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2019| September | Volume 150 | Issue 3
Online since
November 8, 2019
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REVIEW ARTICLES
National Iron Plus Initiative: Current status & future strategy
Umesh Kapil, Radhika Kapil, Aakriti Gupta
September 2019, 150(3):239-247
DOI
:10.4103/ijmr.IJMR_1782_18
PMID
:31719294
Anaemia is a severe public health problem amongst all vulnerable age groups in India. The National Nutritional Anaemia Prophylaxis Programme initiated in 1970, was revised and expanded to include beneficiaries from all age groups namely children aged 6-59 months, 5-10 yr, adolescents aged 10-19 yr, pregnant and lactating women and women in reproductive age group under the National Iron Plus Initiative (NIPI) programme in 2011. The dose of iron, frequency and duration of iron supplementation and roles and responsibilities of the functionaries were described. At present, the coverage of beneficiaries with iron and folic acid has been poor at the national level. The prevalence of anaemia has continued to remain high during the last 60 years, and there has been no significant change in the scenario due to various reasons. The constraints in implementation and measures to improve the NIPI programme are discussed in the current article.
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3
ORIGINAL ARTICLES
DNA damage induced by exposure to pesticides in children of rural areas in Paraguay
Stela Benitez Leite, Deidamia Mercedes Franco de Diana, Jaime Alfredo Segovia Abreu, Domingo Santiago Avalos, Marta Almada Denis, Cristina Coronel Ovelar, María José Samaniego Royg, Boris Alexei Thielmann Arbo, Ramón Corvalan
September 2019, 150(3):290-296
DOI
:10.4103/ijmr.IJMR_1497_17
PMID
:31719300
Background & objectives
:
Chronic exposure to pesticides can damage DNA and lead to cancer, diabetes, respiratory diseases and neurodegenerative and neurodevelopment disorders. The objective of this study was to determine the frequency of DNA damage through the comet assay and micronucleus (MN) test in two groups of children, under 10 yr of age living in rural Paraguay and in relation to pesticide exposure.
Methods
:
Two groups of 5 to 10 yr old children were formed; the exposed group (group A, n=43), born and currently living in a community dedicated to family agriculture and surrounded by transgenic soybean crops, and the control group (group B, n=41), born and living in a community dedicated to family agriculture with biological control of pests. For each child, 2000 cells were studied for the MN test and 200 cells for the comet assay.
Results
:
The comparison between exposed and control children revealed significant differences in biomarkers studied for the measurement of genetic damage (cell death and DNA damage). The median of MN was higher in the exposed group (6 vs. 1) (
P
<0.001). Binucleated cells (2.9 vs. 0.5,
P
<0.001); broken eggs (5.5 vs. 1.0,
P
<0.001); karyorrhexis (6.7 vs. 0.5,
P
<0.001); kariolysis (14.0 vs. 1.0,
P
<0.001); pyknosis (7.4 vs. 1.2,
P
<0.001) and condensed chromatin (25.5 vs. 7.0,
P
<0.001) were significantly higher in the exposed group. The values of tail length (59.1 vs 37.2 μm); tail moment (TM) (32.8 vs. 14.4 μm); TM olive (15.5 vs. 6); % DNA tail (45.2 vs. 27.6) and % DNA head (54.8 vs. 72.4), were significantly different between the two groups.
Interpretations & conclusions
:
In children exposed to pesticides, a greater genotoxic and cytotoxic effect was observed compared to non-exposed children. Our findings suggest that monitoring of genetic toxicity in population exposed to pesticides and agrochemicals should be done.
