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Biomedical subjects

A K Gupta

Publications and source records attributed to A K Gupta.

At least 109 records · Page 6Linked to original sources

Neonatal gastric pull up: reality or myth?

Between 1991 and 1998, 28 out of 356 neonates with esophageal atresia and tracheoesophageal fistula (EATEF) required esophageal substitution. As only 8 returned (28%) for the esophageal replacement after initial esophagostomy and gastrostomy at our center, we were prompted to offer single-stage esophageal replacement when the primary repair had either failed or was not found feasible. Twelve full-term neonates (mean birth weight 2.32 kg) with EATEF who underwent esophageal replacement by gastric pull-up between 1998 and 2000 were reviewed. The indications were: major leak after primary repair (n=9); pure EA (n=2); and EATEF with a very wide gap (n=1). The average ages at presentation and gastric pull-up were 6.0 and 8.5 days, respectively. The patients were evaluated for gastric transit by a colloid radiopharmaceutical, for duodenogastric reflux (DGR) by hepatic immunodiacetic acid (HIDA) scan, and for gastric clearance and transit by contrast studies. Three patients had minimal leaks from the neck site, all of which healed well. Follow-up with nuclear scans and contrast studies to evaluate gastric emptying revealed obstruction in 1 case and DGR in 25% of cases. There were 2 deaths (16%), 1 due to complex congenital cardiac disease and the other due to septicemia. In view of the acceptable morbidity, mortality, and functional outcome following gastric pull-up, we recommend this procedure if it becomes inevitable in the neonatal period.

Esophageal Atresia↗

Motion characteristics of Murrah buffalo bull spermatozoa in various seasons and its relationship with functional integrity of the plasmallema.

Semen was collected from six adult (3.5-7-year-old) Murrah buffalo bulls at weekly intervals for 1 year and evaluated for routine parameters, motion characteristics, reactivity in hypoosmotic solution, and acrosomal and other morphological abnormalities of the spermatozoa. The overall motility (MOT), straight line velocity (VSL), curvilinear velocity (VCL), linearity (LIN), lateral head displacement (ALH) and average path velocity (VAP) were 66.85+/-2.79%, 26.58+/-0.24 and 107.07+/-1.47 microm/s, 26.91+/-0.01%, 11.19+/-0.09 and 61.78+/-2.79 microm/s, respectively. Significant seasonal variation was observed in sperm kinematics and hypoosmotic swelling (HOS) reactivity. Except for LIN, the mean values of sperm dynamics were higher during summer and rainy season and significantly lower in winter season. Sperm kinematics showed significant (P<0.01) positive correlation (r=0.25-0.60) with plasmallemal integrity. Ejaculates with less than 50% HOS-reactive spermatozoa had significantly lowered MOT, VSL, VCL and VAP as compared to the ejaculates with >50% HOS-positive spermatozoa. No significant difference was observed in sperm kinematics among the ejaculates having 50-70% and >70% HOS-reactive spermatozoa. The trend of motion dynamics of the spermatozoa with respect to HOS reactivity was similar in all the three seasons (summer, rainy and winter). The results indicate that ejaculates having more than 50% of HOS-reactive sperm show a higher magnitude of sperm kinematics compared to ejaculates having less than 50% HOS-positive spermatozoa.

Animals↗

Hyperoxia and the cerebral hemodynamic responses to moderate hyperventilation.

