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2013| April | Volume 137 | Issue 4
Online since
May 17, 2013
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CENTENARY REVIEW ARTICLE
Rheumatic fever & rheumatic heart disease: The last 50 years
R Krishna Kumar, R Tandon
April 2013, 137(4):643-658
PMID
:23703332
Rheumatic fever (RF) and rheumatic heart disease (RHD) continue to be a major health hazard in most developing countries as well as sporadically in developed economies. Despite reservations about the utility, echocardiographic and Doppler (E&D) studies have identified a massive burden of RHD suggesting the inadequacy of the Jones' criteria updated by the American Heart Association in 1992. Subclinical carditis has been recognized by E&D in patients with acute RF without clinical carditis as well as by follow up of RHD patients presenting as isolated chorea or those without clinical evidence of carditis. Over the years, the medical management of RF has not changed. Paediatric and juvenile mitral stenosis (MS), upto the age of 12 and 20 yr respectively, severe enough to require operative treatement was documented. These negate the belief that patients of RHD become symptomatic ≥20 years after RF as well as the fact that congestive cardiac failure in childhood indicates active carditis and RF. Non-surgical balloon mitral valvotomy for MS has been initiated. Mitral and/or aortic valve replacement during active RF in patients not responding to medical treatment has been found to be life saving as well as confirming that congestive heart failure in acute RF is due to an acute haemodynamic overload. Pathogenesis as well as susceptibility to RF continue to be elusive. Prevention of RF morbidity depends on secondary prophylaxis which cannot reduce the burden of diseases. Primary prophylaxis is not feasible in the absence of a suitable vaccine. Attempts to design an antistreptococcal vaccine utilizing the M-protein has not succeeded in the last 40 years. Besides pathogenesis many other questions remain unanswered.
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PERSPECTIVE
"Doctor population ratio for India - The reality"
Madhav G Deo
April 2013, 137(4):632-635
PMID
:23703329
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REVIEW ARTICLE
MicroRNA in carcinogenesis & cancer diagnostics: A new paradigm
Javed Ahmad, Seyed E Hasnain, Maqsood A Siddiqui, Maqusood Ahamed, Javed Musarrat, Abdulaziz A Al-Khedhairy
April 2013, 137(4):680-694
PMID
:23703335
MicroRNAs (miRNAs) are small 22-25 nucleotides long non-coding RNAs, that are conserved during evolution, and control gene expression in metazoan animals, plants, viruses, and bacteria primarily at post-transcriptional and transcriptional levels. MiRNAs ultimately regulate target gene expression by degrading the corresponding mRNA and/or inhibiting their translation. Currently, the critical functions of miRNAs have been established in regulating immune system, cell proliferation, differentiation and development, cancer and cell cycle by as yet unknown control mechanism. MiRNAs play an essential role in malignancy, and as tumour suppressors and oncogenes. Thus, discovery of new miRNAs will probably change the landscape of cancer genetics. Significantly different miRNA profiles can be assigned to various types of tumours, which could serve as phenotypic signatures for different cancers for their exploitation in cancer diagnostics, prognostics and therapeutics. If miRNA profiles can accurately predict malignancies, this technology could be exploited as a tool to surmount the diagnostic challenges. This review provides comprehensive and systematic information on miRNA biogenesis and their implications in human health.
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ORIGINAL ARTICLES
Family burden with substance dependence: a study from India
Surendra Kumar Mattoo, Naresh Nebhinani, BN Anil Kumar, Debasish Basu, Parmanand Kulhara
April 2013, 137(4):704-711
PMID
:23703337
Background & objectives:
A substance dependent person in the family affects almost all aspects of family life. This leads to problems, difficulties or adverse events which impact the lives of family members and causes enormous burden on family caregivers. The present study aimed to assess the pattern of burden borne by the family caregivers of men with alcohol and opioid dependence.
Methods:
A cross-sectional study was conducted with ICD-10 diagnosed substance dependence subjects and their family caregivers attending a de-addiction centre at a multispecialty teaching hospital in north India. Family Burden Interview Schedule was used to assess the pattern of burden borne by the family caregivers of 120 men with alcohol and/or opioid dependence.
Results:
Compared to opioid and alcohol+opioid dependence groups, more often the alcohol dependence group was older, married, currently working, having a higher income and with the wife as a caregiver. Family burden was moderate or severe in 95-100 per cent cases in all three groups and more for 'disruption of family routine', 'financial burden', 'disruption of family interactions' and 'disruption of family leisure'. Family burden was associated with low income and rural location. It was associated neither with age, education or duration of dependence of the patients, nor with family size, type of caregiver or caregiver's education and occupation.
