Changes of synovial fluid biomarker levels after opening wedge high tibial osteotomy in patients with knee osteoarthritis.

OBJECTIVE: The purpose of this study was to evaluate the effects of high tibial osteotomy (HTO) on the biological status of knee osteoarthritis (OA) using joint markers in synovial fluid (SF). METHODS: Fifty patients with medial compartmental OA of the knee who underwent opening wedge HTO were enrolled. Paired SF samples from the affected knee and arthroscopic evaluation of articular cartilage were collected at the time of HTO surgery and the time of plate removal (postoperative 17 ± 4 months). The concentrations of the following SF biomarkers were measured: interleukin (IL)-1ß, IL-6, IL-8, IL-10, tumour necrosis factor-α, matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, MMP-13, vascular endothelial growth factor (VEGF), and cartilage oligomeric matrix protein (COMP). The Knee Society Score (KSS) and hip-knee-ankle (HKA) angle were assessed before and 2 years after HTO. RESULTS: The KSS knee and function scores were significantly improved after HTO (mean changes of 36.4 and 23.7, respectively). The mean HKA angle was altered from mechanical varus (-8.6°) to valgus (5.2°). Concentrations of IL-6, IL-8, MMP-2, MMP-3, MMP-13, VEGF, and COMP in SF were significantly decreased after HTO (mean changes of -49.1%, -30.2%, -31.1%, -26.3%, -30.8%, -42.5%, and -13.7% from preoperative baseline, respectively). The cartilage status was improved in 19 cases (38%) after HTO. However, changes of all biomarkers were not significantly different between subjects with and without an improved cartilage status. CONCLUSIONS: SF levels of biochemical markers for cartilage degradation and synovial inflammation were altered after HTO, suggesting an improvement in the OA disease state.

Metabolic cost of lateral stabilization during walking in people with incomplete spinal cord injury.

People with incomplete spinal cord injury (iSCI) expend considerable energy to walk, which can lead to rapid fatigue and limit community ambulation. Selecting locomotor patterns that enhance lateral stability may contribute to this population's elevated cost of transport. The goal of the current study was to quantify the metabolic energy demands of maintaining lateral stability during gait in people with iSCI. To quantify this metabolic cost, we observed ten individuals with iSCI walking with and without external lateral stabilization. We hypothesized that with external lateral stabilization, people with iSCI would adapt their gait by decreasing step width, which would correspond with a substantial decrease in cost of transport. Our findings support this hypothesis. Subjects significantly (p<0.05) decreased step width by 22%, step width variability by 18%, and minimum lateral margin of stability by 25% when they walked with external lateral stabilization compared to unassisted walking. Metabolic cost of transport also decreased significantly (p<0.05) by 10% with external lateral stabilization. These findings suggest that this population is capable of adapting their gait to meet changing demands placed on balance. The percent reduction in cost of transport when walking with external lateral stabilization was strongly correlated with functional impairment level as assessed by subjects' scores on the Berg Balance Scale (r=0.778) and lower extremity motor score (r=0.728). These relationships suggest that as functional balance and strength decrease, the amount of metabolic energy used to maintain lateral stability during gait will increase.

Prevalence and topography of small hypointense foci suggesting microbleeds on 3T susceptibility-weighted imaging in various types of dementia.

