Miracle-dz/UniFAR-FTUs huggingface dataset:
HLA-B*5701 Screening for Hypersensitivity to Abacavir

Mallal S, Phillips E, Carosi G, et al. N Engl J Med. 2008;358(6):568–579 PURPOSE OF THE STUDY. Abacavir is associated with severe and potentially life-threatening hypersensitivity reactions in up to 8% of the white population. In 2002, HLA-B*5701 was noted to be highly associated with this hypersensitivity reaction. The purpose of this study was to evaluate the effectiveness of prospective HLA-B*5701 screening to avoid these reactions. STUDY POPULATION. A total of 1956 HIV-infected patients from 19 countries who had not previously received abacavir were enrolled. METHODS. Individual patients were randomly assigned to undergo prospective HLA-B*5701 screening, with exclusion of previously known HLA-B*5701 positive patients from abacavir treatment, or to undergo a standard approach of abacavir use without screening. All subjects who started abacavir were observed for 6 weeks, the time frame in which a large majority of hypersensitivity reactions occur. The clinical diagnosis of hypersensitivity reaction to abacavir was assessed further by epicutaneous patch testing. RESULTS. The prevalence of HLA-B*5701 was 5.76% (109 of 1956 subjects) of the subjects assigned to receive abacavir. Seventy-two percent were men, 84% were white, and 18% had not received antiretroviral therapy previously. Screening effectively eliminated patch-test–confirmed hypersensitivity. None of the subjects in the prospectively screened group had reactions, compared with 2.7% in the control group. This yielded a negative predictive value of 100% and a positive predictive value of 47.9%. Hypersensitivity reactions to antiretroviral therapy were clinically diagnosed in 93 patients, with a significantly lower incidence in the prospectively screened group (3.4%) than in the control group (7.8%) (P < .001). CONCLUSIONS. HLA-B*5701 screening dramatically reduced the risk of immunologically confirmed hypersensitivity to abacavir. This pharmacogenetic test is useful for reducing the incidence of immunologically mediated hypersensitivity reactions to abacavir. REVIEWER COMMENTS. This expansive study demonstrated the clinical usefulness of pharmacogenomics testing for immunologically mediated hypersensitivity to a particular drug. This is the first such demonstration for reactions to antiretroviral agents. A major limitation in the use of abacavir has been the concern for a severe hypersensitivity reaction. The availability of this inexpensive test (approximately $80 at our institution) substantially reduces that potential and allows antiretroviral therapy selection to be based on the drug's merit as an effective antiretroviral agent. A unique feature of hypersensitivity to this particular drug is that it is a true T-cell–mediated reaction. Patch testing has been used for many decades to identify offending contact hypersensitivity allergens (eg, nickel). The search for additional biomarkers that would reflect a potential for adverse reactions to other drugs is ongoing. This type of study leads the way in demonstrating clinical effectiveness of such an approach
Drug metabolising enzyme polymorphisms in Middle- and Eastern-European Slavic populations

Abstract Inter-individual differences in genes for drug metabolising enzymes and drug transporters are important for understanding efficacy in drug therapy. These differences are important both for the timely estimation of the dosage that should be prescribed to a patient and for the detection of individuals who are prone to side effects from the drug at normal doses. This review summarises the literature concerning the gene variants within nine major drug metabolising enzymes and drug transporters (i.e., CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, and MDR-1) in the Middle European region. Notably, published data are not extensive, and most studies were performed on relatively low numbers of individuals. No country has a complete coverage of all genes. Two variants (C2677T/A and C3435T) within the multidrug resistance-1 (MDR-1) gene and variants within the CYP2C9 gene were analysed within most Slavic populations. Nevertheless, even from this incomplete coverage (where unexpectedly high variability was at times seen both between and within populations), it could be extrapolated that the variants within the drug metabolising enzyme genes are present in roughly the same frequencies as in neighbouring countries.
Fungal rhinosinusitis: A clinicomycological perspective

