Correlation of urine type I collagen-cross-linked N telopeptide levels with bone scintigraphic results in prostate cancer patients

The diagnostic potential of a new bone resorption marker, type I collagen-cross-linked N telopeptide (NTx), for bone metastasis of prostate cancer was evaluated. Ninty-one prostate cancer patients underwent bone scintigraphy, and urine NTx/creatinine (NTx/Cr) was measured. Urine NTx/Cr levels were compared with bone scintigraphic results. Urine NTx/Cr levels in the bone metastasis-positive group (n = 47) were 92.9 +/- 105.1 nmol/L of bone collagen, which is equivalent to per millimole of urinary creatinine (nmol/L BCE/mmol/L Cr), significantly higher than the level of the bone metastasis-negative group (n = 44) (59.0 +/- 41.6 nmol/L BCE/mmol/L Cr). When patients were classified by the extent of disease grade (EOD grade) nomenclature, the urine NTx/Cr level of the EOD (4+) group was 209.5 +/- 186.5 nmol/L BCE/mmol/L Cr. This level was significantly higher than those of the EOD (-) group (59.0 +/- 41.6 nmol/L BCE/mmol/L Cr), EOD (1+) group (59.0 +/- 47.8 nmol/L BCE/mmol/L Cr), and EOD (2+) group (81.1 +/- 41.3 nmol/L BCE/mmol/L Cr). However, no significant difference was observed between the EOD (-) and EOD (1+) groups. The mean change in urine NTx/Cr level 3 to 17 months after the first bone scintigraphy and urine NTx/Cr examination in the bone metastasis-progression group (n = 8) was 11.0 +/- 31.2 nmol/L BCE/mmol/L Cr, significantly higher than that in the bone metastasis-regression group (n = 15) (-26.8 +/- 40.7 nmol/L BCE/mmol/L Cr). In conclusion, urine NTx /Cr can be measured noninvasively and reflects the state of bone metastasis. However, the sensitivity of urine NTx/Cr is not as high as that of bone scintigraphy. Therefore, it may provide an auxiliary diagnostic index for bone scintigraphy.     

Effect of prior portosystemic shunt on early hepatic hemodynamics and sinusoids following 84% hepatectomy in dogs

The effects of a prior portosystemic shunt (PSS) on the hepatic hemodynamics and sinusoids shortly after an 84% hepatectomy (Hx) were investigated in dogs. Fifteen mongrel dogs were divided into three groups, a 70% Hx group (n=5), an 84% Hx group (n=5) and an 84% Hx+PSS group (n=5). In the last group, a shunt was inserted between the splenic and femoral veins prior to the hepatectomy. The systemic and hepatic hemodynamics were measured, before and 180 min after the hepatectomy, and the remaining liver tissue was then examined immuno-histochemically by light microscopy using the thrombomodulin (TM) staining method. The postoperative portal vein pressure and the vascular resistance were significantly lower in the PSS group than in the 84% non-PSS group. The total postoperative hepatic blood flow was higher in the 84% non-PSS group than in the other two groups. Immunohistochemical observation after TM staining indicated that the sinusoidal endothelial cells in the 84% non-PSS group were markedly damaged 3 h after surgery. We conclude that a prior PSS improves the hepatic hemodynamics and is beneficial to the sinusoids within the first few hours of an 84% hepatectomy in dogs.     

Quantitative processed images acquired by histogram-SNR imaging used to evaluate parenchymal heterogeneity in the liver

Purpose: To evaluate a new system for displaying processed images of liver parenchyma based on quantitative estimation of heterogeneity by texture analysis.Methods: We measured the signal to noise ratio, one of the first-order statistics in the histogram of enveloped amplitude of radio-frequency backscattered echoes, using a 3.75-MHz transducer with texture analysis in conjunction with a new method in which the small ROI (region of interest) is segmented into multiple layers to minimize the influence of tissue attenuation and beam diffraction. In our computerized system, gray-display and color-display images, two types of processed images, were produced from the visual intensity of each small ROI, which was based on its signal to noise ratio. We studied 10 cases of normal liver, 10 cases of fatty liver, and 10 cases of cirrhotic liver. The processed images obtained from these livers were reviewed to observe their features and to compare their usefulness in estimating the heterogeneity of the liver parenchyma with that of conventional B-mode images.Results: Gray-display images of cirrhotic livers appeared much blacker than the images produced from other disorders, and color-display images of cirrhotic liver appeared much bluer or greener than the others. Rate of correct diagnosis from B-mode images was 68.3 ±6.8%; from gray-display images, 85.8±7.4%; and from color-display images, 91.7±8.2%. Rate of correct assessment from B-mode images and gray-display images was significantly correlated (p=0.0015), as was rate of correct assessment from the B-mode images and the color-display images (p=0.0060).Conclusion: The processed images obtained using this computerized system contributed to the correct and objective interpretation of the heterogeneity of the liver parenchyma.     

