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Randeep Guleria

Publications and source records attributed to Randeep Guleria.

At least 19 recordsLinked to original sources
PubMed2023

Phylogeny and evolution of SARS-CoV-2 during Delta and Omicron variant waves in India.

SARS-CoV-2 evolution has continued to generate variants, responsible for new pandemic waves locally and globally. Varying disease presentation and severity has been ascribed to inherent variant characteristics and vaccine immunity. This study analyzed genomic data from 305 whole genome sequences from SARS-CoV-2 patients before and through the third wave in India. Delta variant was reported in patients without comorbidity (97%), while Omicron BA.2 was reported in patients with comorbidity (77%). Tissue adaptation studies brought forth higher propensity of Omicron variants to bronchial tissue than lung, contrary to observation in Delta variants from Delhi. Study of codon usage pattern distinguished the prevalent variants, clustering them separately, Omicron BA.2 isolated in February grouped away from December strains, and all BA.2 after December acquired a new mutation S959P in ORF1b (44.3% of BA.2 in the study) indicating ongoing evolution. Loss of critical spike mutations in Omicron BA.2 and gain of immune evasion mutations including G142D, reported in Delta but absent in BA.1, and S371F instead of S371L in BA.1 could explain very brief period of BA.1 in December 2021, followed by complete replacement by BA.2. Higher propensity of Omicron variants to bronchial tissue, probably ensured increased transmission while Omicron BA.2 became the prevalent variant possibly due to evolutionary trade-off. Virus evolution continues to shape the epidemic and its culmination.Communicated by Ramaswamy H. Sarma.

SARS-CoV-2↗
PubMed2006

A comparative study between preoperative and postoperative pulmonary functions and diaphragmatic movements in congenital craniovertebral junction anomalies.

Respiratory dysfunctions in patients with craniovertebral junction (CVJ) anomalies may occur due to compression of brainstem affecting the respiratory centers, and weakening of the muscles of respiration. We assessed pulmonary functions [forced vital capacity (FVC), forced expiratory volume in first second (FEV1), maximum mid-expiratory flow rate (FEF25%-75%), FEV1%], mouth pressures (maximum inspiratory pressure, maximum expiratory pressure), and diaphragmatic movements in 30 patients of CVJ anomalies and compared them with their mean predictive values. These parameters were also assessed in the postoperative period. It was found that the mean values of FVC, FEV1, and FEF25%-75% were significantly lower (P<0.001) than their mean predictive values (2.4+/-0.8 L, 2.0+/-0.7 L, 2.5+/-0.9 L vs. 3.7+/-0.9 L, 3.2+/-0.7 L, and 3.4+/-0.7 L, respectively). In the postoperative period there was significant reduction (P<0.05) in all these parameters (2.2+/-0.8 L, 1.7+/-0.7 L, and 2.1+/-0.8 L, respectively). The postoperative FEV1% was 78.8% compared with the preoperative value of 85.7%. A restrictive pattern of lung disease was observed which persisted in the postoperative period. The postoperative maximum inspiratory pressure and maximum expiratory pressure were comparable to their preoperative values (47.9+/-19.6 and 47.0+/-16.7 cmH2O vs. 42.6+/-17.3 and 43.9+/-18.2 cmH2O, respectively). Similarly, the diaphragmatic movements were also comparable to the preoperative values, both during quiet and deep breathing (13.7+/-3.9 and 38.0+/-9.3 mm vs. 13.8+/-3.9 and 39.0+/-9.1 mm, respectively). There was no improvement of pulmonary functions in the early postoperative period. However, a long-term follow-up is needed to determine subsequent changes of these parameters.

Adult↗
PubMed2006

Circulating cell-free DNA in plasma/serum of lung cancer patients as a potential screening and prognostic tool.

BACKGROUND: Evaluation of tumor-specific circulating DNA in plasma/serum is a promising noninvasive diagnostic and prognostic tool requiring only a blood sample, which circumvents the logistic difficulties associated with the use of invasive procedures for serial tumor samplings during screening of lung cancer. METHODS: We reviewed English-language reports published in the MEDLINE database that provided the results of qualitative and quantitative studies on circulating DNA in serum/plasma of lung cancer patients. We searched the bibliographies of the retrieved reports and reviews. Abstracts presented at the 2003, 2004, and 2005 annual meetings of the American Society of Clinical Oncology were also reviewed. RESULTS: More than 80 citations were retrieved, of which 33 met our criteria: 22 qualitative studies, and 11 quantitative studies. The studies varied in the choice of markers, frequency of alterations, sensitivities of used methodologies, sample sizes, treatment protocols, and prognostic correlates evaluated. CONCLUSIONS: The findings from the studies on serum/plasma DNA suggest that it would be possible to develop a simple blood test with high sensitivity and specificity that has potential for screening of high-risk individuals, for prognostic or staging purposes, and to be used as intermediate end-points of efficacy in chemo-prevention and therapeutic trials. However, further work is needed to identify additional biomarkers and to standardize present techniques for sample collection, processing, and analysis. Large prospective studies with long follow-ups are essential to eventually integrate blood marker-based assays into the clinical setting.

