Ei Sasaki

IL-8 as an important chemoattractant for neutrophils in ulcerative colitis and Crohn's disease.

IL‐8 is generating increasing interest as a powerful neutrophil chemoattractant and activator. To elucidate the mechanisms of neutrophil infiltration in inflammatory bowel disease, we examined 33 patients with ulcerative colitis (UC),18 with Crohns disease (CD), eight with some other type of colitis, and 18 normal control subjects for measurement of IL‐8 in homogenates of colonic biopsy specimens. The affected colonic mucosa was found lo contain significantly more IL‐8 in patients with active inflammatory bowel disease than in patients with inactive disease (UC, P<0.001: CD, P<0.001), in patients with other types of colitis (UC, P<0.05; CD, P<0.01), or in normal control subjects (UC. P<0.001; CD. P<0.001). Colonic IL‐8 levels correlated significantly with the macroscopic grade of local inflammation, especially in patients with UC (P< 0.001). Colonic lL‐8 levels also correlated well with the neutrophil numbers in mucosal tissue (UC, r = 0.950, P<0.001; CD. r=0‐940, P<0.001), and with colonic IL‐1β (r=0.911, P<0.001) and tumour necrosis factor‐alpha (TNF‐a) levels (r=0‐604. P < 0001) in patients with these two conditions. These data suggest a potential role for IL‐8 and its regulatory cytokines IL‐I and TNF‐a in mediating neutrophil infiltration of the gut wall in inflammatory bowel disease.

Colonic Mucosal Interleukin-6 in Inflammatory Bowel Disease

Interleukin-6, a cytokine produced by various cell types, has a major role in inflammatory and immunological reactions. To define its potential role in inflammatory bowel disease, its concentrations in endoscopic biopsy samples from patients with ulcerative colitis and Crohns disease were measured. The involved colonic mucosa from active disease was found to contain significantly larger amounts of interleukin-6 than that from inactive disease or normal controls. Colonic mucosal interleukin-6 levels correlated well with the grade of macroscopic inflammation, especially in patients with ulcerative colitis. The levels of interleukin-6 decreased in parallel with clinical improvement following the start of therapy in patients with both forms of inflammatory bowel disease. Mucosal interleukin-6 is thus concluded to accurately reflect the degree of colonic inflammation and may be importantly associated with inflammatory and immunological phenomena seen in inflammatory bowel disease.

Colonic Mucosal Interleukin 1 Receptor Antagonist in Inflammatory Bowel Disease

To clarify the role of the interleukin 1 receptor antagonist (IL-1ra) in patients with inflammatory bowel disease (IBD), we assessed the local IL-1ra concentrations in tissue homogenates using a specific enzyme-linked immunosorbent assay and examined the immunohistochemical localization using a monoclonal antibody against IL-1ra. In patients with IBD, regardless of the disease activity, the mucosal concentration of IL-1ra in affected areas was elevated, and the concentration during the active phase was comparable to that measured during the inactive phase. In contrast, the IL-1 beta tissue concentration was higher during the active than during the inactive phase. The IL-1ra/IL-1 beta tissue concentration ratio in the affected areas was decreased in patients with active IBD as compared with normal controls or patients with other types of colitis. Immunohistochemical studies identified lamina propria mononuclear cells, especially macrophages, as the major source of IL-1ra in IBD tissue. Our results suggest that IL-1ra plays a pivotal role in regulating inflammation in IBD.

Gastric mucosal blood flow after smoking in healthy human beings assessed by laser Doppler flowmetry

We measured regional gastric mucosal blood flow by laser Doppler flowmetry before and after control (n = 8) or cigarette smoking (n = 8) in healthy human beings. The control group showed no change in both antrum (from 1.15 +/- 0.32 to 1.20 +/- 0.39 V, NS) and corpus gastric mucosal blood flow (from 1.15 +/- 0.32 to 1.12 +/- 0.28 V, NS). In contrast, cigarette smoking caused a significant reduction in gastric mucosal blood flow in the antrum (from 1.08 +/- 0.31 to 0.71 +/- 0.22 V, p < 0.01) and in the corpus (from 0.99 +/- 0.26 to 0.66 +/- 0.24 V, p < 0.01). The magnitude of reduction in gastric mucosal blood flow was similar between the antrum and the corpus (-34% +/- 11% versus -33% +/- 15%, NS). We conclude that cigarette smoking induces a significant reduction in gastric mucosal blood flow and that no heterogeneous response occurs in regional gastric mucosa. In addition, the laser Doppler flowmeter appears to be a sensitive method to assess rapid change in gastric mucosal blood flow in human beings.