Interpretation & conclusions:
Almost all (95-100%) caregivers reported a moderate or severe burden, which indicates the gravity of the situation and the need for further work in this area.
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Prevalence of gestational diabetes mellitus & associated risk factors at a tertiary care hospital in Haryana
Rajesh Rajput, Yogesh Yadav, Smiti Nanda, Meena Rajput
April 2013, 137(4):728-733
PMID
:23703340
Background & objectives:
Prevalence of gestational diabetes mellitus (GDM) is known to vary widely depending on the region of the country, dietary habits, and socio-economic status. This study was undertaken to determine the prevalence of GDM and risk factors associated with it, in women attending an antenatal care (ANC) clinic at a tertiary care hospital in Haryana.
Methods:
This study enrolled women, with their estimated gestational age between 24
th
and 28
th
week, attending antenatal care (ANC) clinic at a tertiary care hospital in Rohtak. After informing, women who consented to participate were given a standardized 2-h 75 g oral glucose tolerance test (OGTT). A proforma containing general information on demographic characteristics, socio-economic status, education level, parity, family history of diabetes and/or hypertension and past history of GDM was filled up. American Diabetes Association (ADA) criteria for 75 g 2-h OGTT was used for diagnosing GDM.
Results:
A total of 607 women participated in the study and GDM was diagnosed in 43 (7.1%) women. A single abnormal value was observed in additional 66 (10.87%) women. On bivariate analysis risk factors found to be significantly associated with GDM were age, educational level, socio-economic status, pre-pregnancy weight and BMI, weight gain, acanthosis nigricans, family history of diabetes or hypertension and past history of GDM but on multivariate analysis only upper middle class and presence of acanthosis nigricans were found to be significantly associated with GDM.
Interpretation & conclusions:
The prevalence of GDM was found to be 7.1 per cent in a tertiary care hospital in Haryana. Appropriate interventions are required for control and risk factor modifications.
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REVIEW ARTICLE
Vitamin D, arterial hypertension & cerebrovascular disease
Katharina Kienreich, Martin Grübler, Andreas Tomaschitz, Johannes Schmid, Nicolas Verheyen, Femke Rutters, Jacqueline M Dekker, Stefan Pilz
April 2013, 137(4):669-679
PMID
:23703334
Vitamin D is mainly derived from endogenous ultraviolet-B induced vitamin D synthesis in the skin, and the current high prevalence of vitamin D deficiency can, therefore, largely be attributed to lifestyle related low sunlight exposure. Regulation of bone and mineral metabolism is a classic vitamin D effect, but the identification of the vitamin D receptor (VDR) in almost all human cells suggests a role for vitamin D also in extra-skeletal diseases. Experimental studies demonstrated several antihypertensive and vascular protective effects of vitamin D, such as suppression of the renin angiotensin aldosterone system, beneficial modulation of classic cardiovascular risk factors, and anti-atherosclerotic properties including improvements of endothelial function. Additional neuroprotective actions of vitamin D have also been reported. In line with this, epidemiological studies have largely shown that vitamin D deficiency is an independent risk factor for arterial hypertension and strokes. Data from randomized controlled trials (RCTs) are, however, limited and less promising, with currently no confirmation that vitamin D reduces stroke incidence. Whereas some RCTs suggest that vitamin D supplementation might modestly reduce blood pressure, this has not been consistently observed in all studies. It is, therefore, premature to recommend vitamin D supplementation for the prevention and treatment of arterial hypertension and stroke. Nevertheless, the fact that patients with arterial hypertension and cerebrovascular disease are at a relatively high risk of vitamin D deficiency, and therewith associated musculoskeletal diseases can serve as a rationale for the evaluation, prevention and treatment of vitamin D deficiency in these patients.
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ORIGINAL ARTICLES
Asymptomatic bacteriuria & obstetric outcome following treatment in early versus late pregnancy in north Indian women
Vaishali Jain, Vinita Das, Anjoo Agarwal, Amita Pandey
April 2013, 137(4):753-758
PMID
:23703344
Background & objectives:
Asymptomatic bacteriuria during pregnancy if left untreated, may lead to acute pyelonephritis, preterm labour, low birth weight foetus,
etc
. Adequate and early treatment reduces the incidence of these obstetric complications. The present study was done to determine presence of asymptomatic bacteriuria (ASB) and obstetric outcome following treatment in early versus late pregnancy.
Methods:
A prospective cohort study was conducted at a tertiary care teaching hospital of north India. Pregnant women till 20 wk (n=371) and between 32 to 34 wk gestation (n=274) having no urinary complaints were included. Their mid stream urine sample was sent for culture and sensitivity. Women having > 10
[5]
colony forming units/ml of single organism were diagnosed positive for ASB and treated. They were followed till delivery for obstetric outcome. Relative risk with 95% confidence interval was used to describe association between ASB and outcome of interest.
