Feeding response following central administration of chicken vasoactive intestinal peptide in chicks.

Vasoactive intestinal peptide (VIP) is expressed in central nervous systems and peripheral tissues across lower and higher vertebrates and is involved in many physiological functions. One of these functions is appetite regulation; however the mechanisms mediating this response are poorly understood. Therefore, the purpose of this study was to investigate central mechanisms of VIP induction of satiety using chicks as models. Intracerebroventricular (ICV) injection of VIP (0.1 and 0.5 nmol) significantly decreased food intake under both ad libitum and food deprivation conditions and chicken VIP (cVIP) was more potent than mammalian VIP. The mechanisms involved with the VIP-induced anorexigenic effect were investigated by studying the involvement of the central corticotrophin-releasing hormone (CRH) systems. ICV injection of cVIP caused increased plasma corticosterone concentration and decreased diencephalic mRNA expression of CRH, CRH receptor-2 (CRH-R2) and urocortin 3 (UCN-3, which has high affinity for CRH-R2). This simultaneous decrease in the expression of ligands and their receptor, with the increase in plasma corticosterone concentration suggests that the anorexigenic effect of cVIP might be related to CRH systems. The cVIP-induced anorexigenic effect was partly attenuated by co-injection of astressin, a CRH-R2 antagonist, supporting this thesis. The present study demonstrated that VIP inhibits feeding behavior via CRH systems in the brain of chicks.

Pulmonary blood transit time and impaired arterial oxygenation in patients with chronic liver disease.

BACKGROUND: Contrast-enhanced echocardiography (CEE) using agitated saline can detect intrapulmonary vasodilatation (IPVD) in patients with hepatopulmonary syndrome (HPS). We estimated the pulmonary transit time of erythrocytes (PTT) by CEE, using microbubbles, and studied its relationship to arterial oxygenation in chronic liver disease. METHODS: Sixteen patients with chronic liver disease and seven healthy subjects were studied. PTT was defined as the time between opacification of the right atrium and left atrium on CEE, using human serum albumin-air microbubble complexes with a mean diameter of 4 microm (Albunex). IPVD was detected by CEE with agitated saline. Arterial blood gases were analyzed with patients in the supine position, and while they were seated. Cardiac output (CO) was determined by Doppler echocardiography. RESULTS: The mean PTT value for all of the patients was 4.0 +/- 1.4 s. One of the 3 patients who showed IPVD was normoxemic. Mild orthodeoxia was observed in the patients with abnormal alveolar-arterial oxygen difference (A-aDO2) values (>15 mmHg), but not in those with normal A-aDO2 values, or in the healthy subjects. PTT was correlated with PaO2 (r = 0.52; P < 0.05; n = 16) and A-aDO2 (r = -0.54; P < 0.05; n = 16) in the seated position. CO was significantly correlated with PTT (r = -0.62; P < 0.05; n = 15), but not with PaO2 and A-aDO2, in both positions. CONCLUSIONS: PTT may be a useful parameter for evaluating arterial oxygenation in patients with chronic liver disease with early HPS.

Hepatic chymase level in chronic hepatitis: co-localization of chymase with fibrosis.

Chymase, secreted by mast cells, is associated with angiotensin II production and fibrosis of myocardium and renal interstitium. Assuming that chymase also is involved in liver fibrosis, we previously established an enzyme-linked immunosorbent assay for chymase in human liver tissue. In the present study, we explored the localization of mast cells in the liver using antibodies against human chymase and also studied relationships between hepatic chymase level and histologic findings in 49 patients with chronic hepatitis. By the international classification, fibrosis was staged from F0 to F4 and activity was graded from A1 to A3. Cells immunoreactive for chymase were seen throughout portal areas and intralobular sinusoidal walls, largely colocalizing with inflammation and fibrosis. Hepatic chymase levels in F3 and F4 cases were greater than in F1 and F2 (F3+F4, 30.8+/-41.2 ng/mg vs. F1+F2, 5.7+/-6.6 ng/mg; P<0.01). Chymase in A3 casese (39.4+/-50.8 ng/mg) was more abundant than in A1 (3.7+/-4.3 ng/mg) or A2 (12.8+/-19.4 ng/mg); P<0.05 for each. Our findings suggest that hepatic chymase level is implicated in fibrosis and activity in human liver disease.

