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2016| May | Volume 143 | Issue 5
Online since
July 28, 2016
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REVIEW ARTICLES
Shigellosis: Epidemiology in India
Neelam Taneja, Abhishek Mewara
May 2016, 143(5):565-576
DOI
:10.4103/0971-5916.187104
PMID
:27487999
Shigellosis is one of the major causes of diarrhoea in India. The accurate estimates of morbidity and mortality due to shigellosis are lacking, though it is endemic in the country and has been reported to cause many outbreaks. The limited information available indicates
Shigella
to be an important food- borne pathogen in India.
S. flexneri
is the most common species,
S. sonnei
and non-agglutinable Shigellae seem to be steadily surfacing, while
S. dysenteriae
has temporarily disappeared from the northern and eastern regions. Antibiotic-resistant strains of different
Shigella
species and serotypes have emerged all over the world. Especially important is the global emergence of multidrug resistant Shigellae, notably the increasing resistance to third generation cephalosporins and fluoroquinolones, and also azithromycin. This calls for a continuous and strong surveillance of antibiotic resistance across the country for periodic updation of the local antibiograms. The prevention of shigellosis is desirable as it will substantially reduce the morbidity associated with diarrhoea in the country. Public health measures like provision of safe water and adequate sanitation are of immense importance to reduce the burden of shigellosis, however, the provision of resources to develop such an infrastructure in India is a complex issue and will take time to resolve. Thus, the scientific thrust should be focused towards development of a safe and affordable multivalent vaccine. this review is focused upon the epidemiology, disease burden and the therapeutic challenges of shigellosis in Indian perspective.
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ORIGINAL ARTICLES
Subinhibitory concentration of ciprofloxacin targets quorum sensing system of
Pseudomonas aeruginosa
causing inhibition of biofilm formation & reduction of virulence
Parul Gupta, Sanjay Chhibber, Kusum Harjai
May 2016, 143(5):643-651
DOI
:10.4103/0971-5916.187114
PMID
:27488009
Background & objectives:
Biofilms formed by pseudomonas aeruginosa lead to persistent infections. Use of antibiotics for the treatment of biofilm induced infection poses a threat towards development of resistance. Therefore, the research is directed towards exploring the property of antibiotics which may alter the virulence of an organism besides altering its growth. The aim of this study was to evaluate the role of subinhibitory concentration of ciprofloxacin (CIP) in inhibiting biofilm formation and virulence of
P. aeruginosa
.
Methods:
Antibiofilm potential of subinhibitory concentration of CIP was evaluated in terms of log reduction, biofilm forming capacity and coverslip assay.
P. aeruginosa
isolates (grown in the presence and absence of sub-MIC of CIP) were also evaluated for inhibition in motility, virulence factor production and quorum sensing (QS) signal production.
Results:
Sub-minimum inhibitory concentration (sub-MIC) of CIP significantly reduced the motility of
P. aeruginosa
stand and strain and clinical isolates and affected biofilm forming capacity. Production of protease, elastase, siderophore, alginate, and rhamnolipid was also significantly reduced by CIP.
Interpretation & conclusions:
Reduction in virulence factors and biofilm formation was due to inhibition of QS mechanism which was indicated by reduced production of QS signal molecules by
P. aeruginosa
in presence of subinhibitory concentration of CIP.
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23
2,058
588
Interleukin-1β (
IL-1β
) &
IL-4
gene polymorphisms in patients with systemic lupus erythematosus (SLE) & their association with susceptibility to SLE
Milad Mohammadoo-khorasani, Saeedeh Salimi, Ehsan Tabatabai, Mahnaz Sandoughi, Zahra Zakeri, Farzaneh Farajian-Mashhadi
May 2016, 143(5):591-596
DOI
:10.4103/0971-5916.187107
PMID
:27488002
Background & objectives:
Interleukin-1 (IL-1) is one of the pro-inflammatory cytokines that plays a main role in the regulation of immune and inflammatory responses. Interleukin 4 (IL-4) as an anti-inflammatory cytokine regulates balance between Th1 and Th2 immune responses. this study was undertaken to investigate the
IL-1β
and
IL-4
genes polymorphisms in patients with systemic lupus erythematosus (SLE) and also association between the polymorphisms and susceptibility to SLE.