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REVIEW ARTICLES
Illicit drugs: Effects on eye
Deepika Dhingra, Savleen Kaur, Jagat Ram
September 2019, 150(3):228-238
DOI
:10.4103/ijmr.IJMR_1210_17
PMID
:31719293
There is a myriad of changes that can be produced in the eye by toxic drugs ranging from mild/no symptoms to severe loss of vision from endophthalmitis. The routes of administration include oral ingestion, smoking, nasal inhalation, intravenous injection, topical application or application to other mucosal surfaces. It is important to recognize certain clinical signs and symptoms in the eye produced by these toxins. This article describes in brief some of the ocular effects of commonly abused drugs. For identification of a particular poisoning, in addition to the clinical presentation, pulse, blood pressure, respiration and body temperature, pupillary size, pupillary reaction to light, ocular convergence and nystagmus can be useful indicators of the type of drug the patient is exposed to. Unmasking these features help the clinician in an early and accurate diagnosis of the offending drug as well as timely management.
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Anti-thymocyte globulin in haematology: Recent developments
Salahuddin Siddiqui, Jessica Cox, Roger Herzig, Senthilnathan Palaniyandi, Gerhard C Hildebrandt, Reinhold Munker
September 2019, 150(3):221-227
DOI
:10.4103/ijmr.IJMR_752_19
PMID
:31719292
Anti-thymocyte globulin (ATG) is a polyclonal antiserum introduced into clinical medicine more than 30 years ago. It induces a broad non-specific immunosuppression. In haematology, standard indications are severe aplastic anaemia and prophylaxis and treatment of graft-versus-host disease (GVHD) (after allogeneic transplantation). For aplastic anaemia, ATG from horses has been found to be superior to ATG from rabbits. In the situation of allogeneic transplantation, ATG lessens the risk of chronic GVHD but may not improve survival. There is current controversy regarding which patients benefit most from ATG and what the ideal dosage is. It is likely that in the coming years a more specific immunosuppressive will be developed that will minimize GVHD while maintaining the graft-versus-malignancy effect.
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ORIGINAL ARTICLES
Targeted sequencing of the
DMD
locus: A comprehensive diagnostic tool for all mutations
Sankaramoorthy Aravind, Berty Ashley, Ashraf Mannan, Aparna Ganapathy, Keerthi Ramesh, Aparna Ramachandran, Upendra Nongthomba, Arun Shastry
September 2019, 150(3):282-289
DOI
:10.4103/ijmr.IJMR_290_18
PMID
:31719299
Background & objectives
:
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder and is caused mainly by deletion, duplication and point mutations in the
DMD
gene. Diagnosis of DMD has been a challenge as the mutations in the
DMD
gene are heterogeneous and require more than one diagnostic strategy for the validation of the mutation. This study was planned to evaluate the targeted next-generation sequencing (NGS) as a single platform to detect all types of mutations in the
DMD
gene, thereby reducing the time and costs compared to conventional sequential testing and also provide precise genetic information for emerging gene therapies.
Methods
:
The study included 20 unrelated families and 22 patients from an Indian population who were screened for DMD based on phenotypes such as scoliosis, toe walking and loss of ambulation. Peripheral blood DNA was isolated and subjected to multiplex ligation-dependent probe amplification (MLPA) and targeted NGS of the
DMD
gene to identify the nature of the mutation.
Results
:
In the study patients, 77 per cent of large deletion mutations and 23 per cent single-nucleotide variations (SNVs) were identified. Novel mutations were also identified along with reported deletions, point mutations and partial deletions within the exon of the
DMD
gene.
Interpretation & conclusions
:
Our findings showed the importance of NGS in the routine diagnostic practice in the identification of
DMD
mutations over sequential testing. It may be used as a single-point diagnostic strategy irrespective of the mutation type, thereby reducing the turnaround time and cost for multiple diagnostic tests such as MLPA and Sanger sequencing. Though MLPA is a sensitive technique and is the first line of a diagnostic test, the targeted NGS of the
DMD
gene may have an advantage of having a single diagnostic test. A study on a larger number of patients is needed to highlight NGS as a single, comprehensive platform for the diagnosis of DMD.
