Effect of Small Focus on Electron Heating and Proton Acceleration in Ultrarelativistic Laser-Solid Interactions.

Acceleration of particles from the interaction of ultraintense laser pulses up to 5×10^{21} W cm^{-2} with thin foils is investigated experimentally. The electron beam parameters varied with decreasing spot size, not just laser intensity, resulting in reduced temperatures and divergence. In particular, the temperature saturated due to insufficient acceleration length in the tightly focused spot. These dependencies affected the sheath-accelerated protons, which showed poorer spot-size scaling than widely used scaling laws. It is therefore shown that maximizing laser intensity by using very small foci has reducing returns for some applications.

Selective blockade of apoptosis by in vivo electroporation-mediated gene transfer combined with portal infusion of plasmid DNA attenuates liver cirrhosis.

AIM: The purpose of the present study was to determine whether in vivo electroporation could achieve selective blockade of apoptosis in a rat liver cirrhosis model. METHODS: A dimethylnitrosamine (DMN)-induced rat liver cirrhosis model was used. In vivo electroporation was performed after portal vein infusion of plasmid DNA. pFas-Fc plasmid DNA was used to block the apoptotic pathway. pUC/HGF and pCAGGS/EGFP were used as positive and negative controls, respectively. Liver collagen content was evaluated by hydroxyproline assay two weeks after gene transfer. Terminal deoxynucleotidyltransferase dUTP nick end-labeling was simultaneously performed in the liver to evaluate suppression of apoptosis. Survival analysis was performed using 10 rats that received the sFas gene, 10 that received the HGF gene, and 13 that received the GFP gene. RESULTS: The apoptotic cell index in the DMN-injected liver was significantly lower in rats that received the sFas gene compared with the negative control. The collagen content of the DMN-injected liver was also lower in rats that received the sFas gene compared with the negative control. There was no significant difference in the apoptotic cell index and collagen content of rats that received the sFas and HGF genes. Ten weeks after the initiation of DMN treatment, the survival rates with the sFas, HGF, and GFP genes were 56%, 100%, and 0, respectively. CONCLUSION: Selective blockade of apoptosis by in vivo electroporation-mediated gene transfer improved the apoptotic cell index, hydroxyproline content, and survival rate. Soluble Fas gene therapy using in vivo electroporation can be a safe and efficient therapy for liver cirrhosis in rats.

A retrospective study of intravascular ultrasound use in patients undergoing endovascular aneurysm repair: its usefulness and a description of the procedure.

OBJECTIVES: To verify the usefulness and limitation of intravascular ultrasound (IVUS) in endovascular aneurysm repair (EVAR). METHODS: A total of 112 consecutive patients, who underwent EVAR to treat abdominal aortic aneurysms, were examined retrospectively. Of these, 33 patients were assigned to the IVUS group because of renal failure, a suspected allergy to contrast agents or anatomical difficulties; the remaining 79 patients were assigned to the non-IVUS group. RESULTS: Patients in the IVUS group required fewer intra-arterial contrast agents (IACAs) than those in the non-IVUS group (67±34ml vs. 123±50ml; p<0.01). Blood loss and operation time were comparable between the two groups. No patients died within 30 days of the operation. Three major renal complications occurred in the non-IVUS group. Renal deterioration evaluated by chronic kidney disease (CKD) stage was found to a greater extent in the non-IVUS group. CONCLUSIONS: IVUS is a powerful auxiliary method in EVAR for reducing the required volume of contrast agents. The combination of IVUS and IACA usage showed good overall performance; thus, we propose the routine use of IVUS in EVAR procedures.

Ion species discrimination method by linear energy transfer measurement in Fujifilm BAS-SR imaging plate.

We have developed a novel discrimination methodology to identify ions in multispecies beams with similar charge-to-mass ratios, but different atomic numbers. After an initial separation by charge-to-mass ratios using co-linear electric and magnetic fields, individual ions can be discriminated by considering the linear energy transfer of ions irradiating a stimulable phosphor plate (Fujifilm imaging plate) by comparison with the Monte Carlo calculation. We apply the method to energetic multispecies laser-driven ion beams and use it to identify silver ions produced by the interaction between a high contrast, high intensity laser pulse; and a sub-micrometer silver foil target. We also show that this method can be used to calibrate the imaging plate for arbitrary ion species in the range of Z ≥ 6 with dE/dx > 0.1 MeV/µm without requiring individual calibration.

