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Maintains that a loss-gain hypothesis (a negative impression gives way to a positive one) is a more powerful indicator and incentive for future friendship than an opposite sequence (positive to negative). Both of these, however, were eclipsed by a positive-positive interaction as a determinant of interpersonal attraction. (MJP)

Background: Aspergillosis, has recently confounded some states of India. Due to major role in fungal cell wall synthesis, in the present study UDP-glycosyltransferase, Glucosamine-6-phosphate synthase and chitin synthase were chosen as an appropriate sites to design drug. The objective of present study was molecular docking of lemon grass essential oil component citral and in vitro validation. GC-FID analysis was used to find out aromatic profile. For docking, Patch-dock analysis was used. Ligand Protein 2D and 3D Interactions were also studied. Drug likeliness, and toxicity profile were also studied. Docking analysis indicated effective binding of citral to UDP-glycosyltransferase, Glucosamine-6-phosphate synthase and chitin synthase. In vitro validation was performed by fungal strain Aspergillus fumigatum. Results: GC-FID profiling revealed the presence of citral as major bioactive compound. Interactions results indicated that, UDP-glycosyltransferase, Glucosamine-6-phosphate synthase and chitin synthase enzymes and citral complexes forms hydrogen and hydrophobic interactions. Citral also depicted drug likeliness by LIPINSKY rule, sufficient level of bioactivity, drug likeliness and toxicity. Conclusion: In vitro results revealed that lemon grass oil was able to inhibit growth of fungal strains toxicity thus signifying its role as potent anti-fungal drug. [ABSTRACT FROM AUTHOR]

Black fungus also known as Mucormycosis, has recently devastated some states of India. It has been declared pandemic now. Inhibitors of glucon synthesis pathways have been evaluated to curtail the Mucormycosis but still at infancy stage. Due to key role in glucon synthesis, in the present study β -glucan synthase has been regarded as a suitable target for drug design. In-silico docking and pharmacological study was designed to evaluate the effect of potent bioactive molecule 1-8 cineole present in essential oils of eucalyptus plant leaves against β -glucan synthase enzyme. Till date there is no work is undertaken on insilico analysis of this compound against β -glucan synthase. Patch-dock analysis was used for docking. Ligand Protein 2D and 3D Interactions were also studied. Drug likes and toxicity profile was also evaluated. Cancer cell line toxicity profile was also studied. The calculated parameters such as docking score indicated effective binding of 1-8 cineole to β - glucan synthase -protein. Interactions results indicated that, β -glucan synthase enzyme and 1-8 cineole complexes forms hydrogen and hydrophobic interactions. 1-8 cineole also depicted sufficient level of cancer cell line toxicity. Drug likeliness profiles by assaying absorption, distribution, metabolism, excretion and toxicity (ADMET) studies provided guidelines and mechanistic scope for identification of 1-8 cineole as potent anti-fungal drug. Therefore, essential oil from eucalyptus may represent potential herbal treatment to act as anti-fungal drug. [ABSTRACT FROM AUTHOR]

Background: Primary congenital glaucoma (PCG), occurs due to the developmental defects in the trabecular meshwork and anterior chamber angle in children. PCG exhibits genetic heterogeneity and the CYP1B1 gene has been widely implicated worldwide. Despite the diverse mutation spectra, the clinical implications of these mutations are yet unclear. The present study attempted to delineate the clinical profile of PCG in the background of CYP1B1 mutations from a large cohort of 901 subjects from India (n=601) and Brazil (n=300). Methods: Genotype-phenotype correlations was undertaken on clinically well characterized PCG cases from India (n=301) and Brazil (n=150) to assess the contributions of CYP1B1 mutation on a set of demographic and clinical parameters. The demographic (gender, and history of consanguinity) and quantitative clinical (presenting intraocular pressure [IOP] and corneal diameter [CD]) parameters were considered as binary and continuous variables, respectively, for PCG patients in the background of the overall mutation spectra and also with respect to the prevalent mutations in India (R368H) and Brazil (4340delG). All these variables were fitted in a multivariate logistic regression model using the Akaike Information Criterion (AIC) to estimate the adjusted odds ratio (OR) using the R software (version 2.14.1). Results: The overall mutation spectrum were similar across the Indian and Brazilian PCG cases, despite significantly higher number of homozygous mutations in the former (p=0.024) and compound heterozygous mutations in the later (p=0.012). A wide allelic heterogeneity was observed and only 6 mutations were infrequently shared between these two populations. The adjusted ORs for the binary (demographic) and continuous (clinical) variables did not indicate any susceptibility to the observed mutations (p>0.05). Conclusions: The present study demonstrated a lack of genotype-phenotype correlation of the demographic and clinical traits to CYP1B1 mutations in PCG at presentation. However, the susceptibility of these mutations to the long-term progression of these traits are yet to be deciphered. [ABSTRACT FROM AUTHOR]

