Accuracy, criteria, and clinical significance of visual assessment on diffusion-weighted imaging and apparent diffusion coefficient quantification for diagnosing acute appendicitis.

PURPOSE: To assess the accuracy, criteria, and clinical significance of diffusion-weighted imaging (DWI) signal intensity and apparent diffusion coefficient (ADC) quantification for diagnosing acute appendicitis. METHODS: Fifty-one patients with right lower abdominal pain [uncomplicated appendicitis (n = 25), complicated appendicitis (n = 10), and non-appendicitis (n = 16)] who underwent MR examination were enrolled in this retrospective study. Two radiologists independently measured appendiceal diameter and wall thickness. They assessed whether a wall defect, an abscess, extraluminal air, or an appendicolith was present on axial T2WI; evaluated intensity on DWI using a 5-point scale; and determined the ADC values of the appendix and peri-appendiceal tissue. Statistical analysis was performed to assess imaging findings for the diagnosis of appendicitis and complicated appendicitis. Cut-off values were determined using receiver operating characteristic analysis. RESULTS: For diagnosing acute appendicitis, the accuracy improved from 78.4% using only T2WI to 86.3% using combined T2WI and DWI for reader 1 and from 82.4 to 86.3% for reader 2. For the appendix, the cut-off ADC values that diagnosed appendicitis were 1.41 × 10-3 and 1.26 × 10-3 mm2/s with accuracies of 78.4% and 76.5%, respectively. For the peri-appendiceal tissue, these values of 1.03 × 10-3 and 0.91 × 10-3 mm2/s differentiated between uncomplicated and complicated appendicitis with an accuracy of 97.1%. CONCLUSIONS: Combined DWI and T2WI provided high accuracy for diagnosing appendicitis. The inflamed appendix had lower ADC value than the normal appendix. The peri-appendiceal tissue presenting low ADC value was a notable finding of complicated appendicitis.

Factors affecting pancreatic hyperamylasemia in patients undergoing peroral single-balloon enteroscopy.

BACKGROUND AND AIM: Acute pancreatitis following balloon-assisted enteroscopy is a rare but serious complication. The causative mechanism is uncertain and prevention strategies are not established. We conducted a retrospective study to clarify the risk factors for pancreatic hyperamylasemia. METHODS: Eighty-four patients undergoing peroral single-balloon enteroscopy (SBE) were enrolled in this study. Serum pancreatic and salivary amylase levels were measured 2 h after endoscopic examination. RESULTS: We experienced three patients with post-SBE pancreatitis. Factors predicting pancreatic hyperamylasemia were: (i) elderly patients; (ii) deeper insertion; and (iii) clockwise insertion. In contrast, younger age at examination was a significant factor observed in salivary hyperamylasemia. CONCLUSIONS: It is important to measure pancreatic amylase and not total amylase after SBE. When carrying out peroral SBE, the distance of insertion should be reduced especially if the scope traces a clockwise loop or the subject is elderly.

[A case report: feasible treatment of adalimumab for Crohn disease during pregnancy].

A 33-year-old woman with Crohn disease complained of diarrhea and hematochezia from the fifth week of her third pregnancy and was hospitalized. Because her CDAI indicated 307.1 points and colonoscopy showed multiple longitudinal ulcers in the distal colon, adalimumab therapy was initiated. The CDAI had decreased to 160.0 points and the colonic ulcers improved by 22 days after beginning the administration of adalimumab. Although adalimumab therapy was continued every 2 weeks during the third trimester, fetus growth was not affected and the woman delivered a healthy child. Adalimumab should be considered as one treatment for Crohn disease during pregnancy.

[A case of anesthetic management using levobupivacaine in epidural anesthesia combined with general anesthesia for thymectomy with thoracoscopy for generalized type myasthenia gravis].

