Revisiting DARPP-32 in postmortem human brain: changes in schizophrenia and bipolar disorder and genetic associations with t-DARPP-32 expression.

Dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32 or PPP1R1B) has been of interest in schizophrenia owing to its critical function in integrating dopaminergic and glutaminergic signaling. In a previous study, we identified single-nucleotide polymorphisms (SNPs) and a frequent haplotype associated with cognitive and imaging phenotypes that have been linked with schizophrenia, as well as with expression of prefrontal cortical DARPP-32 messenger RNA (mRNA) in a relatively small sample of postmortem brains. In this study, we examined the association of expression of two major DARPP-32 transcripts, full-length (FL-DARPP-32) and truncated (t-DARPP-32), with genetic variants of DARPP-32 in three brain regions receiving dopaminergic input and implicated in schizophrenia (the dorsolateral prefrontal cortex (DLPFC), hippocampus and caudate) in a much larger set of postmortem samples from patients with schizophrenia, bipolar disorder, major depression and normal controls (>700 subjects). We found that the expression of t-DARPP-32 was increased in the DLPFC of patients with schizophrenia and bipolar disorder, and was strongly associated with genotypes at SNPs (rs879606, rs90974 and rs3764352), as well as the previously identified 7-SNP haplotype related to cognitive functioning. The genetic variants that predicted worse cognitive performance were associated with higher t-DARPP-32 expression. Our results suggest that variation in PPP1R1B affects the abundance of the splice variant t-DARPP-32 mRNA and may reflect potential molecular mechanisms implicated in schizophrenia and affective disorders.

[Volume reduction surgery for giant coronary sinus with valvular heart disease; report of a case].

A 64-year-old male with giant left atrium and giant coronary sinus, who had aortic valve regurgitation, prosthesis valve paravalvular leakage in mitral position and prosthesis valve malfunction in tricuspid valve position, was successfully treated with double valve replacement, paravalvular leakage repair and volume reduction of left atrium and coronary sinus. Giant coronary sinus was about 70 mm in diameter and was thought to be induced by persistent left superior vena cava, high right atrium pressure and prosthesis valve malfunction in tricuspid valve position. Lung volume was so much increased by volume reduction of left atrium and coronary sinus and patient's symptoms were much improved.

[Full-thickness resection of the focus site for adolescent idiopathic ventricular tachycardia].

We present a case of a 14-year-old male with incessant idiopathic ventricular tachycardia for which both pharmacological and catheter ablation treatments failed. Curative surgery was performed on this patient. By intraoperative epicardial isochronous mapping, arrhythmogenic focus was identified in the right ventricular infundibulum between the large conus branch and the proximal right ventricular coronary branch. After cryoablation both from the epi- and endo-cardial sides failed to terminate the arrhythmia, subsequent full-thickness resection of the identified focus was performed. There was no postoperative recurrence of tachyarrhythmia In idiopathic ventricular tachycardia, arrhythmogenic focus is not always situated on the endo- or epicardial side. Full-thickness resection of the focus site might be necessary in such patients as we experienced this time.

[Reoperation for postoperative pseudoaneurysm after repair for acute aortic dissection associated with disseminated intravascular coagulation and chronic renal failure].

We report a very high risk case of reoperation for pseudoaneurysm after ascending aortic replacement for acute aortic dissection in a 78-year-old man with chronic renal failure and disseminated intravascular coagulation (DIC). Computed tomography 5 years after the 1st operation showed huge pseudoaneurysm originated from the distal anastomosis and the angiogram showed moderate aortic regurgitation. Hemodialysis and congestive heart failure associated with DIC complicated his general condition. Preoperative DIC score was 7 with D-dimer of 39.8 microg/ml. The patient underwent reoperation through night anterior thoracotomy. At 20 degrees C of urinary bladder temperature, we started re-median sternotomy and ablated the adhesion. When the pseudoaneurysm ruptured, we started hypothermic circulatory arrest with selective cerebral perfusion immediately. And Bentall operation and hemi-arch replacement were performed. Postoperative recovery required long period and he was transferred to another hospital at 3 months after the surgery. Postoperative data showed reduction of DIC score to 3.

[Valve-in-valve replacement of primary tissue valve failure of bovine pericardial valve minor].

