Reduction of respiratory motion artifacts in gadoxetate-enhanced MR with a deep learning-based filter using convolutional neural network.

OBJECTIVES: To reveal the utility of motion artifact reduction with convolutional neural network (MARC) in gadoxetate disodium-enhanced multi-arterial phase MRI of the liver. METHODS: This retrospective study included 192 patients (131 men, 68.7 ± 10.3 years) receiving gadoxetate disodium-enhanced liver MRI in 2017. Datasets were submitted to a newly developed filter (MARC), consisting of 7 convolutional layers, and trained on 14,190 cropped images generated from abdominal MR images. Motion artifact for training was simulated by adding periodic k-space domain noise to the images. Original and filtered images of pre-contrast and 6 arterial phases (7 image sets per patient resulting in 1344 sets in total) were evaluated regarding motion artifacts on a 4-point scale. Lesion conspicuity in original and filtered images was ranked by side-by-side comparison. RESULTS: Of the 1344 original image sets, motion artifact score was 2 in 597, 3 in 165, and 4 in 54 sets. MARC significantly improved image quality over all phases showing an average motion artifact score of 1.97 ± 0.72 compared to 2.53 ± 0.71 in original MR images (p < 0.001). MARC improved motion scores from 2 to 1 in 177/596 (29.65%), from 3 to 2 in 119/165 (72.12%), and from 4 to 3 in 34/54 sets (62.96%). Lesion conspicuity was significantly improved (p < 0.001) without removing anatomical details. CONCLUSIONS: Motion artifacts and lesion conspicuity of gadoxetate disodium-enhanced arterial phase liver MRI were significantly improved by the MARC filter, especially in cases with substantial artifacts. This method can be of high clinical value in subjects with failing breath-hold in the scan. KEY POINTS: • This study presents a newly developed deep learning-based filter for artifact reduction using convolutional neural network (motion artifact reduction with convolutional neural network, MARC). • MARC significantly improved MR image quality after gadoxetate disodium administration by reducing motion artifacts, especially in cases with severely degraded images. • Postprocessing with MARC led to better lesion conspicuity without removing anatomical details.

SAPPHIRE: a randomised phase II study of planned discontinuation or continuous treatment of oxaliplatin after six cycles of modified FOLFOX6 plus panitumumab in patients with colorectal cancer.

BACKGROUND: Fluorouracil (5-FU), leucovorin (LV) and oxaliplatin (FOLFOX) plus panitumumab therapy is a commonly used first-line chemotherapy for metastatic colorectal cancer (mCRC). However, the long-term administration of oxaliplatin is associated with peripheral neuropathy (PN). We investigated whether the planned discontinuation of oxaliplatin after FOLFOX plus panitumumab therapy can maintain efficacy and reduce PN incidence. PATIENTS AND METHODS: Chemotherapy-naive patients with RAS wild-type mCRC, aged ≥20 years, were enrolled and received six cycles of modified FOLFOX6 (mFOLFOX6) plus panitumumab as induction therapy. Patients who completed induction therapy without progression were randomised to mFOLFOX6 plus panitumumab (group A) or to 5-FU/LV plus panitumumab (group B). The primary end-point was the progression-free survival (PFS) rate at 9 months after randomisation. The secondary end-points were PFS, overall survival (OS), time to treatment failure (TTF), response rate (RR) and safety. RESULTS: In total, 164 patients were enrolled; of whom, 113 patients were then randomised (group A, n = 56; group B, n = 57). The median follow-up after randomisation was 19.6 months. The PFS rates at 9 months and median PFS were 46.4% (80% confidence interval [CI], 38.1-54.9) and 9.1 months (95% CI, 8.6-11.1) in group A, compared with 47.4% (80% CI, 39.1-55.8) and 9.3 months (95% CI, 6.0-13.0) in group B, respectively. RR, OS and TTF were also similar in both groups. Grade ≥2 PN incidence was lower in group B (9.3%) than in group A (35.7%). CONCLUSION: Planned discontinuation of oxaliplatin after six cycles of mFOLFOX6 plus panitumumab is a potential treatment option in patients with mCRC, achieving similar efficacy while reducing oxaliplatin-associated PN compared with mFOLFOX6 plus panitumumab. TRIAL REGISTRATION NUMBER: NCT02337946.

