Investigation of the pathophysiology of the retina and choroid in Parkinson's disease by optical coherence tomography

International Ophthalmology - The pathology of Parkinson's disease (PD) is suspected to affect the retina and choroid. We investigated changes in the retina and choroid of patients with PD...     

IFN-inducible protein 10 (CXCL10) regulates tubular cell proliferation in renal ischemia-reperfusion injury

Although renal tubular cell proliferation after acute tubular necrosis is an important and essential response in the recovery of renal dysfunction in acute renal failure, the precise factors and mechanisms of tubular cell regeneration remain unclear. Here, we describe our studies using a neutralizing antibody (Ab) against interferon-inducible protein of 10 kDa (IP-10; CXCL10) that indicate a role for CXCL10 in tubular cell proliferation after renal ischemia-reperfusion injury. Tissue necrosis and interstitial infiltrating numbers were comparable between anti-CXCL10 Ab-treated and control mice treated with IgG at the 24 and 48 h time points after reperfusion. In contrast, the numbers of Ki67-positive proliferating tubular cells were significantly increased in anti-CXCL10 Ab-treated mice 48 h after reperfusion. In accordance with the in vivo findings,in vitro studies using murine tubular epithelial cells indicated an antiproliferative effect of CXCL10 upon the intensity of cell proliferation and the number of Ki67-positive cells. These data suggest that CXCL10 plays a role in the regulation of tubular cell proliferation following renal ischemia-reperfusion injury.     

Simultaneous gradual lengthening of both proximal and distal nerve stumps for repair of peripheral nerve defect in rats

We investigated nerve regeneration following the repair of a segmental nerve defect induced by direct end-to-end neurorrhaphy after simultaneous gradual lengthening of both proximal and distal nerve stumps in rats. A 15-mm-long nerve segment was resected from the sciatic nerve of each rat. The proximal and distal nerve stumps, respectively, were directly lengthened at a rate of 1 mm/day using a custom-made external nerve-lengthening device. After being lengthened for 14 days, both nerve stumps were refreshed, and direct end-to-end neurorrhaphy was performed. For a control, 15-mm nerve grafting was performed immediately after nerve resection. Nerve regeneration was evaluated by motor nerve conduction velocity, muscle contraction force, and histological studies at 6, 8, and 14 weeks after initial nerve resection in both groups. As a result, at 8 and 14 weeks, the motor nerve conduction velocity was significantly higher in the nerve-lengthening group than in the autografting group. In addition, at 14 weeks, the tetanic force and wet weight of the gastrocnemius muscle were significantly higher in the nerve-lengthening group than in the autografting group. Histologically, the mean axonal diameter of myelinated nerve fibers and the total number of myelinated nerve fibers were also significantly higher in the nerve-lengthening group than in the autografting group for each evaluation period. It appears that the simultaneous gradual lengthening of both proximal and distal nerve stumps might have potential application in the repair of peripheral nerve defects.     

Omentum transposition surgery for patients with Alzheimer's disease: a case series

OBJECTIVE: To examine effect of omentum transposition surgery (OT) in Alzheimer's disease (AD). METHODS: Within-subjects design, also known as repeated-measures design, was used. OT was performed on six biopsy-confirmed AD patients (three to the left and right hemispheres each). Follow-up was conducted over 16-50 months. Outcome measures included the sum of the sub-scores of the clinical dementia rating scale (CDRSS), dementia severity rating scale (DSRS), mini-mental status exam (MMSE) and neuropsychiatric inventory (NPI), all normalized to 0-1.0. Outcomes were compared to baseline values and to expected decline with and without cholinesterase inhibitors therapy (ChEI). RESULTS: Compared to baseline and to expected decline with ChEI, CDRSS scores were 22 and 39% less impaired at means of 14 and 25 months post-OT, and DSRS scores were 12 and 22% less impaired at means of 14 and 19 months post-OT (p<0.0001). Compared to baseline and expected course with and without ChEI, the MMSE scores of the left hemisphere OT patients were not significantly different for 11, 17 and 22 months respectively (p>0.49), while those of the right hemisphere OT patients more rapidly declined. The two patients with significant pre-operative behavioral problems markedly improved; NPI severity scores decreased by 23 (16%) and 78 (54%) points and were sustained for 22 and 42 months. DISCUSSION: OT yielded cognitive, functional or behavioral improvement for up to 3.5 years in these AD patients. Compared to randomized ChEI clinical trials, OT was 34 times more likely to produce clinically significant improvement. Basic research to identify the mechanisms underlying the therapeutic effect of omentum is warranted.     