Purpose: Chronic rhinosinusitis (CRS) is a widely prevalent condition globally as well as in India. The spectrum of fungal involvement in CRS runs from benign colonisation to potentially life-threatening invasive disease. Successful treatment of such mycotic infections largely depends on the accurate identification of the pathogen, early and appropriate intervention by surgical clearance, supported with antifungal medication as per standard regimen. Thus, this study was undertaken to determine the prevalence of fungal rhinosinusitis (FRS), and to analyse its clinicomycological profile. Materials and Methods: Fifty-two patients with clinical suspicion of CRS attending a tertiary care hospital during a one-year period were included in this retrospective analysis. The sinonasal specimens were subjected to microscopy by KOH mount and fungal culture as per standard mycological technique. Tissue specimens were also subjected to histopathological examination. Results: Male to female ratio was 1.25:1; age varied from 14 years to 62 years with majority of patients (37%) belonging to age group 21-40 years. The prevalence of FRS was 44%, and 74% of it was caused by Aspergillus sp. Aspergillus flavus (A. flavus) (52%) was the most prevalent fungus isolated. Allergic fungal rhinosinusitis (AFRS) was the most common presentation (79%). Conclusion: FRS is a continuous spectrum of disease varying in presentation, treatment and long-term sequelae. Correct identification of the fungus remains essential for appropriate treatment.
EVALUATION OF ETHNOMEDICAL CLAIMS AND BRINE SHRIMP TOXICITY OF SOME PLANTS USED IN TANZANIA AS TRADITIONAL MEDICINES.

Using information from the literature it has been demonstrated that twenty one (21) plants out of 60 (35%) which are used in traditional medicine, in Tabora region (Western Tanzania), are used elsewhere for the treatment of similar conditions or their claims have proven biological results. Ethanol extracts of some of the plants exhibited low, some intermediate, and some high toxicity against brine shrimps. The brine shrimp assay results for Psorospermum febrifugum Spach (Guttiferae) [LC50 12. 7µg/ml], agreed with previous reports of established anticancer activity, while for Phyllanthus engleri Pax. (Euphorbiaceae) [LC50 0. 47µg/ml] they supported literature reports that it is toxic to rabbits and fish. Despite the therapeutic claims, literature reports, and brine shrimp assay results, more rigorous studies are needed to confirm the therapeutic utility of the plants.
Utility of routine real time quantitative PCR monitoring of HCV infection in haemodialysis patients

Background: Hepatitis C virus (HCV) infection causes significant morbidity and mortality in patients of end stage renal disease (ESRD) on haemodialysis (HD). Stringent screening methods can help in its early diagnosis. Objective: The study addresses the utility of real-time quantitative polymerase chain reaction (RQ-PCR) in the diagnosis and monitoring of HCV infection especially on seronegative and normal serum alanine aminotransferase (ALT) HD patients. Material and Methods: This retrospective study was carried out from January 2010 to December 2012. Patients of ESRD on maintenance HD and on whom all the three assays HCV antibody serology, PCR and ALT were done were included in the study (n = 123). Group 1 (n = 57), comprised of patients with negative serology and normal ALT, and Group 2 (n = 66), had either raised ALT and or a positive or equivocal serology. Results: Out of the 123 cases studied, HCV serology was positive in 36.5% (45), ALT raised in 18.6% (23) and PCR positive in 67.4% (83) cases. PCR positivity was significantly higher than serology and raised ALT. Group 2 had a significantly higher PCR positivity than Group 1 (P = 0.0004), but 50.9% patients of Group 1, were also PCR positive and 69% of them had a high viral count of >8 × 10 5 IU/ml at the time of detection. Conclusion: Regular routine screening of HCV by RQ-PCR in ESRD patients can help in early diagnosis of HCV infection in patients with low index of suspicion.
Anterior Segment Changes Produced in Response to Long-Term Overnight Orthokeratology