Methods:
One hundred and sixty three SLE patients and 180 healthy controls were genotyped for the
IL-4
VNTR (variable number tandem repeat), IL-1β C-511T and IL-1β T-31C polymorphisms by polymerase chain reaction (PCR) or PCR-RFLP (restriction fragment length polymorphism) method.
Results:
The frequencies of CC genotype and C allele of the IL-1β T-31C polymorphism were significantly (
P
<0.01) lower in SLE patients than controls. Moreover, the frequencies of RP1/RP2 genotype and RP2 allele of
IL-4
VNTR polymorphism were significantly (
P
<0.05) higher in the SLE patients. No association was observed between
IL-1β
C-511T polymorphism and increased risk of SLE. We observed increased frequency of CT and TT genotypes of IL-1β C-511T polymorphism in SLE patients with malar rash compared to SLE patients without this manifestation.
Interpretation & conclusions:
The present findings suggest that
IL-1β
T-31C and
IL-4
VNTR polymorphisms but not
IL-1β
C-511T polymorphism may contribute in SLE pathogenesis. In addition, CT and TT genotypes of
IL-1β
C-511T polymorphism were associated with SLE.
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Isolation & characterization of
Brucella melitensis
isolated from patients suspected for human brucellosis in India
Anita Barua, Ashu Kumar, Duraipandian Thavaselvam, Smita Mangalgi, Archana Prakash, Sapana Tiwari, Sonia Arora, Kannusamy Sathyaseelan
May 2016, 143(5):652-658
DOI
:10.4103/0971-5916.187115
PMID
:27488010
Background & objectives:
Brucellosis is endemic in the southern part of India. A combination of biochemical, serological and molecular methods is required for identification and biotyping of
Brucella
. The present study describes the isolation and biochemical, molecular characterization of
Brucella melitensis
from patients suspected for human brucellosis.
Methods:
The blood samples were collected from febrile patients suspected to have brucellosis. A total of 18 isolates were obtained from 102 blood samples subjected to culture. The characterization of these 18 isolates was done by growth on
Brucella
specific medium, biochemical reactions, CO
2
requirement, H
2
S production, agglutination with A and M mono-specific antiserum, dye sensitivity to basic fuchsin and thionin. Further, molecular characterization of the isolates was done by amplification of
B. melitensis
species specific IS
711
repetitive DNA fragment and 16S (rRNA) sequence analysis. PCR-restriction fragment length polymorphism (RFLP) analysis of
omp2
locus and IS
711
gene was also done for molecular characterization.
Results:
All 102 suspected samples were subjected to bacteria isolation and of these, 18 isolates could be recovered on blood culture. The biochemical, PCR and PCR-RFLP and 16s rRNA sequencing revealed that all isolates were of
B. melitensis
and matched exactly with reference strain
B. melitensis
16M.
Interpretation & conclusions:
The present study showed an overall isolation rate of 17.64 per cent for
B. melitensis
. There is a need to establish facilities for isolation and characterization of
Brucella
species for effective clinical management of the disease among patients as well as surveillance and control of infection in domestic animals. Further studies are needed from different geographical areas of the country with different level of endemicity to plan and execute control strategies against human brucellosis.
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PERSPECTIVE
Why is the oral cholera vaccine not considered an option for prevention of cholera in India? Analysis of possible reasons
Sanjukta Sen Gupta, Kaushik Bharati, Dipika Sur, Ajay Khera, NK Ganguly, G Balakrish Nair
May 2016, 143(5):545-551
DOI
:10.4103/0971-5916.187102
PMID
:27487997
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597
REVIEW ARTICLES
Zika virus: Indian perspectives
Devendra T Mourya, Pratip Shil, Gajanan N Sapkal, Pragya D Yadav
May 2016, 143(5):553-564
DOI
:10.4103/0971-5916.187103
PMID
:27487998
The emergence of Zika virus (ZiV), a mosquito borne
Flavivirus
like dengue (DEN) and chikungunya (CHIK), in Brazil in 2014 and its spread to various countries have led to a global health emergency.
