Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 31
Filtrar
1.
Proc Natl Acad Sci U S A ; 120(35): e2304190120, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37603742

RESUMO

Interferon-γ (IFNγ) is a critical antitumor cytokine that has varied effects on different cell types. The global effect of IFNγ in the tumor depends on which cells it acts upon and the spatial extent of its spread. Reported measurements of IFNγ spread vary dramatically in different contexts, ranging from nearest-neighbor signaling to perfusion throughout the entire tumor. Here, we apply theoretical considerations to experiments both in vitro and in vivo to study the spread of IFNγ in melanomas. We observe spatially confined niches of IFNγ signaling in 3-D mouse melanoma cultures and human tumors that generate cellular heterogeneity in gene expression and alter the susceptibility of affected cells to T cell killing. Widespread IFNγ signaling only occurs when niches overlap due to high local densities of IFNγ-producing T cells. We measured length scales of ~30 to 40 µm for IFNγ spread in B16 mouse melanoma cultures and human primary cutaneous melanoma. Our results are consistent with IFNγ spread being governed by a simple diffusion-consumption model and offer insight into how the spatial organization of T cells contributes to intratumor heterogeneity in inflammatory signaling, gene expression, and immune-mediated clearance. Solid tumors are often viewed as collections of diverse cellular "neighborhoods": Our work provides a general explanation for such nongenetic cellular variability due to confinement in the spread of immune mediators.


Assuntos
Interferon gama , Melanoma Experimental , Neoplasias Cutâneas , Animais , Humanos , Camundongos , Interferon gama/metabolismo , Melanoma Experimental/imunologia , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Transdução de Sinais , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Técnicas de Cultura de Células
2.
J Matern Fetal Neonatal Med ; 35(10): 1951-1956, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-32510260

RESUMO

OBJECTIVE: The spectrum of pregnancy tests for screening of chromosomal disorders in the unborn child includes maternal serum testing through double, triple and quadruple marker as well as the emerging cell free fetal DNA analysis based noninvasive prenatal test. The aim of this short communication is to summarize our finding's pertaining to high risk serum screening cases with reference to clinical indications and history. METHODS: Data of cases reported high-risk by serum screening including a total of 3368 women with median age of 32 years was included. Serum testing was done in the laboratory using the technology of Chemiluminescence micro particle two-step immunoassay for sensitive quantification of hormones routinely tested for in the double, triple and quadruple marker. Risk estimation using values of hormone levels and the resulting MoM was done using the PRISCA 5.0.2.37. RESULTS: A total of 16,608 samples were tested for serum screening in the study period and specific high risk analysis detected a total of 20% reported as high risk. Trisomy 21 was detected to be the most common finding at 86% followed by neural tube defects at 9%. Advanced maternal age (≥35 years) accounted for a total of 34% of the reported high risk cases. CONCLUSION: The gap between absence of a nation-wide screening mandate, and guidelines for agencies involved in prenatal screening tests can be reduced with studies which focus on trends in recommendation and developing an understanding of the clinical backdrop leading to high risk screening results.


Assuntos
Transtornos Cromossômicos , Síndrome de Down , Adulto , Biomarcadores , Transtornos Cromossômicos/diagnóstico , Feminino , Humanos , Gravidez , Diagnóstico Pré-Natal/métodos , Trissomia
3.
JMIR Form Res ; 5(2): e26130, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33459278