BACKGROUND: A reduction in the arterial partial pressure of CO2 (PaCO2) leads to a rapid reduction in cerebral blood flow (CBF). However, despite continuing hypocapnia there is secondary recovery of CBF over time as a result of increases in lactic acid production. Hyperoxia is thought to modulate the production of lactic acid. This study examined the kinetics of middle cerebral artery flow velocity (MCA FV) reduction during hyperventilation, and its modulation by hyperoxia. METHODS: Cerebral blood flow was assessed using transcranial Doppler ultrasound in nine healthy, awake human volunteers. Subjects were ventilated, via a mouthpiece, to achieve a stable end-tidal CO2 (PETCO2). After a 20-min baseline period the minute volume on the ventilator was passively increased by approximately 20% to reduce PETCO2 by 0.75-1 kPa. After a 10-min stabilization period the new PETCO2 level was maintained at a constant level for 20 min, and MCA FV recovery was measured during this 20-min period. Subjects undertook the protocol breathing air and breathing 100% oxygen. RESULTS: The PETCO2 level was (mean +/- SD) 4.9 +/- 0.4 kPa (normoxia baseline), 4.0 +/- 0.3 kPa (normoxia hyperventilation), 4.6 +/- 0.4 kPa (hyperoxia baseline) and 3.9 +/- 0.4 kPa (hyperoxia hyperventilation). CO2 reactivity was significantly lower with normoxia than hyperoxia (16.5 +/- 3.8 vs. 21.2 +/- 4.6 % kPa-1; P< 0.05). Middle cerebral artery FV recovery was significantly more rapid with normoxia than hyperoxia (0.23 +/- 0.17 vs. 0.08 +/- 0.1 % baseline min-1; P< 0.01). CONCLUSIONS: Our results suggest that cerebral hemodynamic responses to moderate hyperventilation are different in normoxic and hyperoxic conditions. Clinical assessment of CO2 reactivity and CBF recovery during hyperventilation should take the degree of arterial oxygenation into account.

Adult↗

Sinonasal aspergillosis in immunocompetent Indian children: an eight-year experience.

A retrospective study of 40 otherwise healthy children suffering from paranasal aspergillosis is presented. Fifteen percentage of this group was under 10 years of age. The clinical characteristics were marked facial deformity, orbital involvement (52.5%) and skull base erosion (12.5%). Ethmoid sinus was the commonest sinus to be affected. Aspergillus serology was positive in 35% and fungal culture grew the organism in 40%. Histopathology revealed allergic or non-invasive fungal infections without any tissue invasions. Surgery was performed in all except one case. Recurrence was 15% treated by revision surgery and antifungal therapy.

Adolescent↗

A web-based system for teaching, assessment and examination of the undergraduate peri-operative medicine curriculum.

Today's students are generally computer literate and have high expectations of university information technology resources. Most United Kingdom medical schools now provide networked computers for learning, research, communication and accessing the worldwide web. We have exploited these advances to augment and improve the teaching of peri-operative medicine and anaesthesia to medical students in our university, who are taught in several hospitals over a wide geographical area. Course material such as departmental induction information, lecture notes and assessment sheets can be accessed online, contributing to the smooth running of the course. Streamed videos and simulations allow students to familiarise themselves with common practical procedures in advance. Development of a web-based end of course assessment has resulted in substantially less administration and bureaucracy for course organisers and proved to be a valuable research tool. Students' and teachers' opinions of the new course structure have been overwhelmingly positive.

Anesthesiology↗

In vitro susceptibility testing of ciclopirox, terbinafine, ketoconazole and itraconazole against dermatophytes and nondermatophytes, and in vitro evaluation of combination antifungal activity.