Abstract Purpose: To evaluate the effect of overnight orthokeratology (OK) on anterior chamber depth (ACD), posterior radius of corneal curvature (PRCC) and axial length (AL) over one year. Methods: In this prospective longitudinal study, measurements were made in 34 right eyes of 34 subjects at baseline, 15 days, 1 and 12 months after starting OK treatment. ACD and PRCC measurements were obtained using a Pentacam system and AL was measured using an IOL-Master. ACD and PRCC were measured along the horizontal and vertical meridians at 1 mm intervals. These measurements were expressed as the distance from the center in the nasal (N), temporal (T), superior (S) and inferior (I) directions. Results: A significant reduction in ACD was observed in both meridians during treatment. PRCC flattened significantly in the (T) direction after 15 d (1 mm, p < 0.05), at the corneal center after 15 d (p < 0.01), in the (T) direction after 1 month (1 mm, p < 0.05), in the (S) direction after 12 months (1 mm p < 0.05), in the (N) direction after 12 months (1 mm p < 0.05), in the (N) and (T) directions after 12 months (3 mm, p < 0.05) and in the (T) direction after 12 months (4 mm p < 0.05), at the corneal center after 12 months (p < 0.01). AL was significantly reduced during treatment (p < 0.05). Conclusions: A long period of OK reduces ACD and AL and changes PRCC.
Simulated Visual Fields Produced from Macular RNFLT Data in Patients with Glaucoma

Abstract Purpose: We investigated in detail the correlation between structure and function in the macula, and whether optical coherence tomography (OCT)-measured macular structure could be used to simulate the visual field. Materials and methods: This study comprised 60 eyes of 34 patients with open angle glaucoma (Anderson-Patella classification). To assess macular function, reliable data from the Humphrey field analyzer (HFA, SITA-standard, 10-2 program) for threshold, total deviation (TD), and pattern deviation (PD) were used. To assess macular structure, thickness data for the retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), and ganglion cell layer plus inner plexiform layer (GCL + IPL) from macular OCT maps (3D OCT-2000, Topcon) were analyzed. Spearman’s coefficient of correlation analysis was performed to determine the significance of the correlation, as well as the formula for simulation. The formula was used to calculate the simulated threshold, TD, and PD values. The simulation method was validated by comparing results for simulated and actual visual fields in a new data set of 29 eyes from glaucoma patients. Results: In most test points, macular function and the layer-by-layer structure were significantly correlated, however, the distribution of highly-correlated points varied. Simulated grayscale maps of the visual field based on the formula of regression line for RNFLT and thresholds were similar to actual visual fields. There was a significant correlation between simulated visual fields created from RNFLT, GCC and GCL + IPL data and actual average threshold values in all 68 test points (r = 0.63–0.87, p < 0.001) and TD (r = 0.62–0.86, p < 0.001). Conclusion: We found that there was a significant correlation between structure and function in the macular area, and that simulated visual fields from RNFLT data reflected actual visual fields. Such a simulation of macular function from OCT parameters may be useful in assessing glaucoma in patients who have difficulty undergoing actual visual field examinations.
Emergence of novel influenza a H1N1 virus as a pandemic agent.

eight RNA segments that are genetically independent of each other and (ii) a high rate of mutation, especially in the surface heamgglutinin (H) and neuraminidase (N) proteins. These unique molecular features coupled with the ability of the virus to cause infection in a wide host range of humans, domestic animals and birds render it a potential pandemic agent. Domestic pigs and birds because of their proximity to humans provide a great opportunity for the occurrence of mixed influenza infections. Consequently, these two species (pigs and birds) act as ‘melting pots’ for the generation of re-assortment of viruses and play a crucial role in evolution of influenza pandemics. The current outbreak of Influenza 2009 A/H1N1 is a rare recombination of gene segments from swine with avian and human influenza strains. Phylogenetic analysis of sequences of all genes of A/ California/04/2009, the virus isolated from a patient in the recent outbreak in USA, showed that its genome represents a quadruple re-assortment of two swine strains, one human strain, and one avian strain of influenza. [4] The virus has six gene segments (PB2, PB1, PA, HA, NP, and NS) similar to ones previously found, in triple-reasserting swine influenza viruses, circulating in pigs in North America. [5] The North American triple–reasserting virus is itself a combination of the heamagglutinin (HA), nucleoprotein (NP), and nonstructural protein (NS) genes, originating from classic swine influenza A viruses; the polymerase PB2 (PB2) and polymerase (PA) genes from avian influenza viruses from the North American lineage; and the polymerase PB1 (PB1) gene from human influenza A viruses. [5] The genes encoding neuraminidase (NA) and M protein (M) however were most closely related to those in influenza A viruses circulating in swine populations in Eurasia. [6] The largest proportion of genes in this novel virus comes from swine influenza viruses (30.6 per cent from North American swine influenza strains, 17.5 per cent from Eurasian swine influenza strains), followed by North American avian influenza strains (34.4 per cent) and human influenza strains (17.5 per cent) [6]. This particular genetic combination of influenza virus segments had not been seen before in the US or elsewhere. [1,4]
Congenital CMV infection; diagnosis in symptomatic infants.