RESUMO

BACKGROUND: The high global prevalence of intimate partner violence (IPV) and its association with poor physical and mental health underscore the need for effective primary prevention. We previously developed Ghya Bharari Ekatra (GBE), a couples-based primary prevention intervention for IPV among newly married couples residing in slum communities in Pune, India. OBJECTIVE: Through this pilot study, we aimed to explore the acceptance, safety, feasibility, and preliminary efficacy of GBE. METHODS: Between January and May 2018, we enrolled and assigned 20 couples to receive GBE plus information on IPV support services and 20 control couples to receive information on IPV support services alone. The GBE intervention was delivered over 6 weekly sessions to groups of 3 to 5 couples by lay peer educators in the communities in which the participants resided. Intervention components addressed relationship quality, resilience, communication and conflict negotiation, self-esteem, sexual communication and sexual health knowledge, and norms around IPV. Outcome evaluation included exit interviews with participants and peers to examine acceptance and feasibility challenges and baseline and 3-month follow-up interviews to examine change in IPV reporting and mental health (by women) and alcohol misuse (by men). The process evaluation examined dose delivered, dose received, fidelity, recruitment, participation rate, and context. RESULTS: Half (40/83) of the eligible couples approached agreed to participate in the GBE intervention. Retention rates were high (17/20, 85% across all 6 sessions), feedback from exit interviews suggested the content and delivery methods were very well received, and the community was highly supportive of the intervention. The principal feasibility challenge involved recruiting men with the lowest income who were dependent on daily wages. No safety concerns were reported by female participants over the course of the intervention or at the 3-month follow-up. There were no reported physical or sexual IPV events in either group, but there were fewer incidents of psychological abuse in GBE participants (3/17, 18%) versus control participants (4/16, 25%) at 3-month follow-up. There was also significant improvement in the overall mental health of female intervention participants and declines in the control participants (change in mean General Health Questionnaire-12 score: -0.13 in intervention vs 0.13 in controls; P=.10). CONCLUSIONS: GBE has high acceptance, feasibility, and preliminary efficacy in preventing IPV and improving mental health among women. Next steps include refining the intervention content based on pilot findings and examining intervention efficacy through a large-scale randomized trial with longer follow-up. TRIAL REGISTRATION: ClinicalTrials.gov NCT03332134; https://clinicaltrials.gov/ct2/show/NCT03332134. Clinical Trials Registry of India CTRI/2018/01/011596; http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=21443. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/11533.

4.
Toxicol Ind Health ; 36(12): 1019-1023, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33200688

RESUMO

Mercury (Hg) is a toxic heavy metal, and the reported effects of exposure on liver function continue to be inconsistent. The objective of our study was to identify correlations between high blood Hg levels and liver enzymes in a pan-India population including adults ≥19 years of age. This retrospective study analyzed the data from 95,398 individuals tested for blood Hg levels and liver enzymes in our national laboratory. Testing for blood Hg was done by inductively coupled plasma-mass spectrometry, while testing for liver enzymes-aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), and gamma-glutamyl transferase-was done by automated photometry systems. Data from all the individuals inclusive of 52,497 males and 42,901 females were studied. The frequency of high blood Hg levels (>5 µg/L) was found to be 0.6%, and the difference between males and females was not found to be significant. Further correlation by linear regression analysis found no relationship between high blood Hg levels and liver enzymes among females. However, among males, there was a significant correlation between high blood Hg levels, and increased AST as well as ALT. Our report suggested that for males but not females, Hg exposure may be one of the differentials for elevated liver enzymes.


Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Mercúrio/sangue , gama-Glutamiltransferase/sangue , Adulto , Relação Dose-Resposta a Droga , Feminino , Humanos , Índia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Fatores Sexuais
5.
Afr J Paediatr Surg ; 17(1-2): 26-32, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33106450

RESUMO

AIM: To study various risk factors which leads to head injury, severity of head injury and to compare survival as predicted by the Revised Trauma Score (RTS) and Pediatric Trauma Score (PTS) in pediatric patients admitted in a tertiary care hospital. METHODS: 300 consecutive pediatric patients below 12 years of age with head injury admitted in our institute were analysed as per a set proforma. Data pertaining to patient's demographic details, mode of injury, computed tomography (CT) findings, type of management, severity of head injury, and outcome were recorded. The results were tabulated and analyzed. RTS and PTS scores were calculated to predict the survival of an individual patient. RESULTS: The most commonly affected age group was 1-5 years. Boys outnumbered girls in the incidence. Fall was the most common injury, with road traffic accident being the most common cause of mortality. Skull fracture was the most common CT scan finding. Most of the patients presented with mild head injury (Glasgow Coma Scale 13-15), and they improved with conservative management only. RTS and PTS scores were calculated and were equally effective in predicting the outcome for a particular patient. CONCLUSION: Head injury occurs more commonly in 1-5 years' age group due to fall from unprotected roof tops. The overall prognosis in majority of the cases is excellent. However, road traffic accident shows the highest mortality and hence, we propose to include mode of injury as a variable for designing future predictive outcome models.