BACKGROUND: With the development of newer antifungal agents with activity against both yeasts and filamentous fungi, there is an increased need to develop and standardize in vitro assays that will evaluate the activity of antimycotics against filamentous fungi. In vitro analysis of antifungal activity of these agents would also allow for the comparison between different antimycotics, which in turn may clarify the reasons for lack of clinical response or serve as an effective therapy for patients with chronic infection. OBJECTIVES: To determine the in vitro susceptibility of fungal organisms to ciclopirox, terbinafine, ketoconazole and itraconazole and to evaluate the in vitro activity and mode of interaction of ciclopirox in combination with either terbinafine or itraconazole. MATERIALS AND METHODS: In the minimum inhibitory concentration (MIC) study 133 strains were evaluated, including dermatophytes (110 strains; 98 from Trichophyton spp.), Candida spp. (14 strains) and nondermatophyte moulds (nine strains). In vitro susceptibility testing was conducted in microbroth dilutions based on the National Committee for Clinical Laboratory Standards (NCCLS) M27-A proposed standard. The testing MIC ranges were 0.003-2 microg mL-1 for ciclopirox and terbinafine, and 0.06-32 microg mL-1 for itraconazole and ketoconazole. For inoculum preparation, dermatophytes were grown on Heinz oatmeal cereal agar slants. Inoculum suspensions of dermatophytes were diluted in RPMI 1640 (Sigma-Aldrich) with the desired final concentration being 2-5 x 103 c.f.u. mL-1. Once inoculated, the microdilution plates were set up according to the NCCLS M27-A method, incubated at 35 degrees C, and read visually following 7 days of incubation. For azole agents, the MIC was the lowest concentration showing 80% growth inhibition; for terbinafine and ciclopirox, the MIC was the lowest concentration showing 100% growth inhibition. In the synergy studies, 29 strains from nondermatophyte species were evaluated using a checkerboard microdilution method. The concentrations tested were: 0 and 0.06-32 microg mL-1 for itraconazole, and 0 and 0.003-4 microg mL-1 for both terbinafine and ciclopirox. Modes of interaction between drugs were classified as synergism, additivism, antagonism or indifference based on fractional inhibitory concentration index values (FIC index). Synergism was defined as an FIC index of < or = 0.50, additivity as an FIC index of < or = 1.0, and antagonism as an FIC index of > or = 2.0. The drug combination was interpreted as indifferent if neither of the drugs had any visible effect on the presence of the other drug. RESULTS: In the MIC study, the dermatophyte MIC values (microg mL-1) (mean +/- SEM) were: ciclopirox (0.04 +/- 0.02), terbinafine (0.04 +/- 0.23), itraconazole (2.28 +/- 7.42) and ketoconazole (0.83 +/- 1.99). The yeast MIC values (microg mL-1) (mean +/- SEM) were: ciclopirox (0.05 +/- 0.02), terbinafine (1.77 +/- 0.58), itraconazole (0.18 +/- 0.27) and ketoconazole (0.56 +/- 0.60). The non-dermatophyte fungi MIC values (microg mL-1) (mean +/- SEM) were: ciclopirox (1.04 +/- 2.62), terbinafine (1.04 +/- 0.95), itraconazole (17.87 +/- 16.75) and ketoconazole (10.69 +/- 13.09). In the synergy study, with ciclopirox in combination with terbinafine, mainly a synergistic or additive reaction was observed; there were no cases of antagonism. For ciclopirox in combination with itraconazole, there were some instances of additivism or synergism, with indifference in the majority of instances; there were no cases of antagonism. CONCLUSIONS: In vitro susceptibility testing indicates that ciclopirox may have a broad antimicrobial profile including dermatophytes, yeasts and other nondermatophytes. Terbinafine is extremely potent against dermatophytes. In vitro evaluation of activity of ciclopirox and terbinafine suggests many instances of synergy or additivism; for ciclopirox and itraconazole there may be indifference, synergy or additivism.

Antifungal Agents↗

Arthroconidial formation in Trichophyton raubitschekii.

Arthroconidia produced by dermatophytic fungi are considered to be the primary cause of skin and nail infections in humans and animals. Trichophyton rubrum is currently the most common cause of tinea pedis all over the world. The common form of T. rubrum produces a cottony colony in cultures that is characteristically low in conidia formation. The attempts to produce arthroconidia in T. rubrum have shown little success so far. Recently, Trichophyton raubitschekii, an anthropophilic dermatophyte prevalent in Asia, Africa, and the Mediterranean, has been recognized as a variant of T. rubrum. In cultures, T. raubitschekii is characterized by a granular colony form, and an abundance of both micro- and macroconidia. The present study reveals a predominance of arthroconidia in two T. raubitschekii cultures isolated from clinical materials. These isolates were able to maintain arthroconidiation in bimonthly subcultures throughout the entire course of this study. The growth parameters for in vitro cultivation of arthroconidia are described here. Arthroconidia prepared from T. raubitschekii cultures showed greater than 95% germination within 21 h of suspension in phosphate-buffered saline. The availability of arthroconidia in T. raubitschekii cultures appears to offer a practical means of characterizing infective cells in T. rubrum.

Culture Media↗

The efficacy and safety of terbinafine in children.

Terbinafine is an allylamine antifungal agent that has been effective and safe in the treatment of superficial and some deep mycotic infections in adults. An increasing amount of data is available where terbinafine has been used in the paediatric population to treat superficial fungal infections, in particular tinea capitis. The data suggest that terbinafine is effective and safe using treatment regimens that involve short duration therapy, leading to an increased compliance and providing a cost-effective means of treating paediatric superficial fungal infections such as tinea capitis. Terbinafine has been approved for the treatment of tinea capitis in many countries worldwide, and provides good efficacy rates for Trichophyton tinea capitis using shorter regimens than the gold standard griseofulvin. The adverse events profile for children is similar to that in adults with few adverse effects associated with its use. The evidence favours the use of terbinafine in the treatment of superficial infections in children.