BACKGROUND AND PURPOSE: The prevalence and topography of small hypointense foci suggesting microbleeds on 3T SWI in various types of dementia have not been systematically investigated. The purpose of this study was to determine the prevalence and topography of SHF on 3T SWI in patients with different dementia subtypes. MATERIALS AND METHODS: We included 347 consecutive patients (217 women, 130 men; age range, 42-93 years; mean age, 74 years) who attended our memory clinic and underwent 3T SWI. They were divided into 6 groups: subjective complaints, MCI, AD, DLB, VaD, and FTLD. Two neuroradiologists evaluated the number and location of SHF on SWIs. Statistical analyses were performed to evaluate inter- and intragroup differences. RESULTS: Of the 347 patients, 160 (46.1%) exhibited at least 1 small hypointense focus. This was true in 86% with VaD, 54% with DLB, 48% with AD, 41% with MCI, 27% with FTLD, and 22% with subjective complaints. With the subjective complaints group as a reference, the odds ratio adjusted by age, sex, and arterial hypertension was 9.2 (95% CI, 2.0-43.6) for VaD; 5.4 (95% CI, 1.2-24.3) for AD; 3.1 for DLB (95% CI, 1.1-8.8); 2.0 for MCI (95% CI, 0.5-8.1); and 1.5 for FTLD (95% CI, 0.4-5.4). There was a significant lobar predilection for AD, DLB, and FTLD groups (P < .05). CONCLUSIONS: On 3T SWI, patients with VaD, AD, and DLB manifested a high SHF prevalence. In patients with AD, DLB, and FTLD, the SHF exhibited a lobar predilection.

Chemosensitivity of patients with recurrent esophageal cancer receiving perioperative chemotherapy.

Perioperative chemotherapy (CT) and chemoradiotherapy are widely used for advanced esophageal cancer. We evaluated the chemosensitivity of patients displaying recurrent esophageal cancer after esophagectomy with perioperative CT. From the database at National Cancer Center Hospital in Tokyo, we extracted recurrent esophageal cancer cases after perioperative CT and evaluated the effectiveness of the first CT against the recurrent disease according to the duration between termination of the original perioperative CT and recurrence with treatment-free intervals (TFIs) 6 months. Systemic CT for their recurrent disease was performed for 30 esophageal cancer patients after perioperative CT. All patients received 5-fluorouracil and cisplatin as perioperative CT, with relapses occurring at TFIs 6 months in 19 patients (all received platinum-containing regimens). The response rate of patients experiencing a recurrence at TFIs 6 months was 0 and 37% (P = 0.029), the median progression-free survival was 2.8 and 4.8 months (log-rank P = 0.001) and the median overall survival was 6.1 and 10.2 months (log-rank P = 0.012), respectively. Recurrence at the TFI

Impacts of excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase, and epidermal growth factor receptor on the outcomes of patients with advanced gastric cancer.

Using laser-captured microdissection and a real-time RT-PCR assay, we quantitatively evaluated mRNA levels of the following biomarkers in paraffin-embedded gastric cancer (GC) specimens obtained by surgical resection or biopsy: excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase (DPD), methylenetetrahydrofolate reductase (MTHFR), epidermal growth factor receptor (EGFR), and five other biomarkers related to anticancer drug sensitivity. The study group comprised 140 patients who received first-line chemotherapy for advanced GC. All cancer specimens were obtained before chemotherapy. In patients who received first-line S-1 monotherapy (69 patients), low MTHFR expression correlated with a higher response rate (low: 44.9% vs high: 6.3%; P=0.006). In patients given first-line cisplatin-based regimens (combined with S-1 or irinotecan) (43 patients), low ERCC1 correlated with a higher response rate (low: 55.6% vs high: 18.8%; P=0.008). Multivariate survival analysis of all patients demonstrated that high ERCC1 (hazard ratio (HR): 2.38 (95% CI: 1.55-3.67)), high DPD (HR: 2.04 (1.37-3.02)), low EGFR (HR: 0.34 (0.20-0.56)), and an elevated serum alkaline phosphatase level (HR: 1.00 (1.001-1.002)) were significant predictors of poor survival. Our results suggest that these biomarkers are useful predictors of clinical outcomes in patients with advanced GC.

Stage specificity of novel growth factor expression during development of proliferative vitreoretinopathy.

