Adding MRI to ultrasound and ultrasound-guided fine-needle aspiration reduces the false-negative rate of axillary lymph node metastasis diagnosis in breast cancer patients.

AIM: To evaluate whether adding magnetic resonance imaging (MRI) to ultrasound (US) and US-guided fine-needle aspiration (US-FNA) can reduce the false-negative rate (FNR) in the diagnosis of axillary lymph node metastasis (ALNM) in breast cancer patients, and to assess false-negative diagnosis of N2 and N3 disease when adding MRI to US and US-FNA. MATERIALS AND METHODS: From March 2012 to February 2013, 497 breast cancer patients were included in the study. ALNM was evaluated according to US and US-FNA prior to MRI. Second-look US was performed when MRI showed positive findings of ALNM. If second-look US also revealed a positive finding, US-FNA was performed. Diagnostic performance, including FNR, was calculated for US and US-FNA with and without MRI. The negative predictive value (NPV) of N2 and N3 disease was evaluated in negative cases based on US and US-FNA with MRI. RESULTS: A total of 159 of 497 (32.0%) patients were found to have ALNM. Among them, 92 patients were diagnosed with metastasis on US and US-FNA. When adding MRI to US and US-FNA, an additional six patients were diagnosed with metastasis. The FNR of diagnosis of ALNM was improved by the addition of MRI (42.1% versus 38.4%, p = 0.0143). The NPV for N2 and N3 disease was 98% (391/399) based on US and US-FNA with MRI. CONCLUSION: Adding MRI to US and US-FNA could reduce the FNR of the diagnosis of ALNM. Furthermore, US and US-FNA with MRI may exclude 98% of N2 and N3 disease.

Combined motor- and somatosensory-evoked potential monitoring for spine and spinal cord surgery: correlation of clinical and neurophysiological data in 85 consecutive procedures.

STUDY DESIGN: Prospective study. OBJECTIVES: The primary objective of neurophysiological monitoring during surgery is to prevent permanent neurological sequelae. To avoid neurological injury, we applied somatosensory-evoked potentials (SEPs) and/or motor-evoked potentials (MEPs). We evaluated whether the combination of SEP and MEP for spinal surgery may be beneficial. SETTING: Asian Medical Center, University of Ulsan College of Medicine, Seoul, Korea. METHODS: Combined SEP/MEP monitoring was attempted in 100 consecutive procedures for spinal operations. Trains of transcranial electrical stimulation over the motor cortex were used to elicit MEPs from the muscles of the upper/lower limbs. The tibial and median nerves were stimulated to record SEP. RESULTS: Combined SEP/MEP recording was successfully achieved in 85 of 100 operations. In 61 of 85 operations (71%), SEP and MEP were stable, and all patients remained neurologically intact after surgery. Significant MEP changes were recorded in 20 operations, either combined with (n=4) or without (n=16) SEP changes. In 7 of these 20 operations, MEP recovered to some extent after surgical intervention, and these patients showed no neurological changes. In the remaining 13 operations, MEP did not recover and the patients had a transient (n=4) or a permanent (n=3) motor deficit. Significant SEP changes with stable MEP were observed in four operations, all of which were not related to postoperative motor deficit. CONCLUSION: Combined SEP/MEP monitoring provided higher sensitivity and higher positive/negative predictive value than single-modality monitoring techniques. Detection of MEP changes and adjustment of surgical strategy may prevent irreversible pyramidal tract damage.

Effects of hypoxia-inducible factor-1alpha expression and C4d deposition in implantation biopsies on renal allograft.

Upregulation of hypoxia-inducible factor-1alpha (HIF-1alpha) in response to ischemic states has been suggested to have a role in the development of chronic allograft nephropathy. Deposition of C4d in the peritubular capillaries of renal allografts has been reported to be a sensitive marker of acute humoral rejection. The purpose of this study was to determine the effects of HIF-1alpha expression and C4d deposition in implantation biopsies of renal allografts. Implantation biopsies and 22 rejection proved biopsies were performed in 54 renal transplant recipients between December 1996 and July 1999. The mean follow-up was 82.8 months. Immunohistochemical studies were performed using a mouse monoclonal antibody for HIF-1alpha expression and a rabbit polyclonal antibody for C4d detection. HIF-1alpha was demonstrated in 19 of 54 implantation biopsies (35%), and C4d deposition in one (1.9%). The HIF-1alpha-positive group included a higher percentage of deceased donor organs (66.4% vs 17.1%; P = .002) and longer mean cold ischemia times (261.3 +/- 231 vs 103 +/- 40 min; P = .008) compared with the HIF-1alpha-negative group. The relative risks (95% confidence intervals) of expression of HIF-1alpha for allograft rejection, chronic allograft nephropathy, and graft loss were 1.53 (0.82-2.87), 0.61 (0.06-5.50), and 2.45 (0.62-9.85). The C4d-positive patient developed acute accelerated rejection on postoperative day 4. In the present study, the expression of HIF-1alpha showed a significant correlation with the use of a deceased donor kidney and with cold ischemia time. However, there were no significant effects on the prognosis for a graft after implantation of a kidney with HIF-1alpha expression.

Expression of transforming growth factor-beta1 and hypoxia-inducible factor-1alpha in renal transplantation.