Results:
ASB was found in 17 per cent pregnant women till 20 wk and in 16 per cent between 32 to 34 wk gestation. Increased incidence of preeclamptic toxaemia (PET) [RR 3.79, 95% CI 1.80-7.97], preterm premature rupture of membrane (PPROM)[RR 3.63, 45% CI 1.63-8.07], preterm labour (PTL) [RR 3.27, 95% CI 1.38-7.72], intrauterine growth restriction (IUGR)[RR 3.79, 95% CI 1.80-79], low birth weight (LBW) [RR1.37, 95% CI 0.71-2.61] was seen in late detected women (32-34 wk) as compared to ASB negative women, whereas no significant difference was seen in early detected women (till 20 wk) as compared to ASB negative women.
Interpretation & conclusions:
Early detection and treatment of ASB during pregnancy prevents complications like PET, IUGR, PTL, PPROM and LBW. Therefore, screening and treatment of ASB may be incorporated as routine antenatal care for safe motherhood and healthy newborn.
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REVIEW ARTICLE
New trends in glaucoma risk, diagnosis & management
Thomas Kersey, Colin I Clement, Phillip Bloom, M Francesca Cordeiro
April 2013, 137(4):659-668
PMID
:23703333
Recent advances have seen a surge of new ideas and technologies to aid in the detection, treatment and further understanding of glaucoma. These technologies and advances are discussed to provide information on risk-factors, diagnosis and treatment. Glaucoma has never before seen such an advance in research and therapies coming forward in to the clinical workplace. It is an exciting time for physicians and researchers alike and over the next decade will certainly see advances in early detection, efficacious treatments and neuroprotection.
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EDITORIAL
Time to effectively address hypertension in India
Sailesh Mohan, Norm Campbell, Arun Chockalingam
April 2013, 137(4):627-631
PMID
:23703328
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REVIEW ARTICLE
Genes involved in pancreatic islet cell rejuvenation
Vinay S Bansal, C Prasanna Raja, Krishnan Venkataraman, MA Vijayalakshmi
April 2013, 137(4):695-703
PMID
:23703336
Pancreas plays an important role in maintaining the glucose homeostasis. The deterioration of β-cells in the pancreas is a crucial factor in the progression of diabetes mellitus; therefore, the restoration of β-cell mass and its function is of vital importance for effective therapeutic strategies. The precise mechanism for increase in functional β-cell mass is still unknown. This review focuses on the importance of certain genes which are involved in the rejuvenation of pancreas. These genes are divided according to their functions into three categories: participate either in proliferation (mitotic division of differentiated β-cells), neogenesis/transdifferentiation (development from precursor cells) or inhibition of β-cell apoptosis (programmed cell death). The rate of β-cell rejuvenation is the balance among the rates of β-cell proliferation, neogenesis and apoptosis. Understanding these genes and their pathways may lead to the discovery of new drugs, target based gene delivery and development of safer antidiabetic drugs.
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ORIGINAL ARTICLES
Prospective multi-centre sentinel surveillance for
Haemophilus influenzae
type b & other bacterial meningitis in Indian children
Padmanabhan Ramachandran, Sean Patrick Fitzwater, Satinder Aneja, Valsan Philip Verghese, Vishwajeet Kumar, Krishnamoorthy Nedunchelian, Nitya Wadhwa, Balaji Veeraraghavan, Rashmi Kumar, Mohamed Meeran, Arti Kapil, Sudha Jasmine, Aarti Kumar, Saradha Suresh, Shinjini Bhatnagar, Kurien Thomas, Shally Awasthi, Mathuram Santosham, Aruna Chandran
April 2013, 137(4):712-720
PMID
:23703338
Background & objectives:
Haemophilus influenzae
type b (Hib) is one of the leading bacterial causes of invasive disease in populations without access to Hib conjugate vaccines (Hib-CV). India has recently decided to introduce Hib-CV into the routine immunization programme in selected States. Longitudinal data quantifying the burden of bacterial meningitis and the proportion of disease caused by various bacteria are needed to track the impact of Hib-CV once introduced. A hospital-based sentinel surveillance network was established at four places in the country and this study reports the results of this ongoing surveillance.
Methods:
Children aged 1 to 23 months with suspected bacterial meningitis were enrolled in Chennai, Lucknow, New Delhi, and Vellore between July 2008 and June 2010. All cerebrospinal fluid (CSF) samples were tested using cytological, biochemical, and culture methods. Samples with abnormal CSF (≥10 WBC per μl) were tested by latex agglutination test for common paediatric bacterial meningitis pathogens.