A 73-year-old woman who underwent mitral valve replacement with a 31 mm Carpentier Edwards Pericardial Xenograft 19 years ago. She revealed sudden onset of a grade IV/VI a seagull like diastolic murmur at the apex, and severe hematuria. Echocardiography demonstrated severe mitral regurgitation. These findings were consistent with acute primary tissue valve failure. Therefore we performed emergency reoperation. At operation, valve leaflet was torn at the commissural stitch, and bioprosthesis strut was buried in the left posterior ventricular wall. The mitral prosthetic valve replaced with a 25 mm CarboMedics OptiForm using a technique of valve-in-valve replacement. This procedure would be one option for replacement of bioprosthetic mitral valve.

Prognostic factors of gastric cancer tumours of less than 2 cm in diameter: rationale for limited surgery.

BACKGROUND: A recent trend in the surgical treatment of patients with early gastric cancer in Japan has been to limit surgery to an extent that ensures complete cure and improvement in the patient's quality of life. If a gastric cancer tumour can be completely eradicated by laparoscopic surgery, the patient can be cured of cancer without major operative stress. A small gastric cancer tumour of less than 2 cm in diameter is an indication for laparoscopic surgery, but little is known about what protocol of surgical treatment is appropriate for this type of tumour. PATIENTS AND METHODS: The clinicopathological features of 150 patients with gastric cancer tumour of less than 2 cm in diameter were reviewed retrospectively from hospital records between 1985 and 1995. The results of retrospective analysis of clinicopathological data of 24 patients with advanced cancer were compared with those of 126 patients with early cancer. Univariate and multivariate analyses of patients with small gastric cancer tumours were performed to evaluate the prognostic significance of clinicopathological features. RESULTS: A significant difference was seen between the gross tumour appearances in the two groups; Borrmann type-4 tumours were more common in the advanced group. Lymph-node metastasis, lymphatic vessel invasion and vascular invasion were found more frequently in the advanced cancer group than in the early cancer group. Scirrhous type was more common in the advanced cancer group. In univariate analysis, unfavourable prognostic factors included deep cancer invasion, presence of lymph-node metastasis, lymphatic invasion and vascular invasion. Using Cox's proportional hazard regression model, only nodal involvement emerged as an independent statistically significant prognostic parameter associated with long-term survival. CONCLUSION: Laparoscopic surgery should not be performed on tumours that are Borrmann type in macroscopic appearance and scirrhous-type histologically. Lymph-node metastasis is an independent prognostic factor. We recommend laparoscopic surgery involving local resection of the stomach without lymphadenectomy for small, early gastric cancer tumours that satisfy the criteria mentioned above. However, the validity of this recommendation should be tested by a prospective randomized control trial in the future.

Will accident reports filed in hospitals in Japan be used in the future as evidence in malpractice lawsuits?

A major drawback of submission of so-called incident reports for medical institutions is that such reports may be able to be obtained on request by patients and to be used as evidence in malpractice lawsuits. In Japan, there are no established rules concerning the use of accident reports in medical lawsuits. More debate is needed for voluntary report systems to become established in medical institutions throughout Japan.

[Study on the intensity of MMC and UFT in postoperative adjuvant chemotherapy for gastric cancer--study report of JFMTC Study No. 10].

The purpose of this study was to investigate the correlation between efficacy and dose intensity of postoperative adjuvant chemotherapy with MMC and UFT. A total of 1,410 patients from 180 institutions were allocated into a low-dose group and a high-dose group. The patients in the low-dose group received MMC at 8 mg/m2 on the day of surgery and 3 capsules of UFT (300 mg in tegafur) daily for 6 months. The patients in the high-dose group received MMC at 8 mg/m2 on the day of surgery, and in weeks 4, 10, 16, and 22 after surgery and 6 capsules of UFT (600 mg in tegafur) daily for 6 months. The patients in the high-dose group tended to exhibit higher survival rates than those in the low-dose group, although the difference was not significant. For the n(+)ps(-) patients, however, the survival rates were significantly higher in the high-dose group (p = 0.043). The recurrence-free rates showed a similar tendency. The incidence rates of adverse events were significantly higher in the high-dose group than in the low-dose group. Compliance was poorer in the high-dose group. Although the number of adverse events increases, a better prognosis can be expected with a high dose. These results confirmed a dose-dependency in adjuvant chemotherapy with MMC and UFT.