Assessment of renal allograft rejection with diffusion tensor imaging.

OBJECTIVES: To investigate the value of DTI in differentiation of renal allograft rejection from well-functioning stable allograft, using fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values. METHODS: In this prospective study, 22 transplant recipients with well-functioning stable allograft (group A) and 20 patients with renal allograft rejection (group B + C) were recruited over a period of 19 months from January 2018 to July 2019. DTI-MRI was performed in all the patients, and FA and ADC values were measured in cortical and medullary regions of the transplanted kidney. On biopsy, graft rejection was classified as acute (group B) (n = 7) and chronic graft rejection (group C) (n = 13) based on the BANNF scoring system. Statistical analysis was performed using STATA v.14.0. RESULTS: Statistically significant difference between group A and group B + C was noted for cortical (p < 0.001), and medullary (p = 0.003) FA values, and cortical (p = 0.020), and medullary (p = 0.046) ADC values. Cortical(p < 0.001) and Medullary(p = 0.020) FA values showed statistically significant difference between group A and group C, and cortical FA value(p = 0.012) also showed statistically significant difference between group B and group C. AUC (to differentiate between renal allograft rejection and well-functioning stable allograft) for cortical, and medullary FA values and cortical and medullary ADC values were 0.853(p < 0.001), 0.757(p = 0.004), 0.709(p = 0.021) and 0.736(p = 0.009), respectively. CONCLUSION AND ADVANCES IN KNOWLEDGE: DTI is a promising functional MRI technique for the non-invasive assessment of renal allograft function. Diffusion parameters, such as FA and ADC values, can be useful in the differentiation of renal allograft rejection from well-functioning stable allograft.

Carriage rates and antimicrobial sensitivity of pneumococci in the upper respiratory tract of children less than ten years old, in a north Indian rural community.

Pneumococcal carriage studies are important for vaccine introduction and treatment strategies. Pneumococcal carriage rates estimated in this cohort study among children in a rural community of northern India. Between August 2012 and August 2014, trained nurses made weekly home visits to screen enrolled children aged <10 years for acute upper or lower respiratory infections (AURI/ALRI) in Ballabgarh, Haryana. Nasal swab from infants aged <1year and throat swab from children aged ≥1 year were collected. All specimens were cultured for pneumococci; isolates were serotyped and subjected to antimicrobial susceptibility testing. During the study period, 4348 nasal/throat swabs collected from children with clinical features of ARI (836 ALRI, 2492 AURI) and from 1020 asymptomatic children. Overall pneumococcal carriage was 5.1%, the highest carriage rate among children <1 year of age (22.6%). The detection rates were higher among children with ARI (5.6%; 95% CI: 4.8-6.4) than asymptomatic children (3.3%; 95% CI: 2.3-4.6). Among 220 pneumococcal isolates, 42 diverse serotypes were identified, with 6B/C (8.6%), 19A (7.2%), 19F (6.8%), 23F (6.4%), 35A/B/C (6.4%), 15B (5%), 14 (4.5%) and 11A/C/D (3.2%) accounting for 50%. Forty-five percent of the serotypes identified are included in the current formulation of 13-valent pneumococcal conjugate vaccine. Ninety-six percent of isolates were resistant to co-trimoxazole, 9% were resistant to erythromycin, and 10% had intermediate resistance to penicillin with minimum inhibitory concentration ranges (0.125 to 1.5 µg/ml). Pneumococcal detection was relatively low among children in our study community but demonstrated a diverse range of serotypes and half of these serotypes would be covered by the current formulation of 13-valent pneumococcal vaccine.

Azithromycin resistance mechanisms in typhoidal salmonellae in India: A 25 years analysis.

Background & objectives: : Azithromycin has been in use as an alternate treatment option for enteric fever even when the guidelines on the susceptibility testing were not available. There is lack of data on susceptibility and mechanisms of resistance of azithromycin in Salmonella Typhi and S. Paratyphi A. The aim of the present study was to determine the azithromycin susceptibility and resistance mechanisms in typhoidal salmonellae isolates archived in a tertiary care centre in north India for a period of 25 years. Methods: : Azithromycin susceptibility was determined in 602 isolates of S. Typhi (469) and S. Paratyphi A (133) available as archived collection isolated during 1993 to 2016, by disc diffusion and E-test method.PCR was done for ereA, ermA, ermB, ermC, mefA, mphA and msrA genes from plasmid and genomic DNA and sequencing was done to detect mutations in acrR, rplD and rplV genes. Results: : Azithromycin susceptibility was seen in 437/469 [93.2%; 95% confidence interval (CI), 90.5 to 95.1%] isolates of S. Typhi. Amongst 133 isolates of S. Paratyphi A studied, minimum inhibitory concentration (MIC) of ≤16 mg/l was found in 102 (76.7%; 95% CI, 68.8 to 83.0). MIC value ranged between 1.5 and 32 mg/l with an increasing trend in MIC50and MIC90with time. Mutations were found in acrR in one and rplV in two isolates of S. Typhi. No acquired mechanism for macrolide resistance was found. Interpretation & conclusions: : Azithromycin could be considered as a promising agent against typhoid fever on the basis of MIC distribution in India. However, due to emergence of resistance in some parts, there is a need for continuous surveillance of antimicrobial susceptibility and resistance mechanisms. There is also a need to determine the breakpoints for S. Paratyphi A.

