Effect of locally applied prazosin on the kinetics of the pupillary light reflex

The effect of locally applied prazosin on pupillometric measures was studied in healthy volunteers, in an attempt to identify the role of α₁-adrenoceptors in the recovery time of the light reflex. Prazosin antagonized the mydriatic effect of phenylephrine, but did not alter that of tropicamide. Miotic responses to a range of light stimuli were measured under ambient temperature conditions of 22°  C and 40°  C. The 40°  C condition was associated with shorter recovery times of the light reflex; prazosin increased the recovery time under both temperature conditions. Response amplitude was not affected by the temperature condition or prazosin. The results are consistent with the hypothesis that sympathetic neuromuscular transmission is involved in the redilatation of the pupil following a miotic response to light stimulation.     

A technique for studying the effects of drugs on human sweat gland activity

Summary A technique is described for studying the effects of drugs with anticholinergic properties on human forearm sweat glands. The response of sweat glands to intradermal injections of increasing concentrations of acetylcholine (ACh) in saline was measured. The number of glands activated was recorded by painting the injection area with a plastic impression paint one minute after injection. The plastic impression was removed using Sellotape, mounted on a 35 mm slide, projected, and glands counted. Standardisation of conditions was important with respect to ambient temperature and physical activity of subject in order to reduce spontaneous sweat gland activity. The dose response relationship was similar for men and women. In a double blind, controlled, cross over investigation, 8 subjects (4M and 4 F) received lactose dummy and atropine sulphate 1 mg p. o. Sweat gland activity, salivation, heart rate, pupil size and visual near point were measured before and 1 and 2 h after treatment. Significant (P<0.05) reduction occurred in the number of glands responding to 140 and 550 µM ACh and also in the salivary secretion rate 2 h after atropine, compared with values after lactose dummy. No significant changes in pupil size, visual near point or heart rate occurred. It is suggested that inhibition of the response of forearm sweat glands to ACh is at least as sensitive as other measures of parasympathetic functions for assessing parasympatholytic agents.     

Comparison of the effects of venlafaxine, paroxetine and desipramine on the pupillary light reflex in man

Rationale: The time-course of the pupillary light reflex response is determined by the successive activation of the parasympathetic and sympathetic innervations of the iris, the latency and the amplitude reflecting parasympathetic and the recovery time mainly sympathetic activity. Objective: To compare the effects of single doses of three antidepressants (venlafaxine: serotonin/noradrenaline reuptake inhibitor, paroxetine: selective serotonin reuptake inhibitor, and desipramine: tricyclic antidepressant) on resting pupil diameter and the pupillary light reflex response. Methods: Fifteen healthy male volunteers participated in five weekly sessions, each of which was associated with one treatment (venlafaxine 75 mg or 150 mg, paroxetine 20 mg, desipramine 100 mg, or placebo) according to a double-blind, double-dummy, balanced, cross-over design. An infrared binocular television pupillometer was used for the recording of the resting pupil diameter and the pupillary light reflex in darkness, in previously dark-adapted eyes. Resting pupil diameter in darkness was recorded before and after treatment. The pupillary light reflex was elicited after treatment, with six light flashes (green, 565 nm peak wavelength) of 200 ms duration and of incremental illuminance (measured in the plane of the cornea): 3.0 × 10^–3, 8.5 × 10^–3, 2.5 × 10^–2, 7.0 × 10^–2, 0.18, 0.43 mW cm⁻². The parameters studied were: latency, amplitude and 75% recovery time. Results: Analyses of variance followed by post hoc tests (least significant difference test or Dunnett’s test; P < 0.05) revealed that both doses of venlafaxine produced a significant increase in resting pupil diameter, decrease in amplitude and shortening of the 75% recovery time of the light reflex response; venlafaxine 150 mg prolonged the latency, while the other treatments had no significant effects. Conclusions: The increase in resting pupil diameter could be indicative of parasympathetic inhibition and/or sympathetic activation. The shortening of the recovery time of the light reflex response is consistent with sympathetic potentiation resulting from noradrenaline uptake blockade in the iris. The prolongation of the latency and decrease of the amplitude of the light reflex response are indicative of a parasympatholytic effect of venlafaxine. However, as venlafaxine has negligible affinity for muscarinic cholinoceptors, this effect cannot be attributed to the blockade of cholinoceptors in the iris. A possible explanation for this finding is that it reflects a central rather than a peripheral effect of the drug: the blockade of noradrenaline uptake in the brain could lead to the potentiation of the noradrenergic inhibition of central parasympathetic (Edinger-Westphal) neurones. These results demonstrate the ability of therapeutically relevant single doses of venlafaxine to potentiate noradrenergic responses in man, consistent with the blockade of noradrenaline uptake. Received: 29 July 1998/Final version: 17 November 1998     