Role of cytokine-induced neutrophil chemoattractant, a member of the interleukin-8 family, in rat experimental colitis

A study was made of the role of cytokine-induced neutrophil chemoattractant (CINC), regarded as a member of the interleukin-8 family, in rat experimental colitis induced by trinitrobenzene sulfonic acid and ethanol. Colonic myeloperoxidase (MPO) activity, a marker of tissue neutrophil infiltration, was observed to reach a plateau from 24 h to 1 week following the induction of colitis; tissue CINC levels, as measured by enzyme-linked immunosorbent assay, rose rapidly, peaking at 12 h before the rise in myeloperoxidase activity. The time-course of tissue leukotriene B4, another chemoattractant, was followed by that of MPO activity. Neutrophil accumulation into tissue in this model would thus appear to be under the control of CINC. Anti-CINC was also noted to inhibit 32.9 to 58.1% of chemotactic activity determined by bioassay during the same period, this being further evidence that CINC is a major chemotactic agent in this model. The present results indicate that CINC may have a crucial role in initiating neutrophil infiltration in experimental colitis.

Portal pressure after prophylactic sclerotherapy in patients with high-risk varices

Portal hemodynamics and transhepatic portal venographic findings were studied before and after prophylactic sclerotherapy (mean duration = 40 +/- 14 days) in 16 patients with high-risk esophageal varices. Portal pressure, evaluated by the portal venous pressure gradient, increased by a mean of 21% in eight patients (50%) and decreased by a mean of 20% in eight patients (50%) with no statistically significant change overall. The two groups were further analyzed separately to identify the mechanism of the change in portal pressure. Intrahepatic vascular resistance did not change significantly in either group. However, the prevalence of extravariceal portosystemic shunts was greater in patients with decreased portal pressure than in those with increased portal pressure (88% vs. 25%, p < 0.05). Further, the enlargement of extravariceal portosystemic shunts was more marked in patients with decreased portal pressure than in those with increased portal pressure (88% vs. 0%, p < 0.01). In addition, liver function, assessed by intrinsic clearance, was not modified in the two groups. We conclude that prophylactic sclerotherapy increases or decreases portal pressure without modifying liver function. Although the mechanism of these portal pressure changes is not clear, intrahepatic vascular resistance does not play an important role and the presence of extravariceal portosystemic shunts may prevent further increases in portal pressure.

MALT lymphoma arising in giant diverticulum of ascending colon

TO THE EDITOR: Since the first description by Bovin and Bonte in 1946 (1), over 100 cases of giant diverticula of the colon, mostly involving the sigmoid colon, have been reported in English-language literatures (2). Giant colonic diverticulum (GCD) is encountered much less frequently than other forms of diverticular diseases (2, 3), and is characterized by a higher rate of complications such as perforation, abscess formation, and volvulus (2). Two cases of adenocarcinoma arising within GCD have been reported (4, 5). We have described an unusual case of GCD located in the ascending colon and complicated by MALT lymphoma. A 59-yr-old man tested positive for fecal occult blood at an annual medical check, and was admitted to our hospital for examination of possible gastrointestinal malignancy. He had no abdominal pain, fever, history of vomiting or nausea, change of bowel habit, or visible rectal bleeding. He had slight tenderness in the right upper abdominal quadrant. A barium enema demonstrated a large cystic space, approximately 8 cm in diameter, filled by barium contrast in the ascending colon. Nodular margins were seen at the diverticular opening (Fig. 1 A). A typical apple-core sign indicating advanced colon cancer (Borrmann type 2) was noted in the sigmoid colon. Sigmoidectomy for the cancer and partial resection of the ascending colon for the diverticulum were performed. The resected diverticulum measured 4 3 4 3 3 cm and communicated with the colon through a large opening. Histological examination showed a moderately differentiated adenocarcinoma deeply invading the subserosa, and metastasis was found in the regional lymph nodes. The diverticulum had scattered remnants of mucosa, and the muscularis mucosa ended at the diverticulum neck. Smooth muscle bundles were seen in the wall possibly representing the muscularis propia. Atypical lymphoid cells densely infiltrated the entire wall of the GCD with destruction of the normal colon structure. The infiltration extended to the outside of the diverticulum (Fig. 1 B), and contained scattered abortive germinal centers (Fig. 1 C and 1D). Immunohistochemically the lymphoid cells, smallto medium-sized with cleaved nuclei, were positive for CD45, CD20, and bcl-2. Most cases of GCD occur in the sigmoid colon (2), and barium enema is very useful for definitive diagnosis because it visualizes the colonic communication (3). The ascending colon is a fairly unusual site for GCD. Only one previous case involving the ascending colon and two cases involving the transverse colon have been reported (4, 6, 7). Usually, the internal wall of the barium-filled GCD is smooth. However, as a rare complication, a case of adenocarcinoma arising in GCD has been reported (4, 5). In that case, irregular cyst wall margins suggested the presence of additional inflammation or neoplasms. According to Choong’s definition, the term GCD should be applied to diverticula larger than 4 cm, and they also described the classification of GCD into two types based on histology (2). Type I is a pseudodiverticulum that lacks distinct muscle layer, while

