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LR and [d-Gln4]LR peptides bind the monomer-monomer interface of human thymidylate synthase and inhibit cancer cell growth. Here, proline-mutated LR peptides were synthesized. Molecular dynamics calculations and circular dichroism spectra have provided a consistent picture of the conformational propensities of the [Pro n]-peptides. [Pro3]LR and [Pro4]LR show improved cell growth inhibition and similar intracellular protein modulation compared with LR. These represent a step forward to the identification of more rigid and metabolically stable peptides.

TBX15 is a gene involved in the development of mesodermal derivatives. As the ovaries and the female reproductive system are of mesodermal origin, the aim of the present study was to determine the methylation status of the TBX15 gene promoter and the expression levels of TBX15 in ovarian carcinoma, which is the most lethal and aggressive type of gynecological tumor, in order to determine the role of TBX15 in the pathogenesis of ovarian carcinoma. This alteration could be used to predict tumor development, progression, recurrence and therapeutic effects. The study was conducted on 80 epithelial ovarian carcinoma and 17 control cases (normal ovarian and tubal tissues). TBX15 promoter methylation was first determined by pyrosequencing following bisulfite modification, then by cloning and sequencing, in order to obtain information about the epigenetic haplotype. Immunohistochemical analysis was performed to evaluate the correlation between the methylation and protein expression levels. Data revealed a statistically significant increase of the TBX15 promoter region methylation in 82% of the tumor samples and in various histological subtypes. Immunohistochemistry showed an inverse correlation between methylation levels and the expression of the TBX15 protein. Furthermore, numerous tumor samples displayed varying degrees of intratumor heterogeneity. Thus, the present study determined that ovarian carcinoma typically expresses low levels of TBX15 protein, predominantly due to an epigenetic mechanism. This may have a role in the pathogenesis of ovarian carcinoma independent of the histological subtype.

Proteomics and bioinformatics are a useful combined technology for the characterization of protein expression level and modulation associated with the response to a drug and with its mechanism of action. The folate pathway represents an important target in the anticancer drugs therapy. In the present study, a discovery proteomics approach was applied to tissue samples collected from ovarian cancer patients who relapsed after the first-line carboplatin-based chemotherapy and were treated with pemetrexed (PMX), a known folate pathway targeting drug. The aim of the work is to identify the proteomic profile that can be associated to the response to the PMX treatment in pre-treatement tissue. Statistical metrics of the experimental Mass Spectrometry (MS) data were combined with a knowledge-based approach that included bioinformatics and a literature review through ProteinQuest™ tool, to design a protein set of reference (PSR). The PSR provides feedback for the consistency of MS proteomic data because it includes known validated proteins. A panel of 24 proteins with levels that were significantly different in pre-treatment samples of patients who responded to the therapy vs. the non-responder ones, was identified. The differences of the identified proteins were explained for the patients with different outcomes and the known PMX targets were further validated. The protein panel herein identified is ready for further validation in retrospective clinical trials using a targeted proteomic approach. This study may have a general relevant impact on biomarker application for cancer patients therapy selection.

Aberrant methylation of multiple promoter CpG islands could be related to the biology of ovarian tumors and its determination could help to improve treatment strategies. DNA methylation profiling was performed using the Methylation Ligation-dependent Macroarray (MLM), an array-based analysis. Promoter regions of 41 genes were analyzed in 102 ovarian tumors and 17 normal ovarian samples. An average of 29% of hypermethylated promoter genes was observed in normal ovarian tissues. This percentage increased slightly in serous, endometrioid, and mucinous carcinomas (32%, 34%, and 45%, respectively), but decreased in germ cell tumors (20%). Ovarian tumors had methylation profiles that were more heterogeneous than other epithelial cancers. Unsupervised hierarchical clustering identified four groups that are very close to the histological subtypes of ovarian tumors. Aberrant methylation of three genes ( BRCA1 , MGMT , and MLH1 ), playing important roles in the different DNA repair mechanisms, were dependent on the tumor subtype and represent powerful biomarkers for precision therapy. Furthermore, a promising relationship between hypermethylation of MGMT , OSMR , ESR1 , and FOXL2 and overall survival was observed. Our study of DNA methylation profiling indicates that the different histotypes of ovarian cancer should be treated as separate diseases both clinically and in research for the development of targeted therapies.

