Clinical practice at a multi-dimensional treatment centre for individuals with early psychosis in Japan.

Early intervention for psychosis in Japan has lagged behind that in western countries, but has rapidly begun to attract attention in recent years. As part of a worldwide trend, a multi-dimensional treatment centre for early psychosis consisting of a Youth Clinic, which specialises in young individuals with an at-risk mental state for psychosis, and Il Bosco, a special day-care service for individuals with early psychosis, was initiated at the Toho University Omori Medical Center in Japan in 2007. The treatment centre aims to provide early intervention to prevent the development of full-blown psychosis in patients with an at-risk mental state and intensive rehabilitation to enable first-episode schizophrenia patients to return to the community. We presently provide the same programmes for both groups at Il Bosco. However, different approaches may need to be considered for patients with an at-risk mental state and for those with first-episode schizophrenia. More phase-specific and need-specific services will be indispensable for early psychiatric interventions in the future.

Long-term effect of epidural injection with sustained-release lidocaine particles in a rat model of postoperative pain.

BACKGROUND: Single applications of sustained-release local anaesthetics may provide prolonged pain relief without requiring indwelling catheters, but have not yet been investigated for epidural postoperative pain management. We synthesized injectable sustained-release lidocaine particles (SRLPs) from biodegradable polymers and examined their effect in a rat model of postoperative pain. METHODS: Two types of polylactic acid particles, SRLP-10 and SRLP-25, containing 10% or 25% lidocaine, respectively, were generated and the lidocaine release was evaluated in vitro for 14 days. The SRLPs were then injected epidurally in the male Sprague-Dawley rats immediately before they received a hindpaw incision (the postoperative pain model), and hindpaw hypersensitivity was evaluated with the von Frey test. Motor paralysis and coordination were also assessed using a paralysis score and rota-rod test. Neurotoxicity and inflammation of the spinal cord, cauda equina, and tissue surrounding the injection site were histologically evaluated. RESULTS: In vitro, SRLP-10 and SRLP-25 released lidocaine over 7 and 3 days, respectively. The in vivo injection of SRLP-10 (80 mg) produced anti-hypersensitivity with no evidence of motor paralysis for 7 days after the paw incision, and SRLP-25 (60 mg) inhibited postoperative hypersensitivity for 7 days. Temporary motor paralysis (15 min) was observed after the injection of SRLP-25 (even with 40 mg). Foreign body reactions were observed around the SRLP injection site at 1 and 4 weeks after injection. No histopathological changes were observed at 1 or 4 weeks. CONCLUSIONS: The epidural injection of SRLPs produced prolonged anti-hypersensitivity in a rat model of postoperative pain with no major complications.

MCP-1 production in temporomandibular joint inflammation.

Synovitis, which is characterized by the infiltration of inflammatory cells, often accompanies progression of temporomandibular joint disorder (TMD) symptoms. Because IL-1ß is elevated in synovial fluids obtained from TMDs, we hypothesized that IL-1ß-responsive genes in synoviocytes may help identify the putative genes associated with synovitis. Using microarray analysis, we found that monocyte chemoattractant protein-1 (MCP-1) mRNA levels were elevated in IL-1ß-stimulated synoviocytes. MCP-1 is a member of the chemokine superfamily. The production of MCP-1 was increased in synoviocytes treated with IL-1ß. When IL-1ß was injected into the cavities of rat TMJs, inflammatory cells and MCP-1-positive cells were detected in the synovial tissues. Furthermore, MCP-1 levels were higher in synovial fluids from individuals with pain compared with those without pain. Inhibitors of MAP-kinases and NF-κB reduced IL-1ß-induced MCP-1 production. These results suggest that MCP-1 stimulated by IL-1ß is one of the factors associated with the inflammatory progression of TMDs.

Erythropoietin-producing renal cell carcinoma arising from autosomal dominant polycystic kidney disease.

Erythropoietin (EPO)-producing renal cell carcinomas (RCC) in patients with chronic renal failure secondary to autosomal dominant polycystic kidney disease (ADPKD) has not previously been reported. We report a case of EPO-producing RCC associated with ADPKD in a 66-year-old woman, and discuss the clinical and radiological findings.

Interleukin-1beta increases RANTES gene expression and production in synovial fibroblasts from human temporomandibular joint.

