Radiation exposure to anaesthetists during endovascular procedures.

Medical radiation exposure increases the likelihood of cataract formation. A personal dosimeter was attached to the left temple of 77 anaesthetists during 45 endovascular aortic aneurysm repairs and 32 interventional neuroradiology procedures. Compared with interventional neuroradiology, the median (IQR [range]) total radiation dose emitted by fluoroscopic equipment was significantly lower during endovascular aortic aneurysm repair (4175 (3127-5091 [644-9761]) mGy than interventional neuroradiology (1420 (613-2424 [165-10,840]) mGy, p < 0.001). However, radiation exposure to the anaesthetist's temple was significantly greater during endovascular aortic aneurysm repair (15 (6-41 [1-109]) µSv) than interventional neuroradiology (4 (2-8 [0-67]) µSv, p < 0.001). These data suggest that anaesthetists at our institution would have to deliver anaesthesia for ~1300 endovascular aortic aneurysm repairs and ~5000 interventional neuroradiology cases annually to exceed the general occupational limits, and ~10,000 endovascular aortic aneurysm repairs and ~37,500 interventional neuroradiology cases to exceed the ocular exposure limits recommended by the International Commission on Radiological Protection. Nevertheless, anaesthetists should be aware of the risk of ocular radiation exposure, and reduce this by limiting the time of exposure, increasing the distance from the source of radiation, and shielding.

Development of a strongly focusing high-intensity He(+) ion source for a confined alpha particle measurement at ITER.

A strongly focusing high-intensity He(+) ion source has been designed and constructed as a beam source for a high-energy He(0) beam probe system for diagnosis of fusion produced alpha particles in the thermonuclear fusion plasmas. The He(+) beam was extracted from the ion source at an acceleration voltage of 18-35 kV. Temperature distributions of the beam target were observed with an IR camera. The 1/e-holding beam profile half-width was about 15 mm at optimum perveance (Perv) of 0.03 (I(beam)=2.4 A). A beam current about 3 A was achieved at an acceleration voltage of 26.7 kV with an arc power of 10 kW (Perv=0.023).

Effects of a dielectric material in an ion source on the ion beam current density and ion beam energy.

To understand a strong focusing phenomenon that occurs in a low-energy hydrogen ion beam, the electron temperature, the electron density, and the space potential in an ion source with cusped magnetic fields are measured before and after the transition to the focusing state using an electrostatic probe. The experimental results show that no significant changes are observed before or after the transition. However, we found unique phenomena that are characterized by the position of the electrostatic probe in the ion source chamber. Specifically, the extracted ion beam current density and energy are obviously enhanced in the case where the electrostatic probe, which is covered by a dielectric material, is placed close to an acceleration electrode.

High current density ion beam obtained by a transition to a highly focused state in extremely low-energy region.

A high current density (≈3 mA/cm(2)) hydrogen ion beam source operating in an extremely low-energy region (E(ib) ≈ 150-200 eV) has been realized by using a transition to a highly focused state, where the beam is extracted from the ion source chamber through three concave electrodes with nominal focal lengths of ≈350 mm. The transition occurs when the beam energy exceeds a threshold value between 145 and 170 eV. Low-level hysteresis is observed in the transition when E(ib) is being reduced. The radial profiles of the ion beam current density and the low temperature ion current density can be obtained separately using a Faraday cup with a grid in front. The measured profiles confirm that more than a half of the extracted beam ions reaches the target plate with a good focusing profile with a full width at half maximum of ≈3 cm. Estimation of the particle balances in beam ions, the slow ions, and the electrons indicates the possibility that the secondary electron emission from the target plate and electron impact ionization of hydrogen may play roles as particle sources in this extremely low-energy beam after the compensation of beam ion space charge.

Chemosensitization of human renal cell cancer using antisense oligonucleotides targeting the antiapoptotic gene clusterin.

