Home exercises for convergence insufficiency in children.
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Biomedical subjects
Publications and source records attributed to Pradeep Sharma.
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PURPOSE: We present a new technique of anchoring the eyeball to the nasal periosteum using a nonabsorbable suture in acquired isolated third-nerve paresis. METHODS: This was a case series of 4 consecutive adult subjects with isolated third-nerve paresis. After a 12-mm lateral rectus muscle recession in all 4 subjects, we passed 5-O double-armed polyester (NW683 Ethibond; Ethicon, Division of Johnson and Johnson Ltd., Aurangabad, India) on spatulated needles through the periosteum overlying the anterior lacrimal crest (exposed as in a Dacryocystorhinostomy procedure) at its superior part. The needles were brought anterior to the medial rectus muscle insertion and tightened enough to align the eye in 8-10 prism diopters adducted position. RESULTS: Ocular alignment in the primary gaze was satisfactory at 6-12 months of follow up. CONCLUSIONS: The use of a nonabsorbable polyester suture to anchor the globe to the nasal periosteum is an additional technique that holds promise to align the eyes in the primary gaze.
PURPOSE: To evaluate the efficacy of the augmented Anderson procedure in idiopathic infantile nystagmus (IIN). METHODS: Twelve consecutive patients older than 5 years having IIN with eccentric null position and anomalous head position were enrolled in an institution-based study. Best-corrected visual acuity (uniocular and binocular and in both null position and primary position), slit-lamp examination, fundus examination, ocular motility examination, and stereopsis using TNO were recorded. In all cases the augmented Anderson procedure, that is, recession of the yoke muscles (9-mm medial rectus and 12-mm lateral rectus), was performed. Eye movements were recorded before and 3 months after surgery in the primary position, right gaze 15 and 30 degrees, and left gaze 15 and 30 degrees. RESULTS: All patients had improvement in their anomalous head posture after surgery (p = 0.0001). The nystagmus intensity in the primary position decreased from 22.0 +/- 15.9 degrees cycles/s preoperatively to 10.6 +/- 10.2 degrees cycles/s at 3 months postoperatively. The change was statistically significant (p = 0.006). After surgery, binocular visual acuity using the Early Treatment Diabetic Retinopathy Study chart improved in primary position (p = 0.007). No patient developed more than mild limitation of horizontal movements after surgery. CONCLUSION: The augmented Anderson procedure is successful in correcting face turn in patients having IIN with eccentric null position, resulting in an increase in visual acuity and a decrease in nystagmus intensity in primary position. Further studies with a longer follow-up are required to assess the long-term efficacy of this procedure.
Management of complete external third nerve palsy is a challenge to a strabismologist; as four of six extra-ocular muscles are affected, it leaves eye in fixed hypotropic and exotropic position (Srivastava et al., 2004). Although numerous surgical procedures have been described, none has been found to be ideal for all cases. Horizontal supramaximal recession-resection procedure may work in cases having some function of medial rectus (Harley, 1980). In cases of complete external palsy, anchoring of globe to periosteum of medial orbital wall using different structures has been described (Villasenor Solares et al., 2000; Bicas, 1991; Salazar-Leon et al., 1998), as recession-resection may result in large residual deviation and/or eye drifts back to abducted position due to unopposed lateral rectus action (Von Noorder, 1996). These anchoring procedures are with associated problems of skin incision, thigh surgery or loss of superior oblique function (Villasenor Solares et al., 2000; Bicas, 1991; Salazar-Leon et al., 1998). We describe a new and safe technique for management of complete external third nerve palsy by anchoring insertion of medial rectus to medial wall periosteum, posterior to posterior lacrimal crest, along with supra maximal recession of lateral rectus.
A 38-year-old immunocompetent man presented with a horizontal supranuclear gaze palsy as the only neurologic manifestation of a pontine tuberculoma. Although a biopsy of the brain lesion was not performed, it was attributed to tuberculosis because of chest x-ray evidence. The patient was given empirical anti-tuberculous therapy. After one month, the gaze palsy had fully recovered and repeat MRI showed a decrease in the size of the lesion. This is the first reported case of supranuclear gaze palsy without diplopia as a manifestation of a tuberculous brain stem lesion.
