Single 5 µm diameter needle electrode block modules for unit recordings in vivo.

Investigations into mechanisms in various cortical areas can be greatly improved and supported by stable recording of single neuronal activity. In this study, fine silicon wire electrodes (diameter 3 µm, length 160 µm) are fabricated by vapor-liquid-solid (VLS) growth with the aim of stabilizing recording and reducing the invasiveness on the measurement procedure. The electrode is fabricated on a modular 1 × 1 mm2 conductive silicon block that can be assembled into a number of different device packages, for example on rigid or flexible printed circuit boards (PCB). After plating with a 5 µm diameter platinum black, the needle exhibits an electrical impedance of ~100 kΩ at 1 kHz in saline. The in vivo recording capability of the device is demonstrated using mice, and spike signals with peak-to-peak amplitudes of 200-300 µV in the range 0.5-3 kHz are stably detected, including single-unit activities in cortical layer 2/3. In addition, the device packaged with a flexible PCB shows stable unit recordings for 98.5 min (n = 4). Consequently, our modular, low-invasive needle electrode block devices present an effective route for single-unit recordings in vivo, as well as demonstrating adaptability in device design for a diverse range of experiments.

Note: Fabrication of resolution target for super-resolution microscopy.

We fabricated a resolution target for super-resolution microscopes (SRMs). The target was constructed by scattering a dyed photo-resist on a glass cover plate and used UV nano-imprinting to transfer minute line-and-space patterns on to the photo-resist layer. Using this resolution target, an image obtained from a SRM and its properties was evaluated quantitatively.

Hypoxia inhibits invasion of extravillous trophoblast cells through reduction of matrix metalloproteinase (MMP)-2 activation in the early first trimester of human pregnancy.

During early pregnancy, extravillous trophoblast (EVT) cells are exposed to very low pO(2) values. In this study, we investigated the proteolytic functions and invasiveness of human primary EVT cells under hypoxic conditions to show the early placental pathophysiology. Placental samples (from 5 to 10 weeks gestation) were obtained at termination of pregnancy. Cytotrophoblast cells were separated by Percoll(®) gradient method and cultured on Matrigel(®) to obtain an invasive phenotype (similar to EVT). The invasion capacity (Matrigel-coated invasion assay), migration of the cells (wound healing assay), activity and expression of matrix metalloproteinase (MMP)-2 and tissue inhibitor for MMP (TIMP)-2 (gelatin gel zymography, ELISA, and quantitative RT-PCR), and expression of membrane-type (MT)1-MMP (western blot) were investigated. All cultures (except for quantitative RT-PCR) were performed under 20% oxygen, 5% oxygen, and 5% oxygen with 3 repetitions of 0.1% oxygen hypoxic stimulation for 1 h. Invasion and MMP2 activity of the cells were significantly increased in 20% and decreased in 0.1% oxygen. There was no significant difference in cell migration among the oxygen environments. Concentrations of MMP2 in the supernatant and expression of MT1-MMP were increased in both the 0.1% and 20% oxygen environments. The MMP2 mRNA level was increased after 1-h stimulation with 0.1% oxygen. The TIMP2 concentration was increased only in 20% oxygen, but the mRNA level was decreased in 0.1% oxygen. These results suggested that hypoxia might inhibit the invasive capacity and MMP2 activation of EVT cells in the early first trimester of pregnancy. Decrease in TIMP2 production may reduce the MMP2/TIMP2/MT1-MMP complex and lead to this unique behavior of EVT cells under hypoxic conditions.

Cardiopulmonary distress during obstetrical anaesthesia: attempts to diagnose amniotic fluid embolism in a case series of suspected allergic anaphylaxis.

BACKGROUND: Cardiopulmonary distress during obstetrical anaesthesia may result from a drug-induced allergic reaction, but, in the obstetrical setting, allergic anaphylaxis may be inseparable from amniotic fluid embolism in terms of the clinical presentation. Further investigations, using allergy tests and other laboratory analyses, are then needed to pursue a diagnostic clarification. METHODS: Twelve women suspected of having developed anaphylaxis during obstetrical anaesthesia underwent allergy follow-up investigations and further serological tests with the amniotic fluid embolism marker sialyl Tn and complement factors (C3 and C4) in an attempt to differentiate amniotic fluid embolism from drug-induced allergic anaphylaxis. RESULTS: The diagnostic programme revealed one case of probable amniotic fluid embolism and four cases of probable drug-induced allergic anaphylaxis. Of the remaining seven cases, there were two cases that, by diagnostic exclusion, could be classified as possible cases of amniotic fluid embolism. The cause of the reactions remained unresolved in five cases. CONCLUSIONS: It can be difficult to differentiate between anaphylaxis and amniotic fluid embolism, especially amongst survivors. Diagnostic markers that can be applied on peripheral blood samples are promising, but larger studies are needed to validate their use in the diagnosis of causes of cardiopulmonary distress during obstetrical anaesthesia.