Results:
A total of 708 patients with abnormal CSF were identified, 89 of whom had a bacterial pathogen confirmed. Hib accounted for the majority of bacteriologically confirmed cases, 62 (70%), while
Streptococcus pneumoniae
and group B
Streptococcus
were identified in 12 (13%) and seven (8%) cases, respectively. The other eight cases were a mix of other bacteria. The proportion of abnormal CSF and probable bacterial meningitis that was caused by Hib was 74 and 58 per cent lower at Christian Medical College (CMC), Vellore, which had a 41 per cent coverage of Hib-CV among all suspected meningitis cases, compared to the combined average proportion at the other three centres where a coverage between 1 and 8 per cent was seen (
P
<0.001 and
P
= 0.05, respectively).
Interpretation & conclusions:
Hib was found to be the predominant cause of bacterial meningitis in young children in diverse geographic locations in India. Possible indications of herd immunity was seen at CMC compared to sites with low immunization coverage with Hib-CV. As Hib is the most common pathogen in bacterial meningitis, Hib-CV would have a large impact on bacterial meningitis in Indian children.
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Neonatal septicaemia caused by diverse clones of
Klebsiella pneumoniae
&
Escherichia
coli
harbouring
bla
CTX-M-15
Subhasree Roy, Rajni Gaind, Harish Chellani, Srujana Mohanty, Saswati Datta, Arun K Singh, Sulagna Basu
April 2013, 137(4):791-799
PMID
:23703349
Background & objectives:
Information about the genetic diversity of the extended-spectrum β-lactamases (ESBLs) and the clonal relationship of the organisms causing neonatal infections is limited, particularly from India where neonatal mortality is high. This study was undertaken to investigate the molecular epidemiology and risk factors associated with neonatal septicaemia caused by ESBL-producing
Klebsiella pneumoniae
and
Escherichia coli
.
Methods:
Bloodstream isolates (n=26) of
K. pneumoniae
(n=10) and
E. coli
(n=16) from the neonates admitted in a tertiary care hospital in New Delhi during January to May 2008 were characterized. Antimicrobial susceptibility tests were carried out and ESBL production was assessed phenotypically. PCR was carried out for ESBL and
ampC
genes. Genotyping was performed by pulsed-field gel electrophoresis (PFGE). Conjugation experiments were done to determine the mobility of ESBL genes. Risk factors associated with ESBL-producing
K. pneumoniae
and
E. coli
infections were analysed.
Results:
Resistance rates to most of the antibiotics tested were high, except for imipenem. Among the isolates tested, 60 per cent of
K. pneumoniae
and 75 per cent of
E. coli
were ESBL producers. PFGE of the isolates demonstrated a vast diversity of genotypes with no epidemic clones. Despite the clonal diversity,
bla
CTX-M-15
was detected in 100 per cent of ESBL-positive isolates. The other genes present in ESBL-positive isolates were
bla
TEM-1,
bla
SHV-1
,
bla
SHV-28
,
bla
SHV-11
, and
bla
SHV-12
. Class 1 integrons were detected in 7 of 18 ESBL-positive isolates. Moreover, the plasmid carrying
bla
CTX-M-15
, in
E. coli
and
K. pneumoniae
were self transferable. Feeding through an enteral tube was identified as the only risk factor for sepsis by ESBL-producing organisms.
Interpretation & conclusions:
The study emphasises the presence of
bla
CTX-M-15
in clonally diverse isolates indicating probable horizontal transfer of this gene. The widespread dissemination of CTX-M-15 is of great concern as it further confines the limited therapeutic interventions available for neonates.
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Serological & molecular approaches for diagnosis of leptospirosis in a tertiary care hospital in north India: A 10-year study
R Chaudhry, A Das, MM Premlatha, A Choudhary, BK Chourasia, DS Chandel, AB Dey
April 2013, 137(4):785-790
PMID
:23703348
Background & objectives:
Leptospirosis, a spirochetal zoonosis, is underreported from the northern States of India. This study reports results of a 10-year retrospective sero-epidemiological survey of leptospirosis conducted in a tertiary care hospital in New Delhi, India.
Method:
A total of 1453 patients clinically suspected for leptospirosis were included and investigated initially by IgM ELISA. A proportion of these were subjected to culture, microscopic agglutination test (MAT) and polymerase chain reaction (PCR).
