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An 81-year-old man was examined on referral with the presenting complaint of decreased vision in one eye. Tentative diagnosis, later confirmed by pathology evaluation, was malignant melanoma of the ciliary body.

The most feared complications of contact lens wear are keratitis and infectious corneal ulceration. This article first defines terms for the clinical practitioner, and then describes and illustrates clinical presentation and management.

Mice injected with the calcium agonist BAY K 8644 (2-4 mg/kg, i.p.) displayed profound behavioral changes including ataxia, decreased motor activity, Straub tail, arched back, limb clonus and tonus, and an increased sensitivity to auditory stimulation. BAY K 8644 significantly impaired rotorod performance in mice with an ED50 of 0.8 mg/kg. The behavioral effects of BAY K 8644 were antagonized by nifedipine, but not by the non-dihydropyridine calcium channel antagonist verapamil or the alpha-adrenoceptor antagonist prazosin. Further, the actions of BAY K 8644 were not mimicked by the alpha-adrenoceptor agonist methoxamine at doses up to 4.5 mg/kg. These observations, coupled with the findings that BAY K 8644 is a potent, competitive inhibitor of [3H]nitrendipine binding to the dihydropyridine binding site in mouse brain (Ki = 7.0 X 10(-9) M), suggests that BAY K 8644 may produce its behavioral actions via an interaction with the DHP binding site, which has been linked to the control of calcium flux across membranes in peripheral tissues.

The effects of mono- and di-valent cations and the nonhydrolyzable guanyl nucleotide derivative 5'-guanylimidodiphosphate (Gpp(NH)p) on the binding of the selective, high affinity mu-opiate receptor agonist, [3H]DAGO ([3H]Tyr-D-Ala-Gly-Mephe-Gly-ol), to rat brain membranes were studied in a low ionic strength 5 mM Tris-HCl buffer. Na+ and Li+ (50 mM) maximally increased [3H]DAGO binding (EC50 values for Na+, 2.9 mM and Li+, 6.2 mM) by revealing a population of low affinity binding sites. The density of high affinity [3H]DAGO binding sites was unaffected by Na+ and Li+, but was maximally increased by 50 mM K+ and Rb+ (EC50 values for K+, 8.5 mM and Rb+, 12.9 mM). Divalent cations (Ca2+, Mg2+; 50 mM) inhibited [3H]DAGO binding. Gpp(NH)p decreased the affinity of [3H]DAGO binding, an effect that was enhanced by Na+ but not by K+. The binding of the mu-agonist [3H]dihydromorphine was unaffected by 50 mM Na+ in 5 mM Tris-HCl. In 50 mM Tris-HCl, Na+ (50 mM) inhibited [3H]DAGO binding by decreasing the density of high affinity binding sites and promoting low affinity binding. The effects of Na+ in 5 mM and 50 mM Tris-HCl were also investigated on the binding of other opiate receptor agonists and antagonists. [3H]D-Ala-D-Leu-enkephalin binding was increased and inhibited. [3H]etorphine binding increased and was unchanged, and both [3H]bremazocine and [3H]naloxone binding increased by 50 mM Na+ in 5 mM and 50 mM Tris-HCl, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aqueous humor oxygen tension of the in vivo rabbit eye was estimated by a relatively atraumatic procedure. The anterior corneal surface of the eye was first scraped free of its epithelial layer. A polarographic oxygen electrode was then used to measure the oxygen tension at the bare stromal surface. Aqueous humor oxygen tension can be estimated from this measured steady-state stromal surface oxygen tension by correcting the measured oxygen tension for the tension drop across the stroma and endothelium. When animals breathed room air (155 mm Hg oxygen tension), the oxygen tension of the aqueous humor was 13 mm Hg; this rose to 150 mm Hg when the inspired oxygen tension was 713 mm Hg.

Mass should be considered as one of several clinically malleable physical properties of contact lens materials. Lenses with identical posterior surface designs and back vertex powers may have different front surface parameters and thicknesses when manufactured from materials of several refractive indices. Change in anterior surface design affects overall lens volume, which combines with differences in specific gravity to change overall lens weight or mass. Clinical in situ contact lens performance may be affected in many ways by changes in anterior surface profile, volume, and overall mass, although back surface design and effective power is held constant. This study presents methodology for comparing the predicted mass of specific lens designs made from different rigid lens materials. Both theoretical and sample values are presented and discussed. Results suggest that specific gravity by itself may be a good clinical guide to the relative mass of identically designed lenses made of different materials. However, as lens mass can affect lens performance in several ways, it might be worthwhile for the clinician and/or manufacturer to develop methods whereby such calculations were automatically provided in each individual situation.

Mathematical statements are made for the various hypotheses describing the change in radius of curvature of the back surface of a flexible contact lens as it flexes. These hypotheses may now be tested for validity in predicting both optical and physiological behavior of real contact lenses in situ.

Diethylstilbestrol (DES) and 17beta-estradiol elicit significant increases in levels of endogenous and [14C]cyclic AMP in [14C]adeninelabeled hypothalami from immature female rats, but only after incubation of the hypothalami with these estrogenic agents for 40-50 min. Estriol has no effect. The 2-fold accumulation of cyclic AMP elicited by low concentrations (20 muM) of DES appears dependent on catecholamine-related mechanisms, since it is prevented by either alpha- or beta-adrenergic antagonists. Higher concentrations (100 muM) of DES elicit a 3-fold accumulation of [14C]cyclic AMP which is only partially blocked by adrenergic antagonists, haloperidol, or the adenosine antagonist, theophylline. These phenomena appear to be specific for the hypothalamus since incubation of cerebral cortical slabs with estrogens resulted in no significant increases in the levels of cyclic AMP. The slow time course in whole hypothalami and the complete lack of effects of low concentrations of estrogenic agents in chopped hypothalami suggest an indirect mechanism of action. Interaction of estrogens with receptors in cell bodies may result, after a latent period of 40-50 min, in enhanced release of catecholamines from distal synaptic terminals and in stimulation of catecholamine-sensitive adenylate cyclases at post-synaptic sites.

It is necessary to measure several samples with different thicknesses of the same material to be able to determine a value for the oxygen permeability (Dk incm2 ml O2/s ml mm Hg) of that material. Some current contact lens materials are not available in multiple thicknesses, but it might be possible to "stack" several samples of the same thickness as an alternative procedure. This study demonstrates that measurements of Dk for one particular midwater-content hydrogel (Methafilcon, a nominally 55% water-content ionic material) give statistically indistinguishable results whether single samples of various thicknesses (Dk = 20.52 x 10(-11)) or thinner stacked samples to attain similar thicknesses (Dk = 20.05 x 10(-11)) are used in this measurement.

Previous studies have shown that Ro 5-4864 is a potent convulsant and increases the firing rate of substantia nigra zona reticulata neurons. The pharmacologic profile of compounds that antagonize these actions suggested that the effects of Ro 5-4864 were not mediated by "brain-type" benzodiazepine receptors. We examined a number of compounds that are structurally related to Ro 5-4864 for their capacities to displace [3H]Ro 5-4864 from "peripheral-type" binding sites and their potencies as convulsants (or as antagonists of Ro 5-4864-induced convulsions). It was observed that compounds such as KW 3600 (the N-desmethyl analog of Ro 5-4864), which have very low affinities for "peripheral-type" sites, are convulsants with a potency nearly equal to that of Ro 5-4864. In contrast, compounds such as Ro 5-6900 and PK 11195, which bind with very high affinities to "peripheral-type" binding sites, are neither convulsants nor do they antagonize the convulsant actions of Ro 5-4864. Within a series of compounds that are structurally related to Ro 5-4864 there is a good correlation (r = 0.93; p less than 0.01) between their potencies as convulsants and their capacities to displace [35S]t-butylbicyclophosphorothionate from sites that may be associated with the chloride ionophore. Thus, it appears that occupation of "peripheral-type" binding sites by high-affinity ligands may not be directly involved in the convulsant actions of Ro 5-4864 and related compounds.

The presence of an enkephalin-like substance ('humoral endorphin') in human maternal and cord blood, as well as in amniotic fluid, has been demonstrated in this study. Utilizing antibodies to leucine-enkephalin, it was found that the level of this substance in maternal and in cord blood remained stable during pregnancy whereas the concentration in amniotic fluid was significantly higher at mid-trimester than during labor at term.

Previous studies have shown that Ro 5-4864 is a potent convulsant. Investigation of a series of compounds structurally related to Ro-4864 revealed a good correlation (r = .93, p less than 0.01) between their potencies as convulsants and their abilities to displace [35S]t-butylbicyclophosphorothionate from sites associated with the chloride ionophore. In contrast, there appears to be no direct relationship between the convulsant potencies of these compounds and their affinities for "peripheral-type" binding sites for benzodiazepines. These data suggest that "peripheral-type" binding sites for benzodiazepines are not directly involved in the convulsant actions of Ro 5-4864 and related compounds nonetheless, several lines of evidence suggest that "peripheral-type" binding sites for benzodiazepines may be indirectly involved in the convulsant properties of Ro 5-4864.

We studied 11 infants and young children fitted with contact lenses for correction of unilateral or bilateral aphakia. The visual-acuity estimates obtained from behavioral cues (alternate-cover test and central-fixation monitoring) were compared with results obtained from pattern-reversal visual-evoked potentials (VEP). We conclude that VEP may be more sensitive than behavioral observation for monitoring the visual progress in certain aphakic children.

1. The effects of intracarotid administration of Bay K 8644 on the ECG pattern along with their reversal by antianginal drugs were investigated in anaesthetized rats. 2. Intracarotid injections of Bay K 8644 (0.5-50.0 micrograms kg-1) produced a dose-related transient increase in systemic blood pressure. 3. The pressor response was accompanied by ST segment elevation (0.5-10.0 micrograms kg-1), ST segment depression concomitant with the occurrence of arrhythmias (20.0 micrograms kg-1), or A-V block (50.0 micrograms kg-1). 4. ST segment elevation reached its maximal value within 15 s and could be observed for 30-240 s. 5. The increase in blood pressure was immediate (within 5 s) and short lasting (30-120 s). After the initial increase it returned to control levels (0.5-20.0 micrograms kg-1) or dropped below (50.0 micrograms kg-1). 6. The ST segment elevation caused by 5.0 micrograms kg-1 Bay K 8644 (submaximal dose) was blocked by antianginal drugs (e.g. nitroglycerin, nifedipine and diltiazem) and by the peripheral benzodiazepine receptor antagonist PK 11195. However, the pressor response was not blocked by any of the drugs used. 7. ST segment elevation (or depression) induced by intracarotid administration of Bay K 8644 provides a useful tool for the evaluation of potential antianginal drugs.

Oxygen transmissibility, thickness, and water content were measured for three types of collagen shields: six of each type designed to dissolve in 12, 24, and 72 hours. Oxygen transmissibility was measured by a polarographic method at 35 degrees C and was found to be 17.9, 17.3, and 23.8 x 10(-9) cm mL O2/s mL mm Hg, respectively. Thicknesses were measured with an electronic gauge, and the central thicknesses of the 12-hour shields were found to be significantly greater (mean thickness, 0.19 mm) than the central thicknesses of the other two types (0.15 mm each). Water content, as measured by a hand refractometer, was found to be about 63% for all three types of shields, and no statistically significant differences were found. These measurements indicate that collagen shields behave like 63% water-content hydrogel contact lenses (oxygen permeability estimated at 27 x 10(-11) cm2 mL O2/s mL mm Hg) with regard to oxygen transmission.

Young children occasionally suffer from cataracts. Etiology may be trauma or heredity, but surgical removal and proper contact lens care are now considered imperative for visual development. This paper describes the author's method for fitting and caring for young aphakic children.

Fifteen patients discontinued use of extended-wear hydrogel contact lenses. The primary cause was neovascularization (60%), although lens soilage, giant papillary conjunctivitis and ulceration were factors in several patients each. All patients were successfully refitted with daily-wear rigid or thin, hydrogel contact lenses following simple clinical techniques.

The densities of dihydropyridine calcium antagonist binding sites were examined in brains and cardiac issues of representative species from 4 classes of non-mammalian vertebrates (aves, pigeon; amphibia, frog; reptilia, chameleon; and osteichthyes, trout) previously shown to have low or undetectable levels of 'peripheral-type' binding sites for benzodiazepines. Dihydropyridine binding sites were present in brain and cardiac tissue of these 4 classes of non-mammalian vertebrates. The apparent dissociation constants for [3H]nitrendipine in non-mammalian vertebrates were comparable to those found in mammalian (rat) tissues. The densities of [3H]nitrendipine binding sites in brain and cardiac tissues were highest in the pigeon, with lower densities in tissues from chameleon, frog and trout. The densities of dihydropyridine binding sites in the latter tissues were comparable to those observed in the rat. Thus, dihydropyridine binding sites are phylogenetically diverse yet have similar kinetic characteristics in mammals and non-mammalian vertebrates. Despite the pharmacologic evidence that links dihydropyridine binding sites and peripheral binding sites for benzodiazepines in mammals, the earlier evolutionary appearance of the former sites suggest that even though they may share one or more common effector mechanisms, they are discrete entities.

Both clinical impressions and theoretical analysis suggest a slight loss of power with flexure of low-plus-power hydrogel contact lenses. Low-minus-power hydrogel lenses do not appear to change power. This study confirms this effect.

Dopamine (DA) stimulates the cAMP-generating system in the male rat hypothalamus only to a very low extent (25% above control). Diethylstilbestrol (DES), a synthetic estrogen, was found to be extremely potent (a 4- and 16-fold stimulation at 20 micron and 100 micron, respectively). Addition of either one to an incubation medium containing varying concentrations of the other resulted in a synergistic response. The potentiation by 20 micron DES of the effect elicited by 100 micron DA was the most remarkable, namely, a 3-fold stimulation of the combined response. A 4- and 7.5-fold stimulation of cAMP accumulation was observed when adenosine (100 micron) or adenosine (100 micron) + DA (100 micron) were present in the incubation medium. Theophylline (0.5 mM), an adenosine antagonist, could effectively reduce this effect, as did adenosine deaminase (10 microgram/ml). Clomiphene (50 micron), an estrogen antagonist, exhibited a marked decrease in DES + DA-elicited cAMP formation. Pimozide (40 micron) had the ability to significantly block the stimulatory effects of DES and DA.

Recent observations have shown that "peripheral-type" binding sites for benzodiazepines (PBS) are under neural and/or hormonal control in the pineal gland, olfactory bulb, and kidney. These studies resulted in a search for endogenous substances which might physiologically subserve PBS. Acidified methanol or trichloroacetic acid extraction of both peripheral tissues and brain followed by ultrafiltration and/or gel filtration and high performance liquid chromatography revealed the presence of both high (Mr greater than 10,000) and low (Mr less than 500) molecular weight substances which inhibit the binding of [3H] Ro 5-4864 to PBS while only slightly inhibiting the binding of [3H] diazepam to classical "brain-type" benzodiazepine receptors.

The effects of spiroxatrine, a putative antagonist with selectivity for the serotonin (5-HT)1A receptor, were compared with compounds believed to function as agonists at the 5-HT1A receptor. Schedule-controlled responding of pigeons was maintained under a multiple 30-response fixed-ratio (FR), 3-min fixed-interval (FI) schedule or under a schedule in which responding was suppressed by electric shock ("conflict" procedure). Under the multiple schedule, spiroxatrine (0.3-1.0 mg/kg) decreased FR responding but did not affect FI responding; responding was decreased in both schedule components at 3.0 mg/kg. When administered alone, buspirone, a compound believed to produce its anxiolytic effects through 5-HT1A agonist actions, produced effects similar to those of spiroxatrine; in combination, the two drugs produced greater effects than when either was administered alone. As with 5-HT1A agonists such as buspirone and 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) in the pigeon, spiroxatrine (0.01-1.0 mg/kg) increased punished responding. Spiroxatrine and buspirone were potent inhibitors of [3H]8-OH-DPAT binding to pigeon cerebral membranes with IC50 values in the nM range. Neurochemical analyses of metabolite changes produced by spiroxatrine in pigeon cerebrospinal fluid showed buspirone-like effects, with increases in MHPG, DOPAC and HVA at doses that decreased 5-HIAA levels. Spiroxatrine dose-dependently blocked the behavioral effects of the dopamine agonist piribedil indicating that, like buspirone, it also is a potent dopamine antagonist. Spiroxatrine most likely functions as an agonist at the 5-HT1A receptor. As with buspirone, however, spiroxatrine has a prominent dopamine antagonist component.

Extended wear contact lenses are now a reality. Unfortunately, the physiological basis for their apparent success is less based on knowledge than wishful thinking. This paper discusses both what we know and what we don't know with the goal of giving the practitioner in the field a global view of this important and controversial procedure.

Oxygen tensions were calculated under two different oxygen-permeable, flexible contact lenses (daily wear and extended wear) both with and without consideration of tear layers (but without tear exchange). Tear layers do not have significant effects on precorneal oxygen tension.

Electroconvulsive shock (ECS) administrations repeated for 10 consecutive days cause an elevation in the opioid content of the rat brain. Two different endogenous opioids, enkephalin and humoral-endorphin, undergo independent changes that differ in both their time course and intracerebral localization. These metabolic changes parallel long-term behavioral modifications such as the development and dissipation of tolerance to the analgesic effect of ECS. The activation of two different, independent, endogenous opioid systems by ECS is in agreement with previous behavioral and pharmacological studies.

The synthesis of racemic (3 alpha,6a alpha,11a beta)-1,3,4,5,6,11a- hexahydro-2-methyl-2H-3,6a-methanobenzofuro[2,3-c]azocin -10-ol (2d) is described. The route used acid-catalyzed ring closure of enamine 5 to yield the unsaturated phenylmorphan 6. Conversion of 6 to oxide-bridged 2d was accomplished in a multistep fashion that utilized the introduction of a bromine atom, followed by O-demethylation of the phenolic methyl ethers and base-catalyzed intramolecular phenoxide displacement of the bromine. Compound (+/-)-2d represents an oxide-bridged derivative of the potent 5-(m-hydroxyphenyl)morphan class of opioid analgesics 1. Unlike the 5-(m-hydroxyphenyl)morphans that have a freely rotating phenyl group, 2d has the phenyl ring conformationally restricted at an angle of 49 degrees relative to atoms 1, 3, 11a, and 12 of 2d. The low binding of (+/-)-2d to rat brain homogenate receptor preparations [IC50 = 1000 nM] may indicate that the phenyl angle of 49 degrees is not suitable for binding to opioid receptors.

Twenty patients with corneal disease were treated with a recently released soft lens specifically designed for use as a bandage. Patients wore their lenses continuously 24 hr a day. The results were similar to those of previous studies conducted with other lens designs. Improvement was frequent (10 of 12 cases) for bullous keratopathy and corneal graft, burn, or neuroparalytic lesion; limited (1 of 4 cases) for dry-eye syndrome; and absent (4 cases) for irregular cornea and vernal keratoconjunctivitis. No difficulties were found with the concurrent use of medication.

We examined four young men with keratoconus and posterior polymorphous corneal dystrophy. All four patients showed central corneal steepening and irregularity, and large areas of irregular polymorphous opacification at the level of Descemet's membrane (in at least one cornea of each patient), which are consistent with posterior polymorphous dystrophy.

The effects of chemically and electrically-evoked seizures on [3H]nitrendipine binding to voltage-dependent calcium channels in mouse brain were determined 30 and 60 min following the initiation of convulsions. While maximal electroconvulsive shock, pentylenetetrazol and strychnine exhibited either no or marginal effects, Ro 5-4864 produced a decrease (14%) in the Bmax of [3H]nitrendipine at 30 min but not 60 min. The convulsant dihydropyridine calcium channel activator, BAY K 8644, produced a significant increase in the Kd (31%) of [3H]nitrendipine at 30 min, and a significant increase in both the Bmax (21%) and Kd (28%) of [3H]nitrendipine 60 min following the initiation of convulsions. While maximal electroconvulsive shock, pentylenetetrazol and strychnine exhibited either no or marginal effects, Ro 5-4864 produced a decrease (14%) in the Bmax of [3H]nitrendipine at 30 min but not 60 min following the initiation of convulsions. These findings indicate that modulation of voltage-dependent calcium channels by certain convulsants may be important in the genesis of seizures or in post-ictal compensatory processes.

Nalmefene (6-methylene-naltrexone) is a potent, orally active, opiate antagonist. IC50's were obtained for nalmefene, naloxone and naltrexone using radiolabelled prototype ligands for mu, kappa and delta receptors in homogenates of rat brain minus cerebellum. Nalmefene antagonized the bindings of [3H]-dihydromorphine, [3H]-ethylketocyclazocine and [3H]-D-ala-D-leu enkephalin with IC50's in the low nanomolar range. At the central mu receptor, nalmefene bound with an IC50 of 1.0 nM, equal to that of naltrexone and approximately four times lower than that of naloxone. At central kappa and delta sites the IC50's for nalmefene were somewhat lower than those of naltrexone and considerably lower than those of naloxone. All three antagonists had sodium indices less than 1.0. These results indicate that nalmefene is a universal opiate antagonist, has no agonist character at the central mu site and binds more effectively to central opiate receptors than either naloxone or naltrexone.

Buspirone, MJ-13805 and MJ-13653 did not produce a '5-hydroxytryptamine (5-HT) syndrome' in rats at doses up to 20 mg kg-1. These drugs were very weak 5-HT uptake blockers (IC50 much greater than 10 microM) compared to drugs such as chlorimipramine. These drugs did not inhibit either monoamine oxidase (MAO)-A or MAO-B. The Ki values for these agents as inhibitors of [3H]-5-HT and [3H]-ketanserin binding to rat frontal cortex or hippocampal membranes were in the microM range, well above the brain concentrations achieved after an oral dose of 25 mg kg-1. Parenterally administered buspirone blocked apomorphine-induced stereotypy, inhibited the 5-HT syndrome elicited by 5-methoxy-N,N-dimethyltryptamine, and delayed the onset of p-chloroamphetamine induced behaviours.

Basal morning humoral (H)-endorphin blood levels were assessed in ten autistic patients, 12 chronic schizophrenic patients and 11 healthy control subjects. Four autistic patients and four schizophrenic patients were drug free for at least 6 months while all other psychiatric patients were under treatment with antidopaminergic agents. Significantly reduced opioid levels were observed in the autistic group (827 +/- 103 vs 1121 +/- 75 pg-eq/ml, P less than 0.025), although the difference was actually only 26% of the control mean. A similar tendency toward low H-endorphin levels was also observed in the schizophrenic patients; however this difference was not significant (919 +/- 129 vs 1121 +/- 75 pg-eq/ml; NS). No significant difference was obtained between subjects suffering from the two psychiatric disorders (827 +/- 103 vs 919 +/- 129 pg-eq/ml; NS). Various interpretations of the decreased secretion of H-endorphin are discussed.

Surveys of contact lens practice, comparing the use of daily wear and extended wear cosmetic soft contact lenses, were distributed to almost 3,000 members of the Contact Lens Section of the American Optometric Association. There were 759 responses received of which 440 were considered valid for analysis. The results of our analysis suggest that slightly more physiological complications are encountered with extended than with daily wear of contact lenses. Most optometrists (96%), however, are satisfied with this modality and continue prescribing extended wear lenses, although many have decreased the number of days over which patients are advised to use the lenses before removal and cleaning. Most of the respondees now favor medium water content, thin lens designs for extended wear use, with 70% of them suggesting weekly removal, cleaning and aseptization. Peroxide cleaning regimens are most popular for this function.

Four classes of non-mammalian vertebrates were examined for the presence of both 'brain-specific' and 'peripheral-type' binding sites for benzodiazepines in the central nervous system. 'Brain-specific' binding sites for benzodiazepines were found in the central nervous systems of all non-mammalian vertebrates studied. However, in contrast to mammals, either very low or undetectable levels of 'peripheral-type' binding sites for benzodiazepines were observed in the central nervous systems of these non-mammalian vertebrates. Furthermore, the density of 'peripheral-type' binding sites for benzodiazepines in non-mammalian vertebrate heart was less than or equal to 2% of that found in mammalian cardiac tissue. These findings suggest a very late evolutionary appearance of 'peripheral-type' binding sites for benzodiazepines, implying that these sites may have (a) highly specialized function(s) in both peripheral tissues and the central nervous system.

Ro 5-4864 (4'-chlorodiazepam) elicited convulsions in mice with a CD50 of 23.5 mg/kg (i.p.) and increased the firing rate of substantia nigra zona reticulata neurons in a dose dependent fashion (0.5-4 mg/kg i.v.). Diazepam and clonazepam, but not Ro 15-1788, were potent inhibitors of Ro 5-4864 induced convulsions. Ro 15-1788 was also ineffective in reversing Ro 5-4864 induced increases in cell firing of zone reticulata neurons. Muscimol potently inhibited the seizures and reversed increases in cell firing elicited by Ro 5-4864. Phenobarbital and pentobarbital inhibited Ro 5-4864 induced convulsions with moderate potencies, while phenytoin and carbamazepine were ineffective at doses of up to 100 mg/kg. These observations suggest that Ro 5-4864 does not elicit its pharmacologic actions through a direct action at a 'brain-type' benzodiazepine receptor. However, both the profile and potency of compounds effective in inhibiting the electrophysiological and pharmacological effects of Ro 5-4864 suggest that this compound may act by perturbation of a component of the GABA-benzodiazepine receptor chloride ionophore complex. These findings do not, however, rule out a direct involvement of the high affinity 'peripheral-type' benzodiazepine receptors found in brain.

Buspirone, a clinically effective anxiolytic, has not shown robust effects consistently in procedures used traditionally with rodents and nonhuman primates to evaluate potential antianxiety activity. When key pecking by pigeons was maintained by food and was punished alternately under one component of a multiple schedule by the presentation of electric shock (conflict procedure), buspirone (0.03-10.0 mg/kg i.m.) produced increases in punished responding that were up to 30 times those of the control response rate. These doses did not affect or decreased unpunished responding. A buspirone analog, MJ 13805 (gepirone) produced effects similar to buspirone, although unpunished responding was slightly more sensitive to the rate-decreasing effects of MJ 13805 than to those of buspirone. A metabolite of buspirone, 1-pyrimidinyl piperazine (1-PP; MJ 13653), did not affect key pecking across a wide dose range (0.01-3.0 mg/kg i.m.), although slight decreases in both punished and unpunished responding occurred at the highest dose. Increases in punished responding with buspirone were not affected by the benzodiazepine receptor antagonist Ro 15-1788 (0.01-0.1 mg/kg i.m.). [3H]Diazepam binding to pigeon cerebrum or cerebellum in vivo was not altered by buspirone, or did buspirone, MJ 13805, or 1-pyrimidinyl piperazine displace [3H]flunitrazepam binding in vitro at pharmacologically relevant concentrations. These findings confirm previous work demonstrating marked rate-increasing effects of buspirone on punished responding in the pigeon, extend such effects to the buspirone analog MJ 13805 and indicate that the effects of buspirone are not mediated through the benzodiazepine receptor complex.

We report a bacterial corneal ulcer that occurred in a patient who had worn extended-wear rigid gas-permeable contact lenses on a 1-week cycle for 9 months. Pseudomonas aeruginosa was cultured not only from the corneal ulcer but also from the contact lens solutions, suggesting that the patient had been noncompliant with care procedures. To our knowledge, this is the first report of a bacterial corneal ulcer associated with use of a rigid gas-permeable contact lens on an extended-wear basis.

The density of [3H]flunitrazepam and [3H]Ro 5-4864 binding sites was examined 19-21 and 27-31 days after surgical isolation of the olfactory bulbs. While statistically significant reductions in [3H]flunitrazepam binding were observed in the olfactory bulbs at both intervals, a significant reduction in [3H]Ro 5-4864 binding was observed only at 27-31 days after surgery. No consistent changes in the binding of either radioligand were observed in cerebella. Extirpation of the olfactory bulbs resulted in a significant reduction in the convulsant potency (but not efficacy) of Ro 5-4864, while neither the potency nor efficacy of pentylenetetrazole was affected by this procedure. These results suggest that benzodiazepine receptors and 'peripheral-type' binding sites for benzodiazepines are regulated independently, and that at least a subpopulation of peripheral-type binding sites are associated with neuronal elements in the olfactory bulb. These data also suggest that peripheral-type binding sites for benzodiazepines in the olfactory bulbs may influence the convulsant actions of Ro 5-4864.

We examined two soft contact lens wearers who developed keratitis associated with Bacillus contamination of their contact lens care systems. Patient 1 developed a corneal ulcer caused by B. subtilis, and Patient 2 demonstrated multiple, diffuse, punctate corneal epithelial opacities associated with B. cereus contamination in the contact lens and lens case compartment. The contact lens cases of both patients contained Bacillus spores that survived multiple heat disinfection treatments. Three different contact lens chemical disinfection systems used for the minimum recommended time failed to kill the Bacillus organisms.

Many models have been proposed to describe the simultaneous changes which occur in front and back radii of curvature of a hydrogel contact lens flexing or "wrapping" onto the surface of a human eye. This study first discusses the concept that the change in front radius (delta r1) may be related to the change in back radius (delta r2) by a simple constant which may change with lens design, and then develops a separate new general relation from observed lens behavior: delta r1/delta r2 = 1 - 0.05 F, where F is unflexed lens back vertex power.

On the eye a contact lens is bathed in tear fluid, which increases its resistance to oxygen flux. For rigid gas-permeable lenses, this effect should be small during open-eye wear because a large amount of oxygen is provided by air-saturated tears that are pumped under the lens. However, under closed-eye conditions this study suggests substantial decrease in overall lens system oxygen transmissibility when lens transmissibility itself is greater than 20 x 10(-9) cm ml O2/s ml mm Hg and when the average thickness of the tear layer is greater than about 20 micron.

Toric hydrogel contact lenses are used when spherical lenses prove inadequate at correcting refractive error due to astigmatism. A model of hydrogel contact lens flexure effects allows theoretical investigation of the in situ optical power of toric soft contact lenses. Total meridional power is believed to be the sum of meridional lens power and entrapped tear layer power if any, and not due to lens form or flexure when considering low-minus powered lenses. The clinician should reduce astigmatic power correction both to allow for minus tear lens effects in thicker meridians and to decrease variable visual results due to misrotation.

We examined the contact lens care systems of 100 asymptomatic patients who used hard or soft contact lenses for correction of refractive errors for the presence of bacteria, fungi, Acanthamoeba, and endotoxin. Of 100 patients, 52 had contaminated contact lens care systems. Sixteen of 126 bottles (13%) of commercial contact lens care solutions were contaminated. Contaminated commercial solutions were opened and used for a longer period of time than uncontaminated solutions. Contamination was not found in bottles of preserved commercial solutions that were opened and used for less than 21 days. All 12 bottles of homemade saline were contaminated with bacteria, and Acanthamoeba was isolated from two of these bottles. Pseudomonas was found in the care systems of 12 patients. Bacillus species, which form spores resistant to heat, were found in the care systems of seven patients. Endotoxin, which is also resistant to heat, was detected in nine of 35 care systems (26%) tested. Potential pathogens were isolated from the conjunctiva of six patients.

'Peripheral' binding sites for benzodiazepines are under neural or homonal control in the pineal gland, olfactory bulb, and kidney. These observations prompted a search for an endogenous substance which could modulate these sites under physiological conditions. Acidified methanol extracts from several tissues (e.g. stomach, kidney, lung) were found to inhibit the binding of [3H]Ro 5-4864 to 'peripheral' binding sites, but did not significantly affect the binding of [3H]diazepam to 'brain' benzodiazepine receptors. Fractionation of a crude extract prepared from antral stomach by either ultrafiltration or gel filtration chromatography yielded high (Mr greater than 10 000) and low (Mr less than 1000) Mr fractions which competitively inhibited [3H]Ro 5-4864 binding to 'peripheral' sites. These observations suggest the presence of endogenous substances in several rat tissues which may represent physiologically important ligands for 'peripheral' binding sites for benzodiazepines.

Cats subjected to daily (25-30 days) electroconvulsive shock (ECS) demonstrated an elevation of their electroconvulsive threshold or tolerance to ECS. [3H] Nitrendipine binding was measured to brain regions from non-tolerant (sham shocked) and ECS tolerant cats 24 hr following the last shock. ECS produced a significant increase (45%) in the density of [3H] nitrendipine binding sites in the cerebral cortex and a significant decrease (33%) in the apparent affinity of [3H] nitrendipine in the cerebellum. No changes in binding were observed in the hippocampus. The effects of ECS were also investigated in the rat, an animal not displaying tolerance to repeated ECS. [3H] Nitrendipine binding to rat brain was measured 10 min and 24 hr following one shock (acute) or ten shocks delivered transauricularly once daily (chronic). Twenty-four hours following chronic ECS, there was a significant increase (19%) and decrease (11%) in the density, but no change in the apparent affinity of [3H] nitrendipine binding sites in the cerebral cortex and hippocampus respectively. No significant change in [3H] nitrendipine binding was observed in rat cerebellum 24 hr following chronic ECS. There were no changes in [3H] nitrendipine binding in the cerebral cortex and hippocampus 10 min and 24 hr following acute ECS. These results indicate that ECS can alter [3H] nitrendipine binding to calcium channel linked dihydropyridine binding sites in the central nervous system. It is suggested that changes in [3H] nitrendipine binding in the cat cerebellum may be involved in the development of tolerance to ECS.