Renal cortical retention of contrast medium on delayed CT and nephropathy following transcatheter arterial chemoembolisation in patients with high serum creatinine level.

The aim of this study was to investigate the prevalence of renal cortical retention (RCR) of contrast media seen on delayed CT, and nephropathy following transarterial chemoembolisation (TACE) in high-risk patients. The findings of 18 patients with abnormally high serum creatinine levels who underwent TACE were reviewed. Nephropathy was defined as an increase in serum creatinine level of more than 44 micromol l(-1), or more than 25%, on day 1, 3, 7 or 14. RCR was defined as mild (CT value >50) or severe (CT value >100). RCR was seen in 16 cases (89%) and in seven cases (39%) of post-TACE nephropathy. Patients without severe RCR did not develop nephropathy post-TACE, whereas 50% of those with such retention did (p=0.19). Delayed CT appears to have the potential as an early detector of nephropathy post-TACE in high-risk patients.

Renal cortical retention on delayed CT and nephropathy following transcatheter arterial chemoembolisation.

The aim of this study was to examine the relationship between renal cortical retention on delayed CT and contrast medium-associated and/or transarterial chemoembolisation (TACE)-associated nephropathy following TACE. The authors reviewed the findings on 180 treatments in 121 patients with normal serum creatinine levels who underwent TACE for liver tumours. Nephropathy was defined as an increase in the creatinine level of greater than 0.5 mg x dl(-1) (44 micromol x l(-1)) and greater than 25% on days 1, 3, 7 or 14 post TACE. Renal cortical retention was recognized when CT values for the renal cortex showed either mild renal cortical retention (CT value >50) or severe renal cortical retention (CT value >100). There was evidence of renal cortical retention in 81 (45%) cases and of nephropathy in 11 (6%) cases. Only 2% of patients without renal cortical retention showed nephropathy, whereas 11% of those with renal cortical retention showed nephropathy (p=0.02). Stepwise selection using a multivariate logistic regression model showed renal cortical retention and gender to be significant factors for nephropathy following TACE. In conclusion, renal cortical retention is a useful predicator for nephropathy following TACE. Delayed CT could be used not only for assessment of lipiodol retention but also for predicting nephropathy.

Immunologic studies in presumed amniotic fluid embolism.

OBJECTIVE: To evaluate the potential role of immunologic mechanisms that involve mast cell degranulation (anaphylaxis) or complement activation in the mechanism of amniotic fluid embolism. METHODS: This study was a case series of nine women with presumed amniotic fluid embolism and a control group of 22 women who had normal labor. Women were from community and tertiary referral hospitals in Japan and the United States. Main outcome measures were maternal peripartum complement levels (C3 and C4), serum levels of tryptase, urinary histamine concentrations, and serum levels of a fetal antigen (sialyl Tn). RESULTS: Serum tryptase and urinary histamine measurements were negative in women with amniotic fluid embolism; seven of nine had elevated levels of fetal antigen. All eight who had serum available for testing had abnormally low levels of complement. Mean C3 level of 44.0 mg/dL and C4 level of 10.7 mg/dL were significantly lower than corresponding postpartum control values of 117.3 mg/dL and 29.4 mg/dL (P =.018 for C3, P =.012 for C4). Postpartum C3 and C4 levels decreased by 8% and 5%, respectively, compared with intrapartum values (P =.003 for C3, P =.021 for C4) but were still within normal range. CONCLUSION: Serologic findings suggest a role for complement activation in the mechanism of amniotic fluid embolism. Laboratory data from this series did not implicate mast cell degranulation (anaphylaxis) in the pathophysiology of the disease.

[Liver intervention].