Aedes aegypti
is the major vector for ZiV. Fast dissemination of this virus in different geographical areas posses a major threat especially to regions where the population lacks herd immunity against the ZiV and there is abundance of
Aedes
mosquitoes. In this review, we focus on current global scenario, epidemiology, biology, diagnostic challenges and remedial measures for ZiVconsidering the Indian perspective.
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4,889
1,116
ORIGINAL ARTICLES
A clinicopathological study of primary central nervous system lymphomas & their association with Epstein-Barr virus
Mehar Chand Sharma, Rakesh Kumar Gupta, Seema Kaushal, Vaishali Suri, Chitra Sarkar, Manmohan Singh, SS Kale, Ranjit K Sahoo, Lalit Kumar, Vinod Raina
May 2016, 143(5):605-615
DOI
:10.4103/0971-5916.187109
PMID
:27488004
Background & objectives:
Primary central nervous system lymphomas (PCNSLs) are relatively uncommon, accounting for 2-3 per cent of primary brain tumours. Majority of these are diffuse large B cell lymphomas (DLBCL) occurring both in immunocompromised and immunocompetent patients. We undertook this study to classify PCNSL into germinal centre (GC) and non-germinal centre (NGC) type based on Hans classification and to find the role of Epstein-Barr virus (EBV) in pathogenesis both by conventional immunohistochemistry (IHC) and chromogenic
in situ
hybridization (CISH).
Methods:
The consecutive cases of PCNSL during a 10 years period were analysed by IHC for CD45, CD20, CD3, B-cell lymphoma 2 and 6 (Bcl-2 and Bcl-6), B-cell specific octamer binding protein-1 (BOB-1), multiple myeloma oncogene-1 (MUM-1), EBV latent-membrane protein 1 (LMP-1), cyclin-D1, CD10, CD5 and CD23, as well as by CISH for EBV.
Results:
During a period of 10 years, 65 PCNSL were diagnosed which comprised 0.69 per cent (65/9476) of all intracranial tumours. The mean age of presentation was 49 yr with sex ratio (M:F) of 1.4:1. Most common location was supratentorial region with predominant involvement of frontal lobe. Single lesions were seen in 38 (58.4%) and multifocal lesions in 27 (41.5%) patients. None of the patients were immunocompromised. All cases were B cell immunophenotype and were DLBCL except one case of follicular lymphoma. According to Hans classification, majority of them were NGC (n=51, 79.6%) and 13 (20.3%) were GC type. Bcl-2 expression was noted in 34 (52.3%) tumours. EBV was positive in three (4.6%) cases; two were detected both by IHC and CISH and one case by CISH only.
Interpretation & conclusions:
In Indian population, PCNSL occurs mainly in immunocompetent patients, and a decade earlier than in western population. Immunophenotyping revealed that all cases were DLBCL with predominance of NGC type. No prognostic difference was seen between GC and NGC DLBCL. Association of EBV was rare and this virus was possibly not involved in the pathogenesis of PCNSL in immunocompetent individuals. CISH was an easy, economical and less cumbersome method for detection of EBV in PCNSL.
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494
Cystic fibrosis transmembrane conductance regulator (
CFTR
) gene abnormalities in Indian males with congenital bilateral absence of vas deferens & renal anomalies
Rahul Gajbhiye, Kaushiki Kadam, Aalok Khole, Avinash Gaikwad, Seema Kadam, Rupin Shah, Rangaswamy Kumaraswamy, Vrinda Khole
May 2016, 143(5):616-623
DOI
:10.4103/0971-5916.187110
PMID
:27488005
Background & objectives:
The role of cystic fibrosis transmembrane conductance regulator (
CFTR
) gene mutations in congenital bilateral absence of vas deferens and unilateral renal agenesis (CBAVD-URA) has been controversial. Here, we report the cases of five Indian males with CBAVD-URA. The objective was to evaluate the presence or absence of CFTR gene mutations and variants in CBAVD-URA. The female partners of these males were also screened for cystic fibrosis (CF) carrier status.