Combined epidural and general anesthesia has become a standard anesthetic method for thymectomy. We employed levobupivacaine for epidural anesthesia combined with general anesthesia using remifentanil and sevoflurane for thymectomy with thoracoscopy for generalized type of myasthenia gravis. After decreasing the high level of antibodies to acethylcholine receptor by plasmapheresis, we could perform a stable and successful anesthetic management without the use of any muscle relaxants for the thymectomy. And a myasthenic crisis did not occur after the procedure. We concluded that levobupivacaine would be one of the appropriate options in epidural anesthesia for thymectomy for myasthenia gravis.

Multicenter study of plasma diafiltration in patients with acute liver failure.

Plasma diafiltration (PDF) is a blood purification therapy in which simple plasma exchange (PE) is performed using a selective membrane plasma separator while the dialysate flows outside the hollow fibers. A prospective, multicenter study was undertaken to evaluate the changes in bilirubin, IL-18, and cystatin C, as well as the 28-day and 90-day survival rates, with the use of PDF according to the level of severity as measured by the Model for End-Stage Liver Disease (MELD) score. Twenty-one patients with liver failure were studied: 10 patients had fulminant hepatitis and PDF therapies were performed 28 times; 11 had acute liver failure with the therapy performed 96 times. Levels of total bilirubin, IL-18, and cystatin C decreased significantly after treatment. The 28-day survival rate was 70.0% and that at 90 days was 16.7%. According to the severity of the MELD score, each of the results compared well with the use of Molecular Adsorbent Recirculating System or Prometheus therapy. In conclusion, PDF appears to be one of the most useful blood purification therapies for use in cases of acute liver failure in terms of medical economics and the removal of water-soluble and albumin-bound toxins.

Impact of plasma exchange on pharmacokinetic disposition of micafungin.

Change in the pharmacokinetic disposition of an antifungal agent micafungin (MCFG) by 8-hour plasma exchange (PE) with 3200 mL replacement was examined in a stem cell transplant recipient. On pharmacokinetic analysis of the time course of the serum concentrations of MCFG, it was determined that PE shortened the elimination half-life of MCFG from 16.5 hours to 6.3 hours. Total clearance (CL(tot)) was increased from 0.366 L/h to 0.932 L/h by PE. PE-dependent clearance (CL(pe)) accounted for approximately two-thirds of CL(tot), and PE was found to contribute to the removal of nearly 40% of the total body store of MCFG. It was confirmed that a significant amount of MCFG was excluded into apheresed plasma waste. In addition, adsorption of MCFG onto plasma-separating membrane was strongly suggested, because the CL(pe) exceeded the rate of plasma apheresis and MCFG concentrations in apheresed plasma were lower than those in circulating blood collected at the same time. The marked elimination of MCFG during PE can be explained by its low volume of distribution and high affinity for serum proteins. Judging from these findings as well as those of other reports, MCFG can be considered one of the drugs most susceptible to removal by PE. Our findings suggest that an increment in the regular dose of MCFG would be required at the next administration after PE.

Early and sustained systemic and renal hemodynamic effects of intravenous radiocontrast.

BACKGROUND AND AIMS: To measure the extended renal hemodynamic changes induced by intravenous radiocontrast. METHODS: Cross-ewes were studied in a randomized cross-over study. Intravenous saline or radiocontrast were administered, and continuous measurement of cardiac output and renal blood flow (RBF) was performed with flow probes. RESULTS: Radiocontrast induced early but transient increases in cardiac output with vasodilatation, followed by return to baseline values within 2 h. There was an initial decline in RBF (-5.2 +/- 4.5 vs. 2.1 +/- 5.3%; p < 0.0001) and decreased renal vascular conductance (-4.0 +/- 7.2 vs. 3.3 +/- 7.1%, p < 0.0001; vasoconstriction). This renal vasoconstriction resolved within 2 h and was followed by sustained (72 h) renal vasodilatation with higher RBF (270 +/- 13 vs. 236 +/- 11 ml/min; p < 0.0001). CONCLUSIONS: Radiocontrast induces short renal vasoconstriction followed by sustained vasodilatation and increased RBF. Short-term studies are not representative of the overall sustained renal hemodynamic effects of radiocontrast.