Epidemiology of massive hepatocellular carcinoma in dogs: A 4-year retrospective study.

Hepatocellular carcinoma (HCC) is the most common primary liver tumour in dogs. However, the clinical features and risk factors of HCC have not been confirmed. The objective of this study was to investigate the clinical features and risk factors for canine HCC. Medical records of 44 dogs diagnosed with HCC at Hokkaido University Veterinary Teaching Hospital between 2013 and 2017 were retrospectively reviewed. All dogs evaluated at the teaching hospital during the study period were used as the reference population for breed, age, sex predispositions or possible related factors for HCC, including concurrent disorders. Clinical characteristics of HCC were determined using propensity score matching analysis. The prevalence of HCC diagnosis was 0.96%. Multivariate analysis revealed that dogs diagnosed with HCC were significantly older (odds ratio [OR], 1.20; 95% confidence intervals [CI], 1.07-1.33) than the reference population. Welsh Corgis (OR, 3.68; 95% CI, 1.56-8.67) and Beagles (OR, 4.33; 95% CI, 1.58-11.90) were significantly predisposed to HCC. Twenty-seven of 44 dogs with HCC had at least one concurrent disorder. The most common concurrent disorder was hyperadrenocorticism (n = 10), and the adjusted odds of hyperadrenocorticism in dogs with HCC were 4.13 higher than those of the reference population (95% CI, 1.95-8.76). Propensity score matching analysis revealed that thrombocytosis (n = 30/43), increased alanine aminotransferase (n = 41/44), increased alkaline phosphatase (n = 42/44), and hypercalcemia (n = 13/32) were significantly associated with HCC diagnosis. The results of this study suggest that Welsh Corgis and Beagles are breeds with a predisposition for HCC and that hyperadrenocorticism might be a potential risk factor.

Diffuse Liver Metastasis of Small-Cell Lung Cancer Presenting as Acute Liver Failure and Diagnosed by Transjugular Liver Biopsy: A Rare Case in Whom Nodular Lesions Were Detected by Enhanced CT Examination.

Small-cell lung cancer (SCLC) is a subgroup of lung cancer with a high frequency of liver metastasis, which is a predictor of poor prognosis. Diffuse liver metastases of SCLC with no visible nodular lesions in the liver when examined using computed tomography (CT) are relatively rare; however, a few cases with rapid progression to acute liver failure that were diagnosed after death have been reported. In this paper, we report a 63-year-old man with diffuse liver metastases of SCLC that were histologically diagnosed using a transjugular liver biopsy while the patient was alive, even though no lesions were visible during a contrast-enhanced CT examination.

FOLFIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer after first-line bevacizumab plus oxaliplatin-based therapy: the randomized phase III EAGLE study.

BACKGROUND: A targeted agent combined with chemotherapy is the standard treatment in patients with metastatic colorectal cancer (mCRC). The present phase III study was conducted to compare two doses of bevacizumab combined with irinotecan, 5-fluorouracil/leucovorin (FOLFIRI) in the second-line setting after first-line therapy with bevacizumab plus oxaliplatin-based therapy. PATIENTS AND METHODS: Patients were randomly assigned to receive FOLFIRI plus bevacizumab 5 or 10 mg/kg in 2-week cycles until disease progression. The primary end point was progression-free survival (PFS), and secondary end points included overall survival (OS), time to treatment failure (TTF), and safety. RESULTS: Three hundred and eighty-seven patients were randomized between September 2009 and January 2012 from 100 institutions in Japan. Baseline patient characteristics were well balanced between the two groups. Efficacy was evaluated in 369 patients (5 mg/kg, n = 181 and 10 mg/kg, n = 188). Safety was evaluated in 365 patients (5 mg/kg, n = 180 and 10 mg/kg, n = 185). The median PFS was 6.1 versus 6.4 months (hazard ratio, 0.95; 95% confidence interval [CI] 0.75-1.21; P = 0.676), and median TTF was 5.2 versus 5.2 months (hazard ratio, 1.01; 95% CI 0.81-1.25; P = 0.967), respectively, for the bevacizumab 5 and 10 mg/kg groups. Follow-up of OS is currently ongoing. Adverse events, including hypertension and hemorrhage, occurred at similar rates in both groups. CONCLUSION: Bevacizumab 10 mg/kg plus FOLFIRI as the second-line treatment did not prolong PFS compared with bevacizumab 5 mg/kg plus FOLFIRI in patients with mCRC. If bevacizumab is continued after first-line therapy in mCRC, a dose of 5 mg/kg is appropriate for use as second-line treatment. CLINICAL TRIAL IDENTIFIER: UMIN000002557.

