic colitis are also treated for chronic kidney disease or have poor performance status, more attention and early intervention are necessary.

Classification of various muscular tissues using miRNA profiling.

MicroRNAs (miRNAs) are endogenous small RNAs of 18-23 nucleotides that regulate gene expression. Recently, plasma miRNAs have been investigated as biomarkers for various diseases. In the present study, we explored whether miRNA expression profiling of various muscle cells may be useful for the diagnosis of various diseases involving muscle necrosis. miRNA expression profiling was assessed by miRNA array and real-time reverse-transcriptase polymerase chain reaction by using a reverse primer of a stem loop structure. Profiling of various muscle cells of mouse, including cardiac muscles, skeletal muscles, and vascular and visceral smooth muscles, indicated that profiling of miR-1, miR-133a, miR-133b, miR-145, miR-206, miR-208a, miR-208b, and miR499 were adequate to discriminate muscle cells. miR-145 was remarkably highly expressed in smooth muscles. miR-208a and miR-499 were highly expressed in cardiomyocytes. miR-133a was highly expressed in fast-twitch skeletal muscles. miR-206 and miR-208b were expressed in the slow-twitch skeletal muscles, and they can likely discriminate fast- and slow-twitch types of skeletal muscle cells. We observed that brown fat adipose cells had an miRNA expression profile very similar to those of skeletal muscle cells in the mouse. Plasma concentrations of miR-133a and miR-145 were extremely useful in diagnosing skeletal muscle necrosis in a mouse model of Duchenne muscular dystrophy and colon smooth muscle necrosis in a rat ischemic colitis model, respectively. In the present study, we investigated the miRNA expression profiles of various muscular tissues. Our results suggest that expression profiling would be useful for the diagnosis of various diseases such as muscular necrosis.

Predictors of severity in ischaemic colitis.

PURPOSE: Ischaemic colitis (IC) is an inadequate perfusion leading to potentially life-threatening colonic inflammation. The aim was to identify patient characteristics that predict severity in biopsy-confirmed IC. METHODS: A retrospective study of consecutive patients admitted with a robust diagnosis of IC over a 5-year period was performed. As IC is often misdiagnosed, strict inclusion criteria including supporting histopathology, exclusion of inflammatory bowel disease, absence of recent antibiotics or negative stool sampling with testing for Clostridium difficile were adhered to. Due to differing pathophysiology involved, patients suffering IC due to injury to colonic perfusion from vascular procedures or tumours were also excluded. Patients were divided by outcomes into a severe IC group including those that needed surgery or suffered mortality and a non-severe IC group that included patients managed medically with good evolution during their index admission. Patient characteristics were analysed to identify statistically significant predictors of severity (p < 0.05). RESULTS: Thirty-two patients (11 males, 21 females; mean age 72.5) met the inclusion criteria. Medical management was adopted in 23 patients with a single mortality (4.3%). Nine patients were managed surgically with two mortalities (22.2%), giving an overall mortality of 9.4% and a severe IC group consisting of ten patients. Significant prognostic predictors of severity included: right-sided IC (p = 0.0002), guarding (p = 0.001), lack of bleeding per rectum (p = 0.005) and chronic constipation (p = 0.02). CONCLUSIONS: The majority of patients with IC can be managed conservatively. Right-sided IC, guarding, lack of bleeding per rectum and chronic constipation are associated with severe IC.

Rebamipide enema therapy for left-sided ischemic colitis patients accompanied by ulcers: open label study.

AIM: To attempt rectal administration of rebamipide in the treatment of ischemic colitis patients with ulcers, and evaluate its effects. METHODS: We compared 9 ischemic colitis patients (2 men, 7 women) with ulcers treated by bowel rest only from 2000 to 2005 (conventional therapy group), with 6 patients (2 men, 4 women) treated by rebamipide enema therapy in 2006 (rebamipide enema therapy group) and analyzed the mean duration of fasting and hospitalization, degree of ulcer healing, and decrease in WBC count for the two groups. RESULTS: The mean duration of fasting and hospitalization were 2.7+/-1.8 d and 9.2+/-1.5 d in the rebamipide group and 7.9+/-4.1 d and 17.9+/-6.8 d in the control group, respectively, and significantly reduced in the rebamipide group (t= -2.915; P=0.0121 and t= -3.054; P=0.0092). As for the degree of ulcer healing at 7 d after admission, the ulcer score was reduced by 3.5+/-0.5 (points) in the rebamipide group and 2.8+/-0.5 (points) in the control group (t=1.975; P=0.0797), while the decrease in WBC count was 120.0+/-55.8 (x 10(2)/microL) in the rebamipide group and 85.9+/-56.8 (x 10(2)/microL) in the control group (t=1.006; P=0.3360). CONCLUSION: In left-sided ischemic colitis patients with ulcers, rebamipide enema therapy significantly reduced the duration of fasting and hospitalization, recommending its use as a new and effective therapeutic alternative.