Difference in age of onset of psychosis between epilepsy and schizophrenia

To clarify the nature of psychosis development in epilepsy patients, we studied differences in age of onset of psychosis between epilepsy patients with psychosis (epilepsy-psychosis) and schizophrenia patients. Subjects were 282 patients with epilepsy-psychosis (36 postictal, 224 interictal, and 22 bimodal psychoses) and 612 schizophrenia patients. Age of onset was compared between the schizophrenia group and the whole epilepsy-psychosis group as well as its subgroups. Effects of sex and family history of psychosis on age of onset were also evaluated. Epilepsy patients developed psychosis later (mean age 30.1) than schizophrenia patients (mean age 26.6). Among epilepsy-psychosis subgroups, postictal psychosis and interictal psychosis showed a later onset than schizophrenia. In interictal psychosis, while chronic schizophrenia-like psychosis occurred at similar age compared to schizophrenia, brief episodic psychosis occurred at later age. Epilepsy-psychosis patients showed no sex difference in age of onset, whereas female schizophrenia patients showed a later onset than male schizophrenia patients. Both the epilepsy and schizophrenia patients with family history of psychosis tended to develop psychosis at an earlier age, although this did not reach statistically significant level. The findings of the study suggest that the nature of epilepsy-psychosis is not fully equivalent to that of schizophrenia.     

Concurrent and discriminant validity of Spanish language instruments for measuring functional health status

BACKGROUND: Questionnaires translated into languages other than English are often not validated to the same extent as the English versions. This study examined the concurrent and discriminant validity of selected domains related to physical function from Spanish language versions of the Child Health Questionnaire (CHQ), Pediatric Outcomes Data Collection Instrument (PODCI), and Pediatric Evaluation and Disability Inventory (PEDI). METHODS: Concurrent validity was examined in 93 children with cerebral palsy by correlating questionnaire domain scores with Gross Motor Function Measure and Gillette Functional Assessment Questionnaire walking scale scores. Discriminant validity with respect to Gross Motor Function Classification System (GMFCS) level was examined using analysis of variance and nonparametric discriminant analysis. RESULTS: Concurrent validity was demonstrated for 3 domains from the PEDI (Mobility functional skills, tau = 0.62; Mobility caregiver assistance, tau = 0.46-0.55; and Self-care functional skills, tau = 0.30-0.36), 3 domains from the PODCI (Sports and physical function, tau = 0.48-0.51; Transfer and basic mobility, tau = 0.48-0.51; and Upper extremity physical function, tau = 0.28), and 1 domain from the CHQ (Physical function, tau = 0.31-0.36). Discriminant validity was demonstrated for the same domains based on significant decreases in domain scores with increasing GMFCS level. Discriminant validity was highest for the PODCI, which correctly classified 98% (91/93) of subjects into the correct GMFCS level when all 3 domains were considered. CONCLUSIONS: For the first time, concurrent validity and discriminant validity have been demonstrated for the physical function domains of Spanish language versions of the PODCI, PEDI, and CHQ questionnaires. PODCI and PEDI had the highest concurrent validity, and PODCI had the best discriminant ability. CLINICAL RELEVANCE: It is important to examine the validity of instruments when they have been translated from English into other languages. This importance will only increase as the population of non-English-speaking patients expands.     

Screening for prostate cancer using prostate-specific antigen testing in Japanese men on hemodialysis