All-optical switching of 40 Gb/s packets by MMI-BLD optical label memory.

We demonstrated all-optical label storing and switching for 40 Gb/s optical packets by using all-optical signal processing of multimode interference bistable laser diode optical flip-flops. The stored optical labels in the optical flip-flop controlled an all-optical switch to forward the injected optical packets. The 40 Gb/s optical packets were successfully switched in the all-optical scheme with 11-dB extinction ratio. Error-free operation for the output packets from the switch was also obtained with 1.3-dB power penalty. The presented all-optical packet switching has the advantages of ultrafast switching and transparency of data rate and format, suitable for the future optical networks.

Telecontrolled micromanipulator system (NeuRobot) for minimally invasive neurosurgery.

BACKGROUND: To perform less invasive neurosurgery, a telecontrolled micromanipulator system has been developed and applied to clinical situations. Basic experiments for telesurgery have also been conducted. METHOD: A cadaver head was used to carry out surgical simulation of the opening of the sylvian fissure and third ventriculostomy. After obtaining permission from the Ethical Committee of Shinshu University School of Medicine, part of the recurrent meningioma in a 45-year-old man was removed. As basic experiment for telesurgery, surgical simulation was also conducted in a rat brain with the operating console transported to a hospital 40 km distant from the University. FINDINGS: Opening of the sylvian fissure and third ventriculostomy were accurately performed. Tumour removal in a patient with recurrent meningioma was safely achieved. Surgical simulation in the rat brain was accurately and correctly carried out, operated on from a hospital 40 km distant. CONCLUSIONS: The NeuRobot, telecontrolled micromanipulator system, can be used as a tool for less invasive neurosurgery.

Reduced vascular reserve measured by stressed single photon emission computed tomography carries a high risk for stroke in patients with carotid stenosis.

AIM: A few studies have observed reduced vascular reserve measured by single photon emission computed tomography (SPECT) to be a risk factor for stroke in patients with carotid artery occlusion, but stenosis has been excluded from these former studies. This study has evaluated the prognosis of reduced vascular reserve in patients with stenosis, and the effect of carotid endarterectomy (CEA) on these patients. METHODS: Forty patients diagnosed as having >70% stenosis of the carotid artery at the University of Tokyo Hospital, between 2001 and 2004, underwent acetazolamide-stress SPECT test first. A resting SPECT study was performed on a different day from the stressed SPECT study. The patients were grouped as having reduced vascular reserve or normal vascular reserve from the SPECT results. Analysis of risk factors and the stroke-free curve analysis for reduced vascular reserve was performed. RESULTS: Of the 40 patients, 24 (60%) had reduced vascular reserve and 18 underwent CEA. The mean follow-up period was 21.5+/-15.5 months (mean+/-SD). Four strokes occurred during follow-up: in 1 patient with CEA and 3 without CEA. All stroke patients had reduced vascular reserve. The patients with reduced vascular reserve without any surgery had a significantly lower stroke-free rate compared with those with normal vascular reserve or reduced vascular reserve, but also receiving CEA. CONCLUSIONS: We propose performing SPECT tests in patients with severe carotid stenosis regardless of symptoms, and performing CEA on those with a reduction in vascular reserve.

Carotid endarterectomy may reduce the high stroke rate for patients with the disease of abdominal aorta and peripheral arteries.

