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Biomedical subjects

P Mandal

Publications and source records attributed to P Mandal.

At least 19 recordsLinked to original sources

Transport of (22)Na(+) and( 45)Ca(2+) by Xenopus laevis oocytes expressing mRNA from lobster hepatopancreas.

This paper describes the development of a functional assay system to express crustacean epithelial electrogenic 2Na(+)/1H(+) antiporters in Xenopus laevis oocytes. Subsequent publications will use this assay method to establish nucleotide and amino acid sequence information about this transporter by functionally screening an hepatopancreatic cDNA library. In this method, oocytes were injected with hepatopancreatic mRNA (50 ng) isolated from Homarus americanus, while control oocytes received injections of an equivalent volume of distilled water. Three to five days post-injection, oocytes were incubated in media containing either (22)Na(+) or (45)Ca(2+) for specific time intervals and the rates of ion transfer into the oocytes were monitored under a variety of experimental conditions. Uptakes of both radiolabelled cations were stimulated by mRNA injection. mRNA-stimulated (22)Na(+) uptake was significantly (P < 0.05) inhibited by addition of calcium, amiloride, or by an antiporter-specific monoclonal antibody to the external medium. mRNA-stimulated (45)Ca(2+) uptake was significantly (P < 0.05) inhibited by addition of sodium, amiloride, cadmium, zinc, or by the antiporter-specific monoclonal antibody (also inhibitory for (22)Na(+) transport) to the external medium. The kinetics of (22)Na(+) influx in mRNA-injected oocytes were sigmoidal functions of external sodium concentration, exhibiting a Hill Coefficient (n) of approximately 3.0. Both calcium and amiloride significantly (P < 0.05) reduced sigmoidal sodium influx kinetics by alterations in the J(max) (amiloride) or K(Na) (calcium) of the transporter. Size fractionation of hepatopancreatic mRNA resulted in a single fraction that was most stimulatory for sodium and calcium transport and which likely contains the antiporter transcript. The results of this study provide the basis for using (22)Na(+) and (45)Ca(2+) transport assays of lobster mRNA-injected oocytes to functionally screen an hepatopancreatic cDNA library for clones that will provide full length nucleotide and amino acid sequences of the invertebrate electrogenic 2Na(+)/1H(+) antiporter protein.

Amiloride↗

Angle-closure glaucoma in an urban population in southern India. The Andhra Pradesh eye disease study.

OBJECTIVE: To assess the prevalence and features of angle-closure glaucoma (ACG) in an urban population in southern India. DESIGN: A population-based, cross-sectional study. PARTICIPANTS: A total of 2522 (85.4% of those eligible) persons of all ages, including 1399 persons 30 years of age or older, from 24 clusters representative of the population of Hyderabad city. TESTING: The participants underwent an interview and detailed eye examination that included logarithm of minimum angle of resolution visual acuity, refraction, slit-lamp biomicroscopy, applanation tonometry, and gonioscopy; pupil dilatation and stereoscopic fundus evaluation was performed if the risk of angle-closure as a result of dilatation was not believed to be imminent. Humphrey threshold 24-2 visual fields (Humphrey Instruments Inc., San Leandro, CA) were performed when indicated by standardized criteria for disc damage or if intraocular pressure (IOP) was 22 mmHg or more. MAIN OUTCOME MEASURES: An occludable angle was defined as pigmented posterior trabecular meshwork not visible by gonioscopy in three quarters or more of the angle circumference. Manifest primary angle-closure glaucoma (PACG) was defined as IOP of 22 mmHg or more or glaucomatous optic disc damage with visual field loss in the presence of an occludable angle. An IOP of 22 mmHg or more or glaucomatous optic disc damage in the presence of an occludable angle secondary to an obvious cause was defined as secondary ACG. RESULTS: Manifest PACG and occludable angles without ACG were present in 12 and 24 participants, respectively, with age- and gender-adjusted prevalence (95% confidence interval [CI]) of 0.71% (0.34%-1.31%) and 1.41% (0.73%-2.09%) in participants 30 years of age or older, and 1.08% (0.36%-1.80%) and 2.21% (1.15%-3.27%) in participants 40 years of age or older, respectively. With multivariate analysis, the prevalence of these two conditions considered together increased significantly with age (P < 0.001); although not statistically significant, these were more common in females (odds ratio 1.70; 95% CI, 0.82-3.54) and in those belonging to lower socioeconomic strata as compared with middle and upper strata (odds ratio, 1.82; 95% CI, 0.88-3.74). The odds of manifest PACG were higher in the presence of hyperopia of more than 2 diopters ([D]; odds ratio, 3.69; 95% CI, 0.89-15.2). Only four of 12 participants (33.3%) with manifest PACG had been previously diagnosed, and one of 12 (8.3%) had peripheral iridotomy performed previously. Manifest PACG had caused blindness in one or both eyes in five of these 12 participants (41.7%); best-corrected distance visual acuity less than 20/400 in one or both eyes in four patients, and acuity less than 20/200 in one eye in another patient. Most (83.3%) of those with manifest PACG could be classified as having chronic form of the disease. We may have underestimated manifest PACG because visual fields were per- formed only on those with clinical suspicion of optic disc damage. Secondary ACG was present in two participants. CONCLUSIONS: The prevalence of PACG in this urban population in southern India is close to that reported recently in a Mongolian population. A large proportion of the PACG in this population was undiagnosed and untreated. Because visual loss resulting from PACG is potentially preventable if peripheral iridotomy or iridectomy is performed in the early stage, strategies for early detection of PACG could reduce the high risk of blindness resulting from PACG seen in this urban population in India.