BACKGROUND: Renal cell cancer (RCC) is a chemoresistant disease with no active chemotherapeutic agent achieving objective response rates higher than 15%. Clusterin is a cell survival gene that increases in human renal tubular epithelial cells after various states of injury and disease. Downregulation of clusterin, using antisense oligonucleotides (ASO), has recently been shown to increase chemosensitivity in several prostate cancer models. The objectives in this study were to evaluate clusterin expression levels in human RCC and normal kidney tissue, and to test whether clusterin ASO could also enhance chemosensitivity in human RCC Caki-2 cells both in vitro and in vivo. METHODS: Immunohistochemical staining was used to characterize clusterin expression in 67 RCC and normal kidney tissues obtained from radical nephrectomy specimens. Northern blot analysis was used to assess changes in clusterin mRNA expression after ASO and paclitaxel treatment. The effects of combined clusterin ASO and paclitaxel treatment on Caki-2 cell growth was examined using an MTT assay. Athymic mice bearing Caki-2 tumors were treated with clusterin ASO alone, clusterin ASO plus paclitaxel, and mismatch control oligonucleotides plus paclitaxel, over a period of 28 days with measurement of tumor volumes once weekly over 8 weeks. RESULTS: Immunohistochemistry of normal and malignant kidney tissue sections of 67 patients demonstrated positive clusterin staining for almost all RCC (98%) and an overexpression, compared to normal tissue, in a majority of RCC (69%). Clusterin ASO, but not mismatch control oligonucleotides, decreased clusterin mRNA expression in Caki-2 cells in a dose-dependent and sequence-specific manner. Pretreatment of Caki-2 cells with clusterin ASO significantly enhanced chemosensitivity to paclitaxel in vitro. Characteristic apoptotic DNA laddering was observed after combined treatment with ASO plus paclitaxel, but not with either agent alone. In vivo administration of clusterin ASO plus paclitaxel acted synergistically to increase apoptosis and significantly delay Caki-2 tumor growth, compared to mismatch control oligonucleotide plus paclitaxel. In addition, TUNEL staining revealed increased apoptotic cells in tumors treated with clusterin ASO plus paclitaxel compared to treatment with either clusterin ASO or paclitaxel alone. CONCLUSION: These findings confirm that the use of clusterin ASO may be a feasible strategy to enhance chemosensitivity for patients with advanced RCC.

Antithrombotic mechanisms of urokinase immobilized polyurethane.

Urokinase immobilized polymer is highly antithrombotic, which cannot be explained only by fibrinolysis. We immobilized 10 IU/cm2 of urokinase to polyurethane by using maleic anhydride methylvinyl ether copolymer as a carrier. Then we incubated blood in circular tubes made of this material, measured the clotting factors and observed the surface of the tubes after incubation by scanning electronmicroscopy and immunofluorescence microscopy. After 5 min incubation, the relative activities of factors V, VIII, IX, X and XII, fibrinogen, plasminogen and alpha 2 plasmin inhibitor decreased, but the activity of factor VII increased. No platelet adhesion to the surface of the urokinase immobilized polyurethane was observed and there was no significant adsorption of serum proteins, including fibrinogen, fibronectin and vWF antigen, on the surface. Urokinase-immobilized polyurethane catalyzed the digestion of clotting factors as well as fibrinolysis and also inhibited platelet adhesion on its surface probably by inhibiting protein adsorption and its clinical application including vessel prosthesis should be developed further.

Inhibitory effects of antihypertensive drugs on mesangial cell proliferation after anti-thymocyte serum (ATS)-induced mesangiolysis in spontaneously hypertensive rats.

The effects of antihypertensive drugs on mesangial cell proliferation were studied in spontaneously hypertensive rats (SHR) with anti-thymocyte serum (ATS)-induced glomerulo-nephritis. Rats were treated with either enalapril (Group 1), nifedipine (Group 2), or reserpine + hydrochlorothiazide + hydralazine (Group 3), or were untreated (Group 4). The animals were sacrificed 2, 4 and 7 days after ATS injection and the glomerular cell number and degree of mesangial area expansion were examined. A marked, similar decrease in glomerular nuclear cell number (NC) due to severe mesangiolysis was observed in all of the groups on day 2. Thereafter, an increase in NC reflecting mesangial cell proliferation after mesangiolysis occurred in Group 4 on days 4 and 7. In Group 1 and 2, the NC was significantly smaller than that in Group 4 on days 4 and 7, indicating suppression of mesangial cell proliferation. In Group 3, however, the number of NCs did not differ from that in Group 4 on days 4 and 7, indicating a lack of such suppression by conventional antihypertensive drugs. The degree of mesangial area expansion (MS) showed the same pattern as mesangial cell proliferation. That is, the rapid increases in MS seen in Group 4 on days 4 and 7 were apparently suppressed in Groups 1 and 2, but not in Group 3. Our in vivo observations that both an angiotensin converting enzyme (ACE) inhibitor and a calcium channel blocker suppress mesangial cell proliferation and mesangial area expansion suggest that these agents have practical implications in the treatment of mesangial proliferative glomerular diseases through the suppression of excess mesangial cell proliferation.

IgA nephritis associated with plasminogen abnormalities.

Two patients with IgA nephritis associated with hereditary plasminogen abnormalities are described. One patient had dysplasminogenemia and the other had plasminogen deficiency. In both patients, renal biopsy specimens showed significant arteriosclerotic changes in addition to mesangial proliferation. Increased fibrinopeptide A concentration in their plasma suggested increased thrombin generation. In one patient, no systemic arteriosclerosis coexisted, judging from normal optic fundi and the absence of neurological and cardiac abnormalities. In IgA nephritis, renal vascular hyalinosis is often observed, probably resulting from vascular injury. Thus, it was suggested that the decreased fibrinolysis and renal vascular injury of these patients synergistically induced more fibrin thrombi and accelerated arteriosclerosis of the kidney. These cases imply the important role of fibrinolytic disorders in the progression of IgA nephritis.