Results:
Of the 1453 patients, 391 (26.90%) were positive serologically by IgM ELISA. Seropositive and seronegative patients revealed no significant difference in clinical features and laboratory parameters. Amongst the IgM seropositive cases, culture for leptospires was positive in 5 of 192 (2.6%), MAT in 50 of 138 (36.23%), PCR from blood and urine in 10 of 115 (8.7%) and 10 of 38 (26.31%) cases, respectively. In
Leptospira
spp. positive patients co-infections with viral hepatitis E, malaria and dengue fever were diagnosed in 27 cases.
Interpretation & conclusions:
The overall seropositivity for leptospirosis was 26.9 per cent in our study. A decreasing trend in seropositivity was observed in recent years. Co-infections with malaria, dengue, hepatitis A and E were also seen. Since leptospirosis is a treatable disease, correct and rapid diagnosis may help in effective management of patients.
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Evaluation of toxicity & therapeutic efficacy of a new liposomal formulation of amphotericin B in a mouse model
Jyotsna Mishra, Ayan Dey, Niti Singh, Ramesh Somvanshi, Sarman Singh
April 2013, 137(4):767-776
PMID
:23703346
Background & objectives:
Current therapy for leishmaniasis is limited and unsatisfactory. Amphotericin B, a second-line treatment is gradually replacing antimonials, the first-line treatment and is used as the preferred treatments in some regions. Though, presently it is the only drug with highest cure rate, its use is severely restricted by its acute toxicity. In the present study novel lipid-amphotericin B formulations with lower toxicity than the parent drug were evaluated for the treatment of visceral leishmaniasis (VL) in a mouse model.
Methods:
The toxicity and therapeutic efficacy of a new amphiphilic formulation of amphotericin B (Kalsome
TM
10) was compared to that of amphotericin B deoxycholate (Fungizone) in a mouse model of VL using quantitative real-time PCR (qRT-PCR).
Results:
The toxicity of amphotericin B was significantly less with liposomal formulation as compared to the deoxycholate form, evidenced by reduced nephrotoxicity and higher tolerated dose in BALB/c mice. The therapeutic efficacy was evaluated by quantitative real time (RT) PCR using primers highly specific for the
ITS
region of
Leishmania donovani
. There was reduction in parasite load by 2 log unit after 7 days of treatment and finally resulting in complete clearance of parasite from infected mice after 30 days of treatment with Kalsome
TM
10.
Interpretation & conclusions:
This new formulation showed a favourable safety profile and better efficacy when compared to conventional amphotericin B. If production cost is kept low, it may prove to be a feasible alternative to conventional amphotericin B.
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Antimicrobial susceptibility of
Salmonella
enterica
serovars in a tertiary care hospital in southern India
Ashwini Choudhary, Ram Gopalakrishnan, P Senthur Nambi, V Ramasubramanian, K Abdul Ghafur, MA Thirunarayan
April 2013, 137(4):800-802
PMID
:23703350
Background & objectives:
Salmonella enterica
serovars Typhi and Paratyphi are predominantly known to cause enteric fever. Multidrug resistance in
S.
Tphi and
S.
Paratyphi has emerged as a cause of concern. This study was done to evaluate status in antimicrobial susceptibility patterns of
Salmonella enterica
serovar Typhi (
S.
Typhi) and
S
. Paratyphi obtained from blood culture in a tertiary care hospital in south India.
Methods:
Blood isolates of
Salmonella
species over a two year period between May 2009 and June 2011 were studied. A total of 322 isolates of
Salmonella
species were tested for antimicrobial susceptibility by Kirby-Bauer disc diffusion method. The MIC of ciprofloxacin was obtained by E-test, and azithromycin MIC was confirmed by agar dilution method for a limited number of isolates.
Results:
Of the total of 322 isolates studied, 186 (57.8%) were
S
. Typhi, 134 (41.6%) were
S.
Paratyphi A, and two were
S. P
aratyphi B. Of these, 44(13.66%) were resistant to ciprofloxacin (MIC <0.50 ΅g/ml) and 296 (91.9%) were nalidixic acid resistant. Of these 296 nalidixic acid resistant isolates, 278 (94%) were susceptible to ciprofloxacin by MIC criteria (<0.5 ΅g/ml). Of the 262 isolates tested for azithromycin sensitivity, only 120 (46%) were susceptible, whereas 81 (31%) were resistant and 55 (21%) showed intermediate susceptibility. Of the isolates, 322 (90%) were susceptible to ampicillin and (95%) were susceptible to co-trimoxazole. However, all the isolates were susceptible to chloramphenicol and ceftriaxone.
Interpretation & conclusions:
Nalidixic acid resistance screening is not a reliable surrogate indicator of ciprofloxacin resistance. Ciprofloxacin MIC should to be routinely done. Azithromycin resistance appears to be emerging. However, isolates showed a high degree of susceptibility to ampicillin, co-trimoxazole and chloramphenicol. Thus, antibiotics like ampicillin and co-trimoxazole may once again be useful for the management of enteric fever in southern India.