Adolescent↗

Open-angle glaucoma in an urban population in southern India: the Andhra Pradesh eye disease study.

OBJECTIVE: To assess the prevalence and features of open-angle glaucoma in an urban population in southern India. DESIGN: A population-based cross-sectional study. PARTICIPANTS: A total of 2522 persons (85.4% of those eligible) of all ages, including 1399 persons 30 years of age or older, from 24 clusters representative of the population of Hyderabad city. TESTING: The participants underwent an interview and detailed eye examination that included logarithm of minimum angle of resolution visual acuity, refraction, slit-lamp biomicroscopy, applanation tonometry, gonioscopy, dilatation, cataract grading, and stereoscopic fundus evaluation. Automated Humphrey threshold 24-2 visual fields (Humphrey Instruments Inc., San Leandro, CA) and optic disc photography were performed when indicated by standardized criteria for disc damage or if intraocular pressure (IOP) was 22 mmHg or more. MAIN OUTCOME MEASURES: Definite primary open-angle glaucoma (POAG) was defined as obvious glaucomatous optic disc damage and visual field loss in the presence of an open-angle, and suspected POAG was defined as suspected glaucomatous optic disc damage without definite visual field loss. Ocular hypertension (OHT) was defined as IOP of 22 mmHg or more without glaucomatous optic disc damage or visual field loss in the presence of an open-angle. Glaucomatous optic disc damage or IOP of 22 mmHg or more secondary to an obvious cause and with an open-angle was defined as secondary open-angle glaucoma. RESULTS: Definite POAG, suspected POAG, and OHT were present in 27, 14, and 7 participants, respectively, with age- and gender-adjusted prevalence (95% confidence interval) of 1.62% (0.77%-2.48%), 0.79% (0.39%-1.41%), and 0.32% (0.10%-0.78%) in those 30 years of age or older, and 2.56% (1.22%-3.91%), 1.11% (0.43%-1.78%), and 0.42% (0.11%-1.12%) in those 40 years of age or older, respectively. The prevalence of POAG increased significantly with age using multivariate analysis (P < 0.001). Only two of 27 participants (7.4%) with definite POAG had been previously diagnosed and treated, and 66.7% of the previously undiagnosed had IOP less than 22 mmHg. Fourteen of 27 participants (51.9%) with definite POAG had severe glaucomatous damage based on optic disc and visual field criteria, of which five participants (18.5%) had at least one blind eye as a result of POAG (all with best-corrected distance visual acuity less than 20/400 or central visual field less than 10 degrees); the other 13 participants (48.1%) had moderate glaucomatous damage. Because visual fields and optic disc photography were not performed on all participants, the prevalence of POAG may have been underestimated. Secondary open-angle glaucoma was present in one participant as a result of angle recession. CONCLUSIONS: The prevalence of open-angle glaucoma in this urban population in southern India is at least as much as that reported recently from white populations in developed countries. However, the vast majority of persons with glaucoma were undiagnosed in this population, and a large proportion of those having definite POAG already had severe glaucomatous damage.