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EDITORIAL
Patient safety & universal health coverage in India
Chandrakant Lahariya, Lav Agarwal, Hilde de Graeve, Henk Bekedam
September 2019, 150(3):211-213
DOI
:10.4103/ijmr.IJMR_1658_19
PMID
:31719289
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PERSPECTIVE
Influenza pandemic preparedness: A special challenge for India
David S Fedson
September 2019, 150(3):217-220
DOI
:10.4103/ijmr.IJMR_2034_18
PMID
:31719291
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ORIGINAL ARTICLES
Pharmacogenetic analyses of variations of measures of cardiovascular risk in Alzheimer's dementia
Fabricio Ferreira de Oliveira, Juliana Marília Berretta, Guido Veiga de Almeida Junior, Sandro Soares de Almeida, Elizabeth Suchi Chen, Marilia Cardoso Smith, Paulo Henrique Ferreira Bertolucci
September 2019, 150(3):261-271
DOI
:10.4103/ijmr.IJMR_1209_17
PMID
:31719297
Background & objectives
:
Neurodegeneration affects blood pressure variations, while renal function and cerebral perfusion are impaired by vascular risk factors. This study was aimed to estimate variations of measures of cardiovascular risk in Alzheimer's dementia by pharmacogenetic analyses of the effects of angiotensin-converting enzyme (ACE) inhibitors and statins.
Methods
:
Consecutive patients were prospectively followed to study variations of creatinine clearance and blood pressure for one year, estimated by correlating the effects of ACE inhibitors with the
ACE Alu
I/D polymorphism and genotypes or haplotypes of rs1800764 or rs4291, and the effects of statins with
LDLR
(low-density lipoprotein receptor) genotypes or haplotypes of rs11669576 (exon 8) or rs5930 (exon 10), or genotypes of rs2695121 (liver X receptor β gene). Variations of the coronary heart disease (CHD) risk according to these cardiovascular measures were also explored.
Results
:
All polymorphisms of the 193 patients were in Hardy-Weinberg equilibrium. Genetic determinants of cardiovascular effects affected the individual variability of the response to ACE inhibitors and statins. ACE inhibitors, but not statins, reduced blood pressure for all patients. ACE inhibitors protected carriers of alleles that supposedly decrease serum ACE levels (rs1800764-T, rs4291-A,
Alu
II) regarding creatinine clearance variations (
P
<0.005), but carriers of
Alu
DD (
P
<0.02), rs1800764-C (
P
<0.05), or rs4291-AT (
P
<0.04) showed better blood pressure lowering effects. The presence of rs2695121-T (
P
=0.007) or rs5930-A (
P
=0.039) was associated with systolic blood pressure lowering, whereas rs5930-AA was protective against decrease in creatinine clearance (
P
=0.019). Statins lowered creatinine clearance for carriers of rs2695121-CT (
P
=0.026).
Interpretation & conclusions
:
Pharmacological response of blood pressure and creatinine clearance to ACE inhibitors and statins may be genetically mediated.
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STUDENT IJMR
Detection of respiratory syncytial virus &
Mycoplasma pneumoniae
in paediatric lower respiratory tract infections
Sanchit Kumar, Anita Chakravarti, Surinder Kumar, Seema Kapoor
September 2019, 150(3):306-309
DOI
:10.4103/ijmr.IJMR_983_18
PMID
:31719302
Background & objectives
:
Respiratory syncytial virus (RSV) and
Mycoplasma pneumoniae
are considered common cause of lower respiratory tract infections (LRTIs) in children. The present study was conducted to detect
M. pneumoniae
and RSV in paediatric LRTIs employing serology, polymerase chain reaction (PCR) and reverse transcriptase PCR (RT-PCR) analysis.
Methods
:
Seventy five children aged one month to five years with acute LRTIs were investigated for
M. pneumoniae
antibodies and RSV antigen using immunochromatographic test, RT-PCR for RSV and
M. pneumoniae
by PCR on nasopharyngeal aspirates.
Results
:
RSV infection was observed in 33 (44%) and
M. pneumoniae
was positive in 26 (35%) children. No significant difference in infection was noted between male and female children. Clinical and radiological features among RSV and
M. pneumoniae
positive and negative cases were similar. Considering RT-PCR for RSV as gold standard, RSV antigen immunochromatography was 90.90 per cent sensitive and 100 per cent specific.