Interventional radiology is now widely performed for the treatment of liver tumors, because surgery is sometimes limited by poor liver function. Transcatheter arterial chemoembolization(TACE) is an effective therapy for hepatocellular carcinoma. Lipiodol TACE shows a strong antitumor effect because of the overflow of excess iodized oil into the portal veins, and segmental TACE is recommended to avoid deteriorating liver function. Selective CT arteriography is performed in order to decide on the treatment area, and TACE under CT guidance leads to effective results in terms of dense accumulation of the chemotherapeutic drug in the individual tumors that are affected by the ischemic state and anticancer drugs. Percutaneous microwave or radiofrequency coagulation therapy is adequate for a few of the hypovascular tumors. Excessive coagulation through the needle tract is indispensable in these therapies, and precisely designed puncture is necessary to minimize damage to the liver parenchyma. Selective chemotherapy to the tumor-bearing organ is the first step in a number of liver tumors. Continuous intra-arterial infusion chemotherapy is performed for multiple liver metastases. The reservoir implantation technique is percutaneously achieved via the left subclavian artery under ultrasound guidance, without the exposure of an artery in the incision method, which can induce thrombus formation.

Optimal phases of dynamic CT for detecting hepatocellular carcinoma: evaluation of unenhanced and triple-phase images.

BACKGROUND: To determine the optimal phases of dynamic computed tomography (CT) for detecting hepatocellular carcinoma (HCC). METHODS: Fifty-two patients with 85 HCC nodules were examined by means of unenhanced and triple-phase CT images of the whole liver. The time for obtaining the arterial-phase images was 25-55 s after intravenous bolus injection of contrast material, the time for obtaining the portal venous-phase images was 65-100 s, and the time for obtaining late-phase images was 145 s to 4 min. Detectability of the HCC nodules for all phases was statistically compared. RESULTS: The detection rates for the arterial- and late-phase images were significantly higher than for the unenhanced and portal venous-phase images (p < 0.01). The combination of arterial- and late-phase images showed the same number of HCC nodules in the same number of patients as did the combination of unenhanced and triple-phase images. CONCLUSION: The combination of the arterial- and late-phase imagings was best for detecting HCC nodules.

Serological and immunohistochemical diagnosis of amniotic fluid embolism.

The purpose of this study was to evaluate whether serological assays and immunohistochemical staining, employing antibody TKH-2, are sensitive methods for the serological and histologic diagnosis of amniotic fluid embolism (AFE). TKH-2 is a sensitive antibody directed to sialyl Tn (STN), NeuAcalpha2-6GalNAc. Nineteen samples of maternal sera with clinical AFE and 120 control sera and 15 specimen of formalin-fixed, paraffin-embedded lung tissue sections were examined in this study. Tissue sections were stained using the streptavidin-biotin-immunoperoxidase method. The concentration of STN in serum was measured by an immunoradiometric competitive inhibition assay using the monoclonal antibody TKH-2 in a one-step procedure. Remarkable positive TKH-2 stainings were easily seen within the pulmonary vasculature in 14 of the 15 (93%) patients with AFE. The serum STN levels (mean+/-SD) in patients with AFE (110.8+/-48.1 U/ml) showed significantly higher concentrations compared with those of patients with non-AFE (17.3+/-2.6 U/ml) (p <0.01). Seventeen of 19 sera (89%) were diagnosed as AFE by serum TRH-2 level. We conclude that both TKH-2 immunostaining and serum STN assay are sensitive methods to diagnose patients with AFE.

Sensitivity of double-phase helical CT during arterial portography for detection of hypervascular hepatocellular carcinoma.

PURPOSE: The purpose of our work was to determine the usefulness of double-phase helical CT during arterial portography (CTAP) for the detection of hypervascular hepatocellular carcinoma (HCC). METHOD: Eighty-four patients with 176 hypervascular HCC nodules underwent double-phase CTAP. Hypervascular HCCs were diagnosed by iodized oil CT after transcatheter arterial chemoembolization (TACE). The first-phase images were obtained 30 s after the initiation of injection of a nonionic iodinated contrast medium into the superior mesenteric artery or splenic artery, and the second-phase images were obtained after 70 s. These images were interpreted separately for detection of HCC. RESULTS: The double-phase CTAP detected two nodules and six nodules that were missed by the first- and second-phase images, respectively. The sensitivity for hypervascular HCC nodules was 89% for the first phase, 91% for the second phase, and 93% for the first phase and second phase combined. The double-phase CTAP showed significantly superior sensitivity to the first-phase CTAP for detecting HCC nodules (p < 0.05). However, there was no statistically significant difference between the sensitivities of the double-phase CTAP and the second-phase CTAP. The positive predictive values of the double-phase images were inferior to those of either the first-phase or the second-phase images alone. CONCLUSION: Double-phase helical CTAP was found to be no better than second-phase CTAP alone for the detection of hypervascular HCC nodules.

Effects of injection rates of contrast material on arterial phase hepatic CT.