AIM: The prevalence of carotid stenosis is reported to be high among patients with arteriosclerosis, but the hazards of carotid stenosis and the benefits of carotid endarterectomy (CEA) on long-term event-free survival are still unknown. The aim of this prospective study was to screen preoperative patients with arterial disease for carotid stenosis, and to determine whether CEA had any effect on stroke during the postoperative follow-up period. METHODS: From 1999 to 2003, 406 consecutive preoperative patients with arterial disease underwent routine carotid duplex scan. Patients with known carotid stenosis and those due to undergo operation in emergency were excluded from the study. CEA was performed before or simultaneously with vascular surgery if necessary. The prevalence and risk factors for carotid stenosis were studied, and the patients were followed up for stroke or death. RESULTS: Among the 406 patients examined, 19.4% had greater than 50% stenosis and 11.3% had greater than 70% stenosis. The risk factors for carotid stenosis were having occlusive arterial disease (P=0.0001), and history of stroke (P=0.0038). Long-term follow-up study revealed that patients with greater than 70% carotid stenosis without CEA had a higher tendency for stroke or death, but the stroke rate in patients with severe stenosis who underwent CEA remained low, as in patients with less than 70% stenosis. CONCLUSIONS: Patients with greater than 70% carotid stenosis, diagnosed before arterial operation who did not undergo CEA, had a higher risk for stroke during the postoperative follow-up period. However, their risk could be reduced by performing CEA before or simultaneously with scheduled vascular surgery.

Age-related variations in glycosylation of hydroxylysine in human and rat skin collagens.

The extent of glycosylation of hydroxylysine in human skin collagen rapidly decreased during maturation and then gradually increased in proportion to the age. This decrease of glycosylation observed during maturation was also confirmed in whole, soluble and insoluble collagens from rat skin. These findings may contribute to the investigations on the functional role of glycosylation and also on the mechanism of maturational as well as senile processes.

Hypoxia-induced pulmonary blood redistribution in subjects with a history of high-altitude pulmonary edema.

BACKGROUND: Pulmonary hypertension has been suggested to play an important role in development of high-altitude pulmonary edema (HAPE), and individual susceptibility has been suggested to be associated with enhanced pulmonary vascular response to hypoxia. We hypothesized that much greater pulmonary vasoconstriction would be induced by acute alveolar hypoxia in HAPE-susceptible (HAPE-s) subjects and that changes in pulmonary blood flow distribution could be demonstrated by radionuclide study. METHODS AND RESULTS: We performed ventilation-perfusion scintigraphy in 8 HAPE-s subjects and 5 control subjects while each was in the supine position and acquired functional images of pulmonary blood flow and ventilation under separate normoxic and hypoxic (arterial oxygen saturation, 70%) conditions. We also measured acceleration time/right ventricular ejection time (AcT/RVET) with Doppler echocardiography under each condition in both groups. Moreover, we assayed human leukocyte antigen (HLA) alleles serologically in the HAPE-s group. Pulmonary blood flow was significantly shifted from the basal lung region to the apical lung region under hypoxia in HAPE-s subjects, although no significant change in regional ventilation was observed. With Doppler echocardiography, HAPE-s subjects showed increased pulmonary arterial pressure during hypoxia compared with control subjects. The magnitude of cephalad redistribution of lung blood flow was significantly higher in the HLA-DR6-positive than in HLA-DR6-negative HAPE-s subjects. CONCLUSIONS: These findings suggest that acute hypoxia induces much greater cephalad redistribution of pulmonary blood flow that results from exaggerated vasoconstriction in the basal lung in HAPE-s subjects. Furthermore, pulmonary vascular hyperreactivity to hypoxia may be associated with HLA-DR6.

Growth factor usage patterns and outcomes in the community setting: collection through a practice-based computerized clinical information system.

PURPOSE: Although use of colony-stimulating factor (CSF) is widespread and guidelines for use have been disseminated, actual practice patterns of medical oncologists are unknown. The purpose of this study was to collect these data using an office-based computerized clinical information system. PATIENTS AND METHODS: Data were collected on patients at 10 community-based oncology practices. Information regarding CSF use was captured at the time of prescribing through a computerized clinical support tool and stored in a data warehouse, and an analysis was carried out retrospectively. RESULTS: A total of 6,813 cancer regimens administered to 5,034 patients were evaluated for growth factor use. Overall, CSFs were used in 14% of regimens, with breast, lymphoma, lung, and ovarian being the most common cancers for which CSFs were used. In 49.4% of regimens, CSF was initiated during cycle 1, with an average duration of 1 week, and was used in two or three cycles per regimen. Afebrile neutropenia is rarely followed by CSF initiation. Granulocyte colony-stimulating factor (G-CSF) is associated with fewer dose adjustments, delays, and hospitalizations when compared with granulocyte-macrophage colony stimulating factor (GM-CSF). There is wide variation among oncologists in CSF use, and several substantial differences were noted between the prescribing behavior of American Society of Clinical Oncology (ASCO) survey-reported oncologists and actual clinical practice, as captured by the computerized clinical information system. CONCLUSION: Computerized clinical information systems can collect detailed information regarding practice patterns of medical oncologists. ASCO physician practice survey data do not accurately reflect actual practice patterns and must be interpreted with caution. Substantial deviations from ASCO growth factor guidelines remain, and oncologists' use of CSFs demonstrates wide variation. There may be important clinical differences between G-CSF and GM-CSF, but definitive phase III trials are needed for confirmation.