Natural history of bleeding risk in colonic diverticulosis patients: a long-term colonoscopy-based cohort study.

BACKGROUND: The natural history of bleeding risk from colonic diverticulosis remains unclear. AIM: To identify the incidence of bleeding in colonic diverticulosis patients and associated risk factors. METHODS: A cohort of 1514 patients with colonoscopy-confirmed asymptomatic diverticulosis was selected between 2001 and 2013. Age, sex and location of colonic diverticulosis (right or left side, or bilateral) were assessed. The endpoint was a bleeding event, and data were censored at the time of last colonoscopy. The cumulative and overall incidences of bleeding were estimated using the Kaplan-Meier and person-years methods. The Cox proportional hazards model was used to estimate age- and sex-adjusted hazard ratios (aHRs). RESULTS: The median follow-up period was 46 months. Bleeding events occurred in 35 patients, and the median time-to-event interval was 50 months. Kaplan-Meier analysis showed that the cumulative incidence of diverticular bleeding was 0.21% at 12 months, 2.2% at 60 months and 9.5% at 120 months. By the person-years method, the overall incidence rate of bleeding was 0.46 per 1000 patient-years. On multivariate analysis, age ≥70 (aHR. 3.7) and bilateral diverticulosis (aHR, 2.4) were significant risk factors for bleeding. CONCLUSIONS: This long-term follow-up study demonstrated that the cumulative incidence of bleeding from diverticulosis was approximately 2% at 5 years and 10% at 10 years, and the overall incidence was 0.46 per 1000 patient-years. Bilateral diverticulosis increased the risk of bleeding.

Relationship between clinical factors and severity of esophageal candidiasis according to Kodsi's classification.

Severe Candida esophagitis (CE) may lead to development of strictures, hemorrhage, esophagotracheal fistula, and a consequent decrease in quality of life. Although the severity of CE has been classified based on macroscopic findings on endoscopy, the clinical significance remains unknown. The aim of the study was to elucidate the predictive clinical factors for endoscopic severity of CE. Patients who underwent upper endoscopy and answered questionnaires were prospectively enrolled. Smoking, alcohol, human immunodeficiency virus (HIV) infection, diabetes mellitus, chronic renal failure, liver cirrhosis, systemic steroids use, proton pump inhibitor use, H2 blocker use, and gastrointestinal (GI) symptoms were assessed on the same day of endoscopy. GI symptoms including epigastric pain, heartburn, reflux, hunger cramps, nausea, dysphagia, and odynophagia were assessed on a 7-point Likert scale. Endoscopic severity was classified as mild (Kodsi's grade I/II) or severe (grade III/IV). Of 1855 patients, 71 (3.8%) were diagnosed with CE (mild, n = 48; severe, n = 23). In the CE patients, 50.0% (24/48) in the mild group and 23.1% (6/23) in the severe group did not have any GI symptoms. In HIV-infected patients (n = 17), a significant correlation was found between endoscopic severity and declining CD4 cell count (Spearman's rho = -0.90; P < 0.01). Multivariate analysis revealed that GI symptoms (odds ratio [OR], 3.32) and HIV infection (OR, 3.81) were independently associated with severe CE. Patients in the severe group experienced more epigastric pain (P = 0.02), reflux symptoms (P = 0.04), dysphagia (P = 0.05), and odynophagia (P < 0.01) than those in the mild group. Of the GI symptoms, odynophagia was independently associated with severe CE (OR 9.62, P = 0.02). In conclusion, the prevalence of CE in adults who underwent endoscopy was 3.8%. Silent CE was found in both mild and severe cases. Endoscopic severity was associated with characteristic GI symptoms and comorbidity of HIV infection. A decline in immune function correlated with CE disease progression.