Well-designed studies on systemic therapeutic modalities for severe psoriasis in children are rare. Children with severe disease are treated with the support of data extrapolated from that in adult, although management in them differs from adults in several important aspects. Like other systemic modalities, data regarding the use of methotrexate in the treatment of childhood psoriasis is meager. This study aims to analyze the efficacy and safety of methotrexate in severe or disabling childhood psoriasis. The records of all the patients <18 years of age treated with systemic methotrexate at the psoriasis clinic of our institute from January 1993 to December 2006 were retrieved. Information regarding demographic profile, disease characteristics, response to treatment, side effects, etc. was noted from predesigned clinic proforma. Indications of methotrexate use were baseline psoriasis area and severity index (PASI) >10, disease refractory to conventional therapies and disabling psoriasis even though the psoriasis area and severity index was <10. Clinical status of patients was assessed at weekly intervals for the first 2 weeks, fortnightly during next month and then monthly. Response to therapy was graded as good (50–75% decrease in PASI) and excellent (>75% decrease in PASI). Laboratory investigations to detect methotrexate induced toxicity were performed at regular intervals. Of the 29 patients treated with methotrexate, 24 were eligible for the final data analysis. Indication for the institution of methotrexate therapy was severe disease, viz., extensive recalcitrant plaque type psoriasis in 17 patients, erythroderma and generalized pustular psoriasis of von-Zumbusch type in three patients each and severe disabling palmo-plantar involvement along with chronic plaque lesions in one patient. Response to therapy was excellent (>75% decrease in PASI) in all but two patients. The mean time to control the disease, i.e., 50% reduction in PASI was 5.1 weeks. Mean total cumulative dose of methotrexate in the first episode was 215 mg. The duration of remission could be calculated in nine patients only, varying from 1.5 months to 3 years. Side effects were mild, observed in nine children, which included nausea, vomiting, and loss of appetite. Methotrexate is an effective, cheap, easily available, and reasonably safe drug to be used in severe childhood psoriasis under an expert supervision and laboratory monitoring. [ABSTRACT FROM AUTHOR]

Nineteen insertion/deletion and restriction site polymorphisms on autosomal and mitochondrial genomes and mitochondrial DNA hypervariable segment 1 sequences were used to study genetic diversities and affinities among four endogamous groups of Punjab, India. High values of heterozygosity were noted in all four groups, both in the autosomal and mitochondrial genomes. The coefficient of gene differentiation among the groups, however, was found to be low. Genetic distance and phylogenetic analyses based on these data indicated that inferences on affinities among the populations were different when the two sets of loci (autosomal and mitochondrial) were considered separately. We have interpreted these results on the basis of some known historical data on migrations into this region. The results of this study when compared with the findings of some previous studies indicate that there are regional differences in the patterns of correlation between genomic and sociocultural affinities within India. [ABSTRACT FROM AUTHOR]

Abstract Background Melasma is a common disorder of facial hyperpigmentation. Many modalities of treatment are available, but none is satisfactory. Materials and methods Twenty-five nonpregnant female patients with a minimum melasma area and severity index (MASI) of 15 were recruited in the study. After a detailed history and clinical examination under natural light and Wood's light, MASI was calculated and color photographs were taken of all patients. Patients were advised to carry out a prepeel program of daily application of topical sunscreens (sun protection factor-15, SPF-15) and 10% glycolic acid lotion at night for 2 weeks. Patients were then treated with 50% glycolic acid facial peel once per month for three consecutive months. At regular intervals and at the end of the follow-up period (3 months) after the last peel, the degree of improvement in pigmentation was assessed by remeasuring MASI. Side-effects, if any, were also recorded. The data obtained were statistically analyzed using Student's paired t-test and Spearman rank correlation coefficient test. Results Improvement in melasma (reduction in MASI) was observed in 91% of patients (P < 0.01). Patients with epidermal-type melasma demonstrated a better response to treatment than those with mixed-type melasma (P < 0.05). Conclusions The prepeel program followed by 50% glycolic acid facial peel once per month for three consecutive months proved to be an effective treatment modality in Indian patients without any significant side-effects. [ABSTRACT FROM AUTHOR]

Aims We undertook this study to analyse the pattern of childhood cutaneous tuberculosis prevailing in northern India over the past 25 years and to highlight differences from and similarities to adult tuberculosis. Materials and methods Clinical records of children with cutaneous tuberculosis who attended the Nehru Hospital attached to the Postgraduate Institute of Medical Education and Research, Chandigarh, India, between January 1975 to December 1999 were analysed. Results Four hundred and two patients with cutaneous tuberculosis were examined during the 25-year period of observation. These patients formed 0.1% of the total dermatology outpatients. Seventy-five (18.7%) of these 402 cases were children (≤ 16 years). There were 32 (42.7%) boys and 43 (57.3%) girls with a boy: girl ratio of 0.74:1. The majority of the children, 41 (54.7%) were in the 10–14 years age group. There was no significant boy or girl preponderance in any group other than in scrofuloderma (SFD), where girls significantly outnumbered boys at all ages. Of the various patterns of cutaneous tuberculosis seen, 40 (53.3%) had SFD, 30 (40.0%) had lupus vulgaris (LV), 3 (4.0%) had tuberculosis verrucosa cutis (TVC), 1 (1.3%) child each had tuberculids and tubercular gumma. No child had a tubercular chancre or acute miliary cutaneous tuberculosis. The neck was the commonest site afflicted with SFD and the face was the commonest site affected with LV. No child had generalized lymphadenopathy. Eighteen (60.0%) of the 30 children with LV had regional lymphadenopathy of which 15 (83.3%) had Iocalized disease and 3 (16.7%) had disseminated disease. Of the 16 children with systemic organ involvement, 12 (75.0%) had regional lymphadenopathy. Of the 62 children in whom the data regarding vaccination status was available, 31 (50.0%) had been vaccinated and 31 (50.0%) had not. Among the vaccinated group no child had disseminated disease. Three (9.7%) children in the nonvaccinated group had dis... [ABSTRACT FROM AUTHOR]