The complexity of traffic control systems, as well as the growing volume of traffic, interconnected missions types and mission demands on the operators, indicates that critical attention should still be paid to the problem of operator's cognitive workload (WL). On the other hand, the development of traffic control towards on-line measurement of cooperative aspects between humans and machines, is part of the more general need to measure the human agents “situation awareness” in industrial environment. The University of Modena and Reggio Emilia was partner of the European Artemis project “Designing Dynamic Distributed Cooperative Human-Machine Systems” (D3CoS 2011–2014) [1] to define affordable methods, techniques and tools addressing the specification, development and evaluation of cooperative systems where human and machine agents are in charge of common tasks, assigned to the system as a whole. One of the basic keys to reach an optimal human-machine cooperation is the measure of the human operator workload. In order to setup a possible method for the objective evaluation of cognitive workload we had to investigate aspects of the functional status of human operators interacting with a simulator in maritime domains. We recorded objective psycho-physiological measures: eye blinks, respiration rate and amplitude, electrodermal activity, heart rate variability, and blood pressure. They were analyzed and correlated with subjective self-assessed responses from two questionnaires: NASA-TLX and Rating Scale Mental Effort (RSME), with the aim to realize a mathematical model for classifying the operators' mental workload. The purpose of this paper is to present the methods, applied on a pilot study, that we carried out to discriminate the WL intensity, based on psycho-physiological signals alone.

The authors test the hypothesis of systematic errors in photometric and/or densitometric measurements performed by Fundus camera equipment. By means of 2 different methods (reflection and transmission) the non-uniformity of light-distribution on sample surfaces placed in front of the fundus camera is shown. The consequent point by point variability in retinal illumination can be defined as the 'retinal shading problem'. This conclusion must be taken into account when equidensitometric measurements are carried out on eye fundus images with fundus camera, by photographic, cinematographic or TV techniques.

Most types of cancer cells are characterized by aberrant methylation of promoter genes. In this study, we described a rapid, reproducible, and relatively inexpensive approach allowing the detection of multiple human methylated promoter genes from many tissue samples, without the need of bisulfite conversion. The Methylation Ligation-dependent Macroarray (MLM), an array-based analysis, was designed in order to measure methylation levels of 58 genes previously described as putative biomarkers of cancer. The performance of the design was proven by screening the methylation profile of DNA from esophageal cell lines, as well as microdissected formalin-fixed and paraffin-embedded (FFPE) tissues from esophageal adenocarcinoma (EAC). Using the MLM approach, we identified 32 (55%) hypermethylated promoters in EAC, and not or rarely methylated in normal tissues. Among them, 21promoters were found aberrantly methylated in more than half of tumors. Moreover, seven of them (ADAMTS18, APC, DKK2, FOXL2, GPX3, TIMP3 and WIF1) were found aberrantly methylated in all or almost all the tumor samples, suggesting an important role for these genes in EAC. In addition, dysregulation of the Wnt pathway with hypermethylation of several Wnt antagonist genes was frequently observed. MLM revealed a homogeneous pattern of methylation for a majority of tumors which were associated with an advanced stage at presentation and a poor prognosis. Interestingly, the few tumors presenting less methylation changes had a lower pathological stage. In conclusion, this study demonstrated the feasibility and accuracy of MLM for DNA methylation profiling of FFPE tissue samples.

TBX15 is a gene involved in the development of mesodermal derivatives. As the ovaries and the female reproductive system are of mesodermal origin, the aim of the present study was to determine the methylation status of the TBX15 gene promoter and the expression levels of TBX15 in ovarian carcinoma, which is the most lethal and aggressive type of gynecological tumor, in order to determine the role of TBX15 in the pathogenesis of ovarian carcinoma. This alteration could be used to predict tumor development, progression, recurrence and therapeutic effects. The study was conducted on 80 epithelial ovarian carcinoma and 17 control cases (normal ovarian and tubal tissues). TBX15 promoter methylation was first determined by pyrosequencing following bisulfite modification, then by cloning and sequencing, in order to obtain information about the epigenetic haplotype. Immunohistochemical analysis was performed to evaluate the correlation between the methylation and protein expression levels. Data revealed a statistically significant increase of the TBX15 promoter region methylation in 82% of the tumor samples and in various histological subtypes. Immunohistochemistry showed an inverse correlation between methylation levels and the expression of the TBX15 protein. Furthermore, numerous tumor samples displayed varying degrees of intratumor heterogeneity. Thus, the present study determined that ovarian carcinoma typically expresses low levels of TBX15 protein, predominantly due to an epigenetic mechanism. This may have a role in the pathogenesis of ovarian carcinoma independent of the histological subtype.