Objectives The objectives of this study were to evaluate the usefulness of serum prostate-specific antigen (PSA) screening in detecting prostate cancer in Japanese men on hemodialysis, and to analyze features of prostate cancer detected in these patients. Materials and methods This study included 115 male hemodialysis patients aged >55 years who agreed to the measurement of serum PSA value (group A) and 7529 men aged >55 years participating in a PSA mass screening test in Kobe City (group B) between April 2005 and March 2006. Prostate biopsy was recommended in men with serum PSA > 4.0 ng/ml in both groups. Seventy-eight patients with normal renal function aged >55 years diagnosed as having prostate cancer during the same time period as groups A and B were also included as a comparison group (group C). Results There was no significant difference in the distribution of serum PSA values between groups A and B. Prostate biopsy was performed in 8 and 205 men in groups A and B, respectively, and prostate cancer was detected in 5 and 68 in groups A and B, respectively; that is, there was no significant difference in the rate of positive prostate biopsy between these two groups (group A, 62.5%; group B, 33.2%), while the cancer detection rate in group A (4.3%) was significantly greater than that in group B (0.90%). In addition, there was no evident metastasis in five patients on hemodialysis who were diagnosed as having prostate cancer, and their serum PSA, clinical T stage and biopsy Gleason score were similar to those in group C. However, the percent of positive biopsy cores in these five was significantly greater than that in group C. All five were treated by maximal androgen blockade therapy, and all are currently alive without emergence of hormone-refractory diseases. Conclusions These findings indicate that hemodialysis patients may have an increased risk of prostate cancer, and that prostate cancer detected in such patients tends to be relatively advanced. Therefore, it would be recommended for hemodialysis patients to undergo PSA testing to screen for prostate cancer.     

Heavily calcified chronic total occlusion of common iliac artery successfully treated with Tornus microcatheter and rotational atherectomy

A 58-year-old man who required long-term hemodialysis was referred to our institution for the management of life-limiting intermittent claudication of the right lower extremity. The diagnostic arteriography demonstrated heavily calcified chronic total occlusion in the right common iliac artery. The lesion was successfully treated with the combination of a Tornus microcatheter (Asahi Intecc, Aichi, Japan) and rotational atherectomy. We describe in this article a niche application of the Tornus microcatheter and the effect of the combination technique of it with rotational atherectomy in peripheral interventions.     

Adult ABO-incompatible liver transplantation by intraportal transfusion of donor-specific antigen: a case report

A 55-year-old-woman suffering from fluminant hepatitis owing to autoimmune hepatitis underwent ABO-incompatible liver transplantation (LRLD) of blood type A to B. In this study, we investigated whether a new immunosuppressive strategy by intraportal transfusion of donor-specific leukocytes (DSLT) separated from whole blood would yield immunological benefit in adult ABO-LRLD. The operative course was uneventful; she was discharged at 46 days postoperatively without humoral or cellular rejection. On immunologic analysis, 54.6% intrahepatic macrochimerism of donor type CD56+ T cells was recognized at 1 month after transplantation. The interleukin-10 Th2 cytokine level was increased on postoperative day 1. Adult ABO-incompatible liver transplantation can be performed with acceptable patient and graft survival rates with a low risk of antibody-mediated rejection with our strategy of immunosuppression by intraportal administration of DSLT. Donor type CD56+ NKT cells may induce tolerance by a veto mechanism and/or an anti-idiotype network. ABO-incompatible liver transplantation may be improved by this strategy.     

Highly sensitive upregulation of apolipoprotein A-IV by peroxisome proliferator-activated receptor alpha (PPARalpha) agonist in human hepatoma cells

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a key regulator in hepatic lipid metabolism and a potential therapeutic target for dyslipidemia. However, in humans hepatic PPARalpha-regulated genes remain unclear. To investigate the effect of PPARalpha agonism on mRNA expressions of lipid metabolism-related genes in human livers, a potent PPARalpha agonist, KRP-101 (KRP), was used to treat the human hepatoma cell line, HepaRG cells. KRP did not affect AOX or L-PBE, which are involved in peroxisomal beta-oxidation. KRP increased L-FABP, CPT1A, VLCAD, and PDK4, which are involved in lipid transport or oxidation. However, the EC(50) values (114-2500 nM) were >10-fold weaker than the EC(50) value (10.9 nM) for human PPARalpha in a transactivation assay. To search for more sensitive genes, we determined the mRNA levels of apolipoproteins, apoA-I, apoA-II, apoA-IV, apoA-V, and apoC-III. KRP had no or little effect on apoA-I, apoC-III, and apoA-II. Interestingly, KRP increased apoA-IV (EC(50), 0.99 nM) and apoA-V (EC(50), 0.29 nM) with high sensitivity. We identified apoA-IV as a PPARalpha-upregulated gene in a study using PPARalpha siRNA. Moreover, when administered orally to dogs, KRP decreased the serum triglyceride level and increased the serum apoA-IV level in a dose-dependent manner. These findings suggest that apoA-IV, newly identified as a highly sensitive PPARalpha-regulated gene in human livers, may be one of the mechanisms underlying PPARalpha agonist-induced triglyceride decrease and HDL elevation.