Arterial blood gas tensions during upper gastrointestinal endoscopy.
Arterial blood gas tensions were measured before and during upper gastrointestinal endoscopy, with (group I) and without (group 2) sedation with intravenous diazepam. There was a highly significant fall in the PaO2, which occurred in both groups and was therefore not attributable to diazepam. Measurement of FEV, and FVC before endoscopy had no predictive value for those patients whose PaO2 fell the most. (+info)
Neural modulation of cephalexin intestinal absorption through the di- and tripeptide brush border transporter of rat jejunum in vivo.
Intestinal absorption of beta-lactamine antibiotics (e.g., cefixime and cephalexin) has been shown to proceed through the dipeptide carrier system. In a previous study, nifedipine (NFP), an L-type calcium channel blocker, enhanced the absorption of cefixime in vivo but not in vitro, and it was suggested that neural mechanisms might be involved in the effect of NFP. The aim of the present study was to assess the involvement of the nervous system on the intestinal absorption of cephalexin (CFX). To investigate this, we used a single-pass jejunal perfusion technique in rats. NFP and diltiazem enhanced approximately 2-fold the plasma levels of CFX in treated rats versus untreated controls. NFP also increased approximately 2-fold the CFX level in portal plasma and increased urinary excretion of CFX, thus indicating that CFX did effectively increase CFX intestinal absorption. Perfusing high concentrations of dipeptides in the jejunal lumen competitively reduced CFX absorption and inhibited the enhancement of CFX absorption produced by NFP. Hexamethonium and lidocaine inhibited the effect of NFP, whereas atropine, capsaicin, clonidine, and isoproterenol enhanced CFX absorption by the same order of magnitude as NFP. Thus, complex neural networks can modulate the function of the intestinal di- and tripeptide transporter. Sympathetic noradrenergic fibers, intestinal sensory neurons, and nicotinic synapses are involved in the increase of CFX absorption produced by NFP. (+info)
Electrophysiological evidence for tetrodotoxin-resistant sodium channels in slowly conducting dural sensory fibers.
A tetrodotoxin (TTX)-resistant sodium channel was recently identified that is expressed only in small diameter neurons of peripheral sensory ganglia. The peripheral axons of sensory neurons appear to lack this channel, but its presence has not been investigated in peripheral nerve endings, the site of sensory transduction in vivo. We investigated the effect of TTX on mechanoresponsiveness in nerve endings of sensory neurons that innervate the intracranial dura. Because the degree of TTX resistance of axonal branches could potentially be affected by factors other than channel subtype, the neurons were also tested for sensitivity to lidocaine, which blocks both TTX-sensitive and TTX-resistant sodium channels. Single-unit activity was recorded from dural afferent neurons in the trigeminal ganglion of urethan-anesthetized rats. Response thresholds to mechanical stimulation of the dura were determined with von Frey monofilaments while exposing the dura to progressively increasing concentrations of TTX or lidocaine. Neurons with slowly conducting axons were relatively resistant to TTX. Application of 1 microM TTX produced complete suppression of mechanoresponsiveness in all (11/11) fast A-delta units [conduction velocity (c.v.) 5-18 m/s] but only 50% (5/10) of slow A-delta units (1.5 +info)
RINm5f cells express inactivating BK channels whereas HIT cells express noninactivating BK channels.
Large-conductance Ca2+- and voltage-activated BK-type K+ channels are expressed abundantly in normal rat pancreatic islet cells and in the clonal rat insulinoma tumor (RINm5f) and hamster insulinoma tumor (HIT) beta cell lines. Previous work has suggested that the Ca2+ sensitivity of BK channels in RIN cells is substantially less than that in HIT cells, perhaps contributing to differences between the cell lines in responsiveness to glucose in mediating insulin secretion. In both RIN cells and normal pancreatic beta cells, BK channels are thought to play a limited role in responses of beta cells to secretagogues and in the electrical activity of beta cells. Here we examine in detail the properties of BK channels in RIN and HIT cells using inside-out patches and whole cell recordings. BK channels in RIN cells exhibit rapid inactivation that results in an anomalous steady-state Ca2+ dependence of activation. In contrast, BK channels in HIT cells exhibit the more usual noninactivating behavior. When BK inactivation is taken into account, the Ca2+ and voltage dependence of activation of BK channels in RIN and HIT cells is essentially indistinguishable. The properties of BK channel inactivation in RIN cells are similar to those of inactivating BK channels (termed BKi channels) previously identified in rat chromaffin cells. Inactivation involves multiple, trypsin-sensitive cytosolic domains and exhibits a dependence on Ca2+ and voltage that appears to arise from coupling to channel activation. In addition, the rates of inactivation onset and recovery are similar to that of BKi channels in chromaffin cells. The charybdotoxin (CTX) sensitivity of BKi currents is somewhat less than that of the noninactivating BK variant. Action potential voltage-clamp waveforms indicate that BK current is activated only weakly by Ca2+ influx in RIN cells but more strongly activated in HIT cells even when Ca2+ current magnitude is comparable. Concentrations of CTX sufficient to block BKi current in RIN cells have no effect on action potential activity initiated by glucose or DC injection. Despite its abundant expression in RIN cells, BKi current appears to play little role in action potential activity initiated by glucose or DC injection in RIN cells, but BK current may play an important role in action potential repolarization in HIT cells. (+info)
Evaluation of lidocaine as an analgesic when added to hypertonic saline for sclerotherapy.