Predictive value of endoscopic findings in the diagnosis of active intestinal amebiasis.

Endoscopic diagnosis of amebic colitis can be difficult because its appearance may mimic other forms of colonic disease. The aim of this study was to identify predictive endoscopic findings for amebic colitis. Patients with suspected amebic colitis based on distinctive endoscopic findings such as aphthae or erosions, ulcers, exudates, or a bump, were included in the study. A total of 157 patients were selected, 50 of whom had amebic colitis. The sensitivity and specificity of endoscopic findings that were significantly associated with amebic colitis were: cecal lesions (80% and 54%), multiple number of lesions (96% and 29%), presence of aphthae or erosions (84% and 37%), and presence of exudate (88% and 74%). Multivariate analysis revealed that the best combination of findings to predict amebic colitis was the presence of cecal lesions, multiple lesions, and exudates, which corresponded to an area under the receiver operating characteristic curve of 0.89 (95% confidence interval 0.82-0.95).

Recurrence of colonic diverticular bleeding and associated risk factors.

AIM: Colonic diverticular bleeding often recurs, but the risk factors remain unclear. Our aim was to identify risk factors for recurrence in patients with diverticular bleeding. METHOD: Seventy-two hospitalized patients who were diagnosed with diverticular bleeding between 2004 and 2008 were analyzed. Rebleeding was considered as the main outcome measure, with the duration until recurrence identified from medical records. Potential risk factors for rebleeding, such as underlying pathologies, medication and smoking and drinking habits, were investigated from the medical records on initial admission. RESULTS: Of the 72 patients, 19 had a diverticular disease on the right, 16 on the left side and 37 on both sides of the colon. Recurrence was identified in 27 (38%) patients at a median interval of 1535 days. The cumulative incidence of rebleeding at 6, 12 and 24 months was 15%, 20% and 33%. Multivariate analysis revealed nonsteroid anti-inflammatory drugs (NSAIDs) (hazard ratio (HR), 2.57; 95% confidence interval (CI), 0.89-7.46; P=0.08), antiplatelet drugs (HR, 2.39; 95% CI, 1.01-5.67; P=0.05) and hypertension (HR, 4.16; 95% CI, 1.22-14.2; P=0.02) to be risk factors for rebleeding. CONCLUSION: Patients with colonic diverticular bleeding show high recurrence rates within a short period. Risk factors for recurrence have been identified as the use of NSAIDs or antiplatelet drugs and hypertension.

Multicenter phase II study of FOLFOX for metastatic colorectal cancer (mCRC) in Japan; SWIFT-1 and 2 study.

BACKGROUND/AIMS: This study assessed the efficacy and toxicity of the FOLFOX4 (SWIFT1) and mFOLFOX6 (SWIFT2) regimens in Japanese patients with metastatic colorectal cancer (mCRC). METHODOLOGY: Patients with mCRC were required to have ECOG performance status of 0 to 1, and to have adequate organ function. Two multicenter Phase II studies (SWIFT1/SWIFT2) were conducted in chemotherapy naive patients with mCRC. RESULTS: 112 patients were enrolled in these studies (SWIFT1: 54 patients / SWIFT2: 58 patients). The disease sites for each study were the colon in 27 patients and 28 patients, and the rectum in 27 patients and 30 patients, respectively. All patients received a median of 8 courses. After a median follow-up period of 35 months, 54 patients and 58 patients were evaluable in the respective studies, and the overall response rate was 50.0% (CR:31 PR:53). The response rate according to the sites of metastasis were as follows: liver, 54.1% (46/85); lung, 17.4% (4/23); and lymph node, 23.3% (7/30). Grade 3/4 neutropenia occurred in 14 patients (12.5%), while Grade 3/4 non-hematological toxicities were observed in 16 patients (31.0%) and Grade 3 neurotoxicity was observed in 6patients (5.4%) and 5 patients (4.5%), respectively. CONCLUSIONS: FOLFOX4 (SWIFT1) and mFOLFOX6 (SWIFT2) regimens complying with the international standard dosage and schedule can also be administered safely and effectively in Japan.