Risk factors for left ventricular hypertrophy in chronic hemodialysis patients.

Left ventricular hypertrophy is reported to be common in chronic hemodialysis patients, and also to increase the risk for mortality in chronic hemodialysis patients. An echocardiographical and clinical study was carried out to investigate the risk factors for left ventricular hypertrophy in 151 non-diabetic chronic hemodialysis patients without valvular diseases or myocardial infarction in two hemodialysis units in Fukuoka, Japan. The left ventricular mass index (LVMI) correlated positively to age, systolic blood pressure and interdialysis weight gain while it correlated negatively to the duration of hemodialysis therapy and hematocrit. Resorting to a multivariate analysis, the LVMI was found to positively correlate to age and the systolic blood pressure while it correlated negatively with the duration of hemodialysis therapy and the hematocrit level. These findings suggest that hypertension and anemia may thus be independent risk factors for left ventricular hypertrophy.

Patients with renal hypouricemia with exercise-induced acute renal failure and chronic renal dysfunction.

We here report the case of a 38-year-old male with back pain and vomiting occurring after exercise. Serum creatinine level was elevated, and he was admitted to our hospital with diagnosis of acute renal failure (ARF). He had experienced similar attacks at least 4 times, including the present episode, from the age of 22 years. After admission, the patient was managed only by resting, and remission was nearly attained in about 1 month. The renal biopsy specimen performed on day 15 showed findings of acute tubular necrosis, thickening of the tubular basement membrane, and interstitial fibrosis. After remission, the serum uric acid level was 0.7-0.8 mg/dl, fractional excretion of uric acid was 0.63, and the possibility of other diseases facilitating the excretion of uric acid was denied. Therefore, ARF associated with idiopathic renal hypouricemia was diagnosed. Since only mild responses were observed in a pyradinamide loading test and a benzbromarone loading test, the case was considered to be a presecretary reabsorption disorder type. Renal function tests showed the almost complete recovery of the glomerular filtration rate (GFR: 114 ml/min/1.73 m2), but the urine concentrating ability was markedly decreased (specific gravity 1.019 and osmolarity 516 mOsm/kgxH2O in Fishberg test). Past data from this patient indicated that this renal dysfunction had been persisting for ten years. We examined 9 patients with renal hypouricemia and focused on the differences between the two groups (with or without complications). Four patients had a history of exercise-induced ARF or calculus. The urine concentrating ability was significantly lower in these patients (group A) than in the other patients without complications (group B). The glomerular filtration rate in group A was within the normal range, but was lower than in group B. These results suggested the possibility that patients with renal hypouricemia with complications may have chronic renal dysfunction in the future.

Angiotensin-converting enzyme inhibitor withdrawal and ACE gene polymorphism.

AIMS: Withdrawal of angiotensin-converting enzyme (ACE) inhibitors may affect the progression of chronic renal failure and an insertion/deletion (I/D) polymorphism of the ACE gene may influence it. METHODS: We retrospectively collected patients with chronic glomerulonephritis and benign nephrosclerosis who discontinued ACE inhibitor use. The relationship between the decline of renal function after the withdrawal and the influencing factors such as ACE gene polymorphism, blood pressure and proteinuria were evaluated using multiple regression analysis. RESULTS: Forty-two patients (initial serum creatinine 0.5 - 6.5 mg/dl) had been treated and discontinued ACE inhibitor use. Only patients with the II or DI genotypes of the ACE gene developed the deterioration of renal function, starting at 2 months after the withdrawal. Stepwise regression analysis revealed that the level of proteinuria after the withdrawal, presence of the insertion of ACE gene and serum creatinine level at the time of withdrawal mainly influenced the decline of renal function after the withdrawal (adjusted R2 = 0.48). CONCLUSION: Withdrawal of ACE inhibitor causes the deterioration of renal function in patients with the II or DI genotypes, high proteinuria after the withdrawal, and high serum creatinine level at the withdrawal, which probably causes the rebound increase in serum ACE activity.

[One-year experience as a clinical anaesthetist in England].

Current practice of British clinical anaesthesia is introduced, including anaesthesia in the operating theatre as well as obstetric analgesia in the labour ward. Although many people feel that British National Health Service has been affected by their chronic economic recession, the author's general impression is that the standard of anaesthetic care is kept at a quite high level despite financial difficulties. It is still valuable to experience clinical anaesthesia in the United Kingdom and the author encourages young Japanese anaesthetists to get an opportunity to work in British hospitals.

