Feasibility of treating hyperfibrinogenemia with intermittently administered batroxobin in patients with ischemic stroke/transient ischemic attack for secondary prevention.

This study evaluated the safety and efficacy of batroxobin in treating hyperfibrinogenemia for secondary stroke prevention. Patients with ischemic stroke or transient ischemic attack (TIA) were measured for plasma fibrinogen levels. Selected participants had concomitant hyperfibrinogenemia (plasma fibrinogen > or = 3.0 g/l). Patients enrolled between 1 July 2003 and 31 December 2004 were treated with batroxobin; patients enrolled between 1 January 2002 and 30 June 2003 were treated without batroxobin. Batroxobin was administered intermittently via intravenous injection at 3-monthly intervals. Patients in both groups were followed for 1 year. Any cerebrovascular events and suspected adverse events were recorded. In total, 112 ischemic stroke/TIA patients with concomitant hyperfibrinogenemia were enrolled, 52 being treated with batroxobin and 60 without batroxobin. Six patients (11.5%) with batroxobin and 16 patients (26.7%) without batroxobin had recurrent cerebral ischemic events during follow-up. Stroke/TIA recurrence in patients without batroxobin was higher than that in patients with batroxobin (P < 0.05). Two patients with batroxobin and two patients without batroxobin developed hemorrhagic stroke during follow-up. There were five deaths (9.6%) in the batroxobin group, and seven deaths (11.7%) in the nonbatroxobin group during follow-up (P > 0.05). Intermittent intravenous injection of batroxobin can efficiently reduce the risk for stroke/TIA recurrence in patients with concomitant hyperfibrinogenemia.     

Chronic opioid treatment of neuroblastoma X dorsal root ganglion neuron hybrid F11 cells results in elevated GM1 ganglioside and cyclic adenosine monophosphate levels and onset of naloxone-evoked decreases in membrane K+ currents

Prolongation of the action potential duration of dorsal root ganglion (DRG) neurons by low (nM) concentrations of opioids occurs through activation of excitatory opioid receptors that are positively coupled via G_s regulatory protein to adenylate cyclase. Previous results suggested GM1 ganglioside to have an essential role in regulating this excitatory response, but not the inhibitory (APD-shortening) response to higher (μM) opioid concentrations. Furthermore, it was proposed that synthesis of GM1 is upregulated by prolonged activation of excitatory opioid receptor functions. To explore this possibility we have utilized cultures of hybrid F11 cells to carry out closely correlated electrophysiological and biochemical analyses of the effects of chronic opioid treatment on a homogeneous population of clonal cells which express many functions characteristic of DRG neurons. We show that chronic opioid exposure of F11 cells does, in fact, result in elevated levels of GM1 as well as cyclic adenosine monophosphate (AMP), concomitant with the onset of opioid excitatory supersensitivity as manifested by naloxone-evoked decreases in voltage-dependent membrane K⁺ currents. Such elevation of GM1 would be expected to enhance the efficacy of excitatory opioid receptor activation of the G_s/adenylate cyclase/cyclic AMP system, thereby providing a positive feedback mechanism that may account for the remarkable supersensitivity of chronic opioid-treated neurons to the excitatory effects of opioid agonists as well as antagonists. These in vitro findings may provide novel insights into the mechanisms underlying naloxone-precipitated withdrawal syndromes and opioid-induced hyperalgesia after chronic opiatf addiction in vivo. © 1995 Wiley-Liss, Inc.     

Similar motion of a hand-held object may trigger nonsimilar grip force adjustments.

The tight coupling between load (L) and grip (G) forces during voluntary manipulation of a hand-held object is well established. The current study is to examine grip-load force coupling when motion of the hand with an object was either self-generated (voluntary) or externally generated. Subjects performed similar cyclic movements of different loads at various frequencies with three types of manipulations: 1) voluntary oscillation, 2) oscillating the right arm via the pulley system by the left leg (self-driven oscillation), and 3) oscillating the arm via the pulley system by another person (other-driven oscillation). During the self-generated movements: 1) the grip forces were larger and 2) grip-load force modulation was more pronounced than in the externally generated movements. The G-L adjustments are not completely determined by the mechanics of object motion; nonmechanical factors related to movement performance, for instance perceptual factors, may affect the G-L coupling.     

Augmentation of intrarenal angiotensin II levels in uninephrectomized aldosterone/salt-treated hypertensive rats; renoprotective effects of an ultrahigh dose of olmesartan.