OBJECTIVE: To compare the relative levels of connective tissue growth factor (CTGF), platelet-derived growth factor alpha (PDGF-AA), and hepatocyte growth factor (HGF) in glial and retinal pigment epithelial (RPE) cells of epiretinal membranes from proliferative vitreoretinopathy (PVR). METHODS: A total of 37 PVR membranes, of various stages, underwent fluorescent immunohistochemisty and confocal laser scanning microscopy to localize CTGF, HGF, and PDGF-AA in RPE and glial cells. RESULTS: Numerous RPE, and relatively fewer glial cells, were found in all stages of PVR. CTGF immunoreactivity increased from early to late stage PVR and was principally expressed by RPE cells in early stage, and by glial cells in late stage PVR. HGF, expressed by both RPE and glial cells, was principally expressed in mid-stage PVR. PDGF-AA, expressed by both cell types, demonstrated a uniform level of staining throughout all stages of PVR. CONCLUSIONS: RPE and glial cells contribute to the expression of CTGF, HGF, and PDGF-AA during PVR, but with specific developmental patterns. PDGF-AA is expressed uniformly throughout all stages of PVR, while HGF expression peaks during mid stage, and CTGF expression is highest during late stage PVR. These results allow for the development of stage-specific therapeutics for PVR that may allow targeting of the early proliferative and/or the late tractional stages of PVR.

Vitreous leptin levels in retinal disease.

BACKGROUND/AIMS: The purpose of this study was to investigate the relationship between vitreous leptin levels and retinal diseases. METHODS: Levels of vitreous leptin were evaluated in proliferative diabetic retinopathy (PDR) and a variety of other retinopathies including: macular disease, neovascular maculopathies, primary retinal detachments, and vascular occlusive disease. RESULTS: In patients with PDR (N=7), the average vitreous level of leptin (37.4 ng/ml) was significantly higher than that in patients with PVR (<1.0 ng/ml, P<0.05). Vitreous leptin level in patients with PVR or macular disease (N=18), with or without diabetes, was not significantly different from the control subjects who had retinal detachment only (N=7). CONCLUSION: The results show that the leptin level in vitreous taps is elevated in PDR. We suggest that leptin plays an active role in PDR.

The effects of humic substances on the intake of micro-organic pollutants into the aquatic biota.

Humic substances, naturally occurring highly polymerized organic compounds, exist widely in the water and soil environments. It has been known that the humic substances affect the fate of micro-organic pollutants (e.g. intake, accumulation, movement, degradation, toxicity, etc.). Of these, the effect of humic substances on the intake into biota (i.e. living cell) is one of the most important. In this research, the effects of co-existing humic substances on the intake of micro-organic pollutants into aquatic biota were experimentally evaluated. The humic acid filtrate using a 3,000 Da ultra-filtration membrane was used. Two PAHs (i.e. pyrene and phenanthrene) were used as micro-organic pollutants. Liposome for simulating living cell membrane was synthesized in the laboratory, and used for investigating the intake of micro-organic pollutants into aquatic biota precisely. The batch experiment results (PAHs onto humic acid, humic acid into liposome, and PAHs into liposome (K(lipw))) led to the fact that the sorption of PAHs into liposome is suppressed apparently by binding with humic acid in the aqueous phase. This suggests that the accumulation and/or toxicity of micro-organic pollutants is retarded by humic substances in the actual aqueous environment. Moreover, the experimental results indicated that the sorption into liposome (i.e. liposome/water partition coefficient (K(lipw))) could be a better parameter for estimating the intake of micro-organic pollutants into aquatic biota than n-octanol/water partition coefficient (K(ow)) in the aqueous environment.

Clinical results of aortic arch replacement using a four branched prosthetic graft.

