Epinephrine in local anesthetic cancels increase in tongue mucosal blood flow after stellate ganglion block in rabbit

The goal of this study was to compare oral mucosal blood flow and duration of anesthetic action after stellate ganglion block (SGB) using lidocaine, with or without epinephrine, and discuss the effect of epinephrine on SGB. Duration of anesthetic action was defined as elapsed time from finish of injection to recovery of common carotid blood flow (CCBF) to within+/-5% of respective control value. Male Japan White rabbits were anesthetized with isoflurane and mechanically ventilated. Common carotid blood flow and tongue mucosal tissue blood flow (TMBF) were measured with an ultrasound flowmeter and laser Doppler flowmeter, respectively. End-tidal partial pressure of carbon dioxide (ETCO(2)) and hemodynamic variables were continuously monitored, including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP). For SGB, the tip of the needle was placed on the left transverse process of the cervical vertebra, 1-2 mm caudal to the cricoid cartilage. Either 0.1 ml of 1% lidocaine (Group L) or 1% lidocaine containing 10 mug/ml epinephrine (Group LE) was injected for SGB. There were no differences in values at immediately before SGB and at the time when maximal change in CCBF was observed after SGB for ETCO(2), HR, SBP, DBP or MAP in either group. CCBF showed a significant increase in Group L after SGB. In contrast, CCBF only showed a slight increase in Group LE. TMBF showed a significant increase in Group L after SGB, but not in Group LE. No differences in time required for maximal effect were observed between the two groups. In contrast, duration of anesthetic action in Group LE was significantly longer than that in Group L. Addition of epinephrine to local anesthetic solutions is not suitable for SGB, as it may not facilitate an increase in tissue blood flow, which is the primary objective of SGB.     

Atrial fibrillation after coronary artery bypass grafting An increase in high-frequency atrial activity in patients with right coronary artery revascularization

The increase in atrial high-frequency activity has been reported as a marker of the risk of paroxysmal atrial fibrillation. The presence of proximal right coronary artery disease is a predictor of atrial fibrillation after bypass surgery, however, the potential mechanism remains controversial. In this study, high-frequency atrial activity to clarify the electrophysiologic background for the predisposition to have proximal right coronary artery disease leading to atrial fibrillation after coronary revascularization was investigated. Before and soon after coronary revascularization, frequency analyses were performed on the 100 ms segment at the end of signal-averaged P waves in 22 patients with right coronary artery disease as opposed to the 23 patients without disease. Under the spectrum curve, area ratio (AR₅₀) and magnitude ratios (MR) were calculated as follows; AR₅₀ = (area 20–50 Hz/0–20 Hz)×100, and MR = (magnitude at 20, 30, 40 and 50 Hz, respectively/maximal magnitude)×100. In patients with proximal right coronary artery disease, high-frequency atrial components increased significantly in the 20 to 50 Hz range after coronary revascularization, and the incidence of postoperative atrial fibrillation was higher than in those without disease. In patients without right coronary artery disease, the frequency distribution of P waves was unchanged. Postoperatively, the two groups showed the same atrial frequency distribution. This data suggests that the increase in high-frequency atrial activity after right coronary artery revascularization might be associated with the pathogenesis of postoperative atrial fibrillation.     

Interaction of nitrous oxide and propofol to reduce hypertensive response to stimulation

PURPOSE: To evaluate the interaction between nitrous oxide and propofol for the suppression of hypertension following electrical stimulation of the mental nerve in the rabbit. METHODS: Male Japan White rabbits were tracheostomized, cannulated and mechanically ventilated under isoflurane anesthesia. Square wave pulses (5 V, 0.5 msec, 50 Hz for 5 sec) were delivered to the left mental nerve. Animals received nitrous oxide 20, 40, 60 and 80% (Group 1); propofol 200, 400, 600 and 800 microg x kg(-1) min(-1) (Group 2); or combinations of nitrous oxide and propofol at 10 + 100, 20 + 200, 30 + 300 and 40 % + 400 microg x kg(-1) x min(-1) (Group 3). Systolic blood pressure was recorded from immediately before to maximal increase following nerve stimulation. Probit analysis was used to obtain ED(50) values for 50% suppression of blood pressure elevation. Isobolographic analysis was used to evaluate the interaction between nitrous oxide and propofol. RESULTS: ED(50) values are 52.9% for nitrous oxide (Group 1), 464.1 microg x kg(-1) min(-1) for propofol (Group 2), 21.7 % + 217.1 microg x kg(-1) min(-1) for nitrous oxide and propofol combination (Group 3) and 24. 7 % + 247.1 microg x kg(-1) x min(-1) for the theoretically additive combination of nitrous oxide and propofol, respectively. CONCLUSION: The interaction between nitrous oxide and propofol for the suppression of blood pressure elevation following electrical stimulation of the mental nerve is additive.     

Natural killer cell-derived large granular lymphocyte lymphoma of lung developed in a patient with hypersensitivity to mosquito bites and reactivated Epstein-Barr virus infection

A 17-year-old female developed natural killer (NK) cell-derived large granular lymphocyte (LGL) lymphoma of the lung. She had a past history of hypersensitivity to mosquito bites (HMB). After an eight-year chronic, active Epstein-Barr virus (EBV) infection, she developed multiple lung lesions and pleural effusion. In the effusion, 60% of the cells were LGL. They were CD2+, 3−, 16+, 56+, 57+, 45RO+/RA + weak, and possessed strong NK activity. No rearrangement of T-cell–receptor genes was detected. From all these results, a diagnosis of NK-LGL lymphoma of the lung was made. EB virus DNA was detected in cells infiltrating the pleural effusion. The clonality of the LGLs was determined by Southern blot hybridization with the terminal repeat sequence of EB virus as a probe, and by chromosomal abnormalities. The patient died from respiratory failure. Necropsy of the lung revealed diffuse lymphoma composed of polymorphic cells with typical angiocentric lesions. Reportedly, lymphomas of NK lineage show predominantly extranodal involvement, and primary lung lesions are rare. In the pleural effusion of the present case, abnormally high levels of soluble Fas ligand, interleukin-10 and interferon γ were detected. This hypercytokinemia, reflecting the microenvironment of lymphoma cells, may play a role in the progression of the lymphoma and organ injury in the lung. Am. J. Hematol. 59:309–315, 1998. © 1998 Wiley-Liss, Inc.     