Methods:
Direct DNA sequencing of
CFTR
gene was carried out in five Indian infertile males having CBAVD-URA. Female partners (n=5) and healthy controls (n=32) were also screened.
Results:
Three potential regulatory
CFTR
gene variants (c.1540A>G, c.2694T>G and c.4521G>A) were detected along with IVS8-5T mutation in three infertile males with CBAVD-URA. Five novel
CFTR
gene variants (c.621+91A>G, c.2752+106A>T, c.2751+85_88delTA, c.3120+529InsC and c.4375-69C>T), four potential regulatory
CFTR
gene variants (M470V, T854T, P1290P, Q1463Q) and seven previously reported CFTR gene variants (c.196+12T>C, c.875+40A>G, c.3041-71G>C, c.3271+42A>T, c.3272-93T>C, c.3500-140A>C and c.3601-65C>A) were detected in infertile men having CBAVD and renal anomalies
Interpretation & conclusions:
Based on our findings, we speculate that CBAVD-URA may also be attributed to
CFTR
gene mutations and can be considered as CFTR-related disorder (CFTR-RD). The
CFTR
gene mutation screening may be offered to CBAVD-URA men and their female partners undergoing ICSI. Further studies need to be done in a large sample to confirm the findings.
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COMMENTARIES
NAT2
gene polymorphism: covert drug interaction causing phenytoin toxicity
C Adithan, A Subathra
May 2016, 143(5):542-544
DOI
:10.4103/0971-5916.187101
PMID
:27487996
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1,483
465
ORIGINAL ARTICLES
Baseline characteristics of HIV & hepatitis B virus (HIV/HBV) co-infected patients from Kolkata, India
Jayeeta Sarkar, Debraj Saha, Bhaswati Bandyopadhyay, Bibhuti Saha, Deepika Kedia, DN Guha Mazumder, Runu Chakravarty, Subhasish Kamal Guha
May 2016, 143(5):636-642
DOI
:10.4103/0971-5916.187113
PMID
:27488008
Background & objectives:
Hepatitis B virus (HBV) and HIV co-infection has variable prevalence worldwide. In comparison to HBV mono-infection, the course of chronic HBV infection is accelerated in HIV/HBV co-infected patients. the present study was carried out to analyse the baseline characteristics (clinical, biochemical, serological and virological) of treatment naïve HIV/HBV co-infected and HIV mono-infected patients.
Methods:
Between July 2011 and January 2013, a total number of 1331 HIV-seropositive treatment naïve individuals, enrolled in the ART Centre of Calcutta School of Tropical Medicine, Kolkata, India, were screened for hepatitis B surface antigen (HBsAg). A total of 1253 HIV mono-infected and 78 HIV/HBV co-infected patients were characterized. The co-infected patients were evaluated for HBeAg and anti-HBe antibody by ELISA. HIV RNA was quantified for all co-infected patients. HBV DNA was detected and quantified by real time-PCR amplification followed by HBV genotype determination.
Results:
HIV/HBV co-infected patients had proportionately more advanced HIV disease (WHO clinical stage 3 and 4) than HIV mono-infected individuals (37.1 vs. 19.9%). The co-infected patients had significantly higher serum bilirubin, alanine aminotransferase (ALT), alkaline phosphatase and ALT/platelet ratio index (APRI). CD4 count was non-significantly lower in co-infected patients. Majority (61.5%) were HBeAg positive with higher HIV RNA (
P
<0.05), HBV DNA (
p
<0.001) and APRI (
p
<0.05) compared to those who were HBeAg negative. HBV/D was the predominant genotype (73.2%) and D2 (43.7%) was the commonest subgenotype.