During a period of eight years, 132 new leprosy cases were detected in children ages 3 to 19 years. Borderline tuberculoid leprosy was present in 59%, tuberculoid in 7.6%, and indeterminate type in 3.8% patients. Single skin lesions were seen in a significant number (43.9%) of patients. Bacillus-positive disease was detected more often (17.4%) than in adults. A high frequency (66.6%) of nerve involvement was also detected. Deformities were uncommon. Males were more often affected than females, especially in the ages 10 to 14 and 15 to 19 years. A history of contact was available in only 19.7% patients, and the contact was intrafamilial in 84.6%. [ABSTRACT FROM AUTHOR]

Reports on the analysis of water-quality parameters and concentrations of various metals in bed sediments of the River Kali and the River Hindon, India to understand their behavior in subtropical fluvial systems. Existence of metals in bound form in the summer season; Fall in metal concentrations in sediments during and after the monsoon season.

Examines the frequency of various nail changes in patients with psoriasis in Chandigarh, India. Diagnosis of psoriasis; Description of individual nail changes; Comparison of mean number of nail changes per subject with nail fold involvement; Types of nail changes caused by psoriasis.

Eucalyptus essential oil poses various biological activities due to the presence of various bioactive compounds. The objective of this study was to evaluate the effect of direct heat-based hydro distillation (DHBH) and in-direct heat-based hydro-distillation (IDHBH) methods on chemical profile, extraction, and biological activities of essential oils from Eucalyptus polybractea. Eucalyptus Essential Oil (EEO) was extracted from green leaves of eucalyptus plant using DHBH and IDHBH methods. Aroma profile was evaluated by GC-FID technique. Content of phenolics, flavonoids and tannins accompanied by antioxidant activities like iron-chelation and DPPH were studied. Other biological activities like anti-inflammatory and anti-microbial were also analysed. GC-FID chemical profiling revealed a greater number of bioactive compounds in IDHBH extract than DHBH. Relationship between antioxidant activity and chemical composition of extracted oils was investigated. Significant amount of β-pinene, 1,8 cineole, eugenol, Pentadecanoic acid are responsible for antioxidative capacity of both extracts. The concentration of all compounds, especially Pentadecanoic acid and other unique bioactives were higher in IDHBH extract. The level of antioxidants like phenolics, flavonoids and tannins by was high also high in IDHBH extracted oil. This corresponds to higher antioxidant activities like DPPH and iron-chelating activity of IDHBH oil compared with DHBH extract. Similarly, anti-inflammatory, and anti-microbial potential was more in oil extracted with IDHBH than DHBH. The present paper reported that different extraction methods lead to different biochemical composition of essential oils and the choice of a suitable method is extremely important to obtain more preferred compounds with more potent biological activities and this method can be the choice for essential oil-based companies. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about computerized AIDS helplines.

Purpose: Human ocular tissue banking plays an important part in the advancement of translational research for identifying the molecular processes involved in disease etiology and pathogenesis. Timely obtaining a good-quality ocular tissue from a cadaveric donor is exceedingly difficult, especially in remote areas, with a variable transportation time (within 12-24 h), raising concerns about RNA quality and its subsequent applications. Therefore, we assessed the utility of retinal tissues from cadaver donor and enucleated eyes based on the RNA quality and gene expression by real-time polymerase chain reaction (PCR)., Settings and Design: Prospective study., Methods: Retina tissues were separated from the donor/enucleated eyes received in the eye bank within 24 h of death (n = 15) and within an hour from OR (n = 3), respectively, and stored immediately at -80 degree. RNA was isolated using trizol, and the quantity and quality were assessed using Qubit and agarose gel electrophoresis, respectively. QPCR was performed for measuring the expression of different retinal-specific genes. The cellular viability of the retina was assessed by establishing explant primary cell cultures., Statistical Analysis: The data were calculated as an average of normalised Ct values ± standard error of the mean., Results: RNA obtained from cadaveric tissues despite being partially degraded showed a uniform strong gene expression of several retinal-specific genes such as PAX6, RHO, TUBB3, CRX , and ALDH1L1 . The primary cultures established from cadaveric tissues showed viable cells., Conclusion: The cadaver donor tissues collected within 24 hours of death can be effectively utilized for gene expression profiling., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Background: The Plasmodium genome encodes for a number of 6-Cys proteins that contain a module of six cysteine residues forming three intramolecular disulphide bonds. These proteins have been well characterized at transmission as well as hepatic stages of the parasite life cycle. In the present study, a large complex of 6-Cys proteins: Pfs41, Pfs38 and Pfs12 and three other merozoite surface proteins: Glutamate-rich protein (GLURP), SERA5 and MSP-1 were identified on the Plasmodium falciparum merozoite surface., Methods: Recombinant 6-cys proteins i.e. Pfs38, Pfs12, Pfs41 as well as PfMSP-1 65 were expressed and purified using Escherichia coli expression system and antibodies were raised against each of these proteins. These antibodies were used to immunoprecipitate the native proteins and their associated partners from parasite lysate. ELISA, Far western, surface plasmon resonance and glycerol density gradient fractionation were carried out to confirm the respective interactions. Furthermore, erythrocyte binding assay with 6-cys proteins were undertaken to find out their possible role in host-parasite infection and seropositivity was assessed using Indian and Liberian sera., Results: Immunoprecipitation of parasite-derived polypeptides, followed by LC-MS/MS analysis, identified a large Pfs38 complex comprising of 6-cys proteins: Pfs41, Pfs38, Pfs12 and other merozoite surface proteins: GLURP, SERA5 and MSP-1. The existence of such a complex was further corroborated by several protein-protein interaction tools, co-localization and co-sedimentation analysis. Pfs38 protein of Pfs38 complex binds to host red blood cells (RBCs) directly via glycophorin A as a receptor. Seroprevalence analysis showed that of the six antigens, prevalence varied from 40 to 99%, being generally highest for MSP-1 65 and GLURP proteins., Conclusions: Together the data show the presence of a large Pfs38 protein-associated complex on the parasite surface which is involved in RBC binding. These results highlight the complex molecular interactions among the P. falciparum merozoite surface proteins and advocate the development of a multi-sub-unit malaria vaccine based on some of these protein complexes on merozoite surface.