Multicenter phase II trial of combination chemotherapy with weekly paclitaxel and 5-fluorouracil for the treatment of advanced or recurrent gastric carcinoma.

The aim of this study was to investigate the efficacy and safety of combination chemotherapy with weekly paclitaxel and 5-fluorouracil (5-FU) as first-line treatment in patients with advanced or recurrent gastric carcinoma. A total of 65 patients were treated with the following regimen, administered every 28 days; 5-FU 600 mg/m2 by 24-hour continuous infusion from days 1 through 5, and weekly paclitaxel 80 mg/m2 by 3-hour intravenous infusion on days 8, 14, and 21. A total of 272 cycles were conducted with a median of 4 (2-13) cycles per case. Out of 57 patients with measurable disease by RECIST criteria, there were 2 complete responses (3.5%), 20 partial responses (35.1%) and 25 cases with stable disease (43.9%). The overall response rate was 38.6% (95%CI: 26.0-51.2%). The median survival time and 1-year survival rates were 329 days and 47.4%, respectively. Both hematologic and non-hematologic toxicities were well tolerated.

[Bentall operation for a 90-year-old man with root aneurysm; report of a case].

Open heart surgery in nonagenarians is not common. We reported a successful Bentall operation in a 90-year-old man with aortic root aneurysm and aortic regurgitation. He has lived healthfully and independently without a big problem. He was referred to our hospital for acute heart failure. The aortic root enlarged as a diameter of 60 mm and moderate aortic regurgitation were recognized by echocardiography and aortogram. We excised the aneurysm, implanted a composite graft, directly attached the coronary arteries to the aortic graft (Carrel patch technique), and made the distal anastomosis to the divided aorta. Postoperative course was uneventful. To our knowledge, this is the first successful case of Bentall operation for nonagenarians in Japan. If selective criteria identifying risks and benefits for individual patients is applied, the nonagenarian can safely undergo cardiac surgery.

Gelatin-specific cellular immune responses persist for more than 3 years after priming with gelatin containing DTaP vaccine.

BACKGROUND: Gelatin-specific cell-mediated immunity develops in subjects inoculated with gelatin containing DTaP vaccine. However, it is not yet known whether such established sensitization to gelatin disappears or persists with time. OBJECTIVE: The aim of this study was to follow the patients with gelatin sensitization elicited by DTaP vaccination for their lymphocyte responsiveness and IgE, IgG antibody specific to gelatin over several years and to compare the activities with those at the time of enrollment into the study. METHODS: We studied 28 subjects who developed positive lymphocyte proliferation test (LPT) after receiving gelatin containing DTaP vaccine and eight subjects who had a negative LPT after inoculation of non-gelatin DTaP. Determination of IgE, IgG antibodies and specific lymphoproliferative response directed against gelatin were performed at enrollment and on follow up. RESULTS: None of the subjects had antibody to gelatin at enrollment and none developed gelatin IgE or IgG during follow-up. There was no significant difference in the SIs of the subjects receiving gelatin DTaP (P = 0.150, 95% CI, -0.198-0.032), whereas lymphocyte activity to gelatin increased between enrollment and follow-up in the subjects with non-gelatin DTaP (P = 0.011, 95% CI, 0.063-0.338). CONCLUSION: Gelatin-specific lymphocyte activity persists at comparable levels for more than 3 years in subjects who acquire a positive LPT response to gelatin after receiving primary DTaP vaccine containing gelatin. Furthermore, five out of eight subjects initially with negative LPT to gelatin have been shown to acquire specific LPT with time.