Accuracy of cardiac output measured by continuous wave Doppler echocardiography during dynamic exercise testing in the supine position in patients with coronary artery disease.

To estimate the accuracy of cardiac output measured by continuous wave Doppler echocardiography from the suprasternal notch and the utility of this method for evaluating left ventricular function during dynamic exercise, simultaneous thermodilution and Doppler cardiac output were measured in 34 patients with coronary artery disease during multistage ergometer exercise in the supine position. Cardiac output was measured at rest and during each stage of exercise. Twenty-five of the 34 patients whose thermodilution curves were adequate for analysis were studied during exercise. The correlation coefficient for the two methods was 0.85 at rest and 0.84 during exercise. Differences between the two methods were not significant at rest but were significant during exercise, with the thermodilution method giving the higher values. Underestimation by the Doppler method is probably due to technical problems and changes in aortic diameter during exercise. The 25 patients were classified into two groups according to pulmonary artery wedge pressure at peak exercise. There were 11 patients in Group 1 pressure (greater than or equal to 20 mm Hg at peak exercise) and 14 in Group 2 pressure (less than 20 mm Hg at peak exercise). There were significant differences in the change in cardiac index and in peak aortic velocity from rest to peak exercise between the two groups. A significant linear correlation between the percent change in peak aortic velocity and in pulmonary artery wedge pressure from rest to peak exercise was observed (r = -0.66, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of a new second generation calcium channel blocker, nilvadipine (FR34235), on exercise-induced hemodynamic changes in stable angina pectoris.

The mechanism of the antianginal actions of nilvadipine was investigated in 11 patients with effort angina pectoris. Hemodynamic data were obtained by angina-limited supine multistage bicycle ergometer exercise testing before and after a single 6 mg dose of nilvadipine. Compared with chest pain during control exercise testing, pain at peak exercise disappeared or abated and the ST segment at peak exercise also showed less significant depression after administration of nilvadipine. At rest and at peak exercise, mean blood pressure, pulmonary artery wedge pressure and systemic vascular resistance decreased significantly, whereas heart rate and cardiac index increased significantly after nilvadipine. Rate-pressure product and stroke volume index did not change significantly. Coronary sinus flow at peak exercise increased significantly and total coronary vascular resistance at rest and at peak exercise decreased significantly after nilvadipine. The plasma concentrations of nilvadipine 1.5 hours after administration ranged from 1.15 to 8.23 ng/ml. These data suggest that the principal factors in the antianginal actions of nilvadipine are an increase in myocardial oxygen supply due to increased coronary blood flow and a reduction in myocardial oxygen demand mainly by a decrease in afterload and additionally by a decrease in preload.

Long-term results of combined iliac endovascular intervention and infrainguinal surgical revascularization for treatment of multilevel arterial occlusive disease.