Purpose: Mutations in the Norrie disease pseudoglioma (NDP; Xp11.3) gene have been involved in retinal blood vessel formation and neural differentiation and are implicated in familial exudative vitreoretinopathy (FEVR) cases. However, the role of the gene has not been explored in the Indian context. Thus, this study was designed to understand the involvement of NDP among Indian patients with FEVR., Methods: The study cohort comprised 225 subjects, including unrelated patients with FEVR (n = 110) and ethnically matched healthy subjects (n = 115) recruited from a tertiary eye care center in India. The entire coding regions, intron-exon boundaries, along with the 5' and 3' untranslated regions of NDP were screened with resequencing following standard protocols. The spectrum of the observed variants was analyzed in conjunction with data available from other populations., Results: Eight potentially pathogenic mutations (p.His4ArgfsX21, p.Asp23GlufsX9, p.Ile48ValfsX55, p.His50Asp, p.Ser57*, p.Gly113Asp, p.Arg121Gln, and p.Cys126Arg, including five novel ones), were observed in the coding region of the NDP gene in ten unrelated FEVR probands (9%). The novel changes were not observed in the control subjects and were unavailable in the dbSNP, ESP5400, NIEHS95, and ExAC databases. All probands with NDP mutations exhibited classical features of the disease as observed among patients with FEVR worldwide., Conclusions: This is perhaps the first study to demonstrate the involvement of NDP among patients with Indian FEVR that further expands its mutation spectrum. The data generated could have broad implications in genetic counseling, disease management, and early intervention for a better prognosis in FEVR.

Aim: The fork-head transcription factor gene (FOXL2) gene has been implicated in Blepharophimosis Ptosis Epicanthus Inversus Syndrome (BPES) type I and type II. The authors aimed to evaluate the involvement of FOXL2 in familial and sporadic cases of BPES in an Indian cohort., Methods: The present cohort comprised clinically well-characterised BPES cases that included six affected families, two sporadic cases and 60 unaffected normal controls. The 5' untranslated and coding region of FOXL2 was screened by resequencing and confirmed by restriction digestion. Further, genotype-phenotype correlations were done to understand the implications of the observed mutation., Results: Six mutations were observed in eight cases (87.5%). These included a novel deletion (c.860delC), three previously reported duplications (c.663-692dup 30, c.672-701dup30 and c.843-859dup17), a frame shift (c.804dupC) and a homozygous missense mutation (p.E69K). The p.E69k mutation was seen in both heterozygous and homozygous form in a large four-generational family, and disease severity was found to be directly linked to the allelic dosage. Two SNPs (c.501C→T, c.536C→G) were also noted. An unusual coexistence of polycystic ovarian disease (PCOD) with BPES was also seen in one of the families., Discussion: Mutations in the region downstream of the fork-head domain were predominantly responsible for BPES among Indian patients.

Purpose: Recently, the neurotrophin-4 (NTF4), VAV2 and VAV3 genes have been implicated in primary open-angle glaucoma (POAG) in the European and Japanese populations, respectively. This study was conducted to determine their involvement in an Indian population with POAG and primary angle-closure glaucoma (PACG)., Methods: The entire NTF4 gene and the POAG-associated SNPs rs2156323 (VAV2) and rs2801219 (VAV3) and their flanking regions were screened by resequencing in a clinically well-characterized cohort of 537 subjects that included cases of POAG (n = 141), PACG (n = 111), and ethnically matched normal controls (n = 285). The data were analyzed by using appropriate statistical software., Results: Resequencing of NTF4 revealed a nonsynonymous (A88V), silent (P151P) and two changes in the 3'UTR region, along with a known polymorphism (rs11669977) in cases of POAG; the PACG cases exhibited only the A88V variation. Of interest, the A88V mutation observed in Europeans was more prevalent in our normal control subjects (4.91%, 95% CI, 2.95-8.07) than in the POAG (2.14%, 95% CI, 0.73-6.11; P = 0.200) and PACG (2.85%, 95% CI, 0.97-8.06; P = 0.577) cases. There were no major differences in the presenting intraocular pressure, cup-to-disc ratio, and visual field defects among patients harboring the A88V variation. The other variations in NTF4 were not associated with the cases. The risk alleles of rs2156323 and rs2801219 in the Japanese were not associated with POAG (P = 0.533 and 0.133, respectively) and PACG (P = 0.223 and 0.394, respectively) in the Indian cohort., Conclusions: The present data indicate a lack of involvement of variations in NTF4, VAV2, and VAV3 with glaucoma pathogenesis in an Indian population.