A comparison of the effects of muscarinic and nicotinic anticholinergic drugs on habituation and fear conditioning in rats

Comparisons were made between the effects of scopolamine and mecamylamine in two behavioral paradigms that have been found to be sensitive to cholinergic disruption by antimuscarinic compounds (i.e., habituation and fear conditioning). In the habituation paradigm, water deprived rats were exposed to a novel environmental chamber under either scopolamine, methscopolamine, mecamylamine, hexamethonium or saline. Three days later all animals were returned to the same chamber which now contained a drinking tube. Time to complete 100 licks was used to assess habituation. Only the rats trained under scopolamine showed long drinking times (failed to habituate to the apparatus stimuli) thereby demonstrating the central muscarinic nature of the habituation process. In the fear conditioning paradigm, hungry rats, trained to drink milk in a test chamber, received a single electric shock 20 min after injections of either scopolamine, mecamylamine, hexamethonium or saline. Three days later subgroups were tested for conditioned suppression under either the same drug conditions or saline. Conditioned suppression was found in all groups except those trained under scopolamine or mecamylamine and tested under saline. Apparently the processes underlying this asymmetrical dissociation are not predominantly nicotinic or muscarinic in nature.In conducting the research described in this report, the investigators adhered to the Guide for Laboratory Animal Facilities and Care as promulgated by the Committee on the Guide for Laboratory Animal Resources, National Academy of Sciences-National Research Council.     

Behavioural effects of hashish in mice in comparison with other psychoactive drugs

• 1.1. The behavioural effects of hashish extract (10 mgΔ⁹-THC/kg) were compared to those of morphine (20 mg/kg), diazepam (10 mg/kg), imipramine (10 mg/kg), amphetamine (10 mg/kg) and chlorpromazine (10 mg/kg) by testing male mice in a resident-intruder situation.
• 2.2. The drugs were given either to the resident or to the intruder male.
• 3.3. Hashish extract similar to diazepam and chlorpromazine reduced social activities in resident and intruder males.
• 4.4. Intruder males treated with hashish or diazepam were more frequently attacked and submission and flight was increased.
• 5.5. Amphetamine and morphine stimulated locomotion and non-social activities but impaired social behaviour especially in residents.
• 6.6. Imipramine increased aggressive behaviour in resident and intruder males.

     

Daily variation and effects of ambient light and circadian factors on the human light reflex.

Measures of pupillary size and the dynamic light reflex are safe and noninvasive methods to quantify and characterize the mechanism and site of drug action. The effects of variations in ambient light and time of day on pupillary measures were determined. In dark adapted volunteers (n = 13), ambient light was incrementally increased at < 0.1, 4, 40, 100 and 200 foot-candle (ftcd). Subjects adjusted to each light level for 1 min before the light reflex was elicited. Replicate measures were collected with the contralateral eye open and covered with an opaque patch. Data were collected every 3 h between 6 a.m. and 9 p.m. The prestimulus diameter of the dark adapted pupil averaged 6.4 mm at < 0.1 ftcd and 2.3 mm at 200 ftcd. Constriction amplitude decreased with increases in ambient light from 2.1 mm (< 0.1 ftcd) to 0.2 mm (200 ftcd) while constriction and dilatation velocities decreased from 7.7 to 2.8 mm/sec and 4.3 to 2.8 mm/sec, respectively. Time of day effects were small but statistically significant and the interaction of ambient light and time of recording suggests the pupil is differentially sensitive to ambient and phasic light stimuli over the course of the day. A patch over the contralateral eye increased pupil size and velocities of the light reflex. In a second study, 10 volunteers were tested twice a day at 4 and 80 ftcd for four days. While there was wide between subject variability, the within subject differences were small. Such baseline data may be useful in describing the normal variations in these increasingly popular indices of drug action.     

Discriminative effects of phenazepam and gidazepam in rats: comparison with other GABA-related drugs.