Dissociated vertical deviation (DVD) is an intermittent anomaly of the non-fixing eye. Although association of DVD with sensory visual deprivation owing to congenital or acquired opacities of the ocular media has been reported, its association with congenital hereditary endothelial dystrophy (CHED) has not been reported hitherto. We report a case having a bilateral asymmetric DVD, in a know case of bilateral CHED.
PURPOSE: To evaluate the clinical profile, response to dexamethasone treatment and visual function outcome in Indian patients with acute optic neuritis. MATERIALS AND METHODS: We conducted an observational study of patients with acute optic neuritis who were treated with intravenous dexamethasone (100 mg in 250 ml of 5% dextrose over 1-2 hours daily, for three consecutive days) and had completed at least two years of follow-up. Parameters assessed included visual acuity, contrast sensitivity, color vision, visual fields, relative afferent pupillary defect (RAPD) and visually evoked potentials. Out of 40 patients studied, 26 patients (33 eyes) had all visual function parameters assessed. Twenty three patients (28 eyes) had completed two years of follow-up and were included for statistical analysis. RESULTS: Improvement in visual acuity was statistically significant for distance after 24 hours of the first dose (P = < 0.001) and for near vision after 24 hours of the second dose (P = 0.006); improvement in color and contrast sensitivity was statistically significant 24 hours after the third dose (P = < 0.001 for color vision and P = 0.013 for contrast sensitivity). Significant improvement in RAPD and visual fields were seen by 1 month (P = 0.005). Recurrence was seen in 4 eyes of 4 patients. No serious side effects were observed. At two years, 82.14% (23 out of 28) eyes had visual acuity > 20/40. CONCLUSION: Treatment with intravenous pulsed dexamethasone led to rapid recovery of vision in acute optic neuritis, without any serious side effects.
The present investigation attempts to increase intestinal permeability and hence absorption of biopharmaceutic classification system (BCS) Class III (cefotaxime sodium (CX)) and Class IV (cyclosporin A (CSA)) drugs by employing certain absorption enhancers. Drugs were co-perfused with sodium caprate (SC, 0.25% w/v), piperine (P, 0.004% w/v) and sodium deoxycholate (SD, 1.0% w/v) separately in rat in situ single pass intestinal perfusion model. These additives increased intestinal permeability (P(app)) and absorption rate constant (K(a)) up to two and fourfold, respectively. SC exhibited substantial absorption enhancement of both CX and CSA, while SD and P enhanced absorption of CX and CSA, respectively. Co-administration of SC significantly enhanced peroral bioavailability of CX (from 29.4 +/- 1.7 to 69.6 +/- 3.2) and CSA (from 18.4 +/- 15.6 to 49.6 +/- 25.1) in rats, while P increased bioavailability of CSA (from 18.4 +/- 15.6 to 33.1 +/- 17.7). Transmission electron microscopy of intestinal mucosa revealed that SC and SD act on lipid and protein domains of absorptive membrane. P showed no effect on intestinal P(app) and oral bioavailability of CX but has a profound effect on CSA, a known P-glycoprotein (P-gp) substrate. These results indicated that P enhances intestinal absorption of CSA by modulating P-gp mediated efflux transport. Release of lactate dehydrogenase in situ from intestinal mucosa in the presence of absorption enhancer was taken as index of its local toxicity. All the absorption enhancers showed significantly less release of LDH compared to positive control, sodium dodecyl sulfate (60% w/v). Overall, the data indicate that the features of these commonly used food ingredients or endogenous bile salts can effectively improve bioavailability of various BCS Class III and Class IV drugs.