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Tumour necrosis factor (
TNF)-α
-308 gene polymorphism in Indian patients with
Takayasu's arteritis
- A pilot study
P Sandhya, Sumita Danda, Debashish Danda, Shraddha Lonarkar, Shana S Luke, Shanta Sinha, George Joseph
April 2013, 137(4):749-752
PMID
:23703343
Background & objectives:
Tumour necrosis factor-alpha (
TNF-α
)- 308 promoter gene polymorphism has been shown to be associated with several autoimmune disorders and infections such as tuberculosis. There is no study on
TNF-α
gene polymorphism in Takayasu's arteritis (TA) till date. We aimed to study this polymorphism in TA, a granulomatous vasculitis, probably triggered by
Mycobacterium tuberculosis
.
Methods:
TNF-α
- 308 gene polymorphism was studied in 34 patients with TA and 39 healthy controls recruited from Christian Medical College, India. PCR was done followed by enzyme digestion. G and A polymorphisms were analysed. Occurrence of alleles in the disease group was compared with controls as well as with historical controls.
Results:
GG allele was most frequent in TA and in controls. GA allele was detected in four controls but only in one patient who was the oldest in the study group. AA polymorphism was detected in one control but not in TA. When compared with controls from other populations, it was found that our allelic frequency was similar to that in Japan as well as from USA with mixed population. However, predominantly Caucasian population studied from Netherlands, Germany and England, where TA is rare, had a higher frequency of A allele as compared to our controls.
Interpretation & conclusions:
Our preliminary results indicated that G allele at
TNF-α
- 308 was more common in TA patients and controls similar to that in other Indian as well as Japanese population. Compared to the western population, A allele was relatively less common in our study subjects.
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COMMENTARY
The burden of caring: Drug users & their families
Paolo Mannelli
April 2013, 137(4):636-638
PMID
:23703330
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1,125
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ORIGINAL ARTICLES
A rapid & sensitive liquid chromatography- tandem mass spectrometry method for the quantitation of busulfan levels in plasma & application for routine therapeutic monitoring in haematopoietic stem cell transplantation
Salamun Desire, Ezhil Pavai Mohanan, Biju George, Vikram Mathews, Mammen Chandy, Alok Srivastava, Poonkuzhali Balasubramanian
April 2013, 137(4):777-784
PMID
:23703347
Background & objectives:
Busulfan (Bu) in combination with cyclophosphamide is widely used in myeloablative conditioning regimen prior to haematopoietic stem cell transplantation (HSCT). Its narrow therapeutic range and toxic side effects at high systemic exposure and graft rejection at low exposure emphasize the need for busulfan dose optimization using targeted dose adjustment prior to HSCT. We report here a rapid and sensitive method to quantitate busulfan plasma levels in patients receiving busulfan as part of pre-transplant conditioning.
Methods:
The method involves simple protein precipitation of the plasma followed by analysis using a high performance liquid chromatography (HPLC) with tandem mass spectrometry - electrospray ionization technique (LC-ESI MS/MS) in positive ionization mode and quantified using multiple reaction monitoring (MRM). Deuterated busulfan (d
8
-busulf`an) was used as the internal standard.
Results:
The method was linear for the concentration ranging from 0 to 4000 ng/ml of busulfan with a limit of detection of 2 ng/ml and limit of quantitation of 5 ng/ml. The assay was accurate for serial concentrations of Bu in plasma for five consecutive days and the CV was less than 10 per cent.
Conclusion:
Using this rapid and sensitive method, busulfan levels were targeted and subsequent doses adjusted at our center in 26 patients receiving high dose busulfan in combination with cyclophosphamide or fludarabine.
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COMMENTARY
Making a case for universal Hib immunization in India: over interpreting the data
JM Puliyel
April 2013, 137(4):639-641
PMID
:23703331
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1,096
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ORIGINAL ARTICLES
Relationship between VKORC1 single nucleotide polymorphism 1173C>T, bone mineral density & carotid intima-media thickness
Daniela Fodor, Cosmina Bondor, Adriana Albu, Radu Popp, Ioan Victor Pop, Laura Poanta
April 2013, 137(4):734-741
PMID
:23703341
Background & objectives:
The effects of vitamin K-dependent proteins in bone mineralization and vascular calcification and the implication of vitamin K epoxide reductase gene (VKORC1) 1173C>T polymorphism in warfarin sensitivity are well known. The main objective of the study was to investigate the relationship between
VKORC1
1173C>T polymorphism, bone mineral density (BMD), and atherosclerosis (evaluated by intima-media thickness of the carotid artery and the presence of calcified plaques) in patients suspected to have osteoporosis or osteopenia and referred for BMD determination.