Assuntos
Acidentes por Quedas , Traumatismos Craniocerebrais/epidemiologia , Criança , Pré-Escolar , Traumatismos Craniocerebrais/diagnóstico , Feminino , Escala de Coma de Glasgow , Humanos , Incidência , Índia/epidemiologia , Lactente , Recém-Nascido , Masculino , Prognóstico , Fatores de Risco , Tomografia Computadorizada por Raios X
6.
BMJ Case Rep ; 12(11)2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31704802

RESUMO

A 14-year-old boy presented with a painful swelling topped by a bruise overlying the skin of the right inguinal region without peritonitis. This was the area of impact of bicycle handlebar while riding 6 days ago. On contrast-enhanced CT scan, we found a traumatic abdominal wall hernia (handlebar hernia) near the right deep ring without any solid organ, bowel or urinary bladder injury. Inguinal exploration revealed a defect in transversus abdominis and internal oblique muscle which was repaired and meshplasty was done.Delayed presentation and ignorance towards 'handlebar sign' is associated with visceral injury (haematoma/perforation) will incur the risk of rising morbidity and mortality. With CT scan we can assess the abdominal cavity to rule out associated visceral or vascular injury. Surgical repair for restoring disrupted anatomy with or without meshplasty is the preferred approach.


Assuntos
Traumatismos Abdominais/diagnóstico por imagem , Traumatismos Abdominais/cirurgia , Ciclismo/lesões , Contusões/etiologia , Equimose/etiologia , Hérnia Abdominal/diagnóstico por imagem , Hérnia Abdominal/cirurgia , Adolescente , Humanos , Masculino , Telas Cirúrgicas , Tomografia Computadorizada por Raios X
7.
Niger J Surg ; 25(1): 36-41, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31007510

RESUMO

BACKGROUND: The aim of this study is to compare fast-track methodology with traditional methods of surgical care in achieving better patient outcome, and ensuring a timely discharge from the hospital, and also note the factors that are responsible for a delayed discharge from the hospital. MATERIALS AND METHODS: One hundred patients undergoing elective surgeries were randomly allocated into fast-track and traditional protocol of perioperative care. Patients who underwent fast-track protocol (FTP) were started on early oral feeding and were encouraged for early discharge, while the others were made to follow the traditional method of recovery. The gastrointestinal functions, postoperative complications and hospital stay time were recorded. The results were tabulated and analyzed. RESULTS: Early feeding was well tolerated by all the patients in the "fast track" group, while the patients in the control group had increased number of "nil by mouth" days, and this result was statistically significant. Ambulation was started earlier in the case group as compared to the controls, and the mean period of starting of ambulation was statistically significant, in the cases as compared to the controls. The patients in the case group had an earlier discharge from the hospital, as compared to the control group. The most common reason for a delay in discharge from the hospital, in either group, was seen to be inadequate pain relief postoperatively. CONCLUSION: The FTP can significantly shorten the postoperative hospital stay after elective surgery, as compared to the traditional protocol.