Recent studies have suggested that aldosterone plays a role in the pathogenesis of renal injury. In this study, we investigated whether local angiotensin II (Ang II) activity contributes to the progression of renal injury in aldosterone/salt-induced hypertensive rats. Uninephrectomized rats were treated with 1% NaCl in a drinking solution and one of the following combinations for 6 weeks: vehicle (2% ethanol, s.c.; n=9), aldosterone (0.75 mug/h, s.c.; n=8), aldosterone+Ang II type 1 receptor blocker olmesartan (10 mg/kg/day, p.o.; n=8), or aldosterone+olmesartan (100 mg/kg/day, p.o.; n=9). Aldosterone/salt-treated hypertensive rats exhibited severe proteinuria and renal injury characterized by glomerular sclerosis and tubulointerstitial fibrosis. Aldosterone/salt-induced renal injury was associated with augmented expression of angiotensin converting enzyme and Ang II levels in the renal cortex and medullary tissues. Renal cortical and medullary mRNA expression of transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) as well as the collagen contents were increased in aldosterone/salt-treated hypertensive rats. Treatment with olmesartan (10 or 100 mg/kg/day) had no effect on blood pressure but attenuated proteinuria in a dose-dependent manner. Olmesartan at 10 mg/kg/day tended to decrease renal cortical and medullary Ang II levels, TGF-beta and CTGF expression, and collagen contents; however, these changes were not significant. On the other hand, an ultrahigh dose of olmesartan (100 mg/kg/day) significantly decreased these values and ameliorated renal injury. These data suggest that augmented local Ang II activity contributes, at least partially, to the progression of aldosterone/salt-dependent renal injury.     

Can Small Hepatocellular Carcinoma be Cured by Percutaneous Acetic Acid Injection Therapy?

To assess the efficacy of ultrasound (US)-guided percutaneous acetic acid (in concentrations of 15%, 20%, 30%, 40%, and 50%) injection for small hepatocellular carcinomas (HCCs) for long-term prognosis, percutaneous acetic acid injection using 15% to 50% acetic acid was performed in 91 patients with one to four HCCs smaller than 3 cm during the past 6.5 years. During the series of treatment sessions for each patient, the same concentration of acetic acid was used. All tumors could be treated successfully with percutaneous acetic acid injection despite the differences in acetic acid concentration used. The number of treatment sessions to treat similar size of tumor was less when the higher concentration of acetic acid was used. No serious complications occurred as a direct sequela to percutaneous acetic acid injection. None of the tumor treated regrew. The 1-, 2-, 3-, 4-, and 5-year survival rates for 91 patients were 95%, 87%, 80%, 63%, and 49%, respectively. The 1-, 2-, 3-, 4-, and 5-year cancer-free survival rates of these patients were 83%, 54%, 50%, 37%, and 29%, respectively. Both liver function and size of tumor affected both survival rate and cancer-free survival rate significantly, but the number of tumors did not. The concentration of acetic acid did not affect the survival rate. Percutaneous acetic acid using 15% to 50% acetic acid will be effective therapy for small HCCs for long-term prognosis.     

Dynamic evaluation of 18F-FDG uptake by microPET and whole-body autoradiography in a fibrosarcoma-bearing mouse model.

BACKGROUND AND PURPOSE: Fluorine-18-2-deoxy-D-glucose (18F-FDG) has been used in the clinic as a diagnostic radiotracer for monitoring many kinds of tumors, but its value for monitoring fibrosarcoma is not well established. METHODS: In this study, the uptake of 18F-FDG in a fibrosarcoma-bearing mouse model was evaluated using the high resolution positron emission tomography (PET) system microPET. Tumor cells were implanted in 3 FVB/N mice, and static microPET scanning was performed on day 1, 7, 12 and 15 after implantation. A dynamic microPET image was scanned on day 12 to determine the 18F-FDG uptake in 3 other tumor-bearing mice. Time-activity curves were plotted by drawing regions of interest in the tumor, liver, kidneys and muscles. The mice were sacrificed after dynamic microPET imaging and whole-body autoradiography (WBAR) was performed. For biodistribution study, 9 tumor-bearing mice, 3 per experimental group, were studied at 3 time points and the results were compared with the static microPET images. RESULTS: MicroPET images suggested that 18F-FDG could be used to monitor the growth of tumors 7 days after implantation. Dynamic scans of 18F-FDG uptake reached a plateau in the tumor after 20 minutes on day 12 after implantation. Both microPET and WBAR revealed evidence of tumor necrosis. The results of biodistribution and WBAR agreed with those from microPET images. CONCLUSION: MicroPET was useful for monitoring the growth of fibrosarcoma and determination of the maximal uptake time point of 18F-FDG in tumors in this tumor-bearing mouse model.     

Model invariant method for extracting single-channel mean open and closed times from heterogeneous multichannel records.

We present a proof that the mean open (and closed) times of the individual channels in a multichannel record can be found in a model-independent fashion. As the results are model independent, they can be derived by assuming the simplest model for all the channels, namely that they all have the basic CLOSED in equilibrium with OPEN scheme. In particular, the method can be applied to patches where the channel population is heterogenous with respect to open probability. Multichannel simulations are performed to test the limits of applicability of this method to restricted amounts of data. One conclusion is that increasing the number of channels does not substantially reduce the errors in estimating the mean times, in spite of the 'increased information' present. We also prove the general applicability of the algorithm of Fenwick et al. (1982) in estimating the mean times without knowledge of the number of channels present, and discuss its limitations. An illustration using experimental data is also given.     

Announcement

The name of one of the contributing authors to this paper was omitted from the list of authors that appeared on page 373. The correct list of authors and affiliations are printed below: