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Purpose: The purpose of this study is to assess the relationships between optic nerve head drusen (ONHD) volume, retinal nerve fiber layer (RNFL) thickness and visual field (VF) loss., Methods: Patients with ONHD and no other ocular or systemic conditions that can affect RNFL or VF were enrolled. Serial enhanced depth imaging (EDI) optical coherence tomography (OCT) B-scans of the optic nerve head (interval between scans, ~30 μm) were obtained from each participant. ONHD volume was calculated for each eye by delineating the ONHD masses in each OCT B-scan using 3-dimensional reconstruction software., Results: A total of 47 eyes (28 patients) with ONHD were included (mean age, 57±16 y). ONHD volume varied considerably [0.265±0.227 (range, 0.005 to 0.855)] mm. Linear and quadratic regression analyses demonstrated that ONHD volume is significantly associated with both global average RNFL thickness (linear R=0.531, quadratic R=0.557; P<0.001) and VF mean deviation (linear R=0.519, quadratic R=0.522; P<0.001). ONHD were most prevalent in the nasal quadrant (46 eyes, 98%), followed by superior, inferior and temporal quadrants [35 (74%), 30 (64%), and 16 (34%) eyes respectively]. The proportion of eyes with OCT RNFL defects (81%; 38/47 eyes) was significantly greater than that with VF defects (60%; 28/47 eyes) (P<0.001). RNFL defects were detected in 10 of the 19 eyes with no VF defects. RNFL defects were detected in all 28 eyes with VF defects., Conclusions: ONHD volume generally correlates with structural and functional optic nerve damage.

Background/aims: To characterise in vivo Schlemm's canal (SC) and collector channels (CC) microstructures using enhanced-depth imaging (EDI) optical coherence tomography (OCT)., Methods: Serial horizontal EDI OCT B-scans (81 scans, 15×5° rectangle) were prospectively obtained in the nasal and temporal limbus. SC cross-sectional area (CSA) was measured by delineating its lumen in each B-scan. CCs connected to SC were counted. SC CSA and the number of CCs were compared between the nasal and temporal areas., Results: Eleven eyes (11 normal subjects) were included (mean age, 28±5 years). SC and CCs were clearly demarcated in EDI OCT B-scans with excellent repeatability and reproducibility (intraclass correlation coefficients, 0.830-0.886 and 0.793, respectively; all p<0.001). SC CSA varied considerably among subjects, ranging from 1664 to 6007 µm 2 (average, 3514±1235 µm 2 ), and among different regions of the same eye with coefficient of variation in each eye ranging from 23% to 46% (average, 32±7%). The number of CCs in the analysed area also varied considerably among subjects, ranging from 5 to 11 (average, 8.73±1.85). The mean SC CSA (3839±1402 µm 2 vs 3189±1209 µm 2 ; p=0.033) and number of CCs (5.5±1.4 vs 3.3±1.1; p=0.001) were significantly greater nasally than temporally. The mean SC CSA was significantly correlated with the number of CCs (r=0.635, p=0.036)., Conclusions: High-quality images of the aqueous outflow pathway can be obtained with a clinical device, avoiding postacquisition processing. In vivo SC and CC microstructures vary considerably among individuals and regions. SC tends to be larger in regions with more CCs., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: To assess the effects of corneal collagen cross-linking (CXL) on contrast sensitivity (CS), visual acuity, and corneal topography investigating possible predictors of efficacy., Methods: Sixty-eight eyes of 34 patients with progressive keratoconus were enrolled in this prospective study. CXL was performed in one eye and the other eye was left untreated as a control. CS, best spectacle-corrected visual acuity (BSCVA), simulated keratometry in the steepest meridian (SimK-s), mean power in the central 3-mm zone (C-MP), mean power in the paracentral 3- to 5-mm zone (P-MP), maximum keratometric power in the central zone (C-Kmax), and maximum keratometric power in the paracentral zone (P-Kmax) were evaluated at baseline, 40 days, 3 months, 6 months, 1 year, and after 2 years of follow-up., Results: Treated eyes showed an improvement (P < 0.001) of +0.16 logCS and -0.16 logarithm of the minimum angle of resolution (logMAR) and a reduction in SimK-s of -0.61 diopter (D), C-Kmax -1.11 D, P-Kmax -0.99 D, C-MP -0.39 D, and P-MP -0.30 D. Of the treated eyes, 43.3% had a decrease in C-Kmax greater than 1 D, 50% by 0 to 0.99 D, and 6.7% had an increase of up to +0.89 D. Treated eyes with keratometric apex in the central 3-mm zone (CKA) improved BSCVA -0.19 logMAR and CS +0.19 logCS; whereas in treated eyes with paracentral keratometric apex (PKA), the improvement was -0.13 logMAR and +0.16 logCS., Conclusions: CXL with riboflavin and UV-A improved CS and inhibited the progression of keratoconus. As a predictor of treatment efficacy, eyes with CKA showed greater improvement in BSCVA after CXL when compared with eyes with PKA.

The neuropeptide cholecystokinin (CCK) has been implicated in fear and anxiety. CCK is found in the CNS in several molecular forms such as the tetrapeptide (CCK-4) and, mainly, the sulfated octapeptide (CCK-8s) fragments. Administration of CCK-4 induces panic attacks in humans and increases the expression of different anxiety-related behaviors in laboratory animals. The effects of CCK-8s on fear and anxiety are less straightforward and seem to be influenced, among other factors, by the route of the peptide administration and the animal model employed. In other to further investigate the role of CCK-8s in fear and anxiety, in the present study we analyzed the effect of CCK-8s in male Wistar rats submitted to the elevated T-maze. This animal model of anxiety was developed in order to separate generalized anxiety (inhibitory avoidance) and panic-like (escape) responses in the same rat. The effect of CCK-8s in this test was also investigated after injection of the peptide into the dorsal periaqueductal gray (DPAG). This brainstem area is rich in CCK receptors and has consistently been implicated in the mediation of fear and anxiety responses. The results showed that both the intraperitoneal and intra-DPAG injections of CCK-8s potentiated one-way escape behavior, suggesting a panicogenic action. In contrast, the injection of the CCK2 receptor antagonist CR2945 inhibited the expression of this behavior, a panicolytic-like effect. Therefore, the elevated T-maze, in contrast to other animal models of anxiety, can detect the anxiety-eliciting effects of CCK-8s both after its systemic and central administration. Also, the results provide further evidence about the involvement of a CCK-mediated mechanism within the DPAG in the regulation of panic-related defensive behaviors.

Systemic administration of cholecystokinin (CCK) fragments produces anxiogenic effects. The dorsal periaqueductal gray (dPAG) has been related to anxiety and panic reactions. The objective of this study was to investigate a possible anxiogenic effect of CCK-8 microinjected into the dPAG. At 10 min after the last microinjection (0.5 microl) into the dPAG male Wistar rats (N=7-17) were tested in the elevated plus-maze, an animal model of anxiety. The following treatments were tested alone or in combination: sulfated CCK-8 (CCK-8s, 0.5-1 microg), PD 135158 (N-methyl-D-glucamine, 0.1 microg), a CCK-2 receptor antagonist, lorglumide (0.1-0.3 microg), a CCK-1 receptor antagonist. In addition, Fos immunohistochemistry was performed in rats (n=3-4) treated with CCK-8s (1 microg) alone or in combination with PD 135158 (0.1 microg). CCK-8s produced anxiogenic-like effect, decreasing the percentage of time spent in open arm (saline=30.3+/-6.6, CCK 0.5 microg=15.2+/-1.8; CCK 1 microg=14.6+/-2.1). This effect was prevented by pretreatment with PD 135158, but not by lorglumide. CCK-8s injected into the dPAG induced Fos immunoreactivity in several brain areas related to defensive behavior, including the PAG, median, and dorsal raphe nuclei, superior colliculus, lateral septal nuclei, medial hypothalamus, and medial amygdala. This effect was also prevented by pretreatment with PD 135,158. These results suggest that CCK-8s, acting on CCK-2 receptors, may modulate anxiety reactions in the dPAG.

We report here the results obtained in epidemiologic surveys of histoplasmosis and paracoccidioidomycosis carried out in Brazil using the histoplasmin and paracoccidioidin delayed hypersensitivity skin tests. Most of these data have not been previously published in scientific journals and are now reported here in two tables respectively concerning histoplasmosis (88 surveys) and paracoccidioidomycosis (58 surveys). The guidelines to be followed in surveys of this nature are also commented upon.

Anxiety disorders are heterogeneous and existing animal models do not discriminate specific types of anxiety. The elevated T-maze is being developed to fulfill this purpose. The apparatus consists of three elevated arms, one enclosed and two open. Inhibitory avoidance--representing learned fear--is measured by recording the time taken to leave the enclosed arm in three consecutive trials. Unconditioned fear is evaluated by recording the time to escape from the open arm. Restraining the animals at the end of the enclosed arm for 30 s did not change the first (baseline) withdrawal latency, indicating that rats are not escaping from the experimenter's hand. In addition, rats trained in a T-maze with the three arms enclosed did not show the usual increase in withdrawal latency over the three consecutive trials. These results indicate that open arm experience, not handling, motivates inhibitory avoidance learning. The same experiment also showed that the latency to leave the open arm did not undergo habituation over five consecutive trials, thereby providing evidence of an aversive motivation for this response. The anxiolytic agents diazepam (benzodiazepine), buspirone and ipsapirone (5-HT1A agonists) as well as ritanserin (5-HT2 antagonist) selectively impaired inhibitory avoidance while leaving one-way escape unchanged. Similar results were obtained with three putative anxiolytics: the 5-HT2B/2C antagonists SB 200646A and SER 082, and the 5-HT2A antagonist SR 46349B. However, RP 62203, another 5-HT2A antagonist, was ineffective on both tasks. In contrast to the above anxiolytics, the anxiogenic agents yohimbine, TFPP and mCPP facilitated inhibitory avoidance. Escape was not affected by yohimbine, but was moderately attenuated by the two 5-HT2C/2B agonists. The 5-HT releaser and uptake inhibitor D-fenfluramine tended to enhance inhibitory avoidance, while impairing one-way escape in a dose-dependent way. The antidepressant clomipramine also had an anxiogenic-like effect on inhibitory avoidance, but did not affect escape from the open arm. Conversely, the phenethylamine hallucinogen ALEPH 2 did not affect inhibitory avoidance while impairing escape. Nevertheless, the similar compound and 5-HT2A agonist DOI was devoid of any effect. Also ineffective were the psychomotor stimulants D,L-amphetamine and caffeine, the reversible monoaminoxidase-A inhibitor moclobemide and the neuroleptic haloperidol. Finally, micro-injection into the dorsal raphe nucleus of two drugs that stimulate 5-HT neurons, the excitatory amino acid kainic acid and the benzodiazepine inverse agonist FG 7142, facilitated inhibitory avoidance. Kainate also significantly impaired escape. In contrast, intra-raphe 8-OH-DPAT, which inhibits 5-HT neurons, selectively impaired inhibitory avoidance in a manner similar to systemically administered anxiolytics. These behavioral and pharmacological results support the view that inhibitory avoidance in the elevated T-maze may be related to generalized anxiety disorder, while one-way escape may be associated with panic disorder.

To study the role of 5-HT2A and 5-HT2C receptor subtypes in anxiety, the behavioral effects of drugs that either block or stimulate these receptors were measured in an animal model of anxiety, the elevated T-maze. One arm of the maze is enclosed by walls and stands perpendicular to the two open arms. Inhibitory (passive) avoidance--representing learned fear--was measured by placing a rat at the end of the enclosed arm and recording the time to leave this arm with the four paws during three consecutive trials. After 30 s, the same animal was placed at the end of one of the open arms and the time to leave this arm with the four paws was recorded. This one-way escape response represents unconditioned fear. The I.P. injection of the preferential 5-HT2C receptor agonists mCPP and TFMPP (0.1-0.8 mg/kg), 25 min before the experimental session enhanced inhibitory avoidance. In contrast, the same drugs either tended to impair (mCPP) or significantly inhibited (TFMPP) one-way escape. The preferential 5-HT2A agonist DOI (0.03-0.3 mg/kg) did not change either inhibitory avoidance or one-way escape. Inhibitory avoidance was impaired by the selective 5-HT2C antagonists SB 200646A (3.0-30 mg/kg) and SDZ SER 082 (0.1-1.0 mg/kg), by the 5-HT2A antagonist SR 46349B (1.0-10.0 mg/kg), and by the mixed 5-HT(2A,2C) antagonist ritanserin (0.3-3.0 mg/kg). However, it was not affected by the selective 5-HT2A antagonist RP 62203 (0.25-4.0 mg/kg). All the 5-HT2 antagonists used were ineffective on one-way escape. Therefore, conditioned fear seems to be tonically facilitated through 5-HT2C receptor stimulation, although the 5-HT2A receptor may also participate in its regulation. Unconditioned fear might be phasically inhibited by 5-HT2C receptor activation.

One hundred outpatients in a Clinic of Allergy were submitted to intradermic tests with two types of candidins. The main focus of the research was the comparison of two antigens obtained from the same strains of Candida albicans: one a suspension of yeast cells and the other, a polysaccharide. The readings, taken 20 minutes after the intradermic injections, with positive results were considered as hypersensitivity of the immediate type. Positive results were obtained in 74% of the patients with the yeast cell antigen and in 73% with the polysaccharide antigen. This research mainly deals with the advantages that can be obtained by using the polysaccharide antigen in intradermic tests for evaluating hypersensitivity of the immediate type.