Comparative study of incadronate and elcatonin in patients with malignancy-associated hypercalcaemia.

The clinical usefulness of incadronate was compared with elcatonin in 26 patients with malignancy-associated hypercalcaemia. Data from 21 and 24 patients could be used to assess efficacy and safety, respectively. Eleven patients were given a single 10-mg intravenous infusion of incadronate and 10 received twice-daily intramuscular injections of 40 IU of elcatonin for 7 consecutive days. After treatment, corrected serum calcium levels decreased significantly in both groups. The anti-hypercalcaemic effect of elcatonin was characterized by its rapid onset, with serum calcium levels reduced 1 day after administration. In contrast, the anti-hypercalcaemic effect of incadronate was more sustained but only became apparent a few days after infusion. Evaluation of symptoms revealed significantly greater improvement rates in the incadronate group compared with the elcatonin group. Adverse drug reactions were observed in three patients in the incadronate group, i.e. mild and transient fever in two cases and exacerbation of disturbance of consciousness in one case. These findings suggest that incadronate produces more marked and sustained hypocalcaemic effects than elcatonin, and that co-administration of these two drugs may yield both rapid and sustained control of malignancy-associated hypercalcaemia.

Age-associated increase of 8-hydroxydeoxyguanosine in human colorectal tissue DNA.

To clarify the role of oxidative stress in aging of colorectal tissue, we analyzed the 8-hydroxydeoxyguanosine (8-OH-dG) levels in colorectal biopsy samples from normal tissue of patients with either colorectal cancer (n = 15) or benign colorectal polyps (n = 40). An age-associated increase of 8-OH-dG was observed (p =.002), although the 8-OH-dG levels were not significantly different between the patients with cancer and those with polyps. These results suggest an increased level of 8-OH-dG formation in human colorectal tissue with age.

Development of a new method to induce angiogenesis at subcutaneous site of streptozotocin-induced diabetic rats for islet transplantation.

The subcutaneous space is a potential site for clinical islet transplantation. Even though there are several advantages, poor blood supply at this site mainly causes failure of islet survival. In this study, angiogenesis was induced in advance at the diabetic rats subcutis for islet transplantation by implanting a polyethylene terephthalate (PET) mesh bag containing gelatin microspheres incorporating basic fibroblast growth factor (bFGF) (MS/bFGF) and a collagen sponge. The bFGF was incorporated into gelatin microspheres for controlled release of bFGF. As controls, a PET mesh bag with or without either collagen sponges or MS/bFGF was implanted at the subcutaneous site of diabetic rats. Macroscopic and microscopic examinations revealed the formation of capillary network in and around the PET mesh bag containing MS/bFGF and collagen sponges 7 days after implantation when compare with other control groups. When tissue hemoglobin level was also measured, a significantly high level of hemoglobin amount was observed compared with that of control groups. When allogeneic islets mixed with 5% agarose were transplanted into the prevascularized rat subcutis, normoglycemia was maintained for more than 40 days, while other control groups were ineffective. This study demonstrated that combination of gelatin microspheres incorporating bFGF and collagen sponges enabled the mesh to induce neovascularization even at the subcutaneous site of streptozotocin-induced diabetic rats, resulting in improved function of islet transplantation.

[Surgical techniques and results of right ventricular [correction of venericular] outflow tract reconstruction with pedicled autologous tissue].