[Intravenous sedation with target-controlled infusion (TCI) in patients with difficult airways].

Tracheal intubation was facilitated with an intubating laryngeal mask (ILM) in two patients with difficult airways. Target-controlled infusion (TCI) of propofol and fentanyl was used for sedation during placement of an ILM. An ILM was inserted smoothly. Spontaneous ventilation and oxygenation were well maintained throughout the induction. Both patients were satisfied with intravenous sedation using TCI for awake instrumentation of their airways.

Renal disease in an adult with type 1 glycogen storage disease.

The renal disease in an adult woman with Type 1 glycogen storage disease (GSD) is reported. Since she was 15 years old, several episodes of gouty arthritis had developed. At the age of 18, proteinuria was pointed out. Hepatomegaly, renomegaly out of proportion to the impairment of renal function, hyperuricemia, hyperlipidemia, fasting hypoglycemia and lactic acidemia were observed. The diagnosis of GSD was established on the basis of a glucose tolerance test, glucagon test and liver biopsy. The findings of renal biopsies performed at the ages of 24 and 27 years old suggested that glomerular damage might have preceded the tubulo-interstitial lesion.

[A case of secondary amyloidosis complicated with ulcerative colitis].

A 54 year-old woman who had had 4 years history of ulcerative colitis (UC) was admitted to our hospital because of recently developed proteinuria and leg edema. On admission, laboratory findings disclosed massive proteinuria, hypoalbuminemia, acceleration of ESR and elevated of CRP. Her abdominal symptom was remitted. Renal biopsy showed amyloid deposition in glomeruli and arteriole. Amyloid deposition was also found on rectal biopsy. She had no evidence of familial amyloidosis and multiple myeloma. In this case, amyloid deposition might be developed after UC. Secondary amyloidosis due to UC was extremely rare, only 3 cases including ours were reported in Japan.

Self-focusing of a high current density ion beam extracted with concave electrodes in a low energy region around 150 eV.

Spontaneous self-focusing of ion beam with high current density (Jc ∼ 2 mA/cm(2), Ib ∼ 65 mA) in low energy region (∼150 eV) is observed in a hydrogen ion beam extracted from an ordinary bucket type ion source with three electrodes having concave shape (acceleration, deceleration, and grounded electrodes). The focusing appears abruptly in the beam energy region over ∼135-150 eV, and the Jc jumps up from 0.7 to 2 mA/cm(2). Simultaneously a strong electron flow also appears in the beam region. The electron flow has almost the same current density. Probably these electrons compensate the ion space charge and suppress the beam divergence.

Electron density profile measurements at a self-focusing ion beam with high current density and low energy extracted through concave electrodes.

The self-focusing phenomenon has been observed in a high current density and low energy ion beam. In order to study the mechanism of this phenomenon, a special designed double probe to measure the electron density and temperature is installed into the chamber where the high current density ion beam is injected. Electron density profile is successfully measured without the influence of the ion beam components. Estimated electron temperature and density are ∼0.9 eV and ∼8 × 10(8) cm(-3) at the center of ion beam cross section, respectively. It was found that a large amount of electrons are spontaneously accumulated in the ion beam line in the case of self-forcing state.

Quasi-steady carbon plasma source for neutral beam injector.

Carbon plasma is successfully sustained during 1000 s without any carrier gas in the bucket type ionization chamber with cusp magnetic field. Every several seconds, seed plasmas having ∼3 ms duration time are injected into the ionization chamber by a shunting arch plasma gun. The weakly ionized carbon plasma ejected from the shunting arch is also ionized by 2.45 GHz microwave at the electron cyclotron resonance surface and the plasma can be sustained even in the interval of gun discharges. Control of the gun discharge interval allows to keep high pressure and to sustain the plasma for long duration.

Shunting arc plasma source for pure carbon ion beam.

A plasma source is developed using a coaxial shunting arc plasma gun to extract a pure carbon ion beam. The pure carbon ion beam is a new type of deposition system for diamond and other carbon materials. Our plasma device generates pure carbon plasma from solid-state carbon material without using a hydrocarbon gas such as methane gas, and the plasma does not contain any hydrogen. The ion saturation current of the discharge measured by a double probe is about 0.2 mA∕mm(2) at the peak of the pulse.

Development of low-energy and high-current-density ion beam system.

A low-energy ion beam system operating at a dc voltage of less than 300 V was developed using an ion source with a multicusp magnetic field. A high-current-density ion beam of 6.9 mA∕cm(2) was successfully extracted at the electrode. The beam extraction characteristics for flat and concave electrodes were compared. In the case of a concave electrode with a designed focal length of 350 mm, it was observed that the beam profile was sharper than that obtained using a flat electrode.