The aim of this investigation was to study epidemiological aspects of paracoccidioidomycosis, the main endemic systemic mycosis in Brazil. This study was carried out using the paracoccidioidin delayed hypersensitivity test in 96 Latin American wild mammals, including 49 arboreal animals (primates): 33 Cebus apella (weeping-capuchin), 16 Callithrix jacchus (marmoset); and 47 terrestrial animals (carnivora): 37 Nasua nasua (coatimundi), and 10 Felidae [Panthera onca (jaguar), Felis paradalis (ocelot), Felis wiedii (margay), Felis tigrina (wild cat) and Felis geoffroyi (wild cat)], taking their behaviour and habitat into consideration. When the levels of paracoccidiodin positive reactions were examined, terrestrial animals showed significantly higher rates (82.98%) while arboreal animals showed lower reactivity (22.45%) (P < 0.01). The data are relevant because there are quite a few papers regarding domestic and wild animals and this study may help the understanding of some aspects of the parasite ecology. These results point to the soil as the most probable reservoir of Paracoccidioides brasiliensis, and this is possibly the ecological niche of the saprophytic phase in nature.

Sporotrichosis and histoplasmosis are deep mycosis with a high incidence in human beings in Brazil. In domestic animals histoplasmosis has been described only in dogs, but the occurrence of sporotrichosis among domestic animals in Brazil has been described in dogs, cats, mules and asses. There is also a case of this disease reported in a chimpanzee (Pan troglodites). The purpose of this research was to perform an epidomiological study of these mycoses using delayed hypersensitivity tests (histoplasmin and sporotrichin) in Latin American wild mammals. This research was assayed using 96 healthy animals at Parque Zoológico de São Paulo, Brazil: Primates: 33 Cebus apella--weeping-capuchin and 16 Callithrix jacchus--marmoset; Procyonidae: 37 Nasua nasua--coatimundi and 10 Felidae (Panthera onca--jaguar; Felis pardalis--ocelot Felis wiedii--margay; Felis tigrina--wild cat). For intradermic tests, the following antigens were used: Sporothrix schenkii cell suspension (sporotrichin, histoplasmin-filtrate), Histoplasma capsulatum cell suspension (histoplasmin), and Histoplasma capsulatum (polysaccharide). The positivity to histoplasmin was 44.79% (Cebidae 15.15%; Callithricidae 6.25%; Procyonidae 86.49% and Felidae 50.00%, respectively). With respect to sporotrichin, 30.21% (Cebidae 6.06%, Callithricidae 0.0%; Procyonidae 64.86% and Felidae 30.00% respectively). The pattern of infection is similar to that shown by human beings and this may suggest that these animals could be involved in the epidemiologic chain of sporotrichosis and histoplasmosis, the second most prevalent human deep mycoses in Brazil. It is important to point out the absence of similar studies in Latin American wild animals.

A skin test survey with paracoccidioidin and histoplasmin was conducted on 495 residents of Coari in the Brazilian state of Amazonas. Positive dermal reactions to paracoccidioidin and histoplasmin were seen, respectively, in 13.9% and 50.1% of the study subjects. Specific reaction to paracoccidioidin was observed in 1.6% of the individuals, and to histoplasmin in 37.8%. Cross-reactivity between the two antigens in persons who reacted positively to both skin tests was not totally reciprocal. There were no significant differences in dermal reactivity to either of the two antigens in either sex, or among different occupational groups. No precipitating antibody to paracoccidioidin or histoplasmin was detected in the sera of the skin test-positive individuals by the immunodiffusion test. Skin test positivity in the general population of Coari reaffirmed the concept of benign, self-limited infection in paracoccidioidomycosis and histoplasmosis. It also identified the equatorial forests of the Upper Amazon Basin as endemic zones of these two mycoses.

A case of paracoccidioidomycosis by accidental innoculation on the back of the left hand in a female patient is presented. Clinically the manifestation was of a hard and painful nodular lesion. This lesion was completely excised surgically. This lesion was completely excised surgically. The material obtained revealed the "Paracoccidioides brasillensis" by direct and histopathologic microscopic examinations. No culture was obtained. The histopathologic aspect of the lesion was of a tuberculoid granuloma. The immunological study demonstrated a positive intradermic test and negative results by complement fixation and preciptin reactions. The lesion cured completely after the surgical excision and sulfadimetoxin treatment.

Three intratesticulary inoculated bovines revealed to be susceptible to experimental paracoccidioidomycosis. The experimental infection was self limited with no tendency to dissemination during a follow up period of five months. The histopathologic lesions characterized by granulomatous inflammatory foci, associated or not to necrosis, were found in the testicles, spermatic cords and testicular tunicae. In some of both lesions types the yeast cells of P. brasiliensis were present. The experimental infection did not cure in a follow up period of five months. The immunological response either cellular or humoral were delayed in relation to what happens in other animal species. The three experimentally infected bovines were utilized for some standardization of the paracoccidioidin intradermic test. A type and dose of an antigen which gives a clear reading for the positive tests was determined. The humoral responses were detected mainly by the complement fixation reaction. It was not possible to demonstrate humoral antibodies by the agar immunodiffusion test.