Extraocular muscles are generally considered to be spared in Duchenne Muscular Dystrophy (DMD). However, this assumption is based mainly on clinical observations, as systematic eye movement recordings have been performed in a very limited number of cases. Our goal was to analyze several saccade parameters in a higher number of cases, in order to reveal a possible ocular-motor impairment in DMD. Data were collected from a population of 9 subjects with DMD and 9 healthy male subjects of comparable age as controls. We used the electrooculographic (EOG) technique coupled with advanced digital signal processing; saccade duration, amplitude, mean velocity, peak velocity and K factor (ratio mean/peak velocity) were measured. The DMD group showed saccades with significantly longer duration and lower velocity, with respect to controls; these differences were accounted for mainly by the largest movements, whereas there were no significant differences at the smallest eccentricity tested (3 deg). Neither amplitude nor K factor were significantly different from controls for any of the eccentricities tested. To our knowledge, this is the first study to suggest significant impairment of eye movements in Duchenne muscular dystrophy.

The digital board is thought of as a tool that has limited use, primary or secondary school or in a situation of learning for the handicapped. This case study aims to show how these new tools can be used in for higher learning, in scientific and technical universities. The current software available on the market and its use with these tools foresees originality in the approach to teaching in the future. The article explores the use of advanced innovative technology in the lecture hall for effective teaching and learning. The digital whiteboard tool is a flexible and powerful didactic instrument that can greatly enrich the experience of both the learner and the lecturer. This article will explore a completed case study, a case study still in progress and future possibilities.

Prediction is pervasive in human cognition and plays a central role in language comprehension. At an electrophysiological level, this cognitive function contributes substantially in determining the amplitude of the N400. In fact, the amplitude of the N400 to words within a sentence has been shown to depend on how predictable those words are: The more predictable a word, the smaller the N400 elicited. However, predictive processing can be based on different sources of information that allow anticipation of upcoming constituents and integration in context. In this study, we investigated the ERPs elicited during the comprehension of idioms, that is, prefabricated multiword strings stored in semantic memory. When a reader recognizes a string of words as an idiom before the idiom ends, she or he can develop expectations concerning the incoming idiomatic constituents. We hypothesized that the expectations driven by the activation of an idiom might differ from those driven by discourse-based constraints. To this aim, we compared the ERP waveforms elicited by idioms and two literal control conditions. The results showed that, in both cases, the literal conditions exhibited a more negative potential than the idiomatic condition. Our analyses suggest that before idiom recognition the effect is due to modulation of the N400 amplitude, whereas after idiom recognition a P300 for the idiomatic sentence has a fundamental role in the composition of the effect. These results suggest that two distinct predictive mechanisms are at work during language comprehension, based respectively on probabilistic information and on categorical template matching.

We applied the Fos method in rats subjected to horizontal optokinetic stimulation (OKS) to study whether optokinetic information is transferred through the commissural pretectal fibres from one optic tract nucleus (NOT) to the opposite. In binocular as well as in monocular nasalward OKS, the highest Fos immunoreactivity was found in the NOT contralateral to the nasalward stimulation, as expression of the activation either of direction-selective cells and of commissural neurons. Even the opposite NOT showed many Fos-positive cells activated by the opposite nucleus throughout the commissural pretectal pathway. They might be the GABA positive cells, which are thought to allow the activation in one nucleus to be transformed into inhibition of the opposite side. In monocular temporalward OKS, the inhibition on direction-selective cells and the consequent silencing of commissural neurons caused the faint immunoreactivity in the NOT contralateral to eye stimulated. In the opposite nucleus the few Fos-positive cells emerged as a consequence of the lack of the normal tonic commissurally mediated inhibition.