Psoriasis is a common dermatosis in children with about one third of all patients having onset of disease in the first or second decade of life. A chronic disfiguring skin disease, such as psoriasis, in childhood is likely to have profound emotional and psychological effects, and hence requires special attention. Psoriasis in children has been reported to differ from that among adults being more frequently pruritic; plaque lesions are relatively thinner, softer, and less scaly; face and flexural involvement is common and guttate type is the characteristic presentation. Whether onset in childhood predicts a more severe form of psoriasis is a matter of controversy, it may cause significant morbidity particularly if it keeps relapsing. Most children have mild form of psoriasis which can be generally treated effectively with topical agents such as emollients, coal tar, corticosteroids, dithranol, calcipotriol etc. according to age and the sites affected. Narrow band UVB is the preferred form of phototherapy in children for moderate to severe disease or in patients not responding to topical therapy alone. Systemic therapies are reserved for more severe and extensive cases that cannot be controlled with topical treatment and/or phototherapy such as severe plaque type, unstable forms like erythrodermic and generalized pustular psoriasis and psoriatic arthritis. There are no controlled trials of systemic therapies in this age group, most experience being with retinoids and methotrexate with favorable results. Cyclosporine can be used as a short-term intermittent crisis management drug. There is an early promising experience with the use of biologics (etanercept and infliximab) in childhood psoriasis. Systemic treatments as well as phototherapy have limited use in children due to cumulative dose effects of drugs, low acceptance, and risk of gonadal toxicity. More evidence-based data is needed about the effectiveness and long-term safety of topical, phototherapy and systemic therapies in children.

Purpose: Genes involved in the complement cascade such as complement factor B (CFB) and complement component C2 have been implicated in age-related macular degeneration (AMD) worldwide. In continuation of the analysis of CFH and LOC387715/HTRA1, this study was conducted to gain understanding of the role of CFB and C2 in an Indian AMD cohort., Methods: Single nucleotide polymorphisms in CFB and C2 were screened in a cohort of clinically well-characterized patients with AMD (n = 177) and unaffected normal control subjects (n = 175). Screening was accomplished by a combination of customized genotyping followed by validation through resequencing. In addition, genotyping of two CFB variants (rs12614 and rs641153) that were in close proximity had to be resolved by resequencing. Estimates of allele and genotype frequencies, odds ratios, Hardy-Weinberg equilibrium, linkage disequilibrium (LD), and haplotype frequencies were also performed., Results: Three SNPs in C2 (rs547154 [IVS10]; P = 5.4 x 10(-11)) and CFB (rs641153 [R32Q], P = 2.2 x 10(-7) and rs2072633 [IVS17]; P = 2.0 x 10(-4)) were strongly associated with reduced risk of AMD. The rs547154 and rs641153 were in strong LD (D' = 0.90, 95% CI = 0.81-0.96) and a protective haplotype T-A was observed (OR = 0.10, 95% CI = 0.05-0.20). LD was moderate (D' = 0.77, 95% CI = 0.67-0.85) between the rs547154 and the rs2072633 SNPs, and the haplotype T-T generated with these SNPs was relatively less protective (OR = 0.28, 95% CI = 0.18-0.44)., Conclusions: The results of the present study provide an independent validation of the association of rs547154 (C2) and rs641153 (CFB) SNPs with reduced risk of AMD in an Indian cohort.

Purpose: Glaucoma is a complex disease involving multiple genetic factors. Recently, single nucleotide polymorphisms (SNPs) in the LOXL1 gene have been implicated in exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) but not in the primary glaucomas. This study was conducted to determine the possible involvement of these SNPs in cases of primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG)., Methods: The three associated SNPs of LOXL1 (rs1048661, rs3825942, and rs2165241) were screened in 208 unrelated and clinically well-characterized glaucoma cases comprising patients with POAG (n = 112) or PACG (n = 96) along with 105 ethnically matched normal control subjects from Indian populations. Subjects with exfoliative material on the lens and radial pigmentation in the periphery of the lens that could be earlier signs of XFS were excluded. These SNPs were screened by resequencing and further confirmed by PCR-based restriction digestions. Haplotypes were generated with the three SNPs in cases and control subjects, and linkage disequilibrium (LD) and haplotype analysis were performed with the Haploview software, which uses the EM (expectation-maximization) algorithm., Results: The SNPs of LOXL1 did not exhibit any significant association with POAG or PACG, unlike previous studies from Icelandic, Swedish, U.S., and Australian populations with XFS/XFG. Haplotypes generated with these intragenic SNPs did not indicate any significant risk with POAG or PACG phenotypes. The risk haplotype G-G in XFS/XFG in other populations was present in 46% of the normal control subjects in the present cohort., Conclusions: The results from the present study do not indicate the involvement of the LOXL1 SNPs in POAG and PACG.