Administration, Oral↗

Pimecrolimus: a review.

Pimecrolimus (SDZ ASM 981), an ascomycin derivative, is one of the new classes of immunomodulating macrolactams and was specifically developed for the treatment of inflammatory skin diseases. The interest in pimecrolimus has been substantial because of its significant anti-inflammatory activity and immunomodulatory capabilities and its low systemic immunosuppressive potential. The mechanism of action of pimecrolimus is the blockage of T cell activation. Pimecrolimus (like all ascomycins) is an immunophilin ligand, which binds specifically to the cytosolic receptor, immunophilin macrophilin-12. This pimecrolimus-macrophilin complex effectively inhibits the protein phosphatase calcineurin, by preventing calcineurin from dephosphorylating the nuclear factor of activated T cells (NF-AT), a transcription factor. This results in the blockage of signal transduction pathways in T cells and the inhibition of the synthesis of inflammatory cytokines, specifically Th1- and Th2-type cytokines. Pimecrolimus has also been shown to prevent the release of cytokines and pro-inflammatory mediators from mast cells. Several studies have evaluated the effectiveness of pimecrolimus as a treatment for skin diseases. In animal models of allergic contact dermatitis, topical pimecrolimus was found to be effective. In human studies of allergic contact dermatitis pimecrolimus demonstrated significantly more efficacy than the control treatment. As well, the effectiveness of pimecrolimus 0.6% cream was comparable to 0.1% betamethasone-17-valerate; however, pimecrolimus was not associated with any of the side effects characteristic of a topical steroid. Topical application of pimecrolimus is not associated with skin atrophy. Pimecrolimus is effective and safe in both children and adults with atopic dermatitis. When pimecrolimus 1% cream has been applied to adult atopics, improvement has been observed as early as the first week, with a 72% reduction in severity after 3 weeks. Pharmacokinetic studies have shown very low blood levels of pimecrolimus following topical application, with no accumulation after repeated applications. Following application of pimecrolimus cream occasional transient irritation may be experienced at the application site. Similar results have also been found in children aged 3 months and older following application of pimecrolimus 1% cream. Topical pimecrolimus in psoriasis appears to exhibit a dose-dependent therapeutic effect under semi-occlusive conditions. Pimecrolimus has an enormous potential as a new treatment of inflammatory skin diseases. It has been shown to be effective in atopic and allergic contact dermatitis, with a favorable adverse-effects profile, which includes little effect on the systemic immune response.

Administration, Oral↗

Farnesyltransferase inhibitors as radiation sensitizers.

PURPOSE: The inhibition of activated Ras combined with radiotherapy was identified as a potential method for radiosensitization. MATERIALS AND METHODS: Immunoblotting was used to control for prenylation inhibition of the respective Ras isoforms and for changes in activity of downstream proteins. Clonogenic assays with human and rodent tumour cell lines and transfected cell lines served for the testing of radiosensitivity. Xenograft tumours were treated with farnesyl transferase inhibitors and radiation and assayed for ex vivo plating efficiency, regrowth of tumours and EF5 staining for detection of hypoxia. Concurrent treatment with L-778,123 and radiotherapy was performed in non-small cell lung cancer (NSCLC) and head and neck cancer (HNC) patients. RESULTS: Blocking the prenylation of Ras proteins in cell lines with Ras activated by mutations or receptor signalling resulted in radiation sensitization in in vitro and in vivo. The PI3 kinase downstream pathway was identified as a contributor to Ras-mediated radiation resistance. Additionally, increased oxygenation of xenograft tumours was observed after FTI treatment. Combined treatment in a phase I study was safe and effective in NSCLC and HNC. CONCLUSIONS: Tumour cells with activated Ras were sensitized to radiation. Unravelling the underlying mechanisms promises to lead to even more specific drugs with higher potency and safety.

Alkyl and Aryl Transferases↗

A comparison of water quality indices for coastal water.