Establishment of an assay method for human mast cell chymase.

Chymase secreted by mast cells found in fibroblast-containing interstitial connective tissue has been implicated in collagen fiber formation and extracellular matrix production. We established a method for determination of human chymase activity, and applied this technique to measurements in serum and liver tissue. The mean chymase concentration in liver biopsy specimens from 26 patients with chronic hepatitis was 5.23+/-5.98 ng/mg (ranges 0.32-21.4). The serum chymase concentration was below the limit of detection, in both chronic hepatitis patients and healthy individuals. No significant relationship was seen between chymase activity in liver tissue and severity of liver fibrosis, but further investigation in larger numbers of patients is warranted.

Systemic lupus erythematosus related transverse myelitis presenting longitudinal involvement of the spinal cord.

Lupus-related transverse myelitis is a rare but serious complication. A 25-year-old Japanese woman with systemic lupus erythematosus (SLE) was admitted because of numbness of the face and left upper extremity, headache, and intermittent fever. Six days later, she developed tetraplegia. MRI of the spinal cord showed longitudinal high intensity signals from medulla oblongata to C5, and from Th12 to conus medullaris on T2-weighted image. These MRI findings were consistent with acute catastrophic neurological abnormalities. Despite administration of the combination of methylprednisolone and cyclophosphamide pulse therapies, as well as plasmapheresis, her condition did not improve. Any vasculopathy in addition to the autoimmune pathogenesis, and narrow therapeutic window may relate to the present refractory case.

Bleeding portal-hypertensive gastropathy managed successfully by partial splenic embolization.

The use of partial splenic embolization to decrease portal pressure and reduce gastric bleeding from portal-hypertensive gastropathy, a complication of liver cirrhosis, is described. A 62-year-old man with hepatic cirrhosis secondary to hepatitis C and documented portal hypertension was admitted with hypersplenism and bleeding esophageal varices. Endoscopic ligation successfully controlled acute bleeding, but blood loss continued over the next 45 days. Bleeding secondary to portal-hypertensive gastropathy was diagnosed endoscopically. The patient's poor surgical status precluded a portosystemic shunt procedure, so partial splenic embolization was performed radiologically by the injection of Gelfoam squares. Splenic volume decreased 50% following partial embolization. Over 3 weeks, the hemoglobin concentration increased from 8.5 g/dL to 9.8 g/dL, and the platelet count increased from 41,000 to 90,000/microL. Repeat endoscopy found no gastric bleeding 18 days post-procedure. Partial splenic embolization is a radiologic procedure which can be performed safely in patients too ill to undergo portosystemic shunt. This report documents its successful use to manage hypersplenism and reduce portal pressure in a cirrhotic patient with portal-hypertensive gastropathy and hypersplenism.

[A report of questionnaire survey asking teaching staff concerning evaluation of faculty teaching from the students in Nippon Medical School].

A questionnaire survey was conducted to ask teaching staffs about the present activities and opinions of evaluation of faculty teaching from the students (EFS). One hundred and eighty-eight among 336 members (56.1%) responded. Among them sixty-four (34%) replied that they had tried at least once EFS of their lectures and/or practices. Approximately 70% had a opinion that EFS would benefit them for improving their lectures and practices, and/or for improving course planning. Fifty-four per cent of members supported EFS to be introduced, 34% depended upon how to evaluate, and remaining 5% did not support it. These results indicate that the staff members are highly concerned with EFS which should be provided for introduction after a full discussion how to evaluate.

Implementation of integrated medical curriculum in Japanese medical schools.