8.
Mol Clin Oncol ; 10(4): 469-475, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30931120

RESUMO

Lung cancer, one of the most frequently diagnosed cancers worldwide has long relied on testing for the molecular biomarkers EGFR/ALK. However, achieving superior clinical outcomes for patients with lung cancer requires developing comprehensive techniques beyond contemporary EGFR/ALK testing. Current technologies are on par with molecular testing for EGFR/ALK in terms of efficacy, most of them failing to offer improvements perhaps primarily due to skepticism among clinicians, despite being recommended in the NCCN guidelines. The present study endeavored to minimize chemotherapy-dependence in EGFR/ALK-negative patient cohorts, and use evidence-based methods to identify ways to improve clinical outcomes. In total, 137 lung cancer cases obtained from 'PositiveSelect NGS data', comprising 91 males and 46 females, were investigated. EGFR- and ALK-positivity was used for data dichotomization to understand the therapeutic utility of rare gene alterations beyond just EGFR/ALK. Statistics obtained from PositiveSelect were collated with data from international studies to construct a meta-analysis intended to achieve better clinical outcomes. Upon dichotomization, 23% of cases harbored EGFR variants indicating that treating with EGFR TKIs would be beneficial; the remaining 77% exhibited no EGFR variants that would indicate favorable results using specific currently available chemotherapy practices. Similarly, 28% of cases had EGFR+ALK variants favoring EGFR/ALK-based targeted therapeutics; the remaining 72% harbored no EGFR/ALK variants with known beneficial chemotherapy routes. The present study aimed to overcome current inadequacies of targeted therapies in patients with a conventional EGFR/ALK-positive diagnosis and those in EGFR+ALK-negative cohorts. Upon analysis of the negative cohorts, significant and clinically relevant single nucleotide variants were identified in KRAS, ERBB2, MET and RET, with frequencies of 7, 1, 2 and 3% in patients who were EGFR-negative and 6, 1, 1, and 3% in patients who were EGFR and ALK-negative, respectively, enabling the use of targeted therapeutics aside from EGFR/ALK TKIs. From the results of the current study only 35% of the two negative arms (EGFR negative and EGFR+ALK negative) would be recommended NCCN or off-label chemotherapy; prior to the current study, the entire cohorts would have been recommended this treatment. The present study emphasizes the potential of comprehensive genomics in identifying hallmarks of lung cancer beyond EGFR/ALK, using broad-spectrum genetic testing and data-sharing among medical professionals to circumvent ineffective chemotherapy.

9.
JMIR Res Protoc ; 8(1): e11533, 2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30664483

RESUMO

BACKGROUND: Intimate partner violence (IPV) is frequently experienced by women of low socioeconomic status in India. It is a human rights violation and associated with negative effects on physical and mental well-being, underscoring the need for effective prevention strategies. OBJECTIVE: This study aimed to develop a dyadic intervention for the primary prevention of IPV among newly married couples residing in slum communities in India. METHODS: The intervention was developed using a community-based, mixed-methods design rooted in couple-interdependence theory and guided by the intervention mapping (IM) framework. It used the six critical IM steps to inform the content and delivery of the intervention: (1) needs assessment, (2) preparation of matrices of change objectives, (3) selection of theory-based methods and practical applications, (4) production of intervention components and materials, (5) intervention adoption and implementation, and (6) evaluation planning. RESULTS: The resulting Ghya Bharari Ekatra (Take a Flight Together) intervention is intended to be delivered in 6 weekly sessions by a trained pair of male and female lay community educators to groups of 3 to 5 newly married couples in the community in which they reside. It uses games, discussions, self-reflections, and skill-building exercises to cover the following topics: enhancing relationship quality time, self-esteem and resilience, communication and conflict management, goal setting and implementation, sexual communication and sexual health and reproductive health knowledge, and redefining and challenging norms surrounding IPV occurrence. The formative work guided the protocol, including module duration and timing (2-hour sessions of convenience to participants), ordering of modules (based on potential level of interest and sensitivity of the topics), content (ie, informed scripts of role plays and films), intervention delivery methods (ie, interactive activities), and selection of the interventionists (based on capacity to connect with participants) and venue (community-based, convenient, and safe spaces). Ghya Bharari Ekatra was piloted between January and May 2018, and evaluation is presently underway. CONCLUSIONS: Ghya Bharari Ekatra is evidence-based, grounded in intervention-mapping, and developed and iteratively refined using a community-based participatory research approach, suggesting it has great potential to be an acceptable and effective solution to preventing IPV among newly married couples. TRIAL REGISTRATION: ClinicalTrials.gov NCT03332134; https://clinicaltrials.gov/ct2/show/NCT03332134.