Biomarkers, Tumor↗
PubMed2006

Pharmacogenomics of beta2-agonist: key focus on signaling pathways.

Asthma is one of the most common respiratory diseases, where inhalation and exhalation are obstructed due to narrowing of the airways by broncho-constriction or by inflammation. Among all the available anti-asthma therapies, beta2-agonists are the most effective bronchodilators available, and give rapid relief of asthma symptoms. Evidence suggests that the degree of beta2-agonist response varies greatly between patients and genetic factors have a major role in it. Despite several studies on the beta2-agonist pharmacogenetics, significant gaps in knowledge still remain and need to be resolved before the pharmacotyping of beta2-agonist responsiveness comes to clinical practice. As we know, beta2-agonists show their influence by targeting beta2-adrenergic receptors, leading to the activation of beta2-adrenergic receptors and its downstream cascade. Signaling through beta2-adrenergic receptors mediates numerous airway functions by regulating broncho-constriction and dilation pathways. Therefore, it is an important prerequisite to understand these pathways, which will assist in defining the variability in therapeutic responses for beta2-agonists. Owing to the complexity of the action of a beta2-agonist and its therapeutic response, a broader genomics approach will help in optimizing therapy for the individual patient. This might be achieved by considering and focusing on receptor/s at which the drug binds directly, signal transduction cascades or downstream proteins and proteins involved in the relaxation and constriction of the airway smooth muscle. Considering that a drug response may involve a large number of proteins, it seems unlikely that a single polymorphism or haplotype in a single gene would explain a high degree of drug response variability in a consistent fashion. Thus, it shows that a polygenic approach will be more appropriate. In order to follow this, the mode of action of the beta2-agonist and its downstream signaling cascade should essentially be assessed to resolve the beta2-agonist enigma.

Adrenergic beta-Agonists↗
PubMed2005

Mycoplasma pneumoniae and central nervous system complications: a review.

Mycoplasma pneumoniae is a common cause of community-acquired pneumonia. Little is known about the extrapulmonary manifestations of this organism. Numerous central nervous system (CNS) manifestations have been described with M. pneumoniae. CNS involvement is probably the most common site of involvement in addition to the respiratory system. Up to 7% of patients hospitalized with M. pneumoniae may have CNS symptoms. Common CNS presentations include encephalitis, aseptic meningitis, polyradiculitis, cerebellar ataxia, and myelitis. The mechanism behind these CNS manifestations remains unclear. Direct invasion, neurotoxin production, or an immune-mediated mechanism has been proposed. Newer diagnostic techniques for the direct detection of the antigen and the microorganism are proving useful for the detection of extrapulmonary disease. This review comprehensively reviews the CNS complications that have been reported with M. pneumoniae.

Anti-Bacterial Agents↗
PubMed2005

Chemotherapy alone vs. chemotherapy plus high dose multiple antioxidants in patients with advanced non small cell lung cancer.

OBJECTIVE: In vitro and animal studies suggest that antitumor effect of chemotherapeutic agents may be enhanced by antioxidants. Therefore, we initiated a clinical study to test the efficacy of high-dose multiple antioxidants (vitamins C, E and beta carotene) as an adjunct to chemotherapy (paclitaxel and carboplatin) in non-small-cell lung cancer. METHODS: 136 patients of stage IIIb and stage IV NSCLC were randomized to receive chemotherapy (paclitaxel and carboplatin) alone (chemotherapy arm, n = 72) or chemotherapy in combination with ascorbic acid 6100 mg/day, dl-alpha-tocopherol (vitamin E) 1050 mg/day and beta-carotene 60 mg/day (combination arm, n = 64). Survival were calculated by the Kaplan-Meier method and compared using the log-rank test. RESULTS: An overall response rate (RR) of 33% was observed in chemotherapy arm with 24 patients showing a partial response (PR) and none showing a complete response (CR). In combination arm the overall RR was 37% with 24 patients showing PR and two showing CR. The median survival times in chemotherapy arm and combination arm were nine and 11 months respectively. The overall survival (OS) rates in chemotherapy arm and combination arm at one year were 32.9% and 39.1%, and at two years, 11.1% and 15.6% respectively. None of these differences were statistically significant (p = 0.20). Toxicity profiles were similar in both arms. CONCLUSIONS: These results do not support the concern that antioxidants might protect cancer cells from the free radical damage induced by chemotherapy. Larger trials are needed to demonstrate whether high-dose multiple antioxidants in conjunction with chemotherapy increase the response rates and/or survival time in advanced lung cancer.