In questo capitolo indagheremo il ruolo dei meccanismi di anticipazione semantica nella comprensione di espressioni i costituenti delle quali sono tipicamente legati fra loro in una sequenza piu o meno fissa, cioe le espressioni idiomatiche.1

Cloze-probability levels are inversely correlated with N400 amplitude, indicating an easier integration for expected words in semantic-pragmatic contexts. Here we exploited the prespecified standard order of complex prepositions and measured the ERPs time-locked to the last preposition in sentences in which complex prepositions were presented in their standard form or with the last preposition changed. The expected preposition elicited an N280 followed by an N400-700, two ERP components previously associated to the processing of closed-class words. The unexpected preposition elicited only an N280, and the N400-700 was reduced. These results reflect the specificity of the contextual constraints linked to the complex preposition word sequence.

A modified Zeiss slit lamp coupled with a digital image-processing system was used to evaluate objectively changes in lens transparency over 1 year at 4-month intervals in 150 eyes of 92 patients affected by early senile cataract. A total of 59 patients were treated daily with 1.5 g bendazac-lysine, and 33 patients constituted the control group. At follow-up, visual acuity was also tested using Snellen letter charts at variable contrast to provide an additional parameter closer to traditional methods. Results indicate that the minimal angle of resolution at 10% contrast (MAR10) and the mean gray-level value of the lens image obtained by retroillumination (MLR) are sensitive to early changes in lens transparency. Using MAR10 as a parameter, the control group showed a significant, progressive worsening of the lens status over 12 months, whereas the treated group exhibited no significant changes. MRL indicated the same behaviour as MAR10, although lens damage was detected later in the control group. The results show that bendazac-lysine may delay the formation of lens opacities.

Background Brain activity has been investigated by several methods with different principles, notably optical ones. Each method may offer information on distinct physiological or pathological aspects of brain function. The ideal instrument to measure brain activity should include complementary techniques and integrate the resultant information. As a "low cost" approach towards this objective, we combined the well-grounded electroencephalography technique with the newer near infrared spectroscopy methods to investigate human visual function. Methods The article describes an embedded instrumentation combining a continuous-wave near-infrared spectroscopy system and an electroencephalography system to simultaneously monitor functional hemodynamics and electrical activity. Near infrared spectroscopy (NIRS) signal depends on the light absorption spectra of haemoglobin and measures the blood volume and blood oxygenation regulation supporting the neural activity. The NIRS and visual evoked potential (VEP) are concurrently acquired during steady state visual stimulation, at 8 Hz, with a b/w "windmill" pattern, in nine human subjects. The pattern contrast is varied (1%, 10%, 100%) according to a stimulation protocol. Results In this study, we present the measuring system; the results consist in concurrent recordings of hemodynamic changes and evoked potential responses emerging from different contrast levels of a patterned stimulus. The concentration of [HbO2] increases and [HHb] decreases after the onset of the stimulus. Their variation shows a clear relationship with the contrast value: large contrast produce huge difference in concentration, while low contrast provokes small concentration difference. This behaviour is similar to the already known relationship between VEP response amplitude and contrast. Conclusion The simultaneous recording and analysis of NIRS and VEP signals in humans during visual stimulation with a b/w pattern at variable contrast, demonstrates a strong linear correlation between hemodynamic changes and evoked potential amplitude. Furthermore both responses present a logarithmic profile with stimulus contrast.

The aim of this study is to explore the possibility of correlating hemodynamic changes and neural activities in the brain by using an integrated system combining Near Infrared Spectroscopy (NIRS) and electroencephalographic activity (EEG). We present brain hemodynamic changes and EEG recordings obtained from four volunteers during the performance of two different sequential thumb-finger opposition tasks, with and without a related mental activity. The optical and electrical signals were recorded simultaneously on the subject forehead. The coupling of the two systems could be useful to demonstrate correlation between cognitive paradigms and hemodynamic signals.

In the present study we characterised by means of the c-Fos method the neuronal populations of the optokinetic nuclei system of the rat activated by different directions of external visual world motion as well as by saccadic exploration of a patterned stationary scene. A major difference was found between the nucleus of the optic tract (NOT) and the nuclei of the accessory optic system (AOS): dorsal terminal (DTN), lateral terminal (LTN) and medial terminal (MTN). c-Fos-positive cells are expressed in the AOS nuclei only after optokinetic stimulation (OKS) according to the direction for which each nucleus is strictly committed: in the DTN after horizontal OKS, in the LTN and MTN after vertical OKS. No segregation of direction-selective cells was observed in the MTN for opposite directions of motion. In the NOT, c-Fos cells became immunoreactive after OKS of any direction, with the greatest expression induced by horizontal OKS in the nucleus contralateral to the eye stimulated nasalward, and even following the presentation of a non-rotating drum. However, the spatial location of the activated neurones is distributed along the nucleus for horizontal OKS and strongly restricted to its rostral region for other stimuli. Given these findings, a larger spectrum of competencies than previously supposed should be attributed to the NOT.