Purpose: Single nucleotide polymorphisms (SNPs) in the LOC387715 (rs10490924), HTRA1 (rs11200638), and CFH (rs1061170) genes have been implicated in age-related macular degeneration (AMD). The present study was undertaken to determine the involvement of the LOC387715 and HTRA1 in an AMD cohort from India., Methods: The coding region of LOC387715 (exon 1) and the promoter of HTRA1 were screened by resequencing in AMD cases and normal controls. Odds ratios were calculated to assess the risk of individual genotypes. Linkage disequilibrium (LD) and haplotype frequencies were estimated with Haploview software. Population attributable risk (PAR %) for the associated SNPs and their combined effects were calculated., Results: Resequencing revealed seven different SNPs in these genes, of which significant associations were noted with the risk alleles of rs10490924 (T allele; P = 5.34 x 10(-12)) in LOC387715, and rs11200638 (A allele; P = 4.32 x 10(-12)) and rs2672598 (C allele; P = 3.39 x 10(-11)) in HTRA1 among the cases. Correspondingly, the homozygous risk genotypes TT, AA, and CC in these SNPs exhibited higher disease odds and PAR %. rs10490924 and rs11200638 were in tight LD (D', 0.90; 95% CI, 0.84-0.93). G-C-T-A-C was the risk haplotype (P = 8.04 x 10(-15)), whereas the G-C-G-G-T haplotype was protective (P = 2.01 x 10(-4)). The combined effect of the CFH (CC) and LOC387715 (TT) risk genotypes exhibited a PAR of 93.7% (OR, 73.89; 95% CI, 8.69-628.13)., Conclusions: The present data provided an independent validation of the association of LOC387715 and HTRA1 SNPs, along with their risk estimates among Indian patients with AMD. These associations underscore their significant involvement in AMD susceptibility, which may be useful for predictive testing.

Purpose: To screen polymorphisms in complement factor-H (CFH), toll-like receptor 4 (TLR4), and APOE genes as potential risk factors for age-related macular degeneration (AMD) in Indian patients., Methods: One hundred patients with AMD and 120 normal control subjects were screened for the polymorphisms by restriction digestion and resequencing. Five intragenic SNPs in CFH were screened to generate haplotype data in cases and controls. The data were analyzed in conjunction with data from other populations based on genotype and haplotype frequencies, and odds ratios were computed to estimate the risk of AMD in the different genotypes., Results: Significant association was noted with the CFH variant (Tyr402His) among AMD cases (P = 1.19 x 10(-7)). Individuals homozygous for the mutant genotype CC had a significantly higher risk (P < 0.0001) of AMD (OR = 11.52; 95% CI 5.05-26.28) than those carrying a single copy of the C allele (OR = 1.51; 95% CI 0.82-2.80), after adjusting for age, gender, and diabetes. Linkage disequilibrium and haplotype analysis at the CFH locus indicated the C-G-T-C-A-G to be a risk haplotype (P = 0.0003). No significant differences were observed in the genotype frequencies of APOE polymorphisms among patients and control subjects (P = 0.76). The carriers of epsilon4 allele had a reduced risk (P = 0.03) of AMD (OR = 0.42, 95% CI 0.19-0.91). TLR4 did not exhibit any association with AMD., Conclusions: The CFH polymorphism Tyr402His appears indicative of AMD pathogenesis. Diabetes, age, and gender in the presence of the homozygous "CC" genotype in CFH carry an increased risk of AMD. Hence this polymorphism could be used as a potential marker for predictive testing across continents.

Background: Pure neuritic leprosy (PNL) constitutes a significant proportion of all cases in India, however, this form of disease has not been fully recognized and investigated and there is little information in the existing literature., Objective: To study the epidemiological characteristics of PNL in India., Materials and Methods: A retrospective analysis of leprosy clinic records for the period 1993 to 2003 was undertaken. Detailed demographic profiles and clinical findings were noted from the predesigned clinic proforma. A slit-skin smear for acid-fast baclli (AFB) was done in all cases from the area of sensory loss. A skin biopsy was done from the area of sensory impairment to study histopathological changes. Further investigations such as nerve conduction velocity studies (NCV), fine needle aspiration cytology (FNAC), or nerve biopsy (superficial nerve twigs) were done if indicated in patients whenever there was difficulty in clinical diagnosis., Results: Of the total 1542 leprosy patients seen over this period, 65 (4.2%) had PNL. Males were more commonly affected than females (2.6:1.). The majority of patients 40/65(61.5%) were aged between 15 and 35 yrs. Predominant presenting symptoms were paresthesia, pain, sensory/motor deficit, and trophic changes. A majority of the patients 39/65 (60.0%) presented with involvement of 2 or more nerves in the same extremity. Mononeuritis was seen in 26 (40%) patients. The nerves most often involved were the right ulnar nerve in the upper extremity, and the right common peroneal nerve in the lower limb. In general, the nerves of the upper extremity were more commonly involved than in the lower limbs (67 vs. 55). Motor deformities such as claw hand and foot drop were present in 13/75 (20%) and 7/65 (10.8%) patients, respectively. Slit-skin smears were negative in all patients, and skin histopathology from the area of sensory loss revealed non-specific inflammation in the dermis in a majority of patients, with perineural inflammation in a few. All patients were treated with multi-drug therapy (MDT); patients with >/=2 peripheral nerve trunk involvements were treated with WHO MDT MB regimen, while others were administered WHO MDT PB regimen. Follow-up for up to 2 yrs was available in only 32/65 (49.2%) patients, none of whom developed any skin lesions during this period., Conclusion: PNL is a distinct subset of disease frequently seen in India. There is need to pay more attention to this form of leprosy and diagnose and treat patients earlier to prevent deformities and sequelae of nerve damage.