Chronic allograft nephropathy (CAN) includes pathologic changes of interstitial fibrosis, tubular atrophy, and fibrous intimal thickening. Transforming growth factor (TGF)-beta1 is a fibrogenic cytokine involved in renal allograft fibrosis. Hypoxia-inducible factor (HIF)-1alpha is induced as an adaptive response to hypoxia triggering the production of fibrogenic cytokines such as TGF-beta1. Between January 1995 and February 2005, we performed 71 renal allograft biopsies in 61 recipients. Immunohistochemical studies were performed with an immunoperoxidase technique using as the primary antibody either a rabbit anti-human TGF-beta1 polyclonal or a mouse anti-human HIF-1alpha monoclonal reagent. The glomerular TGF-beta1 expression in recipients diagnosed with glomerulonephritis was significantly greater than other pathologic groups (P < .05), and the glomerular TGF-beta1 expression in the heavy proteinuria group (> or =2.5 g/d) was significantly greater than the low proteinuria group (<1.0 g/d; P < .05). The tubular and interstitial TGF-beta1 and HIF-1alpha expressions in CAN were greater than in other groups (P < .05). The tubular TGF-beta1 expression among the graft loss group was significantly greater than the graft function group (P < .05).

Novel entry point for intraoperative ventricular puncture during the transsylvian approach.

OBJECTIVE: In dealing with cases of oedematous brain, relaxation during the transsylvian approach to supratentorial aneurysms has been accomplished by ventricular drainage by using the anatomic point defined by Dr. Paine. However, we have experienced patient complications when using this point. We propose a novel anatomic point to reduce catheter-related complications and facilitate adequate ventricular puncture during ruptured aneurysm operations. METHODS: Ten patients underwent aneurysmal neck clipping for ruptured aneurysm by means of the transsylvian approach. The use of a novel anatomic point for intraoperative drainage was examined using a neuronavigation system. RESULTS: Using the novel point of entry for ventricular cannulation proved to be reliable for puncture and reduced chance of malpositioning. CONCLUSION: Secure intraoperative ventricular cannulation is reliably achieved by pointing the catheter approximately 2 cm beyond a line extending from the anterior limb of the triangle described by Paine. This technique reduces injury to the deep brain and enhances preciseness and safety of ventricular cannulation.

Enhancement of mitogen-stimulated proliferation of low dose radiation-adapted mouse splenocytes.

We have monitored mitogen-stimulated mouse splenocyte proliferation as a biological end point of radiation damages to access adaptive response to ionizing radiation. When cells were pre-exposed to an adapting dose of 0. 01 Gy of low dose gamma-ray 4, 7, and 20 hours prior to an acute challenging dose of 2 Gy, most significant enhancement in splenocyte proliferation was induced at 4 hour interval. When the challenging high dose was varied, an adaptive response was observed at up to 4 Gy of high dose gamma-ray challenge. Gamma-ray-irradiated mouse splenocyte showed characteristic morphology of apoptotic cells. The extent of DNA fragmentation, another characteristic of apoptotic cells, was also reduced in low dose gamma-ray-adapted cells. The addition of protein or RNA synthesis inhibitor, cycloheximide or 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazol (DRFB), respectively during adaptation period, the period between low and high dose irradiations, were able to inhibit the induction of adaptive response. These data suggest that to induce adaptive response to ionizing radiation in mouse splenocytes, both protein and RNA synthesis are required.

Pretreatment of low dose radiation reduces radiation-induced apoptosis in mouse lymphoma (EL4) cells.

Induction of an adaptive response to ionizing radiation in mouse lymphoma (EL4) cells was studied by using cell survival fraction and apoptotic nucleosomal DNA fragmentation as biological end points. Cells in early log phase were pre-exposed to low dose of gamma-rays (0.01 Gy) 4 or 20 hrs prior to high dose gamma-ray (4, 8 and 12 Gy for cell survival fraction analysis; 8 Gy for DNA fragmentation analysis) irradiation. Then cell survival fractions and the extent of DNA fragmentation were measured. Significant adaptive response, increase in cell survival fraction and decrease in the extent of DNA fragmentation were induced when low and high dose gamma-ray irradiation time interval was 4 hr. Addition of protein or RNA synthesis inhibitor, cycloheximide or 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRFB), respectively during adaptation period, the period from low dose gamma-ray irradiation to high dose gamma-ray irradiation, was able to inhibit the induction of adaptive response, which is the reduction of the extent DNA fragmentation in irradiated EL4 cells. These data suggest that the induction of adaptive response to ionizing radiation in EL4 cells required both protein and RNA synthesis.

Repression of deoP2 in Escherichia coli by CytR: conversion of a transcription activator into a repressor.

In the deoP2 promoter of Escherichia coli, a transcription activator, cAMP-CRP, binds at two sites, centered at -41.5 and -93.5 from the start site of transcription, while a repressor, CytR, binds to a space between the two cAMP-CRP complexes. The mechanisms for the cAMP-CRP-mediated transcription activation and CytR-mediated transcription repression were investigated in vitro using purified components. We classified the deoP2 promoter as a class II cAMP-CRP-dependent promoter, primarily by the action of cAMP-CRP at the downstream site. Interestingly, we also found that deoP2 carries an "UP-element" immediately upstream of the downstream cAMP-CRP site. The UP-element overlaps with the DNA site for CytR. However, it was observed that CytR functions with the RNA polymerase devoid of the C-terminal domain of the alpha-subunit as well as with intact RNA polymerase. The mechanism of repression by CytR proposed in this study is that the cAMP-CRP bound at -41.5 undergoes an allosteric change upon direct interaction with CytR such that it no longer maintains a productive interaction with the N-terminal domain of alpha, but instead acts as a repressor to interfere with RNA polymerase acting on deoP2.