BACKGROUND Samples from babies exhibiting clinical symptoms suggestive of congenital infection are referred regularly to NICD, New Delhi,, from Government Hospitals located in Delhi and a home for abandoned children (Palna), for the diagnosis of etiological agents like toxoplasma, rubella, CMV and herpes. Blood samples of mothers of most of the affected babies are also received. OBJECTIVE Evaluation of rapid and accurate technique for the diagnosis of congenital CMV infection. MATERIALS AND METHODS One hundred and twenty five blood samples suggestive of symptomatic congenital CMV infection were selected from samples received at NICD during the period June 2005-March 2007. A request to collect and send the urine samples of the selected babies was sent to the respective hospitals. Serum samples of the babies were tested for CMV-IgM antibodies using micro-capture ELISA. Mothers' serum samples were subjected to CMV-IgM and IgG class antibodies assay by commercial ELISA kits. DNA isolation and amplification was performed in urine samples and some of the serum samples using a commercial PCR kit for detection of HCMV. Blood and urine samples from 20 normal babies were included in the study. RESULTS Twenty Seven serum samples (21.6%) of infants, of the 125 tested, were positive for CMV-IgM antibodies. Twenty five samples (20%) showed amplification of CMV-DNA. All 25 samples positive for PCR were positive for CMV IgM antibodies. Sera of 73 mothers, out of 75 tested (97.3%), were positive for CMV IgG antibodies. However, none of them was positive for CMV IgM antibodies. Mothers of all 27 positive babies were positive for CMV-IgG antibodies. Serum and urine samples from 20 normal babies were negative for ELISA and PCR. CONCLUSION micro-capture ELISA technique was found to be more sensitive than PCR (92.6%) for detection of congenital CMV infection. ELISA is also rapid, less cumbersome and cost effective for diagnosis of CMV infection.
Activities of fourth generation cephalosporins alone and in combination with gentamicin, amikacin, ciprofloxacin and levofloxacin against bloodstream Pseudomonas aeruginosa isolate.

January and June 2004 were obtained from the Department of Infectious Diseases and Clinical Microbiology, Istanbul Faculty of Medicine, Istanbul. As a reference strain, P. aeruginosa ATCC 27853 (American Type Culture Collection, Rockville, Md.) was used. Mueller-Hinton Broth (Difco Laboratories, Detroit, Michigan) supplemented with divalent cations was used for Minimum inhibitory concentration (MIC) determinations and for time-kill curve studies. MICs were determined by the microbroth dilution technique, as described by the Clinical and Laboratory Standards Institute (CLSI). [3]
Immune responses to Epstein-Barr virus in individuals with systemic and organ specific autoimmune disorders.

PURPOSE Autoimmune diseases usually manifest in genetically predisposed individuals following an environmental trigger. There are several viral infections including Epstein-Barr virus (EBV) implicated in the pathogenesis of autoimmune disorders. The aim of this study was to look at the antibody pattern to EBV proteins in the plasma of both systemic and organ specific autoimmune disorders, estimate pro-inflammatory plasma cytokines (IL-8 and TNF-alpha) among these autoimmune patients and compare the observations with those in normal healthy controls. MATERIALS AND METHODS Samples from 44 rheumatoid arthritis patients, 25 Hashimoto's thyroiditis patients, appropriately age and sex matched healthy controls were tested for EBV IgM antibodies by an immunoblot assay and two cytokines (IL-8 and TNF-alpha) by commercial assays. RESULTS Among the rheumatoid arthritis patients, 23 (52%) were positive for EBNA1 antibody, while 13 (52%) of the Hashimoto's thyroiditis patients and 12 (30%) of the healthy controls showed similar bands. The intensity of the bands was high in the autoimmune patients when compared to the bands seen in control samples. The difference in the EBNA1 reactivity between rheumatoid arthritis patients and controls were significant (P = 0.038). There was a significant difference in the IgM reactivity to VCAp19 protein between patients and controls (P = 0.011). CONCLUSION Our study showed an increased EBV activation among the autoimmune patient groups compared to the normal healthy controls. Further studies are required to delineate the association between the aetiology of autoimmune disorders and EBV.
Plasma Homocysteine and Asymmetrical Dimethyl-l-Arginine (ADMA) and Whole Blood DNA Methylation in Early and Neovascular Age-Related Macular Degeneration: A Pilot Study*