Adolescent↗

Unilateral visual impairment in an urban population in southern India.

This study assessed the prevalence and causes of unilateral visual impairment in the urban population of Hyderabad city as part of the Andhra Pradesh Eye Disease Study. Stratified, random, cluster, systematic sampling was used to select 2,954 subjects from 24 clusters representative of the population of Hyderabad. Eligible subjects underwent detailed eye examination including logMAR visual acuity, refraction, slitlamp biomicroscopy, applanation tonometry, gonioscopy, dilatation, cataract grading, and stereoscopic evaluation of fundus. Automated threshold visual fields and slitlamp and fundus photography were done when indicated by standardised criteria. Unilateral visual impairment was defined as presenting distance visual acuity < 6/18 in the worse eye and > or = 6/12 in the better eye, which was further divided into unilateral blindness (visual acuity < 6/60 in the worse eye) and unilateral moderate visual impairment (visual acuity < 6/18-6/60 in the worse eye). A total of 2,522 subjects (85.4% of eligible), including 1,399 > or = 30 years old, participated in the study. In addition to the 1% blindness and 7.2% moderate visual impairment (based on bilateral visual impairment criteria) reported earlier in this sample, 139 subjects had unilateral visual impairment, an age-gender-adjusted prevalence of 3.8% (95% confidence interval 2.7-4.9%). The major causes of this visual impairment 39.9% were refractive error (42.9%), cataract (14.4%), corneal disease (11.5%), and retinal disease (11.2%). Of this unilateral visual impairment was blindness. The major causes of unilateral blindness were corneal disease (23.2%), cataract (22.5%), retinal disease (18%), and optic atrophy (12.9%). On the other hand, the predominant cause of unilateral moderate visual impairment was refractive error (67%) followed by cataract (9%). Of the total unilateral visual impairment, 34.3% was present in those < 30 years old and 36.2% in those 30-49 years old. Unilateral visual impairment afflicts approximately 1 in 25 persons in this urban population. A large proportion of this unilateral visual impairment is present in younger age groups. The causes of unilateral visual impairment, like those of bilateral visual impairment in this population, are varied, suggesting therefore, that in addition to the current focus of eye care in India predominantly on cataract, other causes of visual impairment need to be addressed as well.

Adolescent↗

Population-based assessment of the outcome of cataract surgery in an urban population in southern India.

PURPOSE: To assess the outcome of cataract surgery in an urban population in southern India. METHODS: As part of a population-based cross-sectional epidemiologic study, the Andhra Pradesh Eye Disease Study, 2,522 people of all ages, including 1,399 individuals 30 years of age or older, from 24 clusters representative of the population of Hyderabad in southern India underwent a detailed interview and ocular evaluation including logarithm of minimal angle of resolution (logMAR) visual acuity, refraction, slit-lamp biomicroscopy, applanation tonometry, gonioscopy, dilation, cataract grading, aphakia/pseudophakia status, and stereoscopic fundus evaluation. Automated threshold visual fields and slit-lamp and fundus photography were performed when indicated by standardized criteria. Very poor outcome in an eye that had undergone cataract surgery was defined as presenting distance visual acuity worse than 20/200, and poor outcome was defined as visual acuity worse than 20/60 to 20/200. RESULTS: In subjects 50 years of age or older, after adjustment for age and sex distribution, the rate of having had cataract surgery in one or both eyes was 14.6% (95% confidence interval [CI], 11.4% to 17.8%). Of 131 eyes (91 subjects) that had undergone cataract surgery, 28 (21.4%; 95% CI, 14.4% to 28.4%) had very poor outcome and another 40 (30.5%; 95% CI, 22.6% to 38.4%) had poor outcome. The very poor outcome in 20 (71.4%) of 28 eyes and poor outcome in 23 (57.5%) of 40 eyes could be attributed to surgery-related causes or inadequate refractive correction. With multivariate analysis, very poor outcome as a result of surgery-related causes or inadequate refractive correction was more likely to be associated with intracapsular cataract extraction than with extracapsular cataract extraction (odds ratio, 9.34; 95% CI, 2.49 to 35.06) in subjects belonging to the lowest socioeconomic status (odds ratio, 4.92; 95% CI, 1.16 to 20.93) and with date of surgery 3 or fewer years before the survey than with more than 3 years (odds ratio, 4.52; 95% CI, 1.33 to 15.39). Also, very poor or poor outcome as a result of surgery-related causes or inadequate refractive correction was associated with women (odds ratio, 2.55; 95% CI, 1.06 to 6.16). CONCLUSIONS: The very high rate of very poor and poor visual outcome, predominantly as a result of surgery-related causes and inadequate refractive correction, in this urban population of India suggests that more attention is needed to improve the visual outcome of cataract surgery. In order to deal with cataract-related visual impairment in India, as much emphasis on surgical quality, refractive correction, and follow-up care is necessary as on the number of surgeries.