Interpretation & conclusions:
HIV/HBV co-infected patients had significantly higher serum bilirubin, ALT, alkaline phosphatase and lower platelet count. HBeAg positive co-infected patients had higher HIV RNA and HBV DNA compared to HBeAg negative co-infected patients. Prior to initiation of antiretroviral treatment (ART) all patients should be screened for HBsAg to initiate appropriate ART regimen.
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3
2,060
439
COMMENTARIES
Ascorbic acid co-administration with artemisinin based combination therapies in falciparum malaria
Neelam Marwaha
May 2016, 143(5):539-541
DOI
:10.4103/0971-5916.187100
PMID
:27487995
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2
1,565
585
ORIGINAL ARTICLES
Image guided versus palpation guided core needle biopsy of palpable breast masses: a prospective study
Smriti Hari, Swati Kumari, Anurag Srivastava, Sanjay Thulkar, Sandeep Mathur, Prasad Thotton Veedu
May 2016, 143(5):597-604
DOI
:10.4103/0971-5916.187108
PMID
:27488003
Background & objectives:
Biopsy of palpable breast masses can be performed manually by palpation guidance or under imaging guidance. Based on retrospective studies, image guided biopsy is considered more accurate than palpation guided breast biopsy; however, these techniques have not been compared prospectively. We conducted this prospective study to verify the superiority and determine the size of beneficial effect of image guided biopsy over palpation guided biopsy.
Methods:
Over a period of 18 months, 36 patients each with palpable breast masses were randomized into palpation guided and image guided breast biopsy arms. Ultrasound was used for image guidance in 33 patients and mammographic (stereotactic) guidance in three patients. All biopsies were performed using 14 gauge automated core biopsy needles. Inconclusive, suspicious or imaging-histologic discordant biopsies were repeated.
Results:
Malignancy was found in 30 of 36 women in palpation guided biopsy arm and 27 of 36 women in image guided biopsy arm. Palpation guided biopsy had sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 46.7, 100, 100, 27.3 per cent, respectively, for diagnosing breast cancer. Nineteen of 36 women (52.8%) required repeat biopsy because of inadequate samples (7 of 19), suspicious findings (2 of 19) or imaging-histologic discordance (10 of 19). On repeat biopsy, malignancy was found in all cases of imaging-histologic discordance. Image guided biopsy had 96.3 per cent sensitivity and 100 per cent specificity. There was no case of inadequate sample or imaging-histologic discordance with image guided biopsy.
Interpretation & conclusions:
Our results showed that in palpable breast masses, image guided biopsy was superior to palpation guided biopsy in terms of sensitivity, false negative rate and repeat biopsy rates.
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2
2,004
409
Frequency of Mi
a
antigen: A pilot study among blood donors
Raj Nath Makroo, Aakanksha Bhatia, Mohit Chowdhry, NL Rosamma, Prashant Karna
May 2016, 143(5):633-635
DOI
:10.4103/0971-5916.187112
PMID
:27488007
The Miltenberger (Mi) classes represent a group of phenotypes for red cells that carry low frequency antigens associated with the MNSs blood group system. This pilot study was aimed at determining the Mia antigen positivity in the blood donor population in a tertiary care hospital in New Delhi, India. The study was performed between June to August 2014 on eligible blood donors willing to participate. Antigen typing was performed using monoclonal anti-Mia antiserum by tube technique. Only one of the 1000 blood donors (0.1%) tested was found to be Mia antigen positive. the Mia antigen can, therefore, be considered as being rare in the Indian blood donor population.