The impact of experimental hypoperfusion on subsequent kidney function.

OBJECTIVE: To investigate the short- and medium-term renal hemodynamic and functional responses to both short and sustained hypoperfusion. SUBJECTS: Eleven Merinos ewes. SETTING: Animal laboratory of the University Physiology Institute. DESIGN: Prospective observational study. INTERVENTIONS: Studies were performed in conscious sheep after unilateral nephrectomy with a vascular occluder and flow probe implanted on the remaining renal artery. In five sheep, renal blood flow (RBF) was reduced by 25, 50 and 75%, respectively, by acute vascular occlusion for 30 min at weekly intervals. In another six sheep, RBF was reduced by 80% for 2 h. MEASUREMENTS AND RESULTS: After 25, 50 or 75% renal hypoperfusion for 30 min, there was no associated extended loss of renal function. During 2 h of 80% hypoperfusion, urine output decreased from 80 to 17 ml, and creatinine clearance from 32 to 3 ml/min, whereas plasma creatinine increased from 103 to 132 mumol/l, and fractional excretion of sodium and urea increased. Release of occlusion induced brief hyperemia before all measured variables returned to normal within 8 h and remained normal for the following 72 h. At autopsy, the kidneys were histopathologically normal. CONCLUSIONS: Various degrees of renal hypoperfusion for 30 min did not induce prolonged changes in renal function or blood flow. Even with sustained severe hypoperfusion, there was rapid recovery to baseline function and flow. Unlike total ischemia, severe hypoperfusion alone is insufficient to induce subsequent persistent AKI.

Pneumatosis coli with ulcerative colitis as a rare complication of colonoscopy.

Pneumatosis coli is a relatively rare condition characterized by the presence of gas in the submucosa or subserosa involving mainly the large intestine and, occasionally, the mesenteric attachments. We experienced two cases of pneumatosis coli with ulcerative colitis after colonoscopy that had different clinical courses. Case 1 showed submucosal pneumatosis coli and portal venous air. The air was resolved 30 h later. Case 2 showed subserosal pneumatosis coli and retropneumoperitoneum. The air was eliminated after 3 weeks. The clinical features of pneumatosis coli may depend on the intramural region of the air. Cases 1 and 2 had different air localization, that is, submucosal and subserosal air, and this seems to reflect the differences in the complications. In Case 1 the air expanded to the portal vein, and took only a short time to resolve. In Case 2, however, the air leaked to the retroperitoneal space and took a long time to resolve. In summary, pneumatosis coli as a complication of colonoscopy presented different features depending on the air location. To our knowledge, this is the first report to reveal the difference of air localization and the complications associated with pneumatosis coli after colonoscopy.

Pathophysiology of septic acute kidney injury: what do we really know?

Septic acute kidney injury accounts for close to 50% of all cases of acute kidney injury in the intensive care unit and, in its various forms, affects between 15% and 20% of intensive care unit patients. However, there is little we really know about its pathophysiology. Although hemodynamic factors might play a role in the loss of glomerular filtration rate, they may not act through the induction of renal ischemia. Septic acute renal failure may, at least in patients with a hyperdynamic circulation, represent a unique form of acute renal failure: hyperemic acute renal failure. Measurements of renal blood flow in septic humans are now needed to resolve this pivotal pathophysiological question. Whatever may happen to renal blood flow during septic acute kidney injury in humans, the evidence available suggests that urinalysis fails to provide useful diagnostic or prognostic information in this setting. In addition, nonhemodynamic mechanisms of cell injury are likely to be at work. These mechanisms are likely due to a combination of immunologic, toxic, and inflammatory factors that may affect the microvasculature and the tubular cells. Among these mechanisms, apoptosis may turn out to be important. It is possible that, as evidence accumulates, the paradigms currently used to explain acute renal failure in sepsis will shift from ischemia and vasoconstriction to hyperemia and vasodilation and from acute tubular necrosis to acute tubular apoptosis or simply tubular cell dysfunction or exfoliation. If this were to happen, our therapeutic approaches would also be profoundly altered.