Optimal Combination of Effective ANtihypertensives (OCEAN) study: a prospective, randomized, open-label, blinded endpoint trial--rationale, design and results of a pilot study in Japan

There are limited clinical trials examining the efficacy of antihypertensive drug combinations aimed at preventing cardiovascular events. Therefore, we designed a randomized controlled trial using amlodipine as the base drug of a multi-drug regimen, the Optimal Combination of Effective ANtihypertensives (OCEAN) Study, to determine the drug combination that is most efficacious in the prevention of cardiovascular events, such as stroke. The OCEAN Study is a collaborative study between Japan and China, enrolling 20?000 patients and following them for 3 to 4 years. A pilot study was conducted before the full-scale study to confirm the feasibility of the protocol and that the study groups and infrastructures could function properly. A total of 279 Japanese patients were enrolled from 57 participating medical institutions between June and December 2004. Two hundred and sixty-six patients (mean age: 65.9 years) were treated with amlodipine alone. One hundred and fifty-four of these patients (57.9%) did not reach the treatment targets (<140/90?mm?Hg for the elderly and patients with cerebrovascular disease, <130/80?mm?Hg for those with diabetes mellitus, chronic kidney disease or prior myocardial infarction) and a second agent was added. They were randomly allocated into three different treatment groups using a diuretic, a β-blocker or an angiotensin-converting enzyme inhibitor/angiotensin II receptor antagonist. The pilot study showed that the protocol was appropriate, and the inclusion of patients with slightly higher blood pressures was necessary to increase the randomization rate. It also confirmed that we organized properly functioning study groups and infrastructures.     

Successful endoscopic transpapillary pancreaticobiliary drainage for omental panniculitis by hepatocellular carcinoma complicated by biliary fistula and pancreatic fistula

A 78-year-old man with hepatocellular carcinoma treated by chemoembolization and percutaneous ethanol injection was admitted to our hospital because of acute abdomen. The CT scan showed biliary fistula caused by hepatocellular carcinoma protruding from S3. Endoscopic retrograde cholangiopancreatography showed disruption of an intrahepatic duct and the main pancreatic duct, and contrast agent leaked into the peritoneal cavity from each duct. Omental panniculitis with biliary fistula and pancreatic fistula was diagnosed. The symptoms improved by endoscopic nasobiliary drainage and endoscopic pancreatic stenting. On the 13th day after admission, we added endoscopic nasopancreatic drainage because his abdominal pain had been exacerbated by pancreatic juice leakage. Omental panniculitis by hepatocellular carcinoma complicated by biliary fistula and pancreatic fistula is extremely rare. Endoscopic transpapillary pancreaticobiliary drainage was effective for omental panniculitis in this case.     

Clinical features and varieties of non-motor fluctuations in Parkinson's disease: A Japanese multicenter study

ObjectiveThis multicenter cross-sectional study aimed to investigate the clinical features and varieties of non-motor fluctuation in Parkinson's disease (PD).MethodsTo identify motor and non-motor fluctuation, we employed the wearing-off questionnaire of 19 symptoms (WOQ-19) in 464 PD patients. We compared the frequency of levodopa-related fluctuation as identified by the WOQ-19 with recognition by neurologists. We compared patients with both motor and non-motor fluctuations with those who only had motor fluctuations. Non-motor fluctuations were separated into psychiatric, autonomic, and sensory categories for further analysis.ResultsThe patients' average age was 70.8 ± 8.4 years (mean ± SD) and disease duration was 6.6 ± 5.0 years. The frequency of motor fluctuations was 69% and for non-motor fluctuation 40%. Fifty-three percent of patients with motor fluctuations also had non-motor fluctuations, whereas 93% of patients with non-motor fluctuations also had motor fluctuations. The WOQ-19 showed a sensitivity of 82% but a specificity of only 40%. The patients with both non-motor and motor fluctuations exhibited more severe motor symptoms, more non-motor symptoms and higher levodopa daily doses (p < 0.05). Patients had significantly higher fluctuation rates if they had psychiatric (49%) and sensory (45%) symptoms than patients with autonomic symptoms (32%, p < 0.01). Forty-eight percent of patients with non-motor fluctuations exhibited more than one type of non-motor fluctuation.ConclusionForty percent of PD patients presented with non-motor fluctuations, and almost half of these exhibited more than one type. Appropriate recognition of levodopa-related fluctuations, both motor and non-motor, can lead to treatment modifications in PD patients.     