Serum procalcitonin (PCT) as a negative screening test for colonic ischemia after open abdominal aortic surgery.

BACKGROUND AND AIM: We assessed serum procalcitonin (PCT) as a screening test for early detection of ischemic colitis. PATIENTS AND METHODS: Ninety-three patients (81 men and 12 women) undergoing elective aortic surgery were enrolled in this study. Their mean age was 70.3+/-8.1 years old. Serum procalcitonin was measured postoperatively. RESULTS: Four patients suffered from colon ischemia. Based on a cut off value of serum PCT>/=2.0 ng/ml, fourteen patients had a false positive but none had a false negative result. Sensitivity was 100%, and specificity was 83.9% in detecting ischemic colitis. Negative predictive vale was 100%. CONCLUSION: Serum PCT is a non-invasive test that has a high negative predictive vale in ruling out colon ischemia after aortic surgery.

Use of serologic markers as a screening tool in inflammatory bowel disease compared with elevated erythrocyte sedimentation rate and anemia.

OBJECTIVES: The purpose of this work was to evaluate the use of serologic testing as a screening test for inflammatory bowel disease compared with erythrocyte sedimentation rate and hemoglobin in a referred patient population with suspected inflammatory bowel disease. PATIENTS AND METHODS: A retrospective study was performed, reviewing medical charts of patients who had inflammatory bowel disease serology performed at Prometheus Laboratories from September 2002 to September 2004. Patients were divided into 4 categories: ulcerative colitis, Crohn disease, indeterminate colitis, and noninflammatory bowel disease groups. Patients were categorized based on clinical evaluation by board-certified pediatric gastroenterologists. RESULTS: A total of 227 patients seen at the Lucile Packard Children's Hospital Gastroenterology Clinic had inflammatory bowel disease serology performed at or before the time of diagnosis. Seventeen charts were excluded secondary to inadequate information. Forty children were found to have inflammatory bowel disease, a prevalence of 19%. Overall, serologic testing for inflammatory bowel disease had 60% sensitivity and 92% specificity. A positive laboratory test for anemia or an elevated erythrocyte sedimentation rate had 83% sensitivity, whereas the combination of anemia and elevated erythrocyte sedimentation rate had 96% specificity. The positive predictive value of serologic testing was 60% compared with 79% in patients with anemia and elevated erythrocyte sedimentation rate. The positive predictive value of serologic testing in the subgroup of subjects without rectal bleeding (139 subjects) was only 35% compared with 60% using routine tests. Almost one third of all positive serologic tests were in patients with no demonstrable inflammatory bowel disease. CONCLUSIONS: As a pediatric inflammatory bowel disease screening strategy for the general pediatrician or gastroenterologist, the measurement of the combination of erythrocyte sedimentation rate and hemoglobin has a higher positive predictive value and is more sensitive, more specific, and less costly than commercial serologic testing.

Activation of fibrinolysis and coagulation in non-occlusive intestinal ischaemia in a pig model.

The present study was carried out to explore the dynamics of the fibrinolytic and coagulation systems during non-occlusive intestinal ischaemia in a porcine model. Nineteen pigs underwent laparotomy. The inferior mesenteric artery and the collateral vessels to the rectum were ligated. The superior mesenteric artery (SMA) was isolated at its origin from the aorta, and constriction and flowmeter devices were applied. The blood flow of the SMA was reduced to cause ischaemia in the distal colon within the pHi interval 6.9-7.1. Fibrinogen, soluble fibrin, D-dimer, tissue plasminogen activator/plasminogen activator inhibitor-1 (tPA/PAI-1) complex and albumin were measured. Corrections for pig D-dimer and albumin were performed. Fibrinogen decreased significantly after laparotomy (P < 0.0001) and further after constriction of the SMA (P < 0.05), whereas soluble fibrin increased significantly (P < 0.005) after constriction of the SMA. The tPA/PAI-1 complex increased significantly after laparotomy (P < 0.05) and, after constriction of the SMA, the values first tended to decrease (P = 0.06) and then to increase (P = 0.056). The need to calibrate assays of human plasma proteins when applying them to experimental pig models was demonstrated. After constriction of the SMA, there was a rapidly reversed peak in the coagulation marker soluble fibrin and a strong tendency of alteration of the fibrinolytic marker tPA/PAI-1 complex.

Ischemic colitis revisited: a prospective study identifying hypercoagulability as a risk factor.