Interpretation & conclusions
:
Our study showed the presence of RSV and
M. pneumoniae
infection in 44 and 35 per cent children, respectively with community-acquired LRTIs and aged less than five years.
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COMMENTARY
Ki-67, an elusive marker in the prognosis of breast cancer
Neelam Sood
September 2019, 150(3):214-216
DOI
:10.4103/ijmr.IJMR_827_19
PMID
:31719290
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ORIGINAL ARTICLES
Haplotype analysis of
ADAM33
polymorphisms in asthma: A pilot study
Sangeetha Vishweswaraiah, Nallur B Ramachandra, BS Jayaraj, Amrutha D Holla, Samarpana Chakraborty, Anurag Agrawal, Padukudru A Mahesh
September 2019, 150(3):272-281
DOI
:10.4103/ijmr.IJMR_698_17
PMID
:31719298
Background & objectives
:
ADAM33
is implicated as a potentially strong candidate gene for asthma and bronchial hyper-responsiveness. Many polymorphisms of
ADAM33
have been studied along with ADAM33 expression in various cells of the lungs. Haplotype analysis also showed association with asthma in different populations across the world. Therefore, the aim of this study was to perform a comprehensive screening of
ADAM33
polymorphisms in adult patients with asthma.
Methods
:
Thirty five polymorphisms of
ADAM33
were genotyped in 55 patients with asthma and 53 controls. The association of single nucleotide polymorphisms (SNPs) and haplotypes with phenotypes of asthma was analysed.
Results
:
The genotype, minor allele frequency, odds ratio and Hardy–Weinberg equilibrium did not show any significant difference among cases and controls. No association was found between SNPs of
ADAM33
with the severity of asthma. Correlation analysis of
ADAM33
SNPs to the phenotypes, based on clinical variables and allergen sensitization, did not show significant difference. Haplotype analysis showed that rs2280090 and rs2280091 were associated with asthma in the patient group.
Interpretation & conclusions
:
Haplotype analysis showed an association of the two SNP variations with asthma. These SNPs lead to amino acid change and are prone to phosphorylation, which may affect expression levels and protein function of ADAM33 and asthma susceptibility.
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Diagnostic ability of real-time quantitative polymerase chain reaction versus immunohistochemistry for Ki-67 assessment in breast cancer: An Indian perspective
Anurag Mehta, Dushyant Kumar, Prerna Chadha, Malini Goswami, Gayatri Vishwakarma, Manoj Panigrahi, Moushumi Suryavanshi, Ajit Panaych
September 2019, 150(3):254-260
DOI
:10.4103/ijmr.IJMR_644_18
PMID
:31719296
Background & objectives
:
Breast cancer is the most common cancer of women. Inferior prognosis in some patients has been attributed to the higher proliferative capability of the tumour. Immunohistochemistry (IHC) for Ki-67, despite being a simple and cost-effective method, has not become a valid tool to evaluate this biomarker. This is ascribed to variation in pre-analytical and analytical techniques, variable expression, hotspot distribution and inter-and intra-observer inconsistency. This study was aimed at defining the analytical and clinical validity of real-time quantitative polymerase chain reaction (RT-qPCR) as an alternative to IHC evaluation.
Methods
:
This study included a total of 109 patients with invasive breast cancers. Ki-67 IHC visual assessment was compared with the mRNA value determined by RT-qPCR. Concordance between both the methods was assessed. Receiver operating characteristic (ROC) curve analysis and Cohen's kappa value with intraclass correlation were performed.
Results
:
The threshold value for Ki-67 by RT-qPCR obtained by ROC curve was 22.23 per cent, which was used to divide breast cancer cases into high proliferative and low proliferative groups. A significant correlation was observed between both the breast cancer groups formed using RT-qPCR threshold as well as median laboratory value of Ki-67 labelling index by IHC.
Interpretation & conclusions
:
The study results showed a significant correlation between the two methods. While IHC is subject to technical and interpretative variability, RT-qPCR may offer a more objective alternative.