Methods:
VKORC1
1173C>T polymorphism was evaluated in 239 consecutive patients referred by their physicians for BMD measurement (dual energy X-ray absorptiometry at L2-L4 lumbar spine, femoral neck and total hip). Ultrasonography of the carotid arteries was performed, intima-media thickness (IMT) was measured and the presence of atherosclerotic calcified plaques was recorded.
Results:
In the patients with osteoporosis and osteopenia there was a higher frequency of TT genotype of
VKORC1
1173C>T (
P
=0.04). The TT genotype was significantly more frequent in the osteoporotic group compared to the osteopenic group (
P
=0.01). The mean age and body mass index were lower in the patients with normal BMD and TT genotype (
P
=0.02,
P
=0.03). There was no correlation between the IMT and
VKORC1
1173C>T genotype but the TT genotype had a significant association with the presence of calcified atherosclerotic plaques (
P
=0.05). This finding was not correlated with normal or pathologic BMD.
Interpretation & conclusions:
VKORC1
1173C>T polymorphism (TT genotype) was associated with osteoporosis and calcified plaques in the carotid artery in patients referred for BMD measurement. Different mechanisms are probably involved in these associations. TT genotype may serve as a potential genetic marker for the risk of OP and ATS.
[ABSTRACT]
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[PubMed]
859
352
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Human rights approach to maternal & child health: Has India fared well?
F Ram, Abhishek Singh, Usha Ram
April 2013, 137(4):721-727
PMID
:23703339
Background & objectives:
The objectives of the study were to examine: right to access maternal health; right to access child health; and right to access improved water and sanitation in India.
Methods:
We used large-scale data sets like District Level Household Survey conducted in 2007-08 and National Family Health Surveys conducted during 1992-93, 1998-99, and 2005-06 to fulfil the objectives. The selection of the indicator variables was guided by the
Human Rights'
Framework for Health
and
Convention of the Rights of the Child- Articles 7, 24 and 27
. We used univariate and bivariate analysis along with ratio of access among non-poor to access among poor to fulfil the objectives.
Results:
Evidence clearly suggested gross violation of human rights starting from the birth of an individual. Even after 60 years of independence, significant proportions of women and children do not have access to basic services like improved drinking water and sanitation.
Interpretation & conclusions:
There were enormous socio-economic and residence related inequalities in maternal and child health indicators included in the study. These inequalities were mostly to the disadvantage of the poor. The fulfilment of the basic human rights of women and children is likely to pay dividends in many other domains related to overall population and health in India.
[ABSTRACT]
[FULL TEXT]
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[EPub]
[PubMed]
895
270
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Correlation between reactive oxygen metabolites & atherosclerotic risk factors in patients with type 2 diabetes mellitus
Kazuhiko Kotani, Kokoro Tsuzaki, Tsuzaki Taniguchi, Naoki Sakane
April 2013, 137(4):742-748
PMID
:23703342
Background & objectives:
Oxidative stress plays important roles in the pathophysiology of type 2 diabetes mellitus (T2DM). The diacron reactive oxygen metabolites (d-ROMs) test has been used in the clinics. The present study was aimed to investigate the correlation of the oxidative stress status, as evaluated by the d-ROMs, with atherosclerotic risk factors in T2DM patients, in comparison to controls.
Methods:
The study included 200 subjects (100 patients with T2DM and 100 controls; 86 males/114 females; mean age 59.0 yr). Clinical variables including the body mass index, blood pressure (BP), glucose and lipid panels, in addition to the d-ROMs, were measured.
Results:
Patients with T2DM showed significantly higher d-ROMs levels than controls (322 ± 60
vs
. 345 ± 64 U. Carr.,
P
<0.05). A multiple linear regression analysis revealed that systolic BP (
β
=0.26,
P
<0.05) and high-density lipoprotein cholesterol (HDL-C:
β
= -0.30,
P
<0.05) were independently and significantly correlated with the d-ROMs levels in patients with T2DM, although these correlations were not significant in the controls. The gender-based analysis showed that systolic BP (
β
= 0.44,
P
<0.05) and HDL-C (
β
= -0.36,
P
<0.05) were independently and significantly correlated with the d-ROMs levels in females with T2DM, while there was a marginally significant correlation between HDL-C and the d-ROMs levels (
β
= -0.36,
P
=0.06) in males with T2DM.
Interpretation & conclusions:
The present findings may reinforce the importance of BP control in female patients with T2DM, as well as the management of HDL-C in male and female patients with T2DM, under the linkage between oxidative stress and atherosclerosis.