AIM: The purpose of this study was to investigate the long-term results of combined iliac endovascular intervention and infrainguinal surgical revascularization. METHODS: A retrospective review of 39 infrainguinal bypasses combined with iliac endovascular intervention in 35 patients over a 16-year period was performed (Combined group). These results were compared to those of 43 infrainguinal bypasses performed with suprainguinal bypass operation in 39 patients (Surgical group), who had iliac lesions not amenable to angioplasty/stenting. There was no significant difference in the preoperative limb ischemic symptoms between them. RESULTS: Although the proportion of patients with coronary artery disease in the Combined group was significantly higher than that in the Surgical group, there was a trend toward lower morbidity/mortality in the Combined group compared with the Surgical group (8.6% vs 15.4%; P=0.3706). No significant differences in the rates of clinical and hemodynamic improvement and limb salvage rate were observed between the two groups. The primary patency rate of infrainguinal bypass at 1, 3, and 5 years was 83.2%, 80%, and 71.2% in the Combined group, and 97.1%, 89.9%, and 80.5% in the Surgical group, respectively. The secondary patency rate at 1, 3, and 5 years was 91.9%, 91.9%, and 76.3% in the Combined group, and 97.1%, 89.9%, and 84.6% in the Surgical group, respectively. Importantly, there was no significant difference in the primary/secondary patency rates between the two groups (Kaplan-Meier, log-rank test, primary patency, P=0.116; secondary patency, P=0.4407). CONCLUSIONS: Infrainguinal surgical reconstruction combined with iliac endovascular procedure may reduce operative risk, and further, long-term patency is comparable to that in the Surgical group.

Persistent sciatic artery in a patient with extracranial internal carotid artery aneurysm and infrarenal abdominal aortic aneurysm. A case report.

A rare case of a persistent sciatic artery (PSA) in a patient with aneurysms of the internal carotid artery and abdominal aorta is presented. A 70-year-old man was referred with intermittent claudication of the right lower extremity. Angiography and computed tomography demonstrated that this symptom was due to occlusion of the PSA. On preoperative examinations, aneurysms of the extracranial internal carotid artery and abdominal aorta were incidentally discovered, and then surgically treated prior to the management of PSA. Systemic examinations must be performed in patients with PSA in order to scrutinize associated anomalies or vascular disease.

Human parathyroid hormone inhibits renal 24-hydroxylase activity of 25-hydroxyvitamin D3 by a mechanism involving adenosine 3',5'-monophosphate in rats.

The in vivo effect of PTH on renal 24-hydroxylase activity of 25-hydroxyvitamin D3 (25OHD3) was examined in vitamin D-deficient thyroparathyroidectomized rats by a recently developed sensitive in vitro assay of 25OHD3-hydroxylases using rat kidney homogenates and by an in vivo assay measuring the accumulation of tritiated metabolites in plasma 5 h after injection of 25OH[3H]D3. Infusion for 20 h of either human PTH-(1-34) (except at 800 pmol/h) or cAMP did not significantly change the plasma levels of calcium and phosphorus compared with those in thyroparathyroidectomized rats given 125 ng 1,25-dihydroxyvitamin D3 to induce renal 24-hydroxylase activity. On the other hand, human PTH-(1-34) markedly inhibited renal 24-hydroxylase activity and stimulated 1-hydroxylase activity. The effective concentration of human PTH-(1-34) was much lower for inhibiting 24-hydroxylase than for stimulating 1-hydroxylase activity. Infusion of less than 100 nmol/h cAMP similarly inhibited 24-hydroxylase activity without enhancing 1-hydroxylase activity. Either theophylline (1.0 mumol/h) or a submaximal dose (25 pmol/h) of human PTH-(1-34) alone inhibited 24-hydroxylase activity only slightly, but the concomitant infusion of both chemicals markedly inhibited 24-hydroxylase activity without stimulating 1-hydroxylase activity. These effects of human PTH-(1-34) and cAMP occurred similarly in both the in vitro and the in vivo assays. The present study clearly indicates that besides its well known action in stimulating 1-hydroxylase activity, PTH inhibits renal 25OHD3-24-hydroxylase activity by a mechanism involving cAMP.

Reduced sensitivity of inducible nitric oxide synthase-deficient mice to chronic colitis.