Background: We undertook this study in order to determine the pattern and prevalence of childhood psoriasis in northern India and to highlight the differences and similarities with previous studies., Materials and Methods: In this retrospective epidemiologic study, the data from 419 children (less than 14 years of age) with psoriasis registered at the Psoriasis Clinic between January 1990 and December 2002 were included., Results: The 419 children registered at the Psoriasis Clinic constituted 0.3% of the dermatology outpatients and 12.5% of the total psoriasis patients seen over a period of 13 years in the department. There were 219 (52.2%) boys and 200 (47.7%) girls, with a male to female ratio of 1.09 : 1. The age of onset ranged from 4 days to 14 years. The mean age of onset was 8.1 +/- 2.1 years in boys and 9.3 +/- 2.3 years in girls. The peak age of onset in boys was in the 6-10-year age group, whereas the majority of girls showed an onset of psoriasis between the ages of 10 and 14 years. A positive family history was present in only 19 (4.5%) patients. The extensors of the legs were the most common initial site affected [105 (25%) cases], followed by the scalp [87 (20.7%)]. Classical plaque psoriasis was the most frequent clinical presentation [254 (60.6%) patients], followed by plantar psoriasis [54 (12.8%)]. Nail involvement was observed in 130 (31%) cases. All types of nail changes described in psoriasis were seen in these patients. Pitting was the most common nail change, followed by ridging and discoloration. Five children (1.1%) (three girls and two boys) had psoriatic arthropathy. Precipitating factors that brought about the onset of the disease or were associated with exacerbation could be recalled in only 28 (6.6%) patients. Koebnerization was observed in 27.9% of patients. Pruritus was the most frequent symptom, reported by 365 (87.1%) children. Twenty-seven (6.4%) children had other concurrent mucocutaneous diseases (vitiligo, pityriasis alba, alopecia areata, ichthyosis vulgaris, halo nevus, aphthous stomatitis, urticaria, pityriasis versicolor, nummular eczema, salmon patch, and verrucous epidermal nevus). Eighteen children had systemic disorders, including seizures, bronchial asthma, mitral regurgitation, scleroderma, Down's syndrome, high arched palate, cholelithiasis, anterior mongoloid slant, and prognathism; however, these conditions were possibly chance findings only and no correlation with the age of onset or severity of the disease was found., Conclusions: Our findings differ from those of previous studies in showing a delayed onset, equal sex distribution, less frequent facial involvement, uncommon guttate lesions, more frequent involvement of the soles, and a less frequent history of familial occurrence.

A retrospective analysis of patient's leprosy clinic records at PGIMER, Chandigarh, India for the period 1983 to 1998 was undertaken to study the frequency, time of onset, and risk factors for leprosy reactions. Of the 2600 cases analyzed, 1494 were multibacillary and 1106 had paucibacillary disease. Presentation with reaction was common with 30.9% of our patients having reactions at the time of first visit. The incidence of reversal reaction (RR) was highest during 6 to 12 months after starting multi-drug therapy (MDT), thereafter declining gradually. Late RR occurred in 9.5% of all cases and was noted up to 7 years after treatment. Female gender, widespread disease, and multibacillary disease were identified as risk factors for RR. Erythema nodosum leprosum (ENL) reactions were noted to occur mostly during second or third year after starting MDT. Of the total number of patients who experienced ENL, 64.3% had recurrent episodes which continued for up to 8 years after the start of treatment. Lepromatous leprosy, female gender, and high Bacterial Index (>/=3) were recognized as risk factors for developing ENL. Occurrence of recurrent and late reactions, even though of mild severity, highlights the importance of recognizing and treating them promptly to prevent or reduce morbidity, complications, and further deterioration in the disability status. Although it is hoped that leprosy will have been eliminated at all levels by 2005, the recognition and management of these reactions will continue to be the most essential/significant task in the post elimination era.

Three hundred leprosy patients were recruited to study the pattern and frequency of nail changes. Nail changes, like longitudinal ridging in finger nails, transverse striations involving both finger and toe nails etc. which occurred with similar frequency in the PB and MB patients in comparison with the control group, were excluded from the analysis. Out of a total number of 150 PB patients, 84 (56%) showed nail changes. Fifty-eight (38.6%) patients showed changes in the finger nails, with an average of 3.2 involved nails per patient. Fifty-three (35.3%) patients showed changes in the toe nails, with an average of 3.0 nails per patient. The most common change observed was longitudinal melanonychia (32.4%) in the finger nails and longitudinal ridging (46.3%) in the toe nails.In comparison, 131/150 (87.3%) MB patients showed nail changes. Finger nail changes were seen in 102 (68%) patients with an average of 5.5 nails affected per patient. Changes in toe nails were seen in 116 (77.3%) patients, with an average of 6.0 nails involved per patient. The most common nail change observed was longitudinal melanonychia in 89/523, (17%) of the total involved finger nails and subungual hyperkeratosis in 164/702, (23.4%) of the total toe nails involvement. Out of a total of 32 colony patients, 31 (96.9%) showed nail changes both in finger and toe nails with an average of 7.9 and 8.4 affected nails per patient, respectively. The most common nail change observed was rudimentary nail(s) on fingers (29%) and toes (21.1%). Among MB patients, a significantly higher number had finger nail involvement in LL group. The frequency of nail involvement for both fingers and toes was significantly greater in LL as compared to BL group of patients. The frequency of nail involvement was significantly more in patients having disease for more than 5 years and in those having trophic changes secondary to loss of sensations and impaired circulation.