Adult↗
PubMed2005

Invasive tracheobronchial aspergillosis in an immunocompetent person.

Tracheobronchial involvement is an uncommon form of invasive pulmonary aspergillosis and is found mainly in immunocompromised individuals such as patients with leukemia and prolonged granulocytopenia due to cytotoxic therapy, organ transplant recipients receiving high-dose corticosteroids, or patients with chronic granulomatous diseases. Rarely, such a pattern can also be seen in immunocompetent persons or can involve atypical sites such as the paranasal sinuses, skin, and the tracheobronchial tree. Occasionally, these patients require a prolonged course of antifungal agents. We report a case of aspergillosis involving the tracheobronchial tree in an immunocompetent young male that presented a diagnostic dilemma.

Adult↗
PubMed2005

Beta(2)-adrenergic receptor polymorphisms and response to salbutamol among Indian asthmatics*.

INTRODUCTION: The beta(2)-adrenergic receptor (beta(2)AR or ADRbeta(2)) is the target for beta(2)-agonist drugs used for bronchodilation in asthma and other respiratory diseases. The aim of this study was to identify common single nucleotide polymorphisms (SNPs) and haplotypes in asthmatics and healthy individuals from an Indian population, and determine the influence of beta(2)AR SNPs in responsiveness to beta(2)-agonist therapy in asthma patients. METHODS: Ten variable SNP sites within a span of 2.193 kb were identified in the beta(2)AR gene by sequencing and genotyping 374 bronchial asthma patients and healthy individuals from an Indian population. Spirometry tests were performed on 80 unrelated patients before and after administration of 200 microg of salbutamol. A post-bronchodilator forced expiratory volume in one second (FEV(1)) change of >or= 15.3% was considered a good response, and a change of<15.3% was defined as a poor response, to salbutamol. RESULTS: The pattern of linkage disequilibrium between the ten SNPs showed a single, linked SNP block consisting of sites -468, -367, -47, -20, and 79 having strong linkage disequilibrium, while the SNPs at sites -1023, -654, 46, 252, and 523 showed very low linkage with one another and with the linked region. The SNPs were found to be organized into 16 haplotypes in the studied population. We found that patients with a homozygous Arg-16 form at nucleotide position 46 are poor responders with probability of 0.81, and patients with a homozygous Gly-16 form are good responders with a probability of 0.73. The responder status to salbutamol treatment and the genotype at nucleotide position 46 in beta(2)AR gene of an asthmatic patient are significantly associated in the studied Indian population (chi2=9.98, df=2, p=0.0068). Most importantly, this association for responsiveness to salbutamol at nucleotide position 46 is independent of other SNPs in the beta(2)AR gene. CONCLUSION: This study suggests that the SNP at nucleotide position 46 has particular relevance to pharmacogenetics in the Indian population studied.

5' Untranslated Regions↗
PubMed2005

beta2-Adrenergic receptor polymorphisms and asthma in the North Indian population.

INTRODUCTION: The beta(2)-adrenergic receptor (ADRB2) polymorphisms are known to be functionally relevant and disease modifying in subjects with asthma. However, the association of these polymorphisms with asthma remains to be established. Our objective is to investigate the association of the ADRB2 polymorphisms and haplotypes with asthma in North Indian subjects. METHODS: A subset of 101 unrelated cases and 55 unrelated unaffected individuals were used for a case-control disease-association test. RESULTS: Ten variable single nucleotide polymorphism (SNP) sites within a span of 2.193 kb were identified in the ADRB2 gene by the sequencing and genotyping of 351 bronchial asthma patients and healthy individuals. The distributions of genotype and allele frequencies for individual SNPs in the ADRB2 gene and ADRB2 haplotype frequencies were estimated in unrelated asthmatics and healthy individuals. No significant association was observed between ADRB2 genotypes and alleles with disease status after Bonferroni correction for multiple testing (reference p value = 0.0083). However, haplotype GGCTTTGCAA was found to be significantly associated with asthma (p = 0.021) in the studied population. CONCLUSION: Our results suggest that there is likely to be a functional significance of the ADRB2 gene with asthma.