OBJECTIVE: Our goal was to assess the effects of the i.v. injection rate of contrast material on arterial phase hepatic CT. SUBJECTS AND METHODS: One hundred patients were randomly divided into four groups of 25 with different injection rates of 90 ml of contrast material: 2, 3, 4, or 5 ml/sec. Single-level serial CT was performed at the level of the middle section of the main portal vein before injection and every 2 sec from 12 sec to 60 sec after injection of contrast material. The enhancement value was calculated as the difference in attenuation value between the unenhanced and contrast-enhanced images for the aorta and liver parenchyma. The duration of the arterial phase was defined as the interval beginning when the enhancement value for the aorta reached 100 H and ending when the value for the liver parenchyma reached 20 H. RESULTS: Faster injection rates increased the maximum enhancement of the aorta. Although faster injection rates decreased the time from injection to the beginning and the end of the arterial phase, faster injection rates did not decrease the duration of the arterial phase itself. CONCLUSION: A faster injection rate increases arterial enhancement of the liver, and the duration of the arterial phase remains the same as that occurring with a slower injection rate. We hypothesize that faster injection rates can provide better results using CT to reveal hypervascular liver tumors.

[Gd-DTPA enhanced multi-shot echo-planar MRI: improvement of contrast between metastatic liver cancer and liver parenchyma].

In six patients with metastatic liver cancer, spin-echo multi-shot echo-planar MR imaging 8/2000/80/1 (shot/TR/TE/excitation) of the liver was performed before and 30, 60, 90 and 120 sec after the intravenous injection of Gd-DTPA. Signal-to-noise ratios (SNR) of the liver tumor and liver parenchyma were measured in each phase. The contrast-to-noise ratios (CNR) between the tumor and liver parenchyma were also calculated. While the SNR of the tumor did not change after the injection of Gd-DTPA, the SNR of the liver parenchyma decreased and the CNR between the tumor and liver parenchyma increased.

Helical CT angiography of living renal donors: comparison with 3D Fourier transformation phase contrast MRA.

PURPOSE: The purpose of this study was to determine whether helical CT angiography (CTA) or MR angiography (MRA) is the optimal method to use as a preoperative examination for anatomic arterial assessment of living renal donors. METHOD: Eighteen candidates to be renal donors underwent helical CTA, 3D Fourier transformation phase contrast (3D-FT-PC) MRA, and digital subtraction angiography (DSA). The CTA and MRA were interpreted separately by three readers independently, and these results were correlated with the findings of DSA. RESULTS: DSA showed nine accessory renal arteries and 10 prehilar branches. CTA revealed seven or eight accessory renal arteries. MRA showed six or seven accessory arteries. Of 10 prehilar branches, 7-9 branches were detected with CTA and 5-8 branches with MRA. CONCLUSION: Helical CTA is superior to 3D-FT-PC MRA for evaluating the arterial anatomy of living renal donors.

Sensitivity in detection of hypervascular hepatocellular carcinoma by helical CT with intra-arterial injection of contrast medium, and by helical CT and MR imaging with intravenous injection of contrast medium.

PURPOSE: To determine the effectiveness of i.a. contrast-enhanced helical CT and of i.v. contrast-enhanced helical CT and MR imaging, in detecting hypervascular hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Fifty patients with 125 hypervascular HCC nodules underwent helical CT both during arterial portography (CTAP) and during hepatic arteriography (CTHA). Helical CT and MR imaging of the entire liver with i.v. administration of contrast medium were also performed. Helical CT images were obtained at 30-33 s (arterial-phase CT) and at 5 min (equilibrium-phase CT) after the initiation of an i.v. bolus injection of contrast medium. After T1- and T2-weighted spin-echo MR imaging, gradient-echo images during breath-holding were obtained prior to and 20 s, 1 min, and 2 min after the bolus administration of 0.1 mmol/kg of gadopentetate dimeglumine (dynamic MR). The sensitivity and positive predictive value of the various techniques were evaluated and compared. RESULTS: In terms of sensitivity for hypervascular HCC nodules of less than 1 cm in diameter, CTAP (90%) and CTHA (88%) were significantly superior to dynamic MR imaging (44%), arterial-phase CT (39%), spin-echo MR imaging (20%), and equilibrium-phase CT (7%) (p < 0.001). However, there was no significant difference in the techniques with regard to the detection of lesions equal to or more than 2 cm in diameter. CONCLUSION: For detecting small hypervascular HCCs, helical CT with i.a. contrast enhancement is superior to helical CT and MR imaging with i.v. enhancement.

[Three-dimensional gadolinium-enhanced dynamic MRI of whole liver using spectrally selected enhanced fast gradient recall sequence].