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Development & cross-validation of anthropometric predictive models to estimate the appendicular skeletal muscle mass in middle-aged women in Sri Lanka
Nirmala Rathnayake, Gayani Alwis, Janaka Lenora, Sarath Lekamwasam
September 2019, 150(3):297-305
DOI
:10.4103/ijmr.IJMR_1961_17
PMID
:31719301
Background & objectives
:
Attempts have been made to estimate appendicular skeletal muscle mass (ASMM) using anthropometric indices and most of these are country specific. This study was designed to develop and cross-validate simple predictive models to estimate the ASMM based on anthropometry in a group of healthy middle-aged women in Sri Lanka.
Methods
:
The study was conducted on a randomly selected group of community-dwelling women aged 30-60 years. ASMM (kg) quantified with dual-energy X-ray absorptiometry (DXA) (ASMM
DXA
) was used as the reference standard. Anthropometric measurements such as body weight (kg), height (m), limb circumferences (cm) and skinfold thickness (mm) which showed significant correlations with ASMM
DXA
, were used to develop the models. The models were developed using a group of 165 women (aged 30-60 yr) and were cross-validated using a separate sample of women (n=167) (mean age: 48.9±8.56 yr), selected randomly.
Results
:
Nine anthropometry-based models were developed using weight, height, skinfold thicknesses, circumferences, body mass index, menopausal status (MS) and age as independent variables. Four models which were based on height, weight, triceps skinfold thickness (TSFT), age and MS met all the validation criteria with high correlations (ranged 0.89-0.92) and high predictive values explaining high variance (80-84%) with low standard error of estimate (1.10-1.24 kg).
Interpretation & conclusions
:
The four models (ASMM 1-ASMM 4) developed based on height, weight, TSFT, age and MS showed a high accuracy in estimating the ASMM in middle-aged women.
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REVIEW ARTICLES
The grand challenge of regulating health foods in India
Sesikeran Boindala, Joseph I Lewis
September 2019, 150(3):248-253
DOI
:10.4103/ijmr.IJMR_1719_18
PMID
:31719295
Food is the primary source of nutrients to keep us nourished and healthy. Poor and unhealthy diets implicated with the increase of several non-communicable diseases (NCDs) require a food-based approach to reduce the ongoing rise. Traditional knowledge and science behind food-related health benefits became evident in the last three decades. Active ingredients, bioactive molecules and conventionally used herbs were clinically researched and proven to have beneficial outcomes. In the Indian scenario, the multiplicity of food products, including medicinal type formats, such as health supplements, containing plant, herbs or novel ingredients, brings in a new complexity to regulations. Several of these ingredients are pharmacologically active substances and could overlap with drug regulations. The data generated on the nutritional and health benefit of a supplement should be reproducible, outcomes measurable and disease risk reduction shown by well-designed research studies. Regulatory challenges occur at several levels, namely, harmonization of law, fair trade practice, population exposures to chemicals and contaminants, food borne illness, rise in NCD's, novel ingredients, new technologies and a legacy of regulatory practice. While regulatory and legal challenges will always exist, reliance on the role of scientific research in the regulatory context becomes significant.
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CLINICAL IMAGES
Diffuse large B-cell lymphoma presenting as shoulder swelling
YS Sarma, M Sriharibabu
September 2019, 150(3):310-311
DOI
:10.4103/ijmr.IJMR_802_18
PMID
:31719303
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463
149
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Regional cardiac tamponade
Arun Gopalakrishnan, Vivek V Pillai
September 2019, 150(3):312-312
DOI
:10.4103/ijmr.IJMR_1851_17
PMID
:31719304
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349
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ERRATUM
Erratum: Nutrition rehabilitation of children with severe acute malnutrition: Revisiting studies undertaken by the National Institute of Nutrition
September 2019, 150(3):314-314
DOI
:10.4103/0971-5916.270632
PMID
:31719305
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BOOK REVIEW
The ovary
Reva Tripathi
September 2019, 150(3):313-313
DOI
:10.4103/ijmr.IJMR_1052_19
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