5' Untranslated Regions↗
PubMed2003

Correlations of C-reactive protein levels with anthropometric profile, percentage of body fat and lipids in healthy adolescents and young adults in urban North India.

OBJECTIVE: To investigate the relationships of sub-clinical inflammation and regional and generalized obesity and lipids in adolescent and young adult Asian Indians in north India. METHODS: We determined serum levels of C-reactive protein (CRP), a marker for sub-clinical inflammation, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (W-HR), four skinfolds (biceps, triceps, subscapular and suprailiac), percentage of body fat (% BF) and lipid profile in 377 healthy adolescents and young adults (331 males and 46 females, age range: 14-25 years). RESULTS: Overweight subjects (BMI>85th percentile), and subjects with high values (>85th percentile) of WC and triceps skinfold thickness had significantly higher median CRP levels (P=0.04, P=0.001 and P=0.007, respectively) as compared with subjects with lower values of the variables. Elevated levels of CRP (>2.1 mg/l) were observed in 21.8% of the overweight subjects and 24.5% of the subjects with high (>85th percentile) % BF. After adjusting for age and gender, the odds ratios (95% CI) for elevated levels of CRP were 2.3 (1.1-4.7, P=0.02) for overweight subjects, 2.6 (1.2-5.4, P=0.01) for subjects with high % BF, and 3.7 (1.7-7.9, P=0.001) for subjects with high triceps skinfold thickness. Levels of CRP correlated significantly with % BF (r=0.13, P=0.009), W-HR (r=0.11, P=0.02), biceps skinfolds (r=0.13, P=0.01) and triceps skinfolds (r=0.13, P=0.01) for males only. CONCLUSIONS: The observations of substantial prevalence of elevated CRP levels in adolescents and young adults having increased generalized and abdominal adiposity may be important for the development of metabolic syndrome and atherosclerosis in Asian Indian adults.

Adipose Tissue↗
PubMed2002

Hyperhomocysteinemia, and low intakes of folic acid and vitamin B12 in urban North India.

BACKGROUND AND AIM: An adverse coronary risk profile has been reported amongst rural-to-urban migrant population living in urban slums undergoing stressful socio-economic transition. These individuals are likely to have low intakes of folic acid and vitamin B12, which may have an adverse impact on serum levels of homocysteine (Hcy). To test this hypothesis, we studied serum levels of Hcy in subjects living in an urban slum of North India and healthy subjects from urban nonslum area. METHODS: Group I consisted of 46 subjects (22 males and 24 females) living in an urban slum, while group II consisted of healthy subjects (n = 26, 13 males and 13 females) living in the adjacent non-slum area. Anthropometric measurements, biochemical profile (fasting blood glucose, total cholesterol, serum triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) and fasting serum levels of Hcy were measured. Dietary intakes of folic acid, vitamin B12, vitamin B1, and iron were calculated by the 24-hour dietary recall method. Serum levels of Hcy were correlated with dietary intakes of nutrients, anthropometry, and metabolic variables. RESULTS: Sex-adjusted serum levels of Hcy in micromol/L (Mean +/- SD) were high, though statistically comparable, in both the groups (group I: 20.8 +/- 5.9 and group II: 23.2 +/- 5.9). Overall, higher than normal serum levels of Hcy (> 15 micromol/L) were recorded in 84% of the subjects. A substantial proportion of subjects in both groups had daily nutrient intakes below that recommended for the Asian Indian population (folic acid: 93.4% in group I and 96.7% in group II, vitamin B12: 76.1 % in group I and 88.4% in group II). However, between the two groups, average daily dietary intakes of both the nutrients were statistically comparable. As compared to non-vegetarians, vegetarians showed lower intakes of folic acid (p < 0.01) and vitamin B12 (p < 0.01) in both groups. On multivariate linear regression analysis with serum Hcy as the response variable and vegetarian/non-vegetarian status and sex (male/female) as predictor variables, higher serum levels of Hcy were observed in vegetarians vs non-vegetarians (1 = 4.6, p < 0.05) and males vs females (beta = 5.3, p < 0.01). CONCLUSIONS: Low intakes of folic acid and vitamin B12, and hyperhomocysteinemia, in both the healthy population living in urban slums and adjacent urban non-slum areas, are important observations for the prevention of nutritional and cardiovascular diseases in the Indian subcontinent.

Adult↗
PubMed2002

Telomerase--a potential molecular marker of lung and cervical cancer.