Abstract Purpose/Aim: To compare the plasma levels of homocysteine and asymmetrical dimethyl-l-arginine (ADMA) and the degree of whole blood DNA methylation in patients with early and neovascular age-related macular degeneration (AMD) and in controls without maculopathy of any sort. Materials and methods: This observational case–control pilot study included 39 early AMD patients, 27 neovascular AMD patients and 132 sex- and age-matched controls without maculopathy. Plasma homocysteine and ADMA concentrations and the degree of whole blood DNA methylation were measured. Quantitative variables were compared by Student’s t-test or Mann–Whitney test. Logistic regression models were used to investigate the significance of the association between early or wet AMD and some variables. Results: There were no significant differences in mean plasma homocysteine and ADMA concentrations and in the degree of whole blood DNA methylation between patients with early or neovascular AMD and their controls. Similarly, logistic regression analysis disclosed that plasma homocysteine and ADMA levels were not associated with an increased risk for early or neovascular AMD. Conclusions: We failed to demonstrate an association between early or neovascular AMD and increased plasma homocysteine and/or ADMA. Results also suggest that the degree of whole blood DNA methylation is not a marker of AMD.
Psoriatic erythroderma associated with enalapril.

A 59-year-old man with a 35-year personal and positive family history of psoriasis was admitted to our department for treatment of psoriatic erythroderma. The patient had commenced therapy with enalapril 10 mg b.i. d. for the treatment of hypertension approximately 6 weeks before hospitalization. Five weeks after the initiation of enalapril, his psoriasis began to flare, and for a period of about 1 week it reached the extent of erythroderma. The patient did not associate the psoriatic flare with other factors such as infections, trauma, or stress. The patient presented with diffuse erythema and pronounced desquamation covering his entire trunk, scalp, and extremities (Figure). Nearly 100% of the body surface area was involved. The palms and soles were also affected, displaying erythema, hyperkeratosis, and painful fissures. The nails showed pits, oil spots, and subungual hyperkeratosis. The patient also had psoriatic arthritis affecting the interphalangeal joints of his fingers. Laboratory tests revealed an elevated erythrocyte sedimentation rate, an elevated creatinine level of 180 mmol/L, a blood urea nitrogen level of 10.8 mmol/L, and a uric acid level of 716 mmol/L. Urinalysis showed proteinuria of 1.5 g/24 h. The patient's renal condition was diagnosed as chronic tubulointerstitial nephritis, most probably related to his dermatologic disease. Allopurinol and dietary measures were recommended. Following treatment with methotrexate and replacement of enalapril therapy, the erythema and scaling gradually subsided and became confined to his pre-eruptive chronic plaques (approximately 5% of body surface area). Rechallenge with enalapril was not performed.
Prevalence of Subclinical Mastitis in Cows at Anwara, a Coastal Upazila of Chittagong District in Bangladesh -

The research was performed to estimate the prevalence of subclinical mastitis in cows kept in Bonoful dairy farm and other mini dairy farms at Anwara of Chittagong district in Bangladesh using California Mastitis Test kit (C.M.T tester). Investigation was carried out on 153 milk samples, 100 samples of them revealed positive reaction that denote the cows were suffering from subclinical mastitis (65.5%. In this study, 113 milk samples from crossbred dairy cows and 40 samples from Red Chittagong cows. From the 113 samples 95 were (+ve that is (84% and rest 40 samples from Red Chittagong cows and only 5 were (+ve that is 12.5%. Bacteriological examination for isolation of causative organism was done using those samples which showed strong positive result (+++) in CMT test. In this study, the cows were mostly infected with mixed infection Staphylococcus spp. and E. coli and some cows had mono bacterial infection.