Three-dimensional gadolinium-enhanced dynamic MRI of whole liver using the spectrally selected enhanced fast gradient recall sequence (spec IR-efgre3d) was performed in five patients with HCC. Ten HCC nodules were confirmed by CTA, CTAP and Lipiodol CT, and all of them were detected with dynamic MRI. MIP images reconstructed from 3D gadolinium-enhanced dynamic MR studies clearly showed the main portal vein and its branches in all cases. Portal vein thrombosis was also demonstrated with the MIP images.

[Evaluation of transcatheter hepatic segmental or subsegmental infusion of SMANCS for treatment of hepatocellular carcinoma].

A total of seventeen patients with hepatocellular carcinoma (HCC), nineteen HCCs, who underwent as an initial treatment transcatheter hepatic segmental or subsegmental arterial administration of SMANCS alone for hepatocellular carcinoma (HCC), were studied to evaluate the efficacy and complication of that treatment. The initial treatments provided CR in eight patients (47%), and repeat administrations of SMANCS achieved CR in an additional four patients (24%). The initial treatment provided a dense deposit of Lipiodol in the twelve tumors (63%), in five of which Lipiodol was thereafter washed out in some portions of the tumor. Complete necrosis was obtained in nine (75%) of fourteen hypervascular tumors, and in two (40%) of five intermediately vascular or hypovascular tumors. Segmental or subsegmental administration of SMANCS was well tolerated with self-controlled abdominal pain or fever well responding to medication. Ascites was seen in three cases, and atrophy of the segment infused occurred in five patients. Cholinesterase significantly reduced at one week and one month, then recovered to baseline two to three months after initial treatment. The cumulative survival rates were 77% at 1 year, 66% at 2 years, and 53% at 5 years in the whole patients. The survival rate was 100% at 5 years in the Child A group. In the patients who obtained CR using SMANCS alone, the survival rates were 89% at 1 year, 74% at 2 years and 56% at 5 years. Although this method may transiently deteriorate hepatic function, segmental or subsegmental administration of SMANCS may be an excellent therapeutic method for treatment of HCC and promising for use in properly selected patients.

Helical CT during arterial portography and hepatic arteriography for detecting hypervascular hepatocellular carcinoma.

OBJECTIVE: We assessed whether helical CT hepatic arteriography (CTHA) improves detection of hypervascular hepatocellular carcinoma (HCC) when used in conjunction with helical CT obtained during arterial portography (CTAP). SUBJECTS AND METHODS: One hundred two patients with 254 hypervascular HCC nodules underwent both CTHA and CTAP. CTHA and CTAP were separately interpreted for detection of hypervascular HCC nodules by three observers who were unaware of tumor burden in the liver, lodized oil CT performed 1 week and 1 month after transcatheter arterial chemoembolization with iodized oil was the gold standard. Sensitivity and positive predictive value for CTHA alone, CTAP alone, and CTAP and CTHA combined were calculated and compared using the McNemar test. RESULTS: We found no significant difference between the sensitivity of CTAP (85%) and CTHA (87%) for revealing hypervascular HCC nodules. The combination of CTAP and CTHA showed significantly higher sensitivity than either CTAP or CTHA alone for revealing HCC nodules smaller than 20 mm in diameter (p < .01). CONCLUSION: The combination of CTHA and CTAP is recommended to improve the detection sensitivity of small hypervascular HCC nodules.

CT arterial portography and CT arteriography with a triple-lumen balloon catheter.

PURPOSE: To evaluate the usefulness of the triple-lumen balloon catheter in the serial performance of CT arterial portography (CT-AP) and CT arteriography (CT-A). MATERIAL AND METHODS: A combined CT-AP and CT-A examination of 58 patients was carried out in which a cobra-type triple-lumen balloon catheter was used. CT-AP was performed by injecting contrast medium either into the splenic artery through a side-hole in the catheter proximal to the balloon inflated in the common hepatic artery, or into the superior mesenteric artery through an end-hole in the catheter. Then CT-A was serially performed by delivering contrast medium either to the common hepatic artery or the proper hepatic artery from the end-hole, or to the accessory right hepatic artery through a side-hole proximal to the inflated balloon. RESULTS: Sufficient CT-APs were obtained in 53 of the 58 patients (91%), CT-A in 42 (72%), and both in 42 (72%). Incomplete CT-AP was due to technical failure or anatomical anomaly, as was incomplete CT-A. No complications were seen. CONCLUSION: The triple-lumen balloon catheter technique is useful and convenient in the serial performance of CT-AP and CT-A.