Changing trends of culture-positive typhoid fever and antimicrobial susceptibility in a tertiary care North Indian Hospital over the last decade.

PURPOSE: The present study was undertaken to analyse the trend in prevalence of culture-positive typhoid fever during the last decade and to determine antimicrobial susceptibility profile of Salmonella Typhi and Salmonella Paratyphi A isolated from patients of enteric fever presenting to our hospital. METHODS: All the culture-positive enteric fever cases during 2005-2016 presenting to our Hospital were included in the study. Antimicrobial susceptibility was done against chloramphenicol, amoxicillin, co-trimoxazole, ciprofloxacin, ofloxacin, levofloxacin, pefloxacin, ceftriaxone and azithromycin as per corresponding CLSI guidelines for each year. We also analysed the proportion of culture positivity during 1993-2016 in light of the antibiotic consumption data from published literature. RESULTS: A total of 1066 strains-S. Typhi (772) and S. Paratyphi A (294) were isolated from the blood cultures during the study. A maximum number of cases were found in July-September. Antimicrobial susceptibility for chloramphenicol, amoxicillin and co-trimoxazole was found to be 87.9%, 75.5%, 87.3% for S. Typhi and 94.2%, 90.1% and 94.2% for S. Paratyphi A, respectively. Ciprofloxacin, ofloxacin and levofloxacin susceptibility were 71.3%, 70.8% and 70.9% for S. Typhi and 58.1%, 57.4% and 57.1% for S. Paratyphi A, respectively. Azithromycin susceptibility was 98.9% in S. Typhi. Although susceptibility to ceftriaxone and cefixime was 100% in our isolates, there is a continuous increase in ceftriaxone minimum inhibitory concentration (MIC)50and MIC90values over the time. The proportion of blood culture-positive cases during 1993-2016 ranged from a minimum of 0.0006 in 2014 to a maximum of 0.0087 in 1999. CONCLUSION: We found that the most common etiological agent of enteric fever is S. Typhi causing the majority of cases from July to October in our region. MIC to ceftriaxone in typhoidal salmonellae is creeping towards resistance and more data are needed to understand the azithromycin susceptibility.

Intracellular cAMP assay and Eu-GTP-γS binding studies of chimeric opioid peptide YFa.

In our previous studies chimeric peptide of Met-enkephalin and FMRFa, YGGFMKKKFMRFamide (YFa), demonstrated concentration dependent κ- and µ-opioid receptor mediated antinociception without tolerance development. To gain further insight of the observed behavior of YFa, the present study was undertaken. The effect of chimeric peptide on forskolin-stimulated cAMP formation under acute and chronic treatment and stimulation of Eu-GTP-γS binding in CHO cells stably expressing κ- and µ-opioid receptors was assessed. YFa showed concentration dependent inhibition of forskolin-stimulated cAMP in both hKOR and hMOR-CHO cells; however, the inhibition at 1nM was significantly higher in hKOR cells and comparable to DynA (1-13) than that shown at 20nM in hMOR cells. Chronic treatment of YFa, similar to DynA (1-13), did not show significant change in forskolin-stimulated cAMP level in both hKOR and hMOR cells. However, chronic treatment of morphine and DAMGO showed an increase in forskolin-stimulated cAMP level in hMOR-CHO cells indicating superactivation of adenylyl cyclase. Eu-GTP-γS binding studies of YFa showed a concentration dependent adherent binding with κ- and µ-opioid receptors; however, the latter demonstrated significant binding at higher concentration. Thus the study indicates the chimeric opioid peptide YFa as a potent κ- receptor specific antinociceptive moiety, showing no tolerance and hence may serve as a lead in understanding the mechanism of tolerance development, antinociception and its modulation.