AIM: The aim of this study was to evaluate the operative techniques of total arch replacement, the clinical results and the survival curves of patients following this procedure. METHODS: Since December 2001, 92 patients have undergone surgical treatment for aortic dissection and aneurysm. The total aortic arch replacement was performed in 24 of these patients. There were 16 men and 8 women, and the age range was 42 to 81 years with a mean age of 59.4 years. As the operative technique for total arch replacement, we used the 4-branched prosthetic graft, selective cerebral perfusion (SCP), continuous cold blood cardioplegia (CCBC), and open distal anastomosis under circulatory arrest. The combined operations were coronary bypass grafting in 4 patients, aortic valve suspension in 1 patient and a Bentairs procedure in 1 patient. Eleven (73.3%) patients with acute dissection required emergency operation. RESULTS: The hospital mortality rate was 25% (6 of the 24 patients). The causes of death were multiple organ failure (MOF) due to renal and mesenteric ischemia in 3 patients, cerebral infarction in 2 patients, myonephropathic metabolic syndrome (MNMS) in 1 patient, respectively. The data concerning extracorporeal circulation was 204+/-53 min in total pump time, 136+/-43 min in aortic cross clamp time, 83+/-14 min in SCP time and 48+/-10 min in circulatory arrest time, respectively. The long-term result in actuarial survival rate was 76% for 5 years. CONCLUSION: We consider the technique of total arch replacement using 4-branched prosthetic graft, SCP, CCBC, and open distal anastomosis is a useful operative method in patients with aortic aneurysm.

Immunohistochemical investigations of neurofilament M' and alphabeta-crystallin in the magnocellular layers of the primate lateral geniculate nucleus.

The magnocellular and parvocellular pathways are two major processing streams in the primate visual system. Using high-density grid arrayed cDNA clones to hybridize to cDNA probes from cortical regions of each pathway, a list of candidate differentially expressed genes was produced [Mol. Brain Res. 82 (2000) 11-24]. Magnocellular pathway candidates include neurofilament M' and alphabeta-crystallin. Using antibodies generated against these proteins, immunohistochemical analysis revealed preferential staining of the magnocellular layers in the primate lateral geniculate nucleus, providing verification of two candidate magnocellular-enriched genes.

Recovery of an impalement and transfixion chest injury by a reinforced steel bar.

A 36-year-old man was admitted to our hospital because of impalement injury due to a downwards fall upon some reinforced steel rods. An emergency operation was performed using percutaneous cardiopulmonary support (PCPS). The steel rods were taken out in the operating room. The heart, great vessels, vertebrae, and spinal cord were not involved in the impalement wounds. We performed a bronchoplasty of the torn and separated right main bronchus, and repaired the impaled left lung without any pulmonary resection. He recuperated without sequelae.

The role of leptin in choroidal neovascularization.

PURPOSE: The purpose of this study was to investigate the role of leptin in choroidal neovascularization. METHODS: We examined the localization of leptin by immunohistochemistry in nine choroidal neovascular membranes surgically excised from patients with age-related macular degeneration, idiopathic choroidal neovascularization, and ocular histoplasmosis. Controls included omission of primary antibody, use of an irrelevant primary antibody and leptin staining of posterior segment of four normal donor eyes. RESULTS: Leptin was present in eight membranes and appeared vesicular, within the cytoplasm. The more vascular membranes and those consisting of a larger number of retinal pigment epithelium cells were associated with greater leptin staining. Leptin was not seen in the posterior segment of the four normal eyes. CONCLUSION: We suggest that leptin plays an active role in choroidal neovascularization, although further experiments are necessary to establish a causal relationship.

Coronary artery bypass grafting in octogenarians.

Preoperative profiles, postoperative complications, and the early and late results in 32 patients 80 yrs. of age and older (elderly group) who underwent coronary artery bypass grafting were compared with those in patients under 80 yrs. of age (control group). In the elderly group, the prevalence of patients with preoperative creatinine clearance (Ccr.) <50 l/day (34.4%), unstable angina pectoris (78.1%) and left main trunk disease (40.1%) was significantly higher than those in the control group. The incidences of arrhythmia and intensive care unit(ICU) syndrome were also significantly higher in the elderly group than in the control group, however, there was no death due to these complications. In the elderly group, one patient (3.1%) died in the hospital due to low cardiac output syndrome (LOS), while three patients (2.4%) of the control group died in the hospital. As for the long-term results, the 5-yr. survival rates for the elderly group and the control group were 82.6% and 85.2%, respectively, and the effectiveness of surgery was remarkable, with improved postoperative activity in 96.9% of the elderly group. These findings indicate that although the elderly patients have higher risks by undergoing surgery and have a disadvantage in the rate of postoperative complications, the postoperative improvement in activity and survival rate can be similar to those in the younger patients.

