The Histology of the Lung in Neonates with Tricuspid Valve Disease and Gross Cardiomegaly Due to Severe Regurgitation

Lung autopsies from four neonates with Ebstein's anomaly or tricuspid valve dysplasia and gross cardiomegaly were examined. The mean cardiothoracic ratio was 92 ± 0.5%. The degrees of pulmonary hypoplasia and pulmonary artery muscularization were assessed and were compared with those in lungs from four controls and four patients with diaphragmatic hernias. Lung and body weight ratios and radial alveolar counts, which reflect pulmonary hypoplasia and immaturity, were significantly decreased only in patients with diaphragmatic hernia. The thickness of the medial muscle layer in small pulmonary arteries was greater in patients with diaphragmatic hernia; however, in patients with tricuspid valve disease, it was relatively small. Abnormal vascular muscle extension was seen only in patients with diaphragmatic hernia. In the cases of tricuspid valve disease, although cardiomegaly and lung compression were severe, lung hypoplasia and immaturity were not, and neither abnormal medial thickening nor extension were found. Our results suggest that, at least in full-term infants with tricuspid valve disease, surgical relief of lung compression may improve respiratory function, even if the cardiomegaly is severe.     

Genetic Alterations of Mixed Hyperplastic Adenomatous Polyps in the Colon and Rectum

Some mixed hyperplastic adenomatous polyps (MHAPs) contain dysplastic lesions or even carcinomas. These polyps are considered to be different from ordinary hyperplastic polyps and may have a preneoplastic potential. We investigated APC and K- ras mutations in MHAPs of the colon and rectum, and also in colorectal adenomas and hyperplastic polyps to identify molecular differences between MHAPs, adenomas and hyperplastic polyps, using direct sequencing of mutation cluster regions (MCR) in APC and K- ras . No APC mutations were identified in 12 MHAPs and 8 hyperplastic polyps, whereas 10 of 27 (37.0%) adenomas showed somatic mutations. K- ras mutations were identified in one of 12 (8.3%) MHAPs, one of 8 (12.5%) hyperplastic polyps, and 10 of 27 (37.0%) adenomas. p53 mutation was found in a carcinoma arising in an MHAP. Mutations other than APC mutations may play a role in the development of MHAPs.     

The clinical statistics of the operations at the Department of Urology, Tokatsu Hospital: from 1994 to 1999

We investigated the clinical statistics of the operations and inpatients since the establishment of the department in June 1994 up to May 1999. The total number of inpatients was 1,269 (1,047 males and 222 females), and a total of 1,098 operations were performed. Extracorporeal shock wave lithotriopy (ESWL) was also introduced in 1997, and in addition, it seemed that the number of operations and inpatients would be increasing in future.     

Gene therapy of Parkinson's disease using adeno-associated virus (AAV) vectors

Parkinson's disease (PD) is characterized by the progressive loss of the dopaminergic neurons in the substantia nigra and a severe decrease in dopamine in the striatum. A promising approach to the gene therapy of PD is intrastriatal expression of dopamine-synthesizing enzymes [tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC)]. The most appropriate gene-delivery vehicles for neurons are adeno-associated virus (AAV) vectors, which are derived from non-pathogenic virus. Therefore, TH and AADC genes were introduced into the striatum in the lesioned side using separate AAV vectors in parkinsonian rats, and the coexpression of TH and AADC resulted in better behavioral recovery compared with TH alone. Another strategy for gene therapy of PD is the protection of dopaminergic neurons in the substantia nigra using an AAV vector containing a glial cell line-derived neurotrophic factor (GDNF) gene. Combination of dopamine-supplement gene therapy and GDNF gene therapy would be a logical approach to the treatment of PD.     

Three-dimensional analysis of benign paroxysmal positional nystagmus in a patient with anterior semicircular canal variant.

OBJECTIVE: To show the positional nystagmus in a patient who had suffered from benign paroxysmal positional vertigo (BPPV) that was thought to be caused by involvement of the anterior semicircular canal (ASCC) (A-BPPV). STUDY DESIGN: Retrospective case report. SETTING: City hospital. PATIENT: The present study reports a rare case of A-BPPV in a 41-year-old woman. CASE REPORT: The patient is 41-year-old woman who developed a positional vertigo after playing volleyball on March 22, 2005 and consulted our hospital the next day. When left Dix-Hallpike maneuver was performed, she showed a positional nystagmus of which fast phase direction of the torsional component was clockwise while that of the vertical component was downward. We plotted the slow phase eye velocity of the positional nystagmus during the left Dix-Hallpike maneuver on three-dimensional coordinates that showed the axis of the positional nystagmus to be perpendicular to the plane of the right ASCC. CONCLUSION: These results suggested that the patient was suffering from A-BPPV.     