PURPOSE: The efficacy of sclerosing agents for the treatment of telangiectasias and reticular veins is well established. The injection of these agents is often associated with pain, and it is not uncommon for sclerotherapists to include lidocaine with the sclerosants in an attempt to reduce the pain associated with treatment. However, there are concerns that this may reduce the overall efficacy of the treatment because of dilution of the sclerosant. Patient comfort and overall outcome associated with treatment using HS with lidocaine (LIDO) versus that using HS alone was compared. METHODS: Forty-two patients were prospectively entered into the study and randomized blindly to sclerotherapy with 23.4% HS or 19% LIDO. Study subjects and treating physicians were blinded to the injection solution used. Injection sites were chosen for veins ranging in size from 0.1 to 3 mm. Photographs of the area to be treated were taken, and the patients rated their pain. They were then observed at regular intervals for four months, and clinical data was collected. Thirty-five subjects completed the full follow-up period, and photographs of the injected area were taken again. Three investigators blinded to the treatment assignment then evaluated the photographs and scored the treatment efficacy according to a standardized system. RESULTS: In the HS group, 61.9% (13 of 21) patients rated their pain as none or mild, whereas 90.5% (19 of 21) of patients in the LIDO group had no or mild discomfort. This difference is significant, with a P value of.034. There was no difference in the overall efficacy of treatment between the two groups. The groups had similar rates of vein thrombosis and skin necrosis. CONCLUSION: Although lidocaine is often used with sclerosing agents, there are no previous reports in the literature to evaluate its effectiveness in reducing the pain experienced by the patient. In this study, patients receiving LIDO experienced significantly less discomfort at the time of injection than patients who received HS alone. There were no differences in the effectiveness of treatment or in the incidence of complications between the two groups. (+info)
Dispersion of signal-averaged P wave duration on precordial body surface in patients with paroxysmal atrial fibrillation.
AIMS: This study sought to investigate whether the spatial dispersion of signal-averaged P wave duration would be increased in patients with paroxysmal atrial fibrillation, by use of precordial mapping of the P wave signal-averaged ECG. METHODS AND RESULTS: The P wave signal-averaged ECG was recorded by the P wave-triggering method from 16 precordial leads in 55 patients with paroxysmal atrial fibrillation and 57 control subjects. As an index of the dispersion of signal-averaged P wave duration, we obtained the difference between the maximum and minimum in 16 recording sites. The dispersion was significantly greater in the patients with paroxysmal atrial fibrillation than the controls (26.6 +/- 9.5 vs 14.8 +/- 6.7 ms, P<0.0001). In 25 patients with symptomatic attacks of paroxysmal atrial fibrillation, the signal-averaged ECG was repeated 1 h after a single dose of orally administered pilsicainide, a new class Ic drug. These patients were prospectively followed-up for 10 +/- 11 months with pilsicainide. The rate of freedom from recurrence of paroxysmal atrial fibrillation attacks was significantly (P<0.0001) higher in patients with whom dispersion was decreased by the single dose (54%[7/13]) than in those in whom dispersion increased (8%[1/12]). CONCLUSION: Increased dispersion of signal-averaged P wave duration would play an important role in generating paroxysmal atrial fibrillation and would be useful in the prediction of drug efficacy to evaluate the change in dispersion by a single administration of pilsicainide. (+info)
Profiles of aprindine, cibenzoline, pilsicainide and pirmenol in the framework of the Sicilian Gambit. The Guideline Committee for Clinical Use of Antiarrhythmic Drugs in Japan (Working Group of Arrhythmias of the Japanese Society of Electrocardiology).
The Vaughan Williams classification has been used widely by clinicians, cardiologists and researchers engaged in antiarrhythmic drug development and testing in many countries throughout the world since its initial proposal in the early 1970s. However, a major criticism of the Vaughan Williams system arose from the extent to which the categorization of drugs into classes I-IV led to oversimplified views of both shared and divergent actions. The Sicilian Gambit proposed a two-dimensional tabular framework for display of drug actions to solve these problems. From April to December 1996, members of the Guideline Committee met to discuss pharmacologic profiles of 4 antiarrhythmic drugs (aprindine, cibenzoline, pilsicainide, and pirmenol) that were not included in the original spreadsheet but are used widely in clinical practice in Japan. The discussion aimed to fit the drug profiles into the Gambit framework based on all the important literature published to date regarding the actions of the 4 drugs. This report is a summary of that deliberation. (+info)
Action potentials in the dendrites of retinal ganglion cells.
The somas and dendrites of intact retinal ganglion cells were exposed by enzymatic removal of the overlying endfeet of the Muller glia. Simultaneous whole cell patch recordings were made from a ganglion cell's dendrite and the cell's soma. When a dendrite was stimulated with depolarizing current, impulses often propagated to the soma, where they appeared as a mixture of small depolarizations and action potentials. When the soma was stimulated, action potentials always propagated back through the dendrite. The site of initiation of action potentials, as judged by their timing, could be shifted between soma and dendrite by changing the site of stimulation. Applying QX-314 to the soma could eliminate somatic action potentials while leaving dendritic impulses intact. The absolute amplitudes of the dendritic action potentials varied somewhat at different distances from the soma, and it is not clear whether these variations are real or technical. Nonetheless, the qualitative experiments clearly suggest that the dendrites of retinal ganglion cells generate regenerative Na+ action potentials, at least in response to large direct depolarizations. (+info)