The present article discusses and compares five different water quality indices, viz arithmetic water quality index, multiplicative water quality index, unweighted arithmetic water quality index, unweighted multiplicative water quality index, and Harkin's water quality index, which were considered for characterizing the coastal water quality at the Jawaharlal Nehru Port Trust, Bombay, India. Dissolved oxygen, pH, biochemical oxygen demand (BOD), temperature, suspended solid, and turbidity were used as the parameters of water quality indices. The value function graphs used for above-mentioned variables were developed using harbour water quality standards and aquatic life. The product moment correlation coefficients for various water quality indices were determined using the SPSS software package to evaluate correlation among various indices. It was found that the unweighted arithmetic water quality index was higher than weighted arithmetic water quality index while the multiplicative water quality index was lower than unweighted multiplicative water quality index. All the indices were well correlated with each other except Harkin's water quality index. The Harkin's water quality index was different from other water quality indices. The comparison of different form of indices showed that the multiplicative water quality index was the most suitable water quality index for coastal waters.

Environmental Monitoring↗

A long-term study of oxides of nitrogen, sulphur dioxide, and ammonia for a port and harbor region in India.

A long-term study of oxides of nitrogen (NOx), sulphur dioxide (SO2), and ammonia (NH3) has been performed in a port and harbor region in India from January 1997 to December 2000. Meteorological data was also collected to establish the correlation with gaseous pollutants concentrations. Monthly mean concentrations of NOx were in the range of 19.5-59.0 microg/m3 and were observed to be highest during winter season. Monthly mean concentrations of SO2 were in the range of 8.6-51.3 microg/m3 and were observed to be highest during winter season. The concentrations of SO2 increased gradually from 18.8 microg/m3 in 1997 to 33.3 microg/m3 in 2000. This may be attributed to the increase in port activities and ship traffic, which had an annual growth of about 15%. Monthly mean concentrations of NH3 were in the range of 87.1-235.1 microg/m3 and the maximum concentration was observed during post-monsoon season. It may be concluded that NOx and SO2 have their maximum values during winter season while NH3 has a maximum value during post-monsoon season. Statistical analysis was carried out for air pollutant data for the period 1997-2000 and correlation between gaseous pollutants (NOx, SO2, NH3) and meteorological parameters (temperature and wind speed) was estimated. NH3 was found to be weakly correlated with NOx (0.46), strongly correlated with SO2 (0.75) and negatively correlated with wind speed (-0.60). The highest correlation (0.87) was observed between SO2 and NOx because of common sources. A strong negative correlation was found between wind speed and gaseous pollutants. The above finding is also supported by monitoring results that when the wind velocity doubled, the concentrations of pollutants decreased sharply to about a half. Regression analysis showed that relationship among NOx, SO2, wind speed, and temperature was moderate to strong while that among NH3, wind speed, and temperature was poor. Hence regression equations could be developed for predicting NOx and SO2 concentrations.

Air Movements↗

Cerebral oxygen vasoreactivity and cerebral tissue oxygen reactivity.

There has long been an appreciation that cerebral blood flow is modulated to ensure adequate cerebral oxygen delivery in the face of systemic hypoxaemia. There is increasing appreciation of the modulatory role of hyperoxia in the cerebral circulation and a consideration of the effects of such modulation on the maintenance of cerebral tissue oxygen concentration. These newer findings are particularly important in view of the fact that cerebrovascular and tissue oxygen responses to hyperoxia may change in disease. Such alterations provide important insights into pathophysiological mechanisms and may provide novel targets for therapy. However, before the modulatory effects of hyperoxia can be used for diagnosis, to predict prognosis or to direct therapy, a more detailed analysis and understanding of the physiological concepts behind this modulation are required, as are the limitations of the measurement tools used to define the modulation. This overview summarizes the available information in this area and suggests some avenues for further research.

Animals↗

Effects of propofol on cerebral oxygenation and metabolism after head injury.

BACKGROUND: Flow-metabolism coupling is thought to be deranged after traumatic brain injury, while the effects of propofol on flow-metabolism coupling are controversial. We have used a step increase in target plasma propofol concentration in head injured patients to explore flow-metabolism coupling in these patients. METHODS: Ten patients with a moderate to severe head injury received a step increase in propofol target controlled infusion of 2 microg x ml(-1). Cerebral tissue gas measurements were recorded using a multimodal sensor, and regional chemistry was assessed using microdialysis. Arterial-jugular venous oxygen differences (AVDO(2)) were measured and all patients had cortical function monitoring (EEG). RESULTS: The step increase in propofol led to a large increase in EEG burst-suppression ratio (0% (range 0-1.1) to 46.1% (range 0-61.7), P<0.05); however, this did not significantly change tissue gas levels, tissue chemistry, or AVDO(2). CONCLUSIONS: Flow-metabolism coupling remains intact during a step increase in propofol after traumatic brain injury. The EEG burst-suppression induced by propofol after traumatic brain injury does not appear to be a useful therapeutic tool in reducing the level of regional ischaemic burden.