From 1987 to 2000, 44 patients underwent anatomic repair of anomalies with pulmonary outflow obstruction by using pedicled autologous tissue in reconstructing the pulmonary outflow tract. Twenty-four patients had tetralogy of Fallot with pulmonary atresia (TOF/PA), from 1.7 years to 12.9 years of age (mean 9.0 years). In the group of TOF/PA, slit-widening method was performed in 22, autologous pericardial flap was used in 1, and atrial appendage was used in 4 patients. Eight patients had transposition of the great arteries with ventricular septal defect and pulmonary stenosis (TGA type III), from 9 months to 9.2 years of age (mean 4.5 years). All of the patient with TGA type III under went direct PA-RV anastomosis (natural route non-conduit repair). Three patients had truncus arteriosus, from 1 month to 7.8 years of age (mean 4.5 years). In the group of the truncus, atrial appendage was used in 1 and direct PA-RV anstomosis was made in 2 patients. Six patients had Rastelli's conduit obstruction, from 6.6 years to 20.3 years of age (mean 13.9 years). The conduit was removed and outflow tract was reconstructed with direct PA-RV anastomosis in 5 and using atrial appendage in 1 patients. There was one hospital death (2%) and no late deaths. In 31 patients whose follow-up time exceed 5 years, 7 patients (23%) were found to have pressure gradient more than 40 mmHg at the pulmonary outflow tract. None of the patients with TGA who underwent natural route non-conduit repair developed late stenosis at the pulmonary out flow tract.

In vivo evidence that protease-activated receptors 1 and 2 modulate gastrointestinal transit in the mouse.

1. Protease-activated receptors (PARs) 1 and 2 modulate the gastric and intestinal smooth muscle motility in vitro. In the present study, we examined if activation of PAR-2 and PAR-1 could alter gastrointestinal transit in mice. 2. Intraperitoneal administration of the PAR-2-activating peptide SLIGRL-NH(2), but not the inactive control LSIGRL-NH(2), at 1 - 5 micromol kg(-1), in combination with the aminopeptidase inhibitor amastatin at 2.5 micromol kg(-1), facilitated gastrointestinal transit in a dose-dependent manner. The human PAR-1-derived peptide SFLLR-NH(2) and the specific PAR-1 agonist TFLLR-NH(2), but not the inactive control FSLLR-NH(2), at 2.5 - 10 micromol kg(-1), in combination with amastatin, also promoted gastrointestinal transit. 3. The Ca2+-activated, small conductance K+ channel inhibitor apamin at 0.01 micromol kg(-1) significantly potentiated the actions of SLIGRL-NH(2) and TFLLR-NH(2) at subeffective doses. 4. The increased gastrointestinal transit exerted by either SLIGRL-NH(2) at 5 micromol kg(-1) or TFLLR-NH(2) at 10 micromol kg(-1) was completely abolished by the L-type Ca2+ channel inhibitor verapamil at 61.6 micromol kg(-1). In contrast, the tyrosine kinase inhibitor genistein at 18.5 micromol kg(-1) failed to modify the effects of the agonists for PAR-2 or PAR-1. 5. These findings demonstrate that PAR-1 and PAR-2 modulate gastrointestinal transit in mice in vivo. Our data also suggest that the PAR-1-and PAR-2-mediated effects are modulated by apamin-sensitive K+ channels and are dependent on activation of L-type Ca2+ channels, but independent of tyrosine kinase. Our study thus provides novel evidence for the physiological and/or pathophysiological roles of PARs 1 and 2 in the digestive systems, most probably during inflammation.

[Follicular bronchiolitis associated with pulmonary tuberculosis--report of a case].

The patient, a 39-year-old man, presented in May 1997 with an untreated persistent cough with excessive sputum of 5 years' duration. He was admitted to hospital because of the severity of the symptoms and the presence of acid-fast bacilli in his sputum. These bacilli were identified as Mycobacterium tuberculosis by the polymerase chain reaction method. After treatment with antituberculous drugs was initiated, his symptoms and the patchy infiltrative shadows on his chest radiographs gradually resolved. However, the patient continued to expectorate a purulent sputum, showed diffuse micronodular shadows on chest radiographs, and had hypoxemia as well as mixed ventilatory and small airway disturbances on pulmonary function tests. We performed a video-assisted thoracoscopic biopsy of the lung, which revealed follicular bronchiolitis.