The present study assessed the discriminative stimulus effects of phenazepam (PHZ) (2 mg/kg, i.p.), gidazepam (GDZ) (10 mg/kg, i.p.), pentobarbital (PB) (10 mg/kg, i.p.), and buspirone (B) (5 mg/kg, i.p.) by testing GABA-related drugs in the two-lever liquid reinforced operant discrimination procedure in rats. Diazepam (5-30 mg/kg, i.p.) dose dependently and completely substituted in GDZ-trained rats and in only 40% PHZ-trained rats. Following phenobarbital (40-100 mg/kg, i.p.) injections the mean percentages of PHZ- and GDZ-lever responding generally were a monotonically increasing function of dose, but peaked at 39.3 and 52.9%, respectively. The PB discriminative cue was generalized completely to PHZ, GDZ, and phenobarbital. Picrotoxin (2 mg/kg, s.c.) did not inhibit the PHZ and GDZ discriminations, while it antagonized the PB (10 mg/kg, i.p.) cue. Calcium valproate (200 mg/kg, i.p.) failed to produce PHZ effects, and partially substituted for GDZ. B failed to substitute for the discriminative effects of PHZ, GDZ, or PB, producing a maximum 9.3, 18.0, and 33.3% drug lever responding, respectively. These results suggest that the discriminative stimuli of PHZ and GDZ are similar to those of other benzodiazepine agonists. However, the PHZ cue is more selective than that of GDZ.     

Evaluation of neural reflex activation as a mode of action for the acute respiratory effects of ozone

Exposure to elevated levels of ozone has been associated with a variety of respiratory-related health endpoints in both epidemiology and controlled human exposure studies, including lung function decrements and airway inflammation. A mode of action (MoA) for these effects has not been established, but it has been proposed that they may occur through ozone-induced activation of neural reflexes. We critically reviewed experimental studies of ozone exposure and neural reflex activation and applied the International Programme on Chemical Safety (IPCS) mode-of-action/human relevance framework to evaluate the biological plausibility and human relevance of this proposed MoA. Based on the currently available experimental data, we found that the proposed MoA of neural reflex activation is biologically plausible for the endpoint of ozone-induced lung function decrements at high ozone exposures, but further studies are needed to fill important data gaps regarding the relevance of this MoA at lower exposures. A role for the proposed MoA in ozone-induced airway inflammation is less plausible, as the evidence is conflicting and is also of unclear relevance given the lack of studies conducted at lower exposures. The evidence suggests a different MoA for ozone-induced inflammation that may still be linked to the key events in the proposed MoA, such that neural reflex activation may have some degree of involvement in modulating ozone-induced neutrophil influx, even if it is not a direct role.     

A comparison of the anticholinergic effects of two formulations of disopyramide in healthy volunteers

Eight healthy male volunteers took a single oral dose of one of the following: Rythmodan (conventionally formulated disopyramide) 150 mg; Rythmodan 250 mg; Rythmodan Retard (controlled-release disopyramide) 250 mg; placebo. The subjects were allocated double-blind to sessions and treatments according to a Latin square design. In each session pupil diameter, heart rate, salivation, and QT interval were measured immediately before and at 1, 2, 3, 4, 6, 8, and 24 h after the drug. QT interval was corrected for heart rate (QT60). Plasma concentrations of total and unbound disopyramide were also determined at each time point. Both formulations of disopyramide reduced salivary output and increased QT60 interval, but there was not significant difference between the effects of the three active treatments. Neither formulation had any effect on pupil diameter or heart rate. The peak plasma concentration of unbound disopyramide was reached 2 h after Rythmodan and 4 h after Rythmodan Retard. The peak plasma concentration of disopyramide was significantly lower after Rythmodan Retard 250 mg than after Rythmodan 250 mg. The plasma concentration of unbound disopyramide was positively correlated with the reduction in salivation and prolongation of the QT60 interval. The reduction in salivation is likely to reflect blockade of muscarinic receptors by disopyramide, whereas the increase in QT60 interval is likely to be related to a direct effect of the drug on the heart. The results of this single-dose study do not indicate that disopyramide in the controlled-release formulation would be better tolerated by patients than conventionally formulated disopyramide.     