Is arterial surgery advisable for patients over 80 years of age?

BACKGROUND: Recently life expectancy has become longer and longer. The purpose of this study was to analyse whether arterial surgery for patients over 80 years of age is advisable. METHODS: During the last 14 years, 527 patients, 50 of whom were over 80 and 477 of whom were under 80 years of age, received graft replacement or bypass surgery. They suffered from ruptured abdominal aortic aneurysm (R-AAA, n=21), non-ruptured abdominal aortic aneurysm (N-R AAA, n=133) or arteriosclerosis obliterans (ASO, n=373). Complications such as cerebrovascular disease, ischemic heart disease, respiratory and kidney dysfunction, and risk factors for ASO were also checked. RESULTS: All of the patients over 80 with R-AAA (n=3/3) and 50% of the patients under 80 with R-AAA (n=9/18) died during their stay in the hospital. However, none of the N-R AAA patients over 80 (n=0/7) and only one of the 126 N-R AAA patients (0.8%) under 80 died. For the patients over 80 with ASO, the graft patency rate was better than the patients survival rate. There were no age-specific factors that should condemn arterial surgery for patients over 80 years of age. CONCLUSIONS: Arterial surgery should not be ruled out on the basis of age alone.

The effects of panretinal photocoagulation on the primary visual cortex of the adult monkey.

PURPOSE: To determine the effects of panretinal photocoagulation (PRP) on the levels of cytochrome oxidase (CO), Zif268, synaptophysin, and growth-associated protein 43 (GAP-43) in the primary visual cortex of adult monkeys. METHODS: Ten adult primates underwent unilateral argon laser PRP with instrument settings at 300 to 500 microns spot diameter, 200 to 500 mW power intensity, and 0.1 to 0.2 second duration, causing moderate to severe burns in the peripheral retina. At 20 hours, 12 days, 6 months, and 13 months after laser treatment, the visual cortex was assessed histologically for CO and immunohistochemically for Zif268, synaptophysin, and GAP-43. RESULTS: PRP resulted in transneuronal changes in the relative distributions of CO, Zif268, synaptophysin, and GAP-43 in the primary visual cortex. CO activity was relatively decreased in the lasered eye's ocular dominance columns at 12 days post-PRP, with recovery by 13 months post-PRP. The level of Zif268 was dramatically decreased in the lasered eye's ocular dominance columns at 20 hours post-PRP, with gradual recovery by 13 months post-PRP. Levels of synaptophysin and GAP-43 immunoreactivity were increased in both the lasered and the nonlasered eyes' ocular dominance columns at 6 months post-PRP. CONCLUSION: PRP treatment results in metabolic activity changes in the visual cortex of the adult monkey. These changes are followed chronologically by spatial redistribution of synaptophysin and GAP-43, neurochemicals known to play a role in cortical plasticity. This study demonstrates, for the first time, that PRP as used in the treatment of diabetic retinopathy results in a redistribution of neurochemicals in the adult monkey visual cortex. Such changes may help explain the anomalous visual functional loss often reported by patients after PRP.

Organization of efferent neurons in area 19: the projection to extrastriate area 21a.

The organization of efferent neurons in area 19 of the cat was examined by bulk injections of retrograde tracers, WGA-HRP and CTX-Au, into extrastriate area 21a. In one case, the cortex was cut coronally and retrogradely labeled cells in area 19 were present in columnar register throughout layers 2 to 6, with the majority of labeled cells in layers 2/3. The number of columns per tissue section ranged from 0 to 4 and had a centre-to-centre spacing ranging from 0.6 to 0.9 mm. A few lightly labeled cells were found between the columns. In six other cases, the visual cortex was flattened, and cut in the tangential plane to reveal a pattern of irregular, widely spaced bands that were elongated in the mediolateral direction with a mean centre-to-centre spacing of 2.6 mm. The density of labeled cells within these bands fluctuated such that dense aggregates of cells were found, on average, at 0.9 mm intervals along the bands. This tangential heterogeneity in density, along with the patchy columnar staining witnessed in the coronal plane, suggests that the widely spaced efferent projection bands may have a patchy substructure with a spacing of approximately 1 mm. The pattern of efferent projection bands and its substructure in area 19 is reminiscent of the stripe-like organization of V2 found in primates.