A surviving case of mitochondrial cardiomyopathy diagnosed from the symptoms of multiple organ dysfunction syndrome.

A 49-year-old female cardiomyopathic patient with heart, hepatic, and renal failure and lactic acidosis was transferred to the intensive care unit without a unifying diagnosis. She was of short stature (145 cm tall), had difficulty in hearing, a past history of complete atrioventricular block, and had received a permanent pacemaker. She had been diagnosed and treated as dilated cardiomyopathy by her primary doctor. Treatment in the intensive care unit for 21 days including plasma exchange, continuous hemodiafiltration, artificial ventilation, and administration of catecholamine, carperitide, and a large amount of coenzyme Q10 (210 mg/day) improved the symptoms. Genetic analysis using mitochondrial DNA from leukocytes and sternocleidomastoid muscle revealed a 3243A>G mutation in the mitochondrial tRNA(Leu (UUR)) gene, which is related to mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). The patient recovered through intensive care and could be discharged from hospital without any sequelae. This case was mitochondrial cardiomyopathy diagnosed from the symptoms of multiple organ dysfunction syndrome. Cardiomyopathy due to the mutation of mitochondrial DNA is not a common disease. However, it should be considered as a possible cause of heart failure.

A case of severe acute pancreatitis treated with CTR-001 direct hemoperfusion for cytokine apheresis.

Severe acute pancreatitis is a clinical entity that can develop into multiple organ failure (MOF), and still has a poor prognosis. It is generally agreed that excessive humoral mediators such as pro-inflammatory cytokines play important roles in the pathogenesis of organ failure in patients with severe acute pancreatitis (SAP). Furthermore, it has been reported that continuous hemodiafiltration (CHDF) can remove the excess humoral mediators during the hypercytokinemic state of systemic inflammatory response syndrome (SIRS). We experienced a case of severe acute pancreatitis induced by alcohol abuse, on whom we performed cytokine apheresis. The patient was a 46 year-old male. He received 14 cytokine apheresis procedures, for about 4 hours in each session, using a CTR-001 direct hemoperfusion (DHP) cartridge. His serum levels of pro-inflammatory cytokines such as interleukin-6 (IL-6; 1649.1+/-667.1-1257.1+/-489.4 pg/mL, P=0.013) decreased significantly after the CTR-001 procedures. However tumor necrosis factor-alpha (TNF-alpha) (26.2+/-1.7-24.3+/-1.9 pg/mL, P=0.087), IL-1beta (6.1+/-2.9-3.49+/-1.1 pg/mL, P=0.477), IL-8 (192.5+/-33.4-229.5+/-51.8 pg/mL, P=0.754) and IL-10 (14.4+/-2.7-14.0+/-1.9 pg/mL, P=0.726) did not decrease statistically. Therefore, we conclude that in this case, cytokine apheresis using a CTR-001 cartridge was effective for reducing the pro-inflammatory cytokines during severe acute pancreatitis.

Cross-sectional imaging in Crohn disease.

The role of cross-sectional imaging in the diagnosis of Crohn disease has expanded with recent technologic advances in computed tomography (CT) and magnetic resonance (MR) imaging that allow rapid acquisition of high-resolution images of the intestines. To acquire images of diagnostic quality, administration of a fairly large amount of intraluminal contrast agent prior to examination and scanning with intravenous contrast material injection are necessary. Both CT and MR imaging are reported to have a sensitivity of over 95% for the detection of Crohn disease; however, they may not allow early diagnosis. Colonoscopy and conventional enteroclysis studies are indicated for patients with early-stage disease. At more advanced stages, CT and MR imaging can help identify and characterize pathologically altered bowel segments as well as extraluminal lesions (eg, fistulas, abscesses, fibrofatty proliferation, increased vascularity of the vasa recta, mesenteric lymphadenopathy). These modalities can also clearly depict inflammatory lesion activity and conditions that require elective gastrointestinal surgery, thereby aiding in treatment planning. In the clinical setting, CT is currently the imaging modality of choice at most institutions; however, it is expected that MR imaging will soon play a comparable role. CT or MR imaging should be included in a comprehensive evaluation of patients with Crohn disease, along with conventional imaging and clinical and laboratory tests.