Telomerase, a ribonucleoprotein enzyme that adds hexameric TTAGGG nucleotide repeats onto telomeres is reactivated in most malignancies. Lung cancer is a common malignant disease worldwide as well as in India. Most patients present in advanced stages. As noninvasive diagnostic techniques are preferred, we assayed the telomerase activity in pre-bronchoscopy sputum and compared it with that of bronchial washings and bronchoscopic biopsies by telomeric repeat amplification protocol (TRAP) in 53 cases of lung cancer. These were corroborated with cytopathological/histopathological examinations. Telomerase activity was detected in 58.5% of sputum samples, 70% of bronchial washings and 74% of bronchoscopic biopsies thereby making it a good noninvasive diagnostic marker of lung cancer. Cervical cancer is the 7th most common cancer worldwide, with 100,000 new cases being reported annually in India. It is routinely screened by Papanicolaou's (Pap) smear. Human papilloma virus (HPV) is one of its etiological agents. We have assayed telomerase activity in relation to HPV-16/18 in cervical samples from 93 subjects ranging from normal to precancerous to frank cancers in tissue biopsies and cervical scrapings. HPV infection was detected by polymerase chain reaction (PCR) in 81% of tumor samples, in 6% of control hysterectomy samples and in 2% of cervical scrapings of normal healthy controls with HPV-16 being the predominant type. Telomerase activity was detected in 96.5% of cervical tumor samples, in 68.7% of premalignant cervical scrapings but was not detected in control hysterectomy samples, or in cervical scrapings of normal healthy controls. There was 71% correlation between telomerase activity and HPV-16/18 infection.

Adult↗
PubMed2002

Prevalence of diaphragmatic muscle weakness and dyspnoea in Graves' disease and their reversibility with carbimazole therapy.

OBJECTIVES: Dyspnoea is a common complaint among patients with thyrotoxicosis. However, its causative mechanisms have not been identified. We assessed the role of thoracic diaphragmatic muscle weakness in dyspnoea among patients with active Graves' disease. METHODS: Twenty-seven patients (19 female, 8 male) with active Graves' disease were assessed for the clinical severity of dyspnoea, functional (pressure generating capacity) and anatomical aspects (thickness and excursion) of the diaphragm at presentation. The severity of dyspnoea was assessed using a visual analogue scale (VAS) and the 6 min walk test. Lung function tests, diaphragmatic strength (sniff oesophageal pressure, SniffP(oeso)), maximum inspiratory and expiratory pressures, diaphragmatic thickness and movements on real time ultrasonography were evaluated during normal and deep respiration. Twenty of the 27 patients were reassessed after achieving euthyroidism with carbimazole therapy at a mean interval of 5+/-2 months. RESULTS: Reevaluation after carbimazole therapy revealed a significant reduction in dyspnoea on the VAS (59+/-26 to 23+/-13%). Patients covered a similar distance during the 6 min walk before and after euthyroidism. Significant improvement was observed in the vital capacity (2.57+/-0.62 to 2.94+/-0.60 l), forced expiratory volume in the first second (2.21+/-0.49 to 2.45+/-0.47 l), total lung capacity (3.57+/-1.19 to 4.1+/-1.12 l), diaphragmatic movement during deep respiration (5.5+/-1.0 to 6.6+/-1.1 cm) and SniffP(oeso) (68.7+/-23 to 93.1+/-25.2 cmH(2)O). There was no significant change in the distance walked in 6 min, tidal volume, lung diffusion capacity and diaphragmatic thickness. There was no significant correlation between the net change in dyspnoea score and net change in lung function tests, diaphragmatic movement and SniffP(oeso). CONCLUSIONS: Significant functional weakness of diaphragm muscle is present in patients with active Graves' disease. This weakness is more marked during a maximal respiratory manoeuvre, indicating a diminished diaphragmatic reserve which could be the cause of dyspnoea observed on exertion among patients with thyrotoxicosis.

Adult↗
PubMedDate not supplied

Quality of life measures in lung cancer.

Lung cancer is one of the leading causes of cancer death worldwide. Survival has not improved significantly in spite of newer therapies. In view of the high-symptom burden and severe morbidity, evaluation of quality of life (QOL) becomes important in these patients. Several instruments are now available for this purpose, and have demonstrated good correlation with performance status, symptoms, and survival. Quality of life assessments also help in comparing different therapeutic regimes, thus allowing selection of the appropriate modality. Problems of inconsistent interpretability and high-patient dropout rate poses a challenging problem that needs to be tackled. In spite of these drawbacks, QOL is now considered to be an essential component of lung cancer management and should be performed routinely. Such a practice will help the physician plan appropriate treatment strategies and set practical therapeutic goals.

Attitude to Health↗