A comparison of the efficacy of pyridostigmine alone and the combination of pyridostigmine with anticholinergic drugs as pharmacological pretreatment of tabun-poisoned rats and mice

The ability of two types of pharmacological pretreatment (pyridostigmine alone or pyridostigmine in combination with two anticholinergic drugs) to increase the resistance of rats and mice against tabun and to increase the therapeutic efficacy of common antidotal treatment of tabun-poisoned rats and mice was compared. A significant decrease in the LD50 values of tabun was observed when mice as well as rats were pretreated with the prophylactic antidotal mixture consisting of pyridostigmine, benactyzine and trihexyphenidyle, designated PANPAL. Pyridostigmine-pretreated rats were also more resistant against acute lethal effects of tabun but pyridostigmine-induced resistance of rats was not so high as PANPAL-induced resistance. In addition, the pharmacological pretreatment with pyridostigmine alone was not able to protect mice against tabun-induced acute toxicity. The pharmacological pretreatment with pyridostigmine alone was able to increase the efficacy of currently used antidotal treatment (obidoxime in combination with atropine and diazepam) of tabun-induced poisoning, but PANPAL-induced increase in the efficacy of the same antidotal treatment was significantly higher than an increase induced by pyridostigmine alone. PANPAL-induced increase in the efficacy of antidotal treatment of tabun poisoning was also observed in mice. These findings confirm that PANPAL pretreatment of tabun-poisoned rats and mice seems to be much more suitable than currently used pyridostigmine alone.     

Acute effects of a low‐dose atropine/scopolamine mixture as a food contaminant in human volunteers

To verify the assumptions in our previous risk assessment of an atropine/scopolamine mixture in buckwheat flour, we performed a randomized, double‐blind, placebo‐controlled cross‐over study in 20 healthy, adult volunteers. The volunteers ingested a traditional Slovenian buckwheat meal, made of boiled buckwheat flour to which alkaloids were added. In addition to the placebo they ingested 0.12/0.10, 0.37/0.29, 1.22/0.95, 3.58/2.81 and 12.10/9.50 µg kg^–1 body mass (BM) of the atropine/scopolamine mixture. The changes in body temperature, heart rate, salivary and sweat secretion, pupil size, near‐point vision and subjective symptoms were recorded regularly for 4 h after the ingestion. Decreased salivary and sweat secretion, increased heart rate and pupil size and reduced near‐point vision accompanied by characteristic subjective symptoms were observed at 12.10/9.50 µg kg^–1 BM. At doses of 0.37/0.29 and 1.22/0.95 µg kg^–1 BM, a significant decrease in the heart rate was noted, which we consider to be a critical effect of a low‐dose exposure to the atropine/scopolamine mixture. Although this did not have any clinical relevance in our subjects, it may have serious implications if it occurred in people with pre‐existent cardiac conditions or those on medications that may cause bradycardia. No significant changes in the observed end points were noted at 0.12/0.10 µg kg^–1 BM. We estimate that the NOAEL (No Observed Adverse Effect Level) for the atropine/scopolamine mixture lies between the lower two administered doses. Applying the uncertainty factor of 10, we propose a new provisional Acute Reference Doses (ARfDs) of the mixture, i.e. 0.01 µg kg^–1 BM for each alkaloid, and a further refinement using higher‐tier approaches. Copyright © 2012 John Wiley & Sons, Ltd.     

An assessment of rufinamide as an anti-epileptic in comparison with other drugs in clinical development

This article evaluates rufinamide, a new anti-epileptic drug (AED) in Phase III development. This review is done against the background of therapeutic challenges of epilepsy, old established AEDs, newly introduced AEDs and AEDs in clinical development. Pharmacological properties of 12 AEDs in clinical trials (Phases I - III) are compared: ADCI, AWD 131-138, DP-VPA, ganaxolone, levetiracetam, losigamone, pregabalin, remacemide hydrochloride, retigabine, rufinamide, soretolide and TV1901. One of these, levetiracetam has been approved in the USA and is waiting approval in other countries. The protective index of rufinamide, as shown in rodent models of epilepsy, is much higher than that of most common AEDs. Features which make it a desirable AED are: (i) a broad spectrum of anti-epileptic actions including both partial and symptomatic generalised epilepsy; (ii) a statistically significant reduction in seizure frequency in clinical trials; (iii) efficacy and safety shown in a broad range of age groups including children and the elderly; (iv) rapid oral absorption enabling quick titration to effective dose and (v) a benign adverse event profile. Most of the events did not lead to discontinuation in clinical trials. These features offer considerable advantages over the existing anti-epileptic drugs. It is one of the two drugs in development which have reached Phase III and is expected to be approved by the year 2001 - 2002.     