Inflixmab as a possible treatment for the hemorrhagic type of Crohn's disease.

Acute lower gastrointestinal bleeding is a rare complication of Crohn's disease (CD). Although anti-tumor necrosis factor-alpha (TNF-alpha, infliximab) therapy has been established for patients with inflammatory and fistulous CD, there has been little evidence on whether infliximab is effective for the hemorrhagic type of CD. We report a case of a 31-year-old man with CD who had recurrent sudden-onset bloody stool. After a second surgery, he visited our hospital because of bloody stool. Infusion of infliximab stopped the bleeding and promoted the healing of ulcers in the ileum and ileocolon anastomosis. We suggest that infliximab therapy should be tried to stop acute gastrointestinal bleeding in CD before there is a surgical emergency.

Pro-inflammatory cytokine-induced matrix metalloproteinase-1 (MMP-1) secretion in human pancreatic periacinar myofibroblasts.

Matrix metalloproteinases (MMPs) are the proteases involved in the degradation of the extracellular matrix. MMP-1 is thought to be one of the key enzymes in fibrolysis, a process closely related to tissue remodeling. In the present study, we investigated MMP-1 secretion from human pancreatic periacinar myofibroblasts in response to pro-inflammatory cytokines IL-1beta and TNF-alpha. We also attempted to clarify the intracellular signaling pathways mediating the cytokine-induced MMP-1 secretion. MMP-1 secretion was measured by an enzyme-linked immunosorbent assay. MMP-1 molecules were analyzed by Western blotting. MMP-1 mRNA expression was evaluated by Northern blotting. IL-1l and TNF-alpha stimulated the MMP-1 secretion in a dose- and time-dependent manner. Ninety percent of MMP-1 was secreted as inactive form (pro-MMP-1). The effects of IL-1beta and TNF-alpha were significantly inhibited by PD98059 MEK/ERK inhibitor). In contrast, SB203580 (p38 MAPK inhibitor), GF109203X (PKC inhibitor), and PDTC (NF-kappaB inhibitor) did not alter the MMP-1 secretion induced by IL-1beta and TNF-alpha. These effects were also observed at them RNA level. In conclusion, in human pancreatic periacinar myofibroblasts, MMP-1 secretion was regulated by the pro-inflammatory cytokines via the MEK/ERK cascade. Thus, human pancreatic periacinar myofibroblasts may play an important role in the remodeling of damaged pancreatic tissue in chronic pancreatitis via MMP-1 secretion.

Supplement of a chitosan and ascorbic acid mixture for Crohn's disease: a pilot study.

OBJECTIVE: Although the pathogenesis of Crohn's disease remains unclear, dietary fat is thought to exacerbate intestinal inflammation. Chitosan is a water-insoluble dietary fiber, and a chitosan and ascorbic acid mixture has been shown in rats to increase fecal fat excretion without affecting protein digestibility. However, it remains unclear whether a chitosan and ascorbic acid mixture is safe and effective for patients with Crohn's disease. We designed a pilot trial to investigate the tolerability and amount of fat excretion after the oral administration of a chitosan and ascorbic mixture for inactive Crohn's disease. METHODS: Eleven outpatients were given seven tablets daily of a chitosan and ascorbic mixture (chitosan was given at 1.05 g/d) for 8 wk. Patients did not interrupt their respective therapies for Crohn's disease. RESULTS: The bowel movements of most patients increased slightly during the study. Nutritional and inflammatory markers in patients did not differ before and after treatment. The chitosan and ascorbic acid mixture significantly increased the fat concentration in the feces during treatment. CONCLUSIONS: These results indicated that oral administration of a chitosan and ascorbic acid mixture in patients with Crohn's disease is tolerable and increases fecal fat excretion without affecting disease activity.