The objective of the present investigation was to evaluate an oral 'drug delivery' approach, which involves co-administration of absorption enhancers (AEs). The representative low permeable hydrophilic (biopharmaceutic classification system (BCS) Class III) drugs used in the study comprised of cefotaxime sodium and ceftazidime pentahydrate, whereas low permeable lipophilic (BCS Class IV) drugs include cyclosporin A and lovastatin. AEs from three different chemical classes, namely, medium chain fatty acids (sodium caprylate and caprate), cyclodextrins (beta-cyclodextrin, hydroxypropyl beta-cyclodextrin) and bile salts (sodium cholate and deoxycholate) were evaluated for absorption enhancement efficacy, mechanism of action and toxicity using in vitro everted intestinal sac model. These AEs were found to enhance intestinal permeability of drugs from 2- to 27-fold. Light microscopy studies of intestinal sac incubated with AEs for 120 min revealed morphological changes in absorptive mucosa and rank order of toxicity were cyclodextrins>bile salts congruent with medium chain fatty acids. Fluorescence polarization studies indicated that brush bordered membrane vesicles labeled with lipophilic (DPH, 12AS) and hydrophilic dyes (ANS), when treated with AEs exhibited concentration and time dependent decrease in fluorescence polarization. Total protein released in presence of AEs was more than control but considerably less than EDTA (0.58% w/v), which is known to cause toxic release of proteins from cell. Overall, AEs were found to significantly enhance drug permeability by decreasing lipid membrane fluidity and/or interacting with hydrophilic domains of membrane, and has the potential to improve oral delivery.
Absorption enhancers (AEs) have been shown to be specific in permeation enhancement capabilities because of which they increase absorption of some drug molecules more than others. Present study was designed to investigate the relationship between lipophilicity of drug molecules and the absorption enhancement potential of AEs. Four drug molecules of different lipophilicity were selected as model compounds, namely, cefotaxime sodium, ceftazidime pentahydrate, lovastatin and cyclosporin A. Their apparent permeability coefficients in the absence and presence of three classes of AEs (fatty acids, cyclodextrins, and bile salts) were determined using in vitro everted rat intestinal sac absorption model. Significant relationship was observed between log P of drug and absorption enhancement ratios by AEs. This relationship was found to be functionally directly or indirectly proportional depending upon nature of AE and explain the mechanism of permeation enhancement.
In this study which was carried over a period of 4 years, from 2001 to 2004, 600 adult patients with active TB disease attending the OPD of TBDTC, Agra, were screened for HIV-1/2 antibodies. Of these, 26 were found to be HIV-positive. Seroprevalence of HIV infection among adult TB patients in Agra is 4.3% (26/600). The HIV infection was found to be more in females, i.e. 7.95% (7/88) than in males, 3.71% (19/512). HIV-positivity of 5% was observed in the age groups, 15-24 and 25-34 years, i.e. 3/60 and 13/260, respectively. Among HIV-positive TB patients, 4.2% (22/524) were of pulmonary and 5.3% (4/76) were of extra-pulmonary type. A total of 3.04% (6/197) of HIV-positive TB patients were PPD positive and 4.96% (20/403) were PPD negative and bacillary positivity was 4.4% (15/340) and bacillary negativity was 4.2% (11/260). A total of 3.5% (18/515) of TB patients had a history of positive contact, i.e. spouse or one of the family members was HIV-infected. The difference in signs and symptoms among the HIV positive and HIV negative TB patients was found to be statistically significant.
INTRODUCTION: Existing methods to detect breast cancer in asymptomatic patients have limitations, and there is a need to develop more accurate and convenient methods. In this study, we investigated whether early detection of breast cancer is possible by analyzing gene-expression patterns in peripheral blood cells. METHODS: Using macroarrays and nearest-shrunken-centroid method, we analyzed the expression pattern of 1,368 genes in peripheral blood cells of 24 women with breast cancer and 32 women with no signs of this disease. The results were validated using a standard leave-one-out cross-validation approach. RESULTS: We identified a set of 37 genes that correctly predicted the diagnostic class in at least 82% of the samples. The majority of these genes had a decreased expression in samples from breast cancer patients, and predominantly encoded proteins implicated in ribosome production and translation control. In contrast, the expression of some defense-related genes was increased in samples from breast cancer patients. CONCLUSION: The results show that a blood-based gene-expression test can be developed to detect breast cancer early in asymptomatic patients. Additional studies with a large sample size, from women both with and without the disease, are warranted to confirm or refute this finding.