The functional activity of the superior colliculus (SC) following flash stimulation was examined by means of 2-deoxyglucose (2DG) method in monocularly enucleated Long-Evans rats intraocularly injected with a solution of 2-amino-4-phosphonobutyric acid (APB), able to silence the ON retinal activity. After APB injection SC layers recipient of retinal axons suffered a sustained 2DG decrease as compared to controls. Moreover, whereas glucose utilization in normal rat SC appears unevenly distributed and closely related to retinal axon density, by contrast, APB-treated rats showed a rather uniform metabolic activity throughout the SC surface. Furthermore, we calculated the 2DG uptake percentage reduction in 12 SC loci of APB rats in respect to homologous loci of controls: glucose utilization decreases at the loci largely differ from each other, showing that retinal axons carrying ON activity are dispersed over the SC in a mosaic pattern. Thus, the SC metabolic map should be representative of its retinotopic organization which, in turn, depends on the asymmetric distribution in the rat's retina of W-like as well as of other ganglion cell types.

The authors apply the technique of amplitude histogram analysis to the clinical electronystagmogram (ENG). After a brief survey of the underlying concepts, some typical normal and pathological ENG records are discussed. Comparison of advantages and disadvantages reveals that the quoted technique may be suitable to be profitably introduced in clinical practice.

Corneal reflections produce defects in photographic sections of the lens taken with a slit-lamp biomicroscope for computerized densitometric analysis of cataract opacity. A simple and workable, adjustable antireflection device was built that can be easily adapted to photographic slit lamps, a common instrument in ophthalmology equipment. The slit lamp is a versatile tool for photographing structures in the anterior segment of the eye, particularly the lens. Corneal reflections are eliminated for angles between the light band and a photograph plane ranging from 20 degrees to 90 degrees, with the light band no greater than 0.5 mm and the corneal curvature about 7.6 to 7.9 mm. The device acts by blocking aberrant light rays from the light source that would otherwise be reflected by the mirrorlike surface of the cornea and enter the objective lens. Here we present a prototype designed for the Zeiss slit lamp.

A new method is presented for measuring geometrical parameters of the anterior segment of human eye. A digital imaging technique is employed in conjunction with a slit lamp and TV camera. A method was developed to analyze images and the problem of minimizing measuring errors was studied. The method was tested using a contact lens to simulate the anterior corneal surface.

Little information is available on the functionality of the visual system in neonates. Comparison was made between neonates born at full term and prematures equated for conceptional age, using two methods of investigation: the visual evoked potential (VEP) and the "forced preferential looking" (FPL). The results obtained by the FPL method indicate a greater visual acuity in premature subjects, whereas the results obtained by the VEP method point to no significant difference in implicit time between the two groups.

Patients with Retinal Vein Occlusion (RVO, n = 62) studied within a week after the event showed significant increase of Factor VIII (AHF and RAg), slight decrease of Antithrombin III, and prolongation of Euglobulin Lysis Time, vs. controls (n = 48). The prevalence of “poor responders” after venous occlusion was 23% in RVO vs. 12.5% in controls. Assessment of recanalization of the occluded vein was performed after 3 months in 17 selected cases with retinal branch vein occlusion, by means of dromofluorography (i.e. quantitation of fluorescein dilution curves). Patients who showed poorer recanalization were found to belong to the group of “non responders” and had significantly lower fibrinolytic activity after venous occlusion when compared with those who recanalized. Fibrinolytic response to venous occlusion provides therefore a prognostic indication in regard to spontaneous recanalization of the occluded vein in RVO patients.

Various authors have tried to determine visual acuity both electrophysiologically (Sokol, 1976 and 1978; Marg et al., 1976; Maffei and Fiorentini, 1977) and with psychophysical methods (Teller et al., 1974; Banks and Salapatek, 1976; Atkinson et al., 1976) in awake children. Our experiments try to verify the possibility of assessing visual acuity in children under Ethrane anesthesia. We conclude that under Ethrane anesthesia VEPs produced by phase-alternating square-wave gratings do not allow a fine assessment of visual acuity. Gross indications of visual acuity can however be obtained.