Recently, various integrated medical curricula, which can be defined as courses with subject matter classified by organ systems rather than according to departments such as surgery and internal medicine, are beginning to be introduced to bedside-learning in Japan. For example, in such an integrated medical curriculum, lectures in the course on neurological diseases would be given by a team that would include neurosurgeons, neurologists, and pathologists. Using medical education on neurological diseases as an example of an integrated medical curriculum, we analyzed the factors related to the neurological disease course as an example of an integrated medical curriculum in the clinical medicine course at our school. We also compared our course with those of all private medical schools in Japan, using the syllabuses of these private medical schools for the comparison, and considered elements that measured interdisciplinary participation in presenting the curriculum. For an integrated medical curriculum to gain interdisciplinary acceptance, the curriculum should be constituted using all medical disciplines related to the specific organ involved in the disease process under study, including both basic medicine and clinical medicine. In addition, teachers should be informed of the rationale for such a curriculum to promote their participation and a textbook on the integrated medical curriculum is needed. A curriculum committee should play an important role in promoting this type of medical education.

Increased chymase in livers with autoimmune disease: colocalization with fibrosis.

Chymase, one of the proteases contained in human mast cells, promotes myocardial and renal interstitial fibrosis by converting angiotensin I to II (AII). We previously established a method for measuring chymase in liver tissue and examined the relationship between chymase and fibrosis in chronic hepatitis. In the present study, chymase was determined in liver specimens affected by autoimmune hepatitis (AIH, n=10) or primary biliary cirrhosis (PBC, n=12). To investigate spatial relationships between hepatic fibrosis and human chymase, mast cell distribution in the specimens was determined immunohistochemically using anti-chymase antibody. The mean amounts of chymase in livers with AIH and PBC were 11.56+/-10.64 and 11.67+/-9.96 ng/mg respectively. Hepatic chymase in AIH and PBC was significantly more abundant than in acute hepatitis (AH, 2.72+/-2.23 ng/mg, n=10; p<0.05). When sections from patients with AIH and PBC were immunostained for chymase, immunoreactive mast cells were detected in portal areas and sinusoidal walls, coinciding with zones of fibrosis. Thus chymase appears to be involved in hepatic fibrosis in AIH and PBC.

A case of hepatocellular carcinoma with situs inversus totalis.

We report a case of hepatocellular carcinoma with situs inversus totalis treated by hepatectomy. A 70-year-old asymptomatic female with hepatocellular carcinomas in segments 5, 6 and 8 underwent transarterial embolization in the department of medicine. However, hepatocellular carcinoma in segment 8 relapsed, and she was referred to the department of surgery. Laboratory tests revealed elevation of serum PIVKA2 level (4,690 ng/mL). Angiography revealed tumor stain in segment 8, 3 cm in diameter. No aberrant vessels were detected on angiography. The operator stood on the patient's left, and partial hepatectomy could be performed safety after careful examination of the anatomy. Although aberrant vessels are detected in many patients with situs inversus totalis, operations can be performed safely on them with sufficient understanding of the anatomy.

Intrapulmonary vascular dilatation and nitric oxide in hypoxemic rats with chronic bile duct ligation.

BACKGROUND/AIMS: Nitric oxide (NO) has been suggested as the major cause of pulmonary vascular dilatation and hypoxemia in hepatopulmonary syndrome (HPS). The aim of this study was to assess the effect of NO on arterial oxygenation in rats with common bile duct ligation (CBDL rats), a model of HPS. METHODS: Arterial blood gases were measured in 44 CBDL rats and 44 Sham rats under unrestrained conditions. Intrapulmonary shunting was assessed with (141)Ce-labeled microspheres (15-mum diameter) and serum nitrate/nitrite levels were measured by HPLC. The effect of NOS inhibition on A-aDO(2) was studied using L-NAME. RESULTS: A decrease of PaO(2) below 82.7 mmHg (the mean value-2sigma in Sham rats) was seen in 43% of CBDL rats. Intrapulmonary shunting was greater in CBDL rats than in Sham rats (P<0.001). A correlation between the extent of shunting and A-aDO(2) was found in all animals studied (r=0.89, P<0.001, n=16). Serum levels of nitrate/nitrite increased significantly across the lungs, and the increase was significantly correlated with A-aDO(2) in the total population of animals studied. Administration of L-NAME to CBDL rats achieved a significant improvement of A-aDO(2). CONCLUSIONS: These results suggest that pulmonary vascular dilatation due to NO leads to hypoxemia in CBDL rats.