Adult↗

Burden of moderate visual impairment in an urban population in southern India.

OBJECTIVE: To assess the prevalence and causes of moderate visual impairment in an urban population in southern India. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 2522 (85.4% of the eligible) persons of all ages, including 1399 persons 30 years of age or older, from 24 clusters representative of the population of Hyderabad city. TESTING: The eligible subjects underwent a detailed ocular evaluation, including logarithm of the minimum angle of resolution (logMAR) visual acuity, refraction, slit-lamp biomicroscopy, applanation tonometry, gonioscopy, cataract grading, and stereoscopic dilated fundus evaluation. Automated threshold visual fields and slit-lamp and fundus photography were done when indicated by standardized criteria. MAIN OUTCOME MEASURE: Moderate visual impairment was defined as presenting distance visual acuity less than 20/40 to 20/200 or visual field loss by predefined standardized conservative criteria in the better eye. RESULTS: In addition to the 1% prevalence of blindness in this sample reported earlier, moderate visual impairment was present in 303 subjects, an age-gender-adjusted prevalence of 7.2% (95% confidence interval [CI], 4.5%-9.9%; design effect, 2.7). The major cause of moderate visual impairment was refractive error (59.4%, 95% CI, 52.3%-66.5%) followed by cataract (25.3%, 95% CI, 19%-31.6%). Multivariate analysis showed that the prevalence of moderate visual impairment was significantly higher in those 40 years of age or older (odds ratio, 10.9; 95% CI, 8-15) and females (odds ratio, 1.89; 95% CI, 1.41-2.53) and lower in those belonging to the highest socioeconomic status (odds ratio, 0.27; 95% CI, 0.14-0.51). However, because of the pyramidal age distribution of the population, 38.1% of the total moderate visual impairment was present in those younger than 40 years of age. The proportion of moderate visual impairment caused by refractive error was higher in the younger than in the older age groups (P < 0.0001). CONCLUSIONS: Projecting the results to the 26.5% urban population of India, there would be 18.4 million (95% CI, 11.5-25.2 million) persons with moderate visual impairment in urban India alone. Refractive error was the major cause of moderate visual impairment in the population studied. The absolute proportion of moderate visual impairment in those younger than 40 years of age was considerable. The eyecare policy of India, apart from dealing with blindness, should address the issue of the relatively easily treatable uncorrected refractive error as the cause of moderate visual impairment in an estimated 10.9 million persons in urban India.

Adolescent↗

Solution structure of the extended neuronal nitric oxide synthase PDZ domain complexed with an associated peptide.