The influence of drug-exposure conditions on the development of resistance to methotrexate or ZD1694 in cultured human leukaemia cells

The influence of drug-exposure conditions on the development of resistance to methotrexate (MTX) or ZD1694 was studied by treating MOLT-3 human lymphoblastic-leukaemia cells in a continuous or a pulsatile (high-dose, short-term) drug-exposure schedule. Continuous exposure of the cells to MTX with stepwise escalation of the drug concentrations resulted in a MTX-resistant sub-line (MOLT-3/MTX_10,000) with impaired reduced-folate carrier (RFC) and increased dihydrofolate-reductase (DHFR) activity. Conversely, a MTX-resistant clone (MOLT-3/MTX·P-9) with unaltered RFC and DHFR activity, but with decreased cellular accumulation of antifolates, was selected by high-dose short-term treatment of the cells with MTX. MTX resistance in the latter cells was pronounced after short-term rather than continuous-exposure incubation with MTX, suggesting defective polyglutamation of the drug. On the other hand, 2 ZD1694-resistant sub-lines which were established by continuous (MOLT-3/ZD1694·C) or by pulsatile drug-exposure schedule (MOLT-3/ZD1694·P-9) demonstrated extremely low accumulation and poor retention of [³H]ZD1694, with no change of initial drug uptake and little or no increase of thymidylate-synthase (TS) activity, irrespective of drug-exposure conditions for their establishment. HPLC analysis displayed a virtual absence of ZD1694 polyglutamates in both ZD1694-resistant sub-lines and low accumulation in MOLT-3/MTX·P-9 as compared with the parent line. However, folylpolyglutamate-synthetase (FPGS) mRNA was only moderately decreased in the 2 ZD1694-resistant sub-lines and to an even lesser extent in MOLT-3/MTX·P-9. In addition, γ-glutamyl-hydrolase (GGH) activity was not increased, but was slightly down-regulated in the polyglutamation-defective sublines. These results indicate that the mechanism(s) of the resistance developed may depend not only on drug-exposure conditions while raising resistance but also on the biochemical properties of the drug. © 1996 Wiley-Liss, Inc.     

Functional analysis of LAT3 in prostate cancer: Its downstream target and relationship with androgen receptor

L-type amino acid transporter 3 (LAT3, SLC43A1) is abundantly expressed in prostate cancer (PC) and is thought to play an essential role in PC progression through the cellular uptake of essential amino acids. Here, we analyzed the expression, function, and downstream target of LAT3 in PC. LAT3 was highly expressed in PC cells expressing androgen receptor (AR), and its expression was increased by dihydrotestosterone treatment and decreased by bicalutamide treatment. In chromatin immunoprecipitation sequencing of AR, binding of AR to the SLC43A1 region was increased by dihydrotestosterone stimulation. Knockdown of LAT3 inhibited cell proliferation, migration, and invasion, and the phosphorylation of p70S6K and 4EBP-1. Separase (ESPL1) was identified as a downstream target of LAT3 by RNA sequencing analysis. In addition, immunostaining of prostatectomy specimens was performed. In the multivariate analysis, high expression of LAT3 was an independent prognostic factor for recurrence-free survival (hazard ratio: 3.24; P = .0018). High LAT3 expression was correlated with the pathological T stage and a high International Society of Urological Pathology grade. In summary, our results suggest that LAT3 plays an important role in the progression of PC.     

Neuroanatomical correlates of attention‐deficit–hyperactivity disorder accounting for comorbid oppositional defiant disorder and conduct disorder

Aim: An increasing number of neuroimaging studies have been conducted to uncover the pathophysiology of attention‐deficit–hyperactivity disorder (ADHD). The findings are inconsistent, however, at least partially due to methodological differences. In the present study voxel‐based morphometry (VBM) was used to evaluate brain morphology in ADHD subjects after taking into account the confounding effect of oppositional defiant disorder (ODD) and conduct disorder (CD) comorbidity. Methods: Eighteen children with ADHD and 17 age‐ and gender‐matched typically developing subjects underwent high‐spatial resolution magnetic resonance imaging. The regional gray matter volume differences between the children with ADHD and controls were examined with and without accounting for comorbid ODD and CD in a voxel‐by‐voxel manner throughout the entire brain. Results: The VBM indicated significantly smaller regional gray matter volume in regions including the bilateral temporal polar and occipital cortices and the left amygdala in subjects with ADHD compared with controls. Significantly smaller regional gray matter volumes were demonstrated in more extensive regions including the bilateral temporal polar cortices, bilateral amygdala, right occipital cortex, right superior temporal sulcus, and left middle frontal gyrus after controlling for the confounding effect of comorbid ODD and CD. Conclusion: Morphological abnormalities in ADHD were seen not only in the regions associated with executive functioning but also in the regions associated with social cognition. When the effect of comorbid CD and ODD was taken into account, there were more extensive regions with significantly smaller volume in ADHD compared to controls.