[ABSTRACT]
[FULL TEXT]
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[EPub]
[PubMed]
816
320
-
CORRESPONDENCES
Initial experience with real time endobronchial ultrasound guided transbronchial needle aspiration from a tertiary care hospital in north India
Arjun Srinivasan, Ritesh Agarwal, Nalini Gupta, Ashutosh N Aggarwal, Dheeraj Gupta
April 2013, 137(4):803-807
PMID
:23703351
[FULL TEXT]
[PDF]
[Mobile Full text]
[EPub]
[PubMed]
876
250
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BOOK REVIEWS
Hemodialysis: New methods and future technology
SK Agarwal
April 2013, 137(4):819-819
[FULL TEXT]
[PDF]
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[EPub]
766
246
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ORIGINAL ARTICLES
Expression of γH2AX may help in defining a genetically more stable subtype of infiltrating ductal carcinoma of breast
Alka Bhatia, Pranab Dey, Shubham Goel, Gurpreet Singh
April 2013, 137(4):759-766
PMID
:23703345
Background & objectives:
Gamma H2AX, a marker of DNA double stranded breaks (DSB) has been found to be over expressed in various tumours. The objective of the present work was to study the expression of γH2AX in infiltrating ductal carcinoma (IDC) and fibroadenoma (FA) cases and to associate the expression in IDC with cytomorphological features and DNA ploidy.
Methods:
The expression of γH2AX was studied in fine needle aspirates of 16 cases of IDC and 15 FA cases. The expression in IDC was correlated with the cytological grade, apoptotic (AI) and mitotic indices (MI) and ploidy status.
Results:
A high γH2AX expression was noted in IDC as compared to FA. Amongst the IDC cases the γH2AX was found to be significantly over expressed in DNA diploid IDC cases as compared to the aneuploid ones.
Interpretation & conclusions:
The study suggests a role of γH2AX in breast carcinogenesis which needs to be explored further. Moreover, the γH2AX expression together with ploidy status may serve as a means of assigning the patients of IDC to a better prognostic category irrespective of the cytomorphogical parameters.
[ABSTRACT]
[FULL TEXT]
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[EPub]
[PubMed]
791
205
-
ARTICLES
Anti-inflammatory activity of curcumin analogues
T Srihari Rao, N Basu, HH Siddiqui
April 2013, 137(4):841-845
Full text not available
[PDF]
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[EPub]
637
288
-
CORRESPONDENCES
An analysis on model development for climatic factors influencing prediction of dengue incidences in urban cities
PK Kar, SK Ghosh
April 2013, 137(4):811-812
PMID
:23703353
[FULL TEXT]
[PDF]
[Mobile Full text]
[EPub]
[PubMed]
596
237
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CLINICAL IMAGES
A unique presentation of multiple myeloma in an HIV patient
Sumita Agrawal, Alaka Deshpande
April 2013, 137(4):815-816
PMID
:23703355
[FULL TEXT]
[PDF]
[Mobile Full text]
[EPub]
[PubMed]
548
210
-
CORRESPONDENCES
Management of musculoskeletal trauma & spinal injuries in disasters: stem cells vs. medical rehabilitation
Farooq A Rathore, James E Gosney
April 2013, 137(4):808-810
PMID
:23703352
[FULL TEXT]
[PDF]
[Mobile Full text]
[EPub]
[PubMed]
568
187
-
BOOK REVIEWS
WHO Expert Committee on Biological Standardization, 58
th
Report
T Jacob John
April 2013, 137(4):817-819
[FULL TEXT]
[PDF]
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[EPub]
559
144
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CORRESPONDENCES
Collecting blood just from voluntary repeated blood donors is the wisdom strategy in Vietnam
Seyed Moayed Alavian
April 2013, 137(4):813-813
PMID
:23703354
[FULL TEXT]
[PDF]
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[EPub]
[PubMed]
449
162
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ARTICLES
Re-emergence of malaria in India
VP Sharma
April 2013, 137(4):846-865
Full text not available
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376
192
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CORRESPONDENCES
Authors' response
Le Viet, Hans Husum
April 2013, 137(4):813-814
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423
122
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MOST CITED ARTICLES
Most Cited Articles
April 2013, 137(4):839-840
Full text not available
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218
147
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IJMR CLASSIC
Epidemic dropsy: Epidemiological, clinical & therapeutic observations in 67 cases
MJ Shah, KK Manghani, UK Sheth, JM Mehta, PV Karandikar
April 2013, 137(4):823-838
Full text not available
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213
146
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SOME FORTHCOMING SCIENTIFIC EVENTS
Some Forthcoming Scientific Events
April 2013, 137(4):820-820
Full text not available
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191
161
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