BACKGROUND: Synovial fibroblasts of temporomandibular joint (TMJ) are poorly characterized, although they have important roles in progression of temporomandibular disorders (TMD). In this study, we investigated responses of synovial fibroblasts to interleukin (IL)-1beta. METHODS: We examined gene expression profiles of synovial fibroblasts in response to IL-1beta, using Affymetrix GeneChip. Regulated upon activation normal T-cell expressed and secreted (RANTES) gene expression was confirmed by polymerase chain reaction (PCR) and real-time PCR. RANTES protein levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The RANTES was preferentially up-regulated in synovial fibroblasts by IL-1beta. The increase in RANTES gene expression in response to IL-1beta was confirmed by PCR and real-time PCR. Protein level of RANTES in synovial fibroblasts was also increased by IL-1beta. CONCLUSIONS: The RANTES, a cc-type chemokine, has chemotactic effects on lymphocytes and monocytes. Increased gene expression and protein production of RANTES in synovial fibroblasts, in response to IL-1beta, may play an important role in recruitment of inflammatory cells into synovium and progression of synovitis in TMD.

Case report: endovascular repair of a thoracic aortic aneurysm (saccular type) with a stent-graft.

We describe the repair of a descending thoracic aortic aneurysm (saccular type, maximal size 85 mm) with an endovascular stent-graft in a 69-year-old man with chronic renal failure. The graft consisted of a self-expanding Z-stent covered with a woven polyester graft. An angiogram obtained intraoperatively showed complete thrombosis of the aneurysm. One month after the procedure, a contrast-enhanced computed tomographic (CT) scan showed thrombosis of the aneurysmal sac. A follow-up CT scan obtained 18 months after operation confirmed that the aneurysm had disappeared.

Structure-activity relationships of quinazoline derivatives: dual-acting compounds with inhibitory activities toward both TNF-alpha production and T cell proliferation.

We synthesized 4-chlorophenethylaminoquinazoline derivatives and evaluated their inhibitory activities toward both TNF-alpha production and T cell proliferation responses. Compound 2f, containing a piperazine ring at the C(7)-position of the quinazoline ring, exhibited more potent inhibitory activities toward both than the lead compound la. A smaller N-substituent in the piperazine ring was required for inhibition of TNF-alpha production.

Reoperative coronary artery bypass grafting via a left thoracotomy and a small laparotomy without cardiopulmonary bypass: report of a case.

A 66-year-old woman with aortic stenosis underwent an aortic root replacement with a composite graft and coronary artery reconstruction 2 years before presentation. On coronary angiography performed 2 years after operation, saphenous vein graft (SVG) to right coronary artery and SVG to first diagonal branch had both become totally occluded. SVG to left anterior descending artery showed 75% stenosis on the heel side of the distal anastomosis. The patient underwent a second coronary artery bypass via a left thoracotomy (the left internal thoracic artery was anastomosed to the first diagonal branch by interposing it with the left radial artery) and a small laparotomy (the right gastroepiploic artery was anastomosed to the right coronary artery) without a cardiopulmonary bypass. This approach is preferable to avoiding both a resternotomy and cardiopulmonary bypass in patients requiring repeat surgery.

IL-1beta increases uPA and uPA receptor expression in human gingival fibroblasts.

The binding of urokinase-type plasminogen activator (uPA) to its receptor (uPAR) in various cell types has been proposed as an important feature of many cellular processes requiring extracellular proteolysis, cell adhesion, motility, and invasion. uPAR attaches to the cell surface with a glycosylphophatidylinositol (GPI) anchor, and serves to localize and accelerate the proteolysis cascade. In this study, we examined both uPA and uPAR levels in human gingival fibroblasts treated with an inflammatory cytokine, interleukin-1beta (IL-1beta). PA activity in the cell lysate was increased by treatment with IL-1beta. Further, PA activity released by phosphatidylinositol-specific phospholipase C, which detaches the GPI anchor, was also increased by IL-1beta. The activity was inhibited by amiloride, a specific inhibitor of uPA. In addition, IL-1beta increased the protein and mRNA levels of both uPA and uPAR in gingival fibroblasts. These findings suggest that the enhancement of uPA and uPAR levels by IL-1beta may play an important role in the progression of periodontal diseases through pericellular proteolysis, and subsequent cellular behavior.

Hypoplasia of bilateral humeral trochlea associated with bilateral ulnar nerve palsy.

We document a case of bilateral ulnar nerve palsy that developed in an 27-year-old Japanese man who had bilateral hypoplasia of the humeral trochlea. Surgical management produced good results regarding the ulnar nerve palsy. The pathogenesis of the nerve paresis in this particular condition is discussed. There have been no reports outside Japan. Whether this deformity occurs only in persons of Japanese extraction or is simply overlooked by foreign surgeons is an interesting question.

Pigmented villonodular synovitis of the ankle in an adolescent.

We report a case of pigmented villonodular synovitis (PVNS) in an adolescent with monarticular involvement of the ankle and without congenital anomalies or sibling involvement.