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2
1,358
260
BOOK REVIEWS
Functional and GI motility disorders
Govind K Makharia
May 2016, 143(5):669-669
DOI
:10.4103/0971-5916.187120
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615
259
Diabetes secondary to endocrine and pancreatic disorders
AG Unnikrishnan
May 2016, 143(5):670-671
DOI
:10.4103/0971-5916.187122
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618
280
CLINICAL IMAGES
Hajdu-Cheney syndrome - a rare cause of micrognathia
S Deepak Amalnath, Vinod Babu
May 2016, 143(5):663-664
DOI
:10.4103/0971-5916.187117
PMID
:27488012
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1
970
293
CORRESPONDENCE
M types & toxin gene profile of group A streptococci isolated from children in Dibrugarh district of Assam, India
Utpala Devi, Prasanta Kumar Borah, Vinita Malik, Pratap Parida, Jagadish Mahanta
May 2016, 143(5):659-662
DOI
:10.4103/0971-5916.187116
PMID
:27488011
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1
996
270
ORIGINAL ARTICLES
Dual hit lipopolysaccharide & oleic acid combination induced rat model of acute lung injury/acute respiratory distress syndrome
TN Hagawane, RV Gaikwad, NA Kshirsagar
May 2016, 143(5):624-632
DOI
:10.4103/0971-5916.187111
PMID
:27488006
Background & objectives:
Despite advances in therapy and overall medical care, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) management remains a problem. Hence the objective of this study was to develop a rat model that mimics human ALI/ARDS.
Methods:
Four groups of Wistar rats, 48 per group were treated with (i) intratracheal (IT) lipopolysaccharide (LPS) (5 mg/kg) dissolved in normal saline (NS), (ii) intravenous (iv) oleic acid (OA) (250 μl/kg) suspension in bovine serum albumin (BSA), (iii) dual hit: IT LPS (2 mg/kg) dissolved in NS and iv OA (100 μl/kg) and (iv) control group: IT NS and iv BSA. From each group at set periods of time various investigations like chest x-rays, respiratory rate (RR), tidal volume (TV), total cell count, differential cell count, total protein count and cytokine levels in bronchoalveolar lavage fluid (BALF), lung wet/dry weight ratio and histopathological examination were done.
Results:
It was noted that the respiratory rate, and tumour necrosis factor-α (TNF-α) levels were significantly higher at 4 h in the dual hit group as compared to LPS, OA and control groups. Interleukin-6 (IL-6) levels were significantly higher in the dual hit group as compared to LPS at 8 and 24 h, OA at 8 h and control (at all time intervals) group. IL-1β levels were significantly higher in LPS and dual hit groups at all time intervals, but not in OA and control groups. The injury induced in dual hit group was earlier and more sustained as compared to LPS and OA alone.
Interpretation & conclusions:
The lung pathology and changes in respiration functions produced by the dual hit model were closer to the diagnostic criteria of ALI/ARDS in terms of clinical manifestations and pulmonary injury and the injury persisted longer as compared to LPS and OA single hit model. Therefore, the ARDS model produced by the dual hit method was closer to the diagnostic criteria of ARDS in terms of clinical manifestations and pulmonary injury.
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In vitro
effects of co-incubation of blood with artemether/lumefantrine & vitamin C on the viscosity & elasticity of blood
MG McKoy, P Kong-Quee III, DJ Pepple
May 2016, 143(5):577-580
DOI
:10.4103/0971-5916.187105
PMID
:27488000
Background & objectives:
The antimalarial combination drug artemether/lumefantrine has been shown to be effective against malaria parasite through its haemolytic action. This drug is sometimes co-administered with vitamin C in patients with malaria. Vitamin C is associated with antioxidant properties which would be expected to protect against haemolytic effects of this antimalarial drug. This study was designed to investigate
in vitro
effects of co-incubation of artemether/lumefantrine with vitamin C on the viscosity and elasticity of blood.
Methods:
Blood was collected from 12 healthy female volunteers with normal haemoglobin genotype (HbAA). A Bioprofiler was used to measure the viscosity and elasticity of untreated blood samples (control) and samples exposed to artemether/lumefantrine (0.06/0.36 mg/ml) alone and with low or high dose vitamin C (equivalent to adult doses of 100 or 500 mg).