Oxidized proteins in astrocytes generated in a hyperbaric atmosphere induce neuronal apoptosis

In the present study, we investigated the influence of the oxidative damage to astrocytes on neuronal cell survival using cultures of rat cerebral astrocytes and neurons. The exposure of astrocytes to hyperbaric oxygen induced a time-dependent apoptotic cell death, as observed by DNA ladder assessment. When astrocytes damaged by oxidative stress were cocultured with normal neurons from the cerebrum of a newborn rat, neuronal cell death was markedly induced, although normal astrocytes not subjected to hyperoxia cocultured with normal neurons showed no neuronal cell apoptosis. It was found that either the supernatant from the homogenate of astrocytes cultured in hyperbaric oxygen atmosphere or a protein mixture extracted from the supernatant induced neuronal cell death. The level of protein carbonyls, an index of protein oxidation analysis, in cultured astrocytes increased significantly with oxidative stress, and vitamin E inhibited the increase in the level of such oxidized proteins in astrocytes. Furthermore, a two-dimensional (2D) electrophoresis of a protein mixture extracted from the supernatant showed several changes in proteins. These results imply that reactive oxygen species (ROS) induced by oxidative stress attack astrocytes to induce oxidatively denatured proteins in the cells that act as a neurotoxic factor, and that vitamin E protects neurons by inhibiting astrocyte apoptosis caused by oxidative stress.     

Activation of non-primary motor areas during a complex finger movement task revealed by functional magnetic resonance imaging

We examined the brain activation induced by a complex finger movement task using functional magnetic resonance imaging (fMRI) with echo planar imaging (EPI). Imaging planes were set up for the observation of non-primary motor areas. Among five normal males examined, four subjects naive to the task showed activations in contralateral primary and supplementary motor areas and the ipsilateral superior anterior part of the cerebellar hemisphere. Also, the bilateral premotor areas and the contralateral ventrolateral nucleus of thalamus were occasionally activated. No changes were observed in the putamen and globus pallidus. The subject accustomed to the task showed activation in the narrow areas of the contralateral primary motor and supplementary motor and premotor areas but not in the cerebellum. These results suggest that fMRI has nearly the same degree of detectability to that of positron emission tomography (PET) in regard to motor functions.     

Depolarization-induced suppression of inhibition mediated by endocannabinoids at synapses from fast-spiking interneurons to medium spiny neurons in the striatum

Endogenous cannabinoids (endocannabinoids) act as retrograde inhibitory messengers in various regions of the brain. We have recently reported that endocannabinoids mediate short-term retrograde suppression of excitatory synaptic transmission from the neocortex to medium spiny (MS) neurons, the major projection neurons from the striatum. However, it remains unclear whether endocannabinoids modulate inhibitory transmission in the striatum. Here we show that depolarization of MS neurons induces transient suppression of inhibition that is mediated by retrograde endocannabinoid signalling. By paired recording from a fast-spiking (FS) interneuron and an MS neuron, we demonstrated that FS-MS inhibitory synapses undergo endocannabinoid-mediated retrograde suppression. We verified that GABAergic inhibitory terminals immunopositive for parvalbumin (PV), a marker for FS interneurons, expressed CB1 receptors. These PV-CB1 double-positive terminals surrounded dopamine D1 receptor-positive and D2 receptor-positive MS neurons; these constitute direct and indirect pathways, respectively. These results suggest that endocannabinoid-mediated retrograde suppression of inhibition influences information flow along both direct and indirect pathways, depending on the activity of MS neurons.