Synthesis and biological evaluation of CX-659S and its related compounds for their inhibitory effects on the delayed-type hypersensitivity reaction.

In order to find novel nonsteroidal compounds possessing an inhibitory activity against delayed-type hypersensitivity (DTH) reactions, we conducted random screening using a picryl chloride (PC)-induced contact hypersensitivity reaction (CHR) in mice, and found compound 1 as a lead compound. Then we synthesized and evaluated an extensive series of 5-carboxamidouracil derivatives focused on both the uracil and the antioxidative moieties. Among them, we found that the hindered phenol moiety was necessary to exhibit the activities; especially, compounds 28a-28c having the partial structure of vitamin E were found to exert potent activities against the DTH reaction by both oral and topical administration. And compound 28c showed antioxidative activity against lipid peroxidation with an IC50 of 5.9 microM. Compound 28c (CX-659S) was chosen as a candidate drug for the treatment of cutaneous disorders such as atopic dermatitis and allergic contact dermatitis.

[Continuous monitoring of hepatic venous oxygen saturation (SHVO2) as a new diagnostic indicator of abdominal malperfusion in acute aortic dissection].

A 73-year-old woman was admitted with sudden-onset back and abdominal pain. Computed tomography scanning revealed type B acute aortic dissection with narrowing of the true lumen. We inserted an oximetric catheter into the right hepatic vein and started continuous measurement of ShvO2. The initial value was 20%. Consecutive aortograms showed an intimal tear in the thoracic descending aorta. Endovascular stent graft placement was performed to close the entry, and ShvO2 rose to more than 60% immediately after the stent graft expansion. ShvO2 is an excellent indicator of abdominal blood flow, not only for early diagnosis but also for the evaluation of treatment.

[Clinical outcome of emergency coronary artery bypass grafting for acute myocardial infarction with cardiogenic shock].

From January 1993 through December 1998, Emergency Coronary Artery Bypass Grafting was Performed within 24 Hours after the Onset of Acute Myocardial Infarction (AMI) with Cardiogenic Shock in 22 Patients (17 men and 5 women; aged, 52-81 years). The incidence of AMI involving the left main coronary artery was 50%. The incidence of interventional therapy was 40.9% (PTCA 31.8%; PTCR 9.1%). The condition in 95.5% of the patients could be stabilized hemodynamically by preoperative intraaortic balloon pumping; 4 of the 5 patients suffered from cardiopulmonary arrest required percutaneous cardiopulmonary support. There were 4 (18.2%) deaths overall. Operative mortality was related to the intervals between AMI and operation (less than 6 hours, 25%; 6 to 24 hours, 10%). Three of the 4 patients who received cardiopulmonary support survived. We conclude that early revascularization and minimal reperfusion injury caused by mechanical devices are important determinants of survival in patients who have AMI with cardiogenic shock.

[A case of emergency surgery for acute mitral regurgitation due to complete papillary muscle rupture as complication of acute inferior myocardial infarction].

We experienced a case with acute mitral regurgitation caused by complete posterior papillary muscle rupture as complication of acute inferior myocardial infarction, who underwent successfully emergency operation of mital valve replacement and coronary revascularization in acute stage. A 64-year-old woman developed sudden cardiogenic shock shortly after the onset of acute inferior myocardial infarction. The diagnosis of acute inferior myocardial infarction was based on the electrocardiographic findings. Under IABP support, preoperative coronary angiography visualized total occlusion of segment 3 of the right coronary artery, and preoperative left ventriculography showed akinesis of inferior wall and severe mitral regurgitation. At 6 hours after onset of papillary muscle rupture, emergency operation was performed. At operation, posterior papillary muscle was found to be totally ruptured. Coronary artery revascularization and mitral valve replacement were performed. Postoperative course was uneventful, with 4 days of IABP and 5 days of ventilatory support. She was discharged on the twentieth postoperative day in NYHA class I. Reports of successful emergency operation for total papillary muscle rupture following acute myocardial infarction are rare. Early diagnosis and surgical treatment are mandatory to save this group of patients.

[Type A acute aortic dissection: late reoperations for dilatation of the distal false lumen and aortic regurgitation].

From January 1990 to December 1996, 71 patients aged 33 to 79 years (mean 60 +/- 11) underwent an emergency operation for type A acute aortic dissection. Fifty-three (74.6%) survived, and were followed 7 to 94 months (mean follow up 2.9 +/- 1.8 years) after the first operation. Five patients underwent reoperation for dilatation of the distal false lumen 7 to 52 months (mean period, 25 months) after primary repair. One patient underwent replacement of the arch and descending aorta, three patients underwent replacement of the descending aorta, and one patient underwent the stented graft implantation, resulting in closure of the entry site. Three patients underwent reoperation for severe aortic valve regurgitation 12 to 31 months (mean period, 24 months) after primary repair. Two patients underwent aortic valve replacement, and one patient underwent aortic root replacement. The actuarial freedom from reoperations was 81 +/- 6.9% at 3 years, and 73 +/- 9.9% at 5 years.