Adult↗

Estimation of thyroid mass in Graves' disease by a scintigraphic method.

scintigraphic method for the estimation of the thyroid mass in patients with Graves' disease is described. The method was first standardized using thyroid phantoms with eight different volumes ranging from 5 to 110 cm(3). The planar and single photon emission computed tomography (SPECT) images of each phantom were acquired with four different activities [3.7 MBq (100 microCi), 11.1 MBq (300 microCi), 22.2 MBq (600 microCi) and 37 MBq (1.0 mCi) of 99mTc-pertechnetate] with a 20% window symmetrically placed over the photopeak of 99mTc. The thyroid lobes were enclosed with the help of regions of interest (ROI) tools and a threshold was selected to identify the thyroid boundaries. The same threshold was used in all slices of an image. In the phantom study, a 20% threshold for planar images and a 30% threshold for SPECT were found to be optimum for measuring the thyroid volume. The volume from planar images was calculated by the formula described by Allen and Goodwin (The scintillation counter as an instrument for in-vivo determination of thyroid weight. Radiology 1952; 58: 68-79), whereas, in SPECT images, the sum of the slice areas was multiplied by the slice thickness. The estimated volume of each phantom was compared and correlated with its actual volume. After standardization of the technique with phantom studies, planar scintigraphy (with 20% threshold) in 51 patients and SPECT (with 30% and 35% threshold) in 40 patients with Graves' disease were performed to estimate the thyroid size. The thyroid size was also estimated by ultrasonography, which showed good agreement with the scintigraphic method, particularly with SPECT.

Graves Disease↗

Epilepsy patients treated with vigabatrin exhibit reduced ocular blood flow.

BACKGROUND/AIM: Reduced cerebral blood flow and decreased glucose metabolism have been identified in epilepsy patients receiving vigabatrin. It is likely that such a change may extend to the eye and may be linked to previously reported irreversible visual field defects. The aim of this study was to determine whether patients who have undergone anti-epileptic drug (AED) therapy with vigabatrin have altered ocular haemodynamics. METHODS: The study cohort comprised 11 normal subjects (mean age 42.6 (SD 12.7) years and 17 epilepsy patients, of which 10 were either currently or previously treated with vigabatrin (38.6 (11.7) years) and seven were treated with AEDs excluding vigabatrin (46.0 (9.8) years). The three groups were matched at baseline for pulse rate, diastolic and systolic blood pressure, and intraocular pressure (IOP). At a single visit, the ocular blood flow analyser (OBFA; Paradigm Medical Instruments Inc, UT, USA) was used to measure pulsatile ocular blood flow (POBF) and pulse amplitude (PA) in each eye of all subjects. One way ANCOVA (with age as a covariate) was used to identify differences in POBF and PA between the groups. For the vigabatrin group only, Pearson's product moment correlation coefficient was used to explore potential interactions between ocular blood flow parameters and cumulative vigabatrin dose, duration, and maximum dose. RESULTS: Both the vigabatrin treated epilepsy group and conventionally treated epilepsy group exhibited significantly reduced POBF (p=<0.001, p=0.040) and PA (p=<0.001, p=0.005) compared to normal subjects. Patients treated with vigabatrin exhibited a further reduction in POBF (p=0.046) and PA (p=0.034) compared to conventionally treated epilepsy patients. No significant correlations were found between drug dosage and POBF and PA for the vigabatrin treated epilepsy group. CONCLUSIONS: A significant reduction in POBF and PA is apparent in epilepsy patients treated with AEDs when compared to normal subjects. A further reduction in POBF and PA is apparent between vigabatrin treated and conventionally treated patients. The reduction in ocular perfusion, which is more pronounced in patients previously treated with vigabatrin, may have implications in the impairment of visual function associated with the drug.

Adult↗