10.
Clin Chim Acta ; 487: 309-310, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30326216

RESUMO

OBJECTIVES: Selenium is a very important micronutrient. Food is the major source for selenium uptake and the average blood levels is seen to be highly affected by dietary habits as selenium levels in food naturally depend on the kind of soil they are grown upon and in processed foods its levels depend on fortification. Deficiency of this vital nutriment needs to be assessed to understand deficiency prevalence. DESIGN AND METHODS: A total number of 529,461 subjects were tested for their blood selenium levels. The study cohort consisted of 284,189 males and 245,272 females respectively. Average blood selenium levels have been analyzed across both the genders using the analytical platform of Inductively Coupled Plasma - Mass Spectrometry. RESULTS: For borderline low analysis of selenium, values of

Assuntos
Selênio/sangue , Estudos de Coortes , Feminino , Humanos , Índia , Masculino , Espectrometria de Massas
11.
PLoS One ; 13(5): e0197303, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29771949

RESUMO

Domestic violence (DV) is prevalent in low-income and slum-dwelling communities in India. To date, the focus of DV prevention in resource-poor settings has largely been with women. We herein aim to identify correlates of DV perpetration to help inform future primary prevention efforts that focus on behavioral change in men. Utilizing a cross-sectional design, potential correlates of DV perpetration were explored among a geographically-clustered random sample of 100 recently-married men residing in slums in Pune, India. In multivariable regression, DV perpetration was associated with less time spent alone in the relationship post-marriage (standardized ß = -0.230, p<0.01), not attaining the "husband ideal" (standardized ß = -0.201, p<0.05), poor resilience (standardized ß = -0.304, p < .01), having limited definitions of behaviors constituting DV (standardized ß = -0.217, p<0.05), and reporting greater jealousy if the participant's spouse were to talk to men outside the family (standardized ß = 0.272, p<0.01). The identified correlates should inform components of future DV primary prevention interventions that target men as potential perpetrators or the couple as a unit.


Assuntos
Violência Doméstica , Adulto , Estudos Transversais , Violência Doméstica/psicologia , Humanos , Índia/epidemiologia , Ciúme , Masculino , Casamento/psicologia , Pobreza , Resiliência Psicológica , Fatores de Risco , Fatores de Tempo , População Urbana
12.
PLoS One ; 13(4): e0195152, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29608581

RESUMO

The high risk of experiencing domestic violence (DV) among married women in India who reside in slum communities underscores the need for effective, evidence-based, and culturally-tailored primary prevention. To inform such DV primary prevention strategies for this population, we herein aimed to identify correlates of DV experience in early marriage. Utilizing a cross-sectional design, potential correlates of DV experience were explored among a geographically-clustered random sample of 100 recently-married women residing in slums in Pune, India. In multivariable regression, DV experience was associated with less educational attainment by the participant's spouse (standardized ß = -0.281, p = 0.004), less satisfaction of the spouse's family with the maanpaan (wedding-related gifts provided by the bride's family) they received at the time of marriage (standardized ß = -0.298, p<0.001), poorer conflict negotiation skills (standardized ß = -0.308, p<0.001), and greater acknowledgement of DV occurrence in family and friends (standardized ß = 0.436, p<0.001). These correlates suggest strategies that could be incorporated into future DV primary prevention interventions for this vulnerable population (i.e. promoting completion of formal education of boys alongside girls, mitigating causes of familial dowry harassment, improving conflict negotiation skills, and challenging norms surrounding DV).


Assuntos
Violência Doméstica/estatística & dados numéricos , Maus-Tratos Conjugais/estatística & dados numéricos , Adolescente , Adulto , Feminino , Humanos , Índia/epidemiologia , Masculino , Fatores de Risco , Adulto Jovem
13.
J Clin Diagn Res ; 11(3): PD02-PD03, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28511444

RESUMO

Pseudoangiomatous Stromal Hyperplasia (PASH) of the breast is a rare benign proliferating breast condition. We report a case of a 26-year-old female who was being worked up for infertility and was incidentally noted to have a well defined lump in the left breast. Fine Needle Aspiration Cytology (FNAC) and core needle biopsy of the lump were suggestive of benign breast disease. Patient underwent excision of the lump. Histopathology report of which was suggestive of PASH of the breast.