Dose-related effects of controlled release dihydrocodeine on oro-cecal transit and pupillary light reflex. A study in human volunteers

It is well accepted that long-term administration of opioids results in a dose-related constipation. No data so far have demonstrated conclusively whether such constipation is also seen after intake of a controlled release formulation. It was therefore of interest to evaluate whether increasing doses of a controlled release formulation of dihydrocodeine (DHC, CAS 125-28-0) after oral administration also induces a dose-related increase in constipation. Additionally, it was of interest to study whether such a peripheral opioid-related side effect is also seen in another, central receptor-mediated effect, the constriction of the pupil, at clinically relevant doses. Twelve volunteers were given controlled release DHC (60 and 120 mg, respectively) or placebo orally within a randomized, double-blind cross-over study. In order to determine the degree of constipation, oro-cecal transit time was measured using the H2-exhalation test. Additionally, in order to evaluate a centrally mediated effect, the response of the pupil to light was quantified using the pupillary light reflex technique. Both, peripherally and centrally mediated effects were compared to placebo. DHC at both dosages induced a significant (p < 0.01) prolongation of oro-cecal transit time when compared to placebo. However, prolongation of oro-cecal transit was not significantly longer when comparing the lower (60 mg) with the higher dose (120 mg). DHC also induced a significant (p < 0.005) depression of the pupillary light reflex from 53.9 mm (control) to 8.3 and 7.4 mm, respectively. Similar to intestinal transit, the pupillary light reflex was not significantly different among the two doses of DHC. Also, both dosages induced a similar amount of side effects. Tiredness and dry mouth were reported in 80% after both doses while vertigo was reported in 5% and 1% complained of headache. None of the volunteers reported nausea or emesis. It is concluded that opioid receptor sites, which are located in the plexus myentericus of the intestinal wall, are responsible for the delay in propulsion. Because of the controlled release of a fixed amount of DHC over time there is constant binding of the ligand followed by a constant conformational change of peripheral and central receptor sites. Thus constant release induces no dose-related increase in oro-cecal transit and inhibition of the pupillary light reflex.     

An assessment of rufinamide as an anti-epileptic in comparison with other drugs in clinical development

This article evaluates rufinamide, a new anti-epileptic drug (AED) in Phase III development. This review is done against the background of therapeutic challenges of epilepsy, old established AEDs, newly introduced AEDs and AEDs in clinical development. Pharmacological properties of 12 AEDs in clinical trials (Phases I - III) are compared: ADCI, AWD 131-138, DP-VPA, ganaxolone, levetiracetam, losigamone, pregabalin, remacemide hydrochloride, retigabine, rufinamide, soretolide and TV1901. One of these, levetiracetam has been approved in the USA and is waiting approval in other countries. The protective index of rufinamide, as shown in rodent models of epilepsy, is much higher than that of most common AEDs. Features which make it a desirable AED are: (i) a broad spectrum of anti-epileptic actions including both partial and symptomatic generalised epilepsy; (ii) a statistically significant reduction in seizure frequency in clinical trials; (iii) efficacy and safety shown in a broad range of age groups including children and the elderly; (iv) rapid oral absorption enabling quick titration to effective dose and (v) a benign adverse event profile. Most of the events did not lead to discontinuation in clinical trials. These features offer considerable advantages over the existing anti-epileptic drugs. It is one of the two drugs in development which have reached Phase III and is expected to be approved by the year 2001 - 2002.     

Analgesic effects of Neurotropin in mice, and a comparison with analgesic effect of other drugs in SART-stressmice]

Analgesic effects of a neuroleptica "Neurotropin" (NSP) were studied in mice while the analgesic effects of other agents were studied in SART-stress mice (specific stress caused by alterating rhythm in temperature) and the results compared with those in normal mice. NSP is an extract containing many conjugated polysaccarides isolated from the skin or tissues of rabbits which had been inoculated with the living cowpox virus. (a) NSP given alone to normal mice resulted in slight analgesic effects as observed with the application of the acetic acid-, phenylquinon-writhing method or the modified Randall-Selitto method. Little effect was seen when the D'Amour-Smith was used. (b) Synergism was evident when NSP and aminopyrine or NSP and morphine were given concomitantly and the acetic acid- or phenylquinon-writhing methods were applied. (c) Analgesic effects of morphine, levomepromazine, imidazole acetic acid and particularly NSP were greater in SART-stress mice than in normal mice. With the D'Amour-Smith method, only NSP had a greater effect in SART-stress mice than in normal mice.     