Clinical efficacy of heparin-bonded bypass circuits related to cytokine responses in children

BACKGROUND: Cardiopulmonary bypass (CPB) induces numerous systemic reactions. This study examined the efficacy of heparin-bonded CPB circuits on inflammatory responses and postoperative status in children. METHODS: Thirty-four infants undergoing elective cardiac surgery were randomly divided into two groups: a heparin-bonded CPB group (n = 17) and a non-heparin-bonded group (n = 17). Plasma levels of the inflammatory cytokines were measured before, during, and after CPB, and postoperative status was determined by examining the respiratory index, blood loss, and the post- and preoperative body weight percent ratio. RESULTS: Significant differences in tumor necrosis factor-alpha, interleukin-6, and interleukin-8 patterns were observed during and after CPB between the two groups (p < 0.01, p < 0.01, p < 0.05, respectively). All cytokines measured were significantly lower in the heparin-bonded group just after CPB (p < 0.05). There were no differences in duration of intubation, intensive care unit or hospital stay, or postoperative blood loss, but the respiratory index 3 hours after CPB and body weight percent ratio 24 and 48 hours after CPB were significantly reduced in the bonded group (p < 0.05, p < 0.01, p < 0.05, respectively). CONCLUSIONS: Our findings suggest that heparin bonding of the bypass circuits affects early postoperative status and reduces cytokine responses in pediatric cardiac surgery.     

Gamma-rays enhance rAAV-mediated transgene expression and cytocidal effect of AAV-HSVtk/ganciclovir on cancer cells

Adeno-associated virus (AAV) vector has several unique properties suited for gene therapy applications. However, relatively low efficiency of transgene expression, which is mainly due to a limited second-strand synthesis from the single-stranded AAV genome, can be a problem in some applications that require potent gene expression such as antitumor applications. Recently, gamma-ray irradiation has been reported to enhance the second-strand synthesis of the AAV genome, and consequently transgene expression. We demonstrate here that an AAV vector harboring the herpes simplex virus type-1 thymidine kinase (HSVtk) is able to kill cancer cells more efficiently when used in combination with gamma-ray irradiation. A human maxillary sinus cancer cell line, NKO-1, was efficiently killed in combination with HSVtk transduction and ganciclovir (GCV), as expected. More importantly, gamma-ray irradiation of practical dosages augmented the cytocidal effect of the HSVtk/GCV system. Southern analysis indicated that gamma-rays enhanced the double-strand synthesis of the rAAV genome in NKO-1 cells. These findings suggest that the combination of rAAVtk/GCV suicide gene therapy with radiotherapy has synergistic effects in the treatment of cancers and may lead to a reduction of the potential toxicity of both rAAVtk/GCV and gamma-ray irradiation.     

SARC-F scores can predict health status and daily activity in patients with idiopathic pulmonary fibrosis

BackgroundThe strength, assistance in walking, rising from a chair, climbing stairs, and falls questionnaire (SARC-F) is widely used for screening sarcopenia. We aimed to examine the association of SARC-F scores with the measurements of quality of life and activity in patients with idiopathic pulmonary fibrosis (IPF).MethodsThis cross-sectional pilot study prospectively enrolled 54 patients with IPF who completed pulmonary function tests, the 6-min walk test, the chronic obstructive pulmonary disease assessment test (CAT), St. George’s Respiratory Questionnaire (SGRQ), the Hospital Anxiety and Depression Scale, and a daily step count. The daily step count was measured continuously for 7 consecutive days using a tri-axis accelerometer device.ResultsThe mean age was 73.6±7.9 years and the mean percent predicted forced vital capacity was 80.4%±15.6%. The median [interquartile range] SARC-F score, SGRQ total scores, and CAT scores were 2 [1–3.25], 28.8 [14.4–46.9], and 13 [7–22], respectively. SARC-F scores were correlated with the percent predicted forced vital capacity (r=−0.51, P<0.001), CAT score (r=0.57, P<0.001), SGRQ total score (r=0.77, P<0.001), Hospital Anxiety and Depression Scale anxiety score (r=0.31, P=0.025), and Hospital Anxiety and Depression Scale depression score (r=0.28, P=0.041). Linear regression analyses revealed that the 6-minute walk test (6MWT) (standardized β=0.33, P=0.011) and SARC-F score (standardized β=−0.39, P=0.005), but not the CAT score and SGRQ total score, were significant predictors for daily step count.ConclusionsSARC-F scores were correlated with health status and daily activity in patients with IPF. Further studies are warranted to validate the utility of the SARC-F in patients with IPF.