Treatment of patients with severe psoriasis is difficult. Among the number of systemic drugs that are available, methotrexate has long been used, but cyclosporine has been recently recommended for the management of severe psoriasis. The purpose of this study was to compare the efficacy and safety of daily cyclosporine with weekly methotrexate in the management of severe psoriasis. Thirty consecutive patients with severe psoriasis were randomly assigned to treatment with cyclosporine or methotrexate. The initial dose of cyclosporine was 3 mg/kg/day, which was increased to a maximum of 4 mg/kg after two weeks of therapy when the response was not adequate. Methotrexate was administered weekly at a dose of 0.5 mg/kg. Clinical response was assessed by calculating PASI score in all patients at biweekly intervals. Patients were followed up fortnightly up to a maximum of 12 weeks. The doses of both drugs were gradually tapered once >75% reduction in disease severity was attained. Marked improvement (>75%) reduction in PASI was noted in all patients except for one in the cyclosporine group. The median time for marked improvement was 5.3 weeks with methotrexate and 6.8 weeks with cyclosporine. Patients on methotrexate were found to have more rapid and complete clearance than those on cyclosporine. Both drugs were well tolerated. Side effects in both the treatment groups were minor, transient, and manageable. At doses with comparable safety profiles, methotrexate resulted in more rapid and cost effective clearance of patients with severe psoriasis. Cyclosporine can provide an effective and safe alternative.

A total of 136 patients with BI > or = 2 having been followed up for at least 2 years or more were included in the analyses. Seventy-seven out of 136 patients had completed three years follow up. All patients were given WHO/MDT MB regimen for 12 months and additionally 4 doses of Mycobacterium w. vaccine at 3-month intervals. The age of the patients varied from 6 to 77 years (mean 34 +/- 11.3 years) and they had the disease varying from 3 months to 7 years (mean = 1.9 +/- 1.4 years). The mean of the BI before starting treatment was 3.6 +/- 1.3. At the end of 2 years follow-up, a total of 54 patients out of the 136 (39.7%) had become smear-negative. A larger proportion of patients, 39/46 (84.8%) with BI of < or = 3 had become smear-negative, whereas, only 10/32 (31.3%) patients with BI between 3.1 to 4 and 5/58 (8.6%) highly bacillated patients having initial BI > 4 had become smear-negative at the end of 2 years. Out of the 77 patients who were available for follow up at 3 years, 30/33 (90.9%) patients with BI of < or = 3, 15/20 (75%) patients with BI between 3.1 to 4 and 13/24 (54.2%) patients having initial BI > 4, respectively, had attained smear negativity. Reactions occurred more frequently after 6 months of therapy and over a period of time their frequency gradually decreased, however, they continued to occur even two years after RFT. During the course of MDT and thereafter in follow up 4.6% and 1.3% of the patients developed new deformities or an increase in the existing grade of deformities, respectively. Three relapses (2 in LL and 1 in BL) occurred in patients having initial BI of > 4. One patient relapsed in the second year and the other two relapsed in the third year of follow up and were successfully treated with reintroduction of the same MDT MB regimen. Local ulceration healing with scar formation and regional lymphadenopathy were the only local reactions to the vaccine seen in 47/136 (34.5%) patients. All the patients showed histopathological improvement in the form of a gradual reduction of granuloma fraction. Although the results of this limited period follow up are satisfactory, a long-term follow-up in larger number of patients will settle the issue of safety and efficacy of shortened MDT MB regimen and the place of immunotherapy with M. w. vaccine in multibacillary patients.

Although palmoplantar psoriasis can be severely disabling, there are very few large clinico-epidemiological studies on this condition. Our purpose was to study the morphology and pattern of lesions in Indian patients with palmoplantar psoriasis and to elucidate the role of occupation in the incidence/localization of these lesions. All patients attending our Psoriasis Clinic from 1993 to 2000 were screened for palmoplantar lesions and their demographic characteristics, occupation and the exact localization of the lesions were noted. Out of 3,065 patients screened, 532 had palm and/or sole involvement. Plantar lesions were seen in 91.9% and palmar lesions in 55.6% of these patients. Four distinct patterns of lesion localization were noted on the palms and 5 patterns on the soles. Almost half of the men involved in regular manual labor had palmar lesions restricted to areas exposed to pressure, whereas only a quarter of other men had this type of lesion pattern. All patients with unilateral palmar lesions had them on their dominant hand and these patients were involved in regular manual labor. In our patients, the prevalence of plantar lesions was much higher than that of palmar lesions. The possible role of occupational trauma in lesion localization in Indian patients with palmoplantar psoriasis is discussed.