Results:
artemether/lumefantrine significantly (
p
<0.05) reduced viscosity of blood from 4.72 ± 0.38 to 3.78 ± 0.17 mPa.s. Addition of vitamin C (500 mg) further reduced blood viscosity to 2.67 ± 0.05 mPa.s. The elasticity of blood was significantly (
p
<0.05) reduced from 0.33 ± 0.04 mPa.s to 0.24 ± 0.03 mPa.s by the antimalarial drug, and further reduced to 0.13 ± 0.02 mPa.s in the presence of vitamin C (500 mg).
Interpretation & conclusions:
Co-incubation of blood with vitamin C and antimalarial combination drug potentiates the haemolytic effects of the latter on reducing blood viscosity and elasticity
in vitro
. This may possibly have implications in relation to haemolysis in patients receiving vitamin C supplementation with artemether/lumefantrine during malaria therapy.
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1
1,069
385
BOOK REVIEWS
How gut and brain control metabolism
BS Ramakrishna
May 2016, 143(5):670-670
DOI
:10.4103/0971-5916.187121
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262
BOOKS RECEIVED
Nutrition and growth: Yearbook 2016
May 2016, 143(5):671-671
DOI
:10.4103/0971-5916.187170
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597
285
CLINICAL IMAGES
Giant virilizing adrenocarcinoma: Rare presentation & management dilemma
Jayashri S Pandya, Ravikiran Vutha
May 2016, 143(5):665-666
DOI
:10.4103/0971-5916.187118
PMID
:27488013
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786
274
Tuberous sclerosis with bilateral giant renal angiomyolipomas
Suresh Kumar, Pranjal Modi
May 2016, 143(5):667-668
DOI
:10.4103/0971-5916.187119
PMID
:27488014
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896
287
EDITORIAL
Why understanding the asthma chronic obstructive pulmonary disease overlap syndrome (ACOS) is important to the clinician
TE Albertson
May 2016, 143(5):535-538
DOI
:10.4103/0971-5916.187099
PMID
:27487994
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ORIGINAL ARTICLES
N-acetyltransferase 2 (
NAT2
) gene polymorphism as a predisposing factor for phenytoin intoxication in tuberculous meningitis or tuberculoma patients having seizures - A pilot study
Prashant S Adole, Parampreet S Kharbanda, Sadhna Sharma
May 2016, 143(5):581-590
DOI
:10.4103/0971-5916.187106
PMID
:27488001
Background & objectives:
Simultaneous administration of phenytoin and isoniazid (INH) in tuberculous meningitis (TBM) or tuberculoma patients with seizures results in higher plasma phenytoin level and thus phenytoin intoxication. N-acetyltransferase 2 (
NAT2
) enzyme catalyses two acetylation reactions in INH metabolism and
NAT2
gene polymorphism leads to slow and rapid acetylators. The present study was aimed to evaluate the effect of allelic variants of
N
-acetyltransferase 2 (
NAT2
) gene as a predisposing factor for phenytoin toxicity in patients with TBM or tuberculoma having seizures, and taking INH and phenytoin simultaneously.
Methods:
Sixty patients with TBM or tuberculoma with seizures and taking INH and phenytoin simultaneously for a minimum period of seven days were included in study. Plasma phenytoin was measured by high performance liquid chromatography.
NAT2
gene polymorphism was studied using restriction fragment length polymorphism and allele specific PCR.
Results:
The patients were grouped into those having phenytoin intoxication and those with normal phenytoin level, and also classified as rapid or slow acetylators by
NAT2
genotyping. Genotypic analysis showed that of the seven SNPs (single nucleotide polymorphisms) of
NAT2
gene studied, six mutations were found to be associated with phenytoin intoxication. For rs1041983 (C282T), rs1799929 (C481T), rs1799931 (G857A), rs1799930 (G590A), rs1208 (A803G) and rs1801280 (T341C) allelic variants, the proportion of homozygous mutant was higher in phenytoin intoxicated group than in phenytoin non-intoxicated group.
Interpretation & conclusions:
Homozygous mutant allele of
NAT2
gene at 481site may act as a predisposing factor for phenytoin intoxication among TBM or tuberculoma patients having seizures.
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