The effects of a new benzodiazepine derivative,ID-540, on the averaged photopalpebral reflex in man

The effects of 7-chloro-5-(2-fluorophenyl)-1-methyl-1 H, 1·4-benzodiazepin-2(3 H)-one (ID-540), a recently introduced benzodiazepine derivative, on the averaged photopalpebral reflex (PPR), subjective symptoms, and serum levels of ID-540 and its principal metabolite, N-desmethyl-ID-540, following an oral dose of 0.5 mg or placebo were investigated in six male Japanese students in a double-blind, crossover design. The peak latencies of PPR showed a statistically significant prolongation, with maximum level at 3h after administration, which recovered to the initial level within 4h. The amplitude of PPR failed to show a definite response to the drug. The serum concentration of ID-540 reached a peak level 2–3h after administration, and then decreased at 4h. N-Desmethyl-ID-540 exhibited a slow, gradual rise in serum. The latencies of PPR were positively correlated with the serum level of ID-540 but not with the N-desmethyl-ID-540. It is concluded that the PPR test may be a useful method for predicting the clinical effects of psychotropic drugs.To whom requests for offprints should be sent     

Dose-dependent opposite effects of gabapentin on the depressive action of morphine on a C-fibre reflex in the rat

Gabapentin is a structural analogue of gamma-amino-butyric acid with anticonvulsant activity. Recently, indications for its use were extended to the management of acute pain in the postoperative period. The effects of pre-administration of gabapentin on the depressive action of intravenous morphine were studied on the C-fibre reflex elicited by a wide range of stimulus intensities.The reflex was elicited by electrical stimulation of the sural nerve and recorded from the ipsilateral biceps femoris muscle in halothane anaesthetized rats with either an intact neuraxis or a brainstem previously transected at the level of the obex.As previously reported, 6 mg/kg intravenous morphine both increased the threshold and decreased the slope of the stimulus-response recruitment curve. The C-fibre reflex was not modified following intravenous gabapentin. Gabapentin pre-treatment at lower doses (0.01-7.5 mg/kg) not only antagonized the depressive effect of morphine, but caused facilitation of the reflex. At higher doses (10-50 mg/kg), gabapentin pre-treatment potentiated the depressive effect of morphine. In obex-transected rats, the facilitation of the C-fibre reflex, seen following 1 mg/kg gabapentin and 6 mg/kg morphine, disappeared and was replaced by a strong reinforcement of the depressive effect of morphine.It is concluded that a strong synergy between the effects of gabapentin and morphine can be seen at the spinal level. However, radically opposite effects with supraspinal origins thwart this mechanism. From the clinical standpoint, these results incite cautiousness in the use of combinations of gabapentin and opioids.     

Comparison of the effects of diazepam on the fear-potentiated startle reflex and the fear-inhibited light reflex in man.

It has been shown previously that the amplitude of the acoustic startle reflex is enhanced, and the amplitude of the light reflex reduced, when subjects anticipate an aversive event, compared to periods when subjects are resting ('fear-potentiated startle reflex' and 'fear-inhibited light reflex'). We examined whether the anxiolytic diazepam would reverse the effects of threat on the startle and pupillary reflexes. Twelve male volunteers participated in three weekly sessions in which they received oral treatment with placebo, diazepam 5 mg and diazepam 10 mg, according to a balanced crossover double-blind design. One hour after ingestion of the treatments, miotic responses to light pulses and electromyographic responses of the orbicularis oculi muscle to sound pulses were elicited during alternating periods in which the threat of an electric shock (electrodes attached to the subject's wrist) was present (THREAT) and absent (SAFE). The THREAT condition was associated with a significant increase in the amplitude of the electromyographic (EMG) response, a significant reduction of the miotic response amplitude, and an increase in self-rated anxiety. Diazepam attenuated all these effects of THREAT. Diazepam did not affect the amplitude of the miotic response under the SAFE condition, but did suppress the EMG response under this condition. These results confirm the validity of the fear-potentiated startle reflex and fear-inhibited light reflex as laboratory models of human anxiety, and reveal some differences between the effects of diazepam on the two reflexes.     

冷光源与常规蓝光治疗新生儿黄疸的临床效果比较

目的比较冷光源与常规蓝光在新生儿黄疸治疗中的临床疗效。方法选取本院收治的新生儿黄疸患儿,随机分为冷光源蓝光组和常规蓝光组,比较和分析两组的临床治疗效果和血清胆红素浓度。结果冷光源蓝光组的临床显效率和总有效率均显著高于常规蓝光组,无效率显著低于常规蓝光组,治疗后48、96h的血清胆红素浓度均显著低于常规蓝光组,差异有统计学意义（P〈0．05）。结论冷光源蓝光在新生儿黄疸的临床治疗过程中较常规蓝光具有更显著的疗效,可作为新生儿黄疸较理想的治疗方案进行临床推广和应用。