[Assessment of quality of life in long-term results of patients over 75 years old after emergent cardiovascular surgery].

Long-term results in QOL of patients over 75 years old after emergent cardiovascular surgery were examined. From January 1991 to June 1996, 46 patients underwent cardiovascular surgery. 22 patients who had elective surgery (elective group) and 15 patients who had emergency surgery (emergency group) tolerated with the operation: Two-year survival rate after surgery was 80.7% in the elective group and 78% in the emergency group, and relative survival rate was 0.89 in the elective group and 0.86 in the emergency group. As regards to the ability to live independently, 89% of elective group and 75% of emergency group showed good improvement, and there was no significant difference between two groups. The rate of patients who did not feel anxiety for disease at all was 61.1% in the elective group and 41.7% in the emergency group. The relationship between the patient and his family was good in both groups. For physical condition, the emergency group was superior to the elective group with no significant difference. Although QOL was relatively good after emergency surgery, some items were inferior compared with elective surgery. To improve the long-term results, elective surgery is required to avoid emergency surgery.

[Surgery for acute aortic dissection extending to the aortic root using gelatine-resorcine-formol biological glue--a case report].

A 73-year-old woman was admitted with chest pain of sudden onset and hypotension. Enhanced CT showed the dilated ascending aorta with an intimal flap. Emergency surgery was performed under a diagnosis of type A acute aortic dissection and cardiac tamponade. Replacement of the ascending aorta was planned, but during the operation we found that the dissection had extended to the aortic root and that the laceration of the adventitia was located just distal to the aortic annulus. Since the laceration was closer to the aortic annulus than the coronary ostium, it was impossible to reconstruct the aortic stump by classical techniques using Teflon felt strips. Gelatine-Resorcine-Formol (GRF) glue was therefore used to reinforce the proximal aortic stump. We then curved the suture line of the proximal anastomosis so as to resect the laceration while preserving the ostia of the coronary arteries. We were thus able to perform simple replacement of the ascending aorta successfully and the postoperative course was uneventful. By using GRF glue, replacement of the aortic root can be avoided in such cases.

[Surgical treatment for active infective endocarditis : septic embolization and mycotic aneurysms].

From 1978 through 1995, surgical treatment for active infective endocarditis (native valve) was performed in 17 patients. The indication for operation at the active phase was progressive heart failure in 5 (A-group) and uncontrolled infection in 12 (B-group). Operative findings showed vegetations in all cases, perforations of the valve in 6, rupture of tendon in 2, and annular abscesses in 2. One patient in B-group died 14 days after the operation with postoperative mediastinitis and sepsis. There was no perioperative complications in A-group. In B-group before operations 8 patients (66.7%) has an embolic event before operations. The anatomic sites of embolization were the central nervous system (3 patients), viscera (2 patient) and peripheral arteries (3 patients). And after operation there were 2 mycotic aneurysms of the hepatic artery and the popliteal artery, and 1 pyogenic spondylitis. We conclude that the risk of embolization is high in patients undergoing surgery at active phase of infective endocarditis because of uncontrolled infection ; thus, such patients should be carefully monitored for emboli and mycotic aneurysms.

Chronic oral toxicity of a synthetic antioxidant, 2,2'-methylenebis(4-ethyl- 6-tert-butylphenol), in rats.

Groups of 30 Wistar rats of each sex were treated with 2,2'-methylenebis(4-ethyl-6-tert-butylphenol) (MBEBP) in the diet at levels of 0, 0.03, 0.1 and 0.3% for up to 18 months. In both sexes, survival rates of treated groups were similar to those of the controls. Body weight gain was depressed (0.3% group in males, 0.1 and 0.3% groups in females). Slight anaemia (0.3% groups in both sexes) and increase of blood urea nitrogen (0.3% groups in both sexes) were observed. Histopathologically, vacuolization of the parathyroid gland cells (0.3% group in males and all treated groups in females) and degenerative changes of the kidney (0.1 and 0.3% groups in males) were observed. No neoplastic responses following MBEBP administration were noted. From these results, the no-observed-adverse-effect level (NOAEL) for MBEBP toxicity was estimated as 12 mg kg-1 body wt. day-1 in male rats. In female rats, the lowest-observed-adverse-effect level (LOAEL) was estimated as 15 mg kg-1 body wt. day-1.