BACKGROUND: Although causes for ischemic colitis have been identified, many cases are deemed idiopathic. Some reports suggest an association between ischemic colitis and coagulation disorders. Our purpose was to explore the relationship of ischemic colitis and clotting abnormalities. METHODS: Eighteen patients consented to undergo a hypercoagulability evaluation. Tests included protein C, protein S, activated protein C resistance, factor V Leiden, anticardiolipin antibodies, antineutrophil cytoplasmic antibodies, rheumatoid factor, antithrombin III, anti-smooth muscle antibody, lupus anticoagulant panel, and prothrombin 20210G/A mutation (in women undergoing hormone replacement therapy). RESULTS: Five of 18 patients tested positive for coagulation abnormalities, including factor V and activated protein C resistance, protein S deficiency, prothrombin 20210G/A mutation, and anticardiolipin antibody. CONCLUSION: To our knowledge, this is the largest series of patients with ischemic colitis studied for coagulation defects in the United States. The prevalence of clotting disorders in our study (28%) was higher than that in the general population (8.4%). Coagulation disorders should be considered in some cases of ischemic colitis that are thought to be idiopathic.

Low plasma protein Z levels in patients with ischemic colitis.

Hypercoagulable states have been suggested to play an important role in the pathogenesis of ischemic colitis. Since protein Z is, as recently demonstrated, important in the regulation of coagulation, we investigated the plasma levels of protein Z in connection to factor V Leiden (FVL) and anti-phospholipid antibodies in patients with a definite diagnosis of ischemic colitis. The plasma levels of protein Z were measured using a commercially available enzyme-linked immunosorbent assay in 33 patients with ischemic colitis, 13 patients with diverticulitis, and 33 healthy controls. Mean plasma protein Z levels were 1.38 +/- 0.52 microg/ml in patients with ischemic colitis and were significantly lower compared to healthy controls (1.86 +/- 0.49 microg/ml) and patients with diverticulitis (1.72 +/- 0.53 microg/ml) (P = 0.001). Protein Z deficiency was found in patients cases with ischemic colitis (18.2%) compared to one with diverticulitis (7.7%) and one healthy control (3.0%). In conclusion, our results suggest that low plasma protein Z levels may play a role in the disease development in some cases with ischemic colitis.

The effect of transient intestinal ischemia on inflammatory parameters.

BACKGROUND AND AIMS: To determine the early biological changes occurring in intestinal ischemia in vivo. PATIENTS AND METHODS: We studied the effects of acute transient intestinal ischemia in 15 patients undergoing elective open surgery for the treatment of abdominal subrenal aortic aneurysm induced by clamping of the aorta at subrenal level and above the branching of the inferior mesenteric artery. Blocking the blood flow results in hypoperfusion of the inferior mesenteric artery and then to rectal mucosal ischemia. RESULTS: With the introduction of a mucosal ischemic period the basal intestinal mucosal pH decreased during ischemia, and showed a rapid increase during reperfusion to the level preceding ischemia. Parameters were evaluated in blood taken from inferior mesenteric vein. A rectal dialysis was put into the rectum to evaluate eicosanoid concentrations in rectal fluid collected before and during clamping and after declamping. Significant enhancement in plasma level of xanthine, a marker for tissue damage, was observed during reperfusion. Interleukin-6 levels were significantly elevated from 11.28+/-3.4 pg/ml (preischemic) to 109+/-85.9 pg/ml (ischemic) and to 189.33+/-120.24 pg/ml (reperfusion); and tromboxane B(2) levels from 141.57+/-51.20 pg/ml preoperation to 473.01+/-319.01 pg/ml during the surgical procedure. CONCLUSION: These observations indicate that even transient ischemia modifies the inflammatory pattern.

Ischemic colitis during pregnancy and contraceptive medication.

Ischemic bowel disease is generally considered a disease of the elderly and usually consists of reversible colopathy. Nonocclusive causes of ischemic colitis include low-flow states due to cardiac dysfunction and hypovolemia and use of certain medications including progestational medication. We report 2 cases of ischemic colitis in young women. The first one occurred in a young patient who developed three consecutive episodes of ischemic colitis during her pregnancy, whereas the second woman presented with ischemic colitis in relation with the estrogen use. Each episode had a favorable outcome. Having ruled out an infectious cause, or a low blood flow state and in the absence of known thrombogenic disease, we hypothesized the etiology of these ischemic episodes to a high level of circulating estrogens due to pregnancy in the first case and oral contraceptive medication in the second. Physicians treating hemorrhagic colitis in young women should consider the use of contraceptive medication containing estrogens or pregnancy as possible causes.

Ischemic colitis and acquired resistance to activated protein C in a woman using oral contraceptives.

We present the case history of a 22-yr-old woman diagnosed with ischemic colitis associated with the use of oral contraceptives (OC). At the time of her presenting symptoms activated protein C (APC) resistance, a risk factor for thrombosis, was demonstrated. There was no laboratory evidence of inherited thrombophilia; that is, antithrombin III, protein C and protein S levels were normal and the factor V Leiden mutation was not present. The OC were discontinued and the patient's symptoms improved. Subsequent evaluation revealed that the activated protein C resistance had resolved. This case illustrates APC resistance as a potential link between OC use and its known association with ischemic colitis.