Externally Supported, Noncoated, Knitted Dacron Graft and Gelatin-Coated Knitted Dacron Graft with Rings for Peripheral Arterial Reconstruction.

During the last 14 years, externally supported noncoated knitted Dacron grafts (EXS) and gelatin-coated knitted Dacron grafts with rings (GEL) were used in 176 patients for femoropopliteal bypass (F-P), femorofemoral bypass (F-F) and axillofemoral bypass (Ax-F). In the EXS group, 58 F-P above knee (ak), 42 below knee (bk), 25 F-F, and 19 Ax-F surgeries were performed. Twenty-three F-Pak, 5 F-Pbk, 26 F-F, and 8 Ax-F surgeries were performed in the GEL group. In the F-Pak, primary patency at 5 and 9 years was 75.5 and 53% for the EXS and that at 3 and 5 years was 75.0 and 60.0% for the GEL (n.s.). In the F-Pbk, primary patency at 5 and 10 years was 60.5 and 29.5% for the EXS, while patency at 1 year was 11.1% for the GEL (P < 0.05). In both the EXS and the GEL groups, the F-Pak surgery showed better outcomes than the F-Pbk surgery. The outcomes of the F-P grafts implanted into the legs with claudication were better than those performed for the limb salvage cases. Primary patency of the F-F and the Ax-F showed no differences and there were also no differences between the graft types. For F-Pak surgery, the EXS is the graft of choice. The GEL is not suitable for F-Pbk surgery. For F-F and Ax-F reconstruction, both the EXS and the GEL are acceptable.

Columnar distribution of serotonin-dependent plasticity within kitten striate cortex.

Recent studies have identified the potential for an important role for serotonin (5-HT) receptors in the developmental plasticity of the kitten visual cortex. 5-HT(2C) receptors are transiently expressed in a patchy fashion in the visual cortex of kittens between 30-80 days of age complementary to patches demarcated by cytochrome oxidase staining. 5-HT, operating via 5-HT(2C) receptors, increases cortical synaptic plasticity as assessed both in brain slices and in vivo. Herein, we report that bath application of 5-HT substantially increases the probability of long-term potentiation within 5-HT(2C) receptor-rich zones of cortex, but this effect is not observed in the 5-HT(2C) receptor-poor zones. Instead, in these zones, 5-HT application increases the probability of long-term depression. These location-specific effects of 5-HT may promote the formation of compartment-specific cortical responses.

The projection from V1 to extrastriate area 21a: a second patchy efferent pathway colocalizes with the CO blob columns in cat visual cortex.

The different patchy organizations of neurons projecting from primary visual cortex (area 17) to the various extrastriate areas may contribute to functional differences in the output to each of these areas. The pattern of neurons projecting to extrastriate area 21a was examined using large injections of retrograde tracers and compared to the pattern shown by neurons projecting to the lateral suprasylvian area (LS). Patches of neurons projecting to 21a showed a bimodal laminar distribution, with numerous labeled cells in the upper and lower third of layer 3 bracketing a sparsely labeled central third; LS-projecting neurons were confined to the lower and middle thirds of layer 3. The 21a projecting cells were relatively tighter in their clustering pattern than the LS projecting cells, i. e. the difference in labeling density between patch and interpatch zones was greater for 21a-projecting cells than for LS-projecting cells. As previously shown for the LS-projecting cells, patches of 21a-projecting cells colocalized with CO blob columns in area 17. Combined with our earlier results, this study shows that the CO blob compartments in area 17 give rise to at least two distinct efferent pathways, one projecting to LS and the other to 21a, and furthermore suggest that each pathway may carry unique information to its extrastriate target.