Cotton leaf curl geminivirus is a whitefly (Bemisia tabaci Genn.) transmitted Begomovirus (Family Geminiviridae) causing a serious disease of cotton in northern India. The very typical symptoms of present isolate (CLCuV-HS2) showed thickened veins, dark green discoloration of the leaves with upward curling and leaf like structure known as enation (one in number), which develops into cup-shaped on the reverse side of leaves. The polymerase chain reaction (PCR) based technique can detect the viral DNA in samples stored upto 3 days after the collection and have wide application for the field diagnosis. The complete nucleotide sequence of the Indian isolate of cotton leaf curl geminivirus (CLCuV-HS2) coat protein (CP) gene component was determined using CP specific primers through PCR amplification from field infected cotton plants growing in Haryana, India. Comparison of the amino acid sequence of the putative CP with some other mono and bipartite geminiviruses revealed a maximum of 97.3% identity with Pakistan cotton leaf curl virus (CLCuV-62). A nuclear localization signal located close to the N-terminal of CP gene was determined.
The authors present a case of optic nerve cysticercosis in a 32-year-old patient who presented with sudden blurring of vision in the left eye and a transient visual improvement on systemic steroids. The ocular findings were unremarkable other than a relative afferent pupillary defect (RAPD). An ultrasound of the orbit, CT and MRI scans revealed a cystic lesion in the orbital portion of the optic nerve close to the eyeball. A presumed diagnosis of optic nerve cysticercosis was made on the basis of imaging and a positive serum ELISA. The patient improved dramatically on a 4-week therapeutic trial of albendazole and oral steroids. The post-treatment ultrasound and CT scan showed an involution of the cyst with some residual thickening of the optic nerve.
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PURPOSE: To determine the incidence of scleral perforations in strabismus surgery in a tertiary centre setting in India and to evaluate the risk or benefit, if any, of prophylactic cryotherapy following experimental scleral perforations in rabbits. METHODS: Seven hundred eyes of patients that had undergone strabismus surgery (1121 procedures) were examined postoperatively by indirect ophthalmoscopy. In the experimental component, 20 rabbit eyes were perforated with a 6-0 polyglactin suture. In each rabbit, one eye acted as a control while the other eye received a 20 seconds application of prophylactic cryo at the perforation site. They were then monitored for 6 weeks before subjecting some to histopathological examination by light and electron microscopy. RESULTS: Ten scleral perforations were detected in 9 of the patients (incidence of 1.42% of the eyes and 0.89% of the strabismus procedures). In the rabbits, a chorioretinal scar was seen in all perforated eyes. A mild cryo reaction was observed in the cryoed eyes. No other sequelae were seen. Histopathologic studies showed changes consistent with the normal healing process. CONCLUSIONS: Of the human eyes screened, 1.42% showed evidence of scleral perforation following strabismus surgery. In no case were sequelae leading to visual loss observed. In the rabbits no sequelae were observed at 6 weeks of follow-up apart from a chorioretinal scar and a cryoreaction in those eyes in which cryoprophylaxis had been given. Mild cryoprophylaxis did not exert any positive or negative influence on the natural course of scleral perforation in our short-term animal study.
The tenets of biopharmaceutics, solubility and permeability, are of pivotal importance in new drug discovery and lead optimization due to the dependence of drug absorption and pharmacokinetics on these two properties. A classification system for drugs based on these two fundamental parameters, Biopharmaceutic Classification System (BCS), provides drug designer an opportunity to manipulate structure or physicochemical properties of lead candidates so as to achieve better "deliverability". Considering the facts for failure of NCEs, drug research, once concentrating on optimizing the efficacy and safety of the leads, dramatically transformed in the past two decades. With the enormous number of molecules being synthesized using combinatorial and parallel synthesis, high throughput methodologies for screening solubility and permeability has gained significant interest in pharmaceutical industry. Ultimate aim of the drug discovery scientist in pharmacokinetic optimization is to tailor the molecules so that they show the features of BCS class I without compromising on pharmacodynamics. Considerations to optimize drug delivery and pharmacokinetics right from the initial stages of drug design propelled need for "High Throughput Pharmaceutics" (HTP). In silico predictions and development of theoretical profiles for solubility and lipophilicity provides structure based biopharmaceutical optimization, while in vitro experimental models (microtitre plate assays and cell cultures) validate the predictions. Thus, biopharmaceutical characterization during drug design and early development helps in early withdrawal of molecules with insurmountable developmental problems associated with pharmacokinetic optimization.