Effects of vasopressin and nicardipine on hemodynamics and liver function in patients with cirrhosis: comparison with vasopressin alone

The effects of a combination of vasopressin and a calcium channel blocker (nicardipine) on portohepatic hemodynamics and liver function were compared with the effects of vasopressin alone in 18 patients with portal hypertension. Nine patients received 0.4 units/min of vasopressin and 9 patients received the same dose of vasopressin plus 0.3 mg/min of nicardipine for 40 min. Vasopressin plus nicardipine induced a significant reduction in both free portal venous pressure and the portal venous pressure gradient. These effects were similar to the changes with vasopressin alone (-14% vs. -16% in free portal venous pressure; -29% vs. -31% in portal venous pressure gradient). Vasopressin decreased both hepatic blood flow (-34%, P < 0.01) and intrinsic clearance of indocyanine green (-22%, P < 0.05). In contrast, these two parameters did not significantly change after vasopressin plus nicardipine (-8% and -3%, respectively). These results suggest that the addition of nicardipine improves hepatic impairment induced by vasopressin but causes no further reduction on portal pressure.

Development of Gastroesophageal Varices and Risk of Variceal Bleeding in Patients With Cirrhosis

Abstract: We studied the relationships between portal pressure measured using the portal venous pressure gradient, the development of gastroesophageal varices, and the risk of variceal bleeding in 56 patients with cirrhosis. Portal pressure was higher in patients with varices than in those without (P>0.01), and 11 mmHg was the lowest portal pressure measured in the patients with varices. The size of the varices was not associated with the portal pressure. There was no difference in the value of portal pressure measurements for the patients with variceal bleeding and those without and there was no linear‐relationship between the degree of portal hypertension and the rate of variceal bleeding. 12 mmHg was the lowest portal pressure measured in the patients with variceal bleeding. The size of the varices was related to the rate of variceal bleeding (P>0.05). We conclude that (a) a portal pressure of 11 mmHg is necessary for the formation of varices, (b) 12 mmHg of portal pressure is necessary for variceal bleeding to occur but the degree of portal hypertension has no predictive value for the risk of variceal bleeding, and (c) the size of the varices does not depend on the degree of portal hypertension but is associated with the risk of variceal bleeding.

A case of pneumatosis cystoides coli associated with Sjogren's syndrome

Abstract: We report a case of pneumatosis cystoides coii associated with Sjogrens syndrome. This 53‐year‐old woman initially developed constipation and had bloody stools while she was taking prednisolone 5 mg daily for Sjogrens syndrome. Plain abdominal X‐ray revealed a gaseous pattern that resembled a bunch of grapes in the left abdomen. Endoscopic examination of the large intestine revealed numerous hemispheric cystic protrusions in the sigmoid colon and at the splenic flexure of the colon. Pneumatosis cystoides coli was thus diagnosed. Treatment included oxygen inhalation, 5 L/min for 5 hours/day. The X‐ray image indicating the collection of gas cleared 17 days after starting treatment. This disorder may merit consideration in the differential diagnosis of intestinal disorders in patients with collagen disease.