A general purpose image processing system is described including B/W TV camera, high resolution image processor and display system (TESAK VDC 501), computer (DEC PDP 11/23), and monochrome and color monitors. Images may be acquired from a microscope equipped with a TV camera or using the TV in direct viewing; the A/D converter and the image processor provides fast (40 ms) and precise (512×512 data points) digitization of TV signal with a 256 gray levels maximum resolution. Computer programs have been developed in order to perform qualitative and quantitative analyses of autoradiographs obtained with the 2-DG method, which are written in FORTRAN and MACRO 11 Assembly Language. They include: (1) procedures designed to recognize errors in acquisition due to possible image shading and correct them via software; (2) routines suitable for qualitative analyses of the whole image or selected regions of it, providing the opportunity for pseudocolor coding, statistics, graphic overlays; (3) programs permitting the conversion of gray levels into metabolic rates of glucose utilization and the display of gray- or color-coded metabolic maps.

The amplitude of the pattern visual evoked potential (VEP) of a binocular stimulus has been shown to be generally larger than the VEP obtained monocularly. There is evidence that this effect can be considered an electrophysiological index of fusion. To study how binocular vision develops in infancy we evaluated the incremental binocular amplitude (IBA) in three infants in a longitudinal investigation during the first five months of life. The stimuli were phase-alternating square-wave gratings with spatial and temporal parameters chosen to be appropriate for neonates. IBA was defined as the percentage increment of the largest binocular response compared with the monocular response. In the first two months of life IBA values were near zero, that is, no summation occurred. Between the second and third month IBA values rose markedly and after the third month its value was greater than 100%, demonstrating binocular facilitation. Thus in the first two months of life the eyes do not seem to cooperate as in adults. By the second and third month the binocular pattern VEP reflects an increasing binocular interaction. Other studies of the development of stereopsis have also found evidence of binocularity at similar ages.

The Zeiss slit lamp has been modified in order to extend its use to measurements of lens transparency. Two major modifications have been introduced: (1) a support for a high-sensitivity TV camera that is connected to an image processing system; (2) two potentiometers for recording electrical signals proportional to the rotation angle of the slit-supporting arm with respect to the visual axis and the slit tilting angle. As a result, the slit lamp output consists of three signals; one TV signal for the images and two analog signals for measurement of the angles. With the aid of an image-processing system connected to a minicomputer, software has been developed to enable the operator to acquire reliable digital images of the anterior segment of the eye in real time. The software provides the user with an easy-to-follow menu.

A differentiation of two types of head-turns due to nystagmus, by means of electromyography (EMG) is demonstrated in this paper. The first type is represented by patients who actively block the nystagmus, by means of an increase of discharge of the extraocular muscles who are synergistic and responsible for the head-turn. This block has the same features of the block of nystagmus in convergence and usually exceeds 10-15 degrees from the primary position. The second type is made out of patients whose head-turn is explained with the null-position of Kestenbaum. Here the nystagmus simply disappears in the position of head-turn, which usually is of no more than 10-15 degrees. Both types of patients show the same electronystagmographic features in the position of head-turn. This differentiation is useful from the clinical standpoint. In fact, only the first type of head-turn may require, besides a classical Anderson or Kestenbaum procedure, also a posterior fixation suture according to Cuppers. This operation would be useless in the second type of head-turn. Clinical signs useful for differentiating these two types of head-turn are presented as well.

• Television fluoroangiography is used in order to obtain fluorescein dilution curves (dromofluorograms [From the Greek word: δ ρ ο μ ο, which means flowing. We coined this word because dilution curves do not afford a true measurement of the blood circulation, or simply of a dilution, but of the fluorescein transport in the circulation!]) from single retinal vessels. An optical fiber conveys the light from a single retinal artery, vein, or any other retinal area on the video screen to a photomultiplier. After lowpass electronic filtration, the dilution curves are recorded on a strip-chart recorder. The measurements considered are all related to time: the time interval between initial instants of the arterial and venous curve; the time interval between maximum instants; the arterial and venous curve rising times. It is seen that (1) the method is sensitive enough to enable variations in the quantities in pathologic cases to be detected; (2) owing to the great variability from part to part of the vessels, it is important to specify where the retinal dromofluorogram has been recorded. ( Arch Ophthalmol 95:302-307, 1977)