The PDZ domain of neuronal nitric oxide synthase (nNOS) functions as a scaffold for organizing the signal transduction complex of the enzyme. The NMR structure of a complex composed of the nNOS PDZ domain and an associated peptide suggests that a two-stranded beta-sheet C-terminal to the canonical PDZ domain may mediate its interaction with the PDZ domains of postsynaptic density-95 and alpha-syntrophin. The structure also provides the molecular basis of recognition of Asp-X-Val-COOH peptides by the nNOS PDZ domain. The role of the C-terminal extension in Asp-X-Val-COOH peptide binding is investigated. Additionally, NMR studies further show that the Asp-X-Val-COOH peptide and a C-terminal peptide from a novel cytosolic protein named CAPON bind to the same pocket of the nNOS PDZ domain.

Adaptor Proteins, Signal Transducing↗

Is current eye-care-policy focus almost exclusively on cataract adequate to deal with blindness in India?

BACKGROUND: India's National Programme for Control of Blindness focuses almost exclusively on cataract, based on a national survey done in the 1980s which reported that cataract caused 80% of the blindness in India. No current population-based data on the causes of blindness in India are available. We assessed the rate and causes of blindness in an urban population in southern India. METHODS: We selected 2954 participants by stratified, random, cluster, systematic sampling from Hyderabad city. Eligible participants were interviewed and given a detailed ocular assessment, including visual acuity, refraction, slitlamp biomicroscopy, applanation intraocular pressure, gonioscopy, dilatation, grading of cataract, stereoscopic fundus assessment, and automated-threshold visual fields. FINDINGS: 2522 participants, including 1399 aged 30 years or more, were assessed. 49 participants (all aged > or =30 years) were blind (presenting distance visual acuity <6/60 or central visual field <200 in the better eye). The rate of blindness among those aged 30 years or more, adjusted for age and sex, was 3.08% ([95% CI 1.95-4.21]). Causes included cataract (29.7%), retinal disease (17.1%), corneal disease (15.4%), refractive error (12.5%), glaucoma (12.1%), and optic atrophy (11.0%). 15.7% of the blindness caused by visual-field constriction would have been missed without visual-field examination. Also without visual-field and detailed dilated-fundus assessments, blindness attributed to cataract would have been overestimated by up to 75.8%. If the use of cataract surgery in this urban population was half that found in this study, which simulates the situation in rural India, cataract would have caused 51.8% (39.4-64.2) of blindness, significantly less than the 80% accepted by current policy. INTERPRETATION: Much of the blindness in this Indian population was due to non-cataract causes. The previous national survey did not include detailed dilated-fundus assessment and visual-field examination which could have led to overestimation of cataract as a cause of blindness in India. Policy-makers in India should encourage well-designed population-based epidemiological studies from which to develop a comprehensive long-term policy on blindness in addition to dealing with cataract.

Adult↗

Calculation of inspired oxygen fraction during anaesthesia based on awake oxygen saturation.

One hundred ASA grade 1 or 2 patients were studied to assess the use of awake oxygen saturation to determine the necessary inspired oxygen fraction during anaesthesia. The inspired oxygen fraction was adjusted gradually to the lowest possible value to maintain the pre-operative oxygen saturation at a constant level. Normocapnic ventilation was maintained and analgesia was provided with 0.5mg.kg-1 of pethidine given intravenously. In addition to routine monitoring and measurement (electrocardiograph, oxygen saturation, expired carbon dioxide concentration and noninvasive blood pressure), arterial samples for blood gas analysis and venous samples for lactate and pyruvate levels were taken when awake and 30 min after achieving a steady state with a minimum inspired oxygen fraction. The mean inspired oxygen fraction required in these patients was 20.91 (SD 1.92%) ranging from 18-25%. The arterial pH were 7.34 (SD 4.04) (awake) and 7.35 (SD 3.15) (after 30 min), the partial pressure of oxygen 13.17 (SD 1.97) (awake) and 13.83 (SD 1.6 kPa) (after 30 min) and the partial pressure of carbon dioxide and base excess were normal. Serum lactate levels were 1.04 (SD 0.25) (awake) and 1.15 (SD 0.48) (after 30 min) mmol.l-1, whilst pyruvate levels were 0.1 (SD 0.02) (awake) and 0.12 (SD 0.21) (after 30 min) mmol.l-1. Patients' recovery and postoperative course were uneventful.

Adolescent↗