BACKGROUND: Overproduction of nitric oxide by the inducible form of nitric oxide synthase (iNOS) has been implicated in colitis. Different authors have postulated both toxic and protective effects of nitric oxide (NO) in the pathophysiology of active inflammation. The objective of this study was to examine the role of iNOS in experimental chronic colitis using iNOS-deficient mice. METHODS: For induction of colitis, mice received three cycles of 2% of dextran sodium sulfate (DSS) (M.W. 40,000) treatment in drinking water. The degree of colonic inflammation, leukocyte infiltration, and the expression of cell adhesion molecules were determined. INOS expression and nitrotyrosine were also determined by immunohistochemistry. RESULTS: After DSS treatment, a moderate colitis with marked cell infiltration was observed. Intense expression of iNOS was observed on infiltrating cells as well as on the colonic mucosal epithelium in these animals. In the iNOS-deficient mice, tissue damage was significantly diminished. No iNOS or nitrotyrosine staining was found in iNOS-deficient mice. The number of infiltrating cells and the expression of mucosal adressin cell adhesion molecule-1 were significantly attenuated in the DSS-treated colon of iNOS-deficient mice. CONCLUSION: Induction of iNOS seems to act as a critical toxic effector molecule in the pathogenesis of chronic colonic inflammation.

Lipoprotein abnormalities in survivors of cerebral infarction with a special reference to apolipoproteins and triglyceride-rich lipoproteins.

Serum lipid and apolipoprotein concentrations were measured in 37 male survivors of cerebral infarction (CI) and in 30 healthy controls. Both groups had similar total cholesterol levels, but the HDL-cholesterol level was significantly lower and the serum triglyceride level was significantly higher in the CI patients than in the controls. The ApoB level was significantly higher in the CI patients but there was no significant difference between the 2 groups in the levels of the other apolipoproteins (ApoA-I, A-II, C-II, C-III, and E). The HDL-cholesterol/ApoA-I ratio was significantly lower in the CI patients. Both the VLDL-triglyceride and VLDL-cholesterol levels were higher in the CI patients but the VLDL-cholesterol especially its cholesterol ester level was conspicuously high. A population of VLDL particles that bound to heparin on heparin-Sepharose columns was increased in the CI patients. We suggest that cholesterol ester is excessively transferred from HDL to VLDL during the disturbed catabolism of VLDL in CI patients.

Lp(a) lipoprotein as a risk factor for coronary heart disease and cerebral infarction.

Attempts were made to prepare antisera monospecific for Lp(a) lipoprotein and to investigate the distribution of subjects according to plasma levels of Lp(a) in Japanese controls and patients with coronary heart disease or cerebral infarction. Positive plasma reactions to the double diffusion test for Lp(a) (Ouchterlony) were observed in 32.3% of the healthy Japanese subjects, which is similar to results previously reported in western countries. The plasma threshold level of 17 mg/dl was considered an appropriate point for dividing subjects into positive and negative groups depending on reactions to the double diffusion test. When subjects were divided into two groups at 17 mg/dl, a significant association was found between a high plasma level of Lp(a) and either coronary heart disease or cerebral infarction in the distribution of the cortical artery. These results suggest that Lp(a) may play an important part as a risk factor for coronary heart disease and cerebral infarction.

Microchimeric cells from the peripheral blood associated with cardiac grafts are bone marrow derived, long-lived and maintain acquired tolerance to minor histocompatibility antigen H-Y.

BACKGROUND: Although it has been well established that the microchimerism occurs in the peripheral blood of the recipients after various settings in both clinical and experimental organ transplantation, nevertheless, their roles in inducing and maintaining acquired transplantation tolerance are controversial. Furthermore, regarding the cell lineages, kinetics, and functions of the cells that constitute the microchimerism after organ transplantation, solid information is not available. METHODS: Using rat heterotopic heart isografts from bone marrow chimeras between cross-sex and applying polymerase chain reaction with specific primers to rat sex determining region of Y chromosome, a relationship between a state of microchimerism and induction as well as maintenance of acquired tolerance to H-Y antigen were examined. RESULTS: Microchimeric cells of the peripheral blood (MCPB) after cardiac grafting contain bone marrow-derived and radiation-sensitive cells. Furthermore, removal of the primary cardiac grafts revealed that microchimeric cells in the peripheral blood are long-lived cells, i.e., more than 6 months. When the female rats that had contained long-lasting MCPB, were innoculated with syngeneic male dendritic cells, failure to sensitize female toward male specific antigen H-Y was found to occur. CONCLUSIONS: Thus it was suggested that radiation-sensitive, bone marrow derived, long-lived MCPB play a significant role in maintaining acquired transplantation tolerance to minor histocompatibility antigen H-Y.