14.
Clin Chim Acta ; 455: 99-101, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26851649

RESUMO

INTRODUCTION: Arsenic, a well-known toxic element, has become one of the biggest causes for clinical concerns among elemental toxicities. Arsenicosis has been reported from many regions of the country, especially on exposure induced by ground water contamination. The clinical effects of chronic arsenic toxicity are generally varied and its timely diagnosis and management pose a big challenge. METHODOLOGY: Our study reports analysis of blood arsenic levels in a pan-India cohort of 205,530 including 111,737 males and 93,793 females respectively. The cohort included all age groups from infants to old adults. Arsenic levels were analyzed using the analytical platform of ICP-MS touted to be the gold standard for elemental analysis. RESULT: Blood arsenic levels of ≥5 µg/L were considered high in our study. The total frequency of high arsenic cases detected in the study is 1.37%. The frequency in males was 1.47% and in females it was detected to be 1.25%. Also, maximum cases of high arsenic levels were detected to be from the state of Kerala and in cities from Mumbai. CONCLUSION: Very few studies have recorded the frequency of high arsenic levels in Indians as well as its average blood levels in a pan-India cohort. Our study has made a pilot attempt to highlight the same to generate awareness about this elemental menace in the Indian context.


Assuntos
Intoxicação por Arsênico/epidemiologia , Arsênio/sangue , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Humanos , Índia/epidemiologia , Lactente , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
15.
Clin Chim Acta ; 451(Pt B): 161-4, 2015 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-26409784

RESUMO

INTRODUCTION: Elements form a basic and natural constituent of the Earth's crust and are released into the atmosphere due to many human activities like mining and manufacturing. Of all, the elements, lead toxicity is a prevailing as well as a growing concern the world over because of its ability to affect multiple clinical functions. METHODOLOGY: Blood lead levels have been analyzed in a large pan-India cohort of 222,668 comprising of 121,115 males and 101,553 females respectively. The cohort included all age groups from <2 to >55 years old. The analytical platform of Inductively Coupled Plasma-Mass Spectrometry has been used to assess lead levels. RESULT: Blood lead levels of ≥150 µg/L was considered high for analysis. The total frequency of high lead levels detected in our study was 1.16%. The frequency of males affected were higher than females, with the difference being statistically significant.. CONCLUSION: Lead being ubiquitous in its presence and also serving no biological function, has grown today to become a serious threat to human health. The high frequency of affected detected in our study raises a cause for concern. Determining its presence and the most affected geography in any country will aid in charting guidelines on controlling its release as well as exposure.


Assuntos
Intoxicação por Chumbo/diagnóstico , Intoxicação por Chumbo/epidemiologia , Chumbo/sangue , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Índia/epidemiologia , Lactente , Chumbo/efeitos adversos , Intoxicação por Chumbo/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
16.
Clin Chim Acta ; 444: 229-33, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25721910

RESUMO

OBJECTIVES: Variations in hemoglobin structure as well as number of globin chains give rise to a wide spectrum of heritable disorders. As such, their detection is significant from epidemiological perspective, especially in India in which there is a large multi-cultural population with distinct geographic distribution. Although a few variants present severe clinical symptoms in homozygotes, co-existence of heterozygous mutants can lead to deleterious conditions. The aim of the present study is to provide an overview on the prevalence of different hemoglobinopathies among Asian Indians. DESIGN AND METHODS: A large cohort of samples from all regions of India was analyzed by high performance liquid chromatography (HPLC) (n=25,297) and capillary electrophoresis (CE) (n=21,219). RESULTS: Using HPLC, 8029 hemoglobin variants were detected. HbS trait was detected at the highest frequency (33.03%), principally from the Chattisgarh region. Using CE, 6524 variants were detected. HbS trait, again, represented the most common mutation (25.67%). A total of 40 variants including compound heterozygous cases were detected by HPLC and CE. CONCLUSIONS: Our report is one of the few to analyze a large cohort and report on the spectrum of hemoglobin variants in India.


Assuntos
Hemoglobinopatias/epidemiologia , Hemoglobinopatias/genética , Hemoglobinas/genética , Cromatografia Líquida de Alta Pressão , Estudos de Coortes , Eletroforese Capilar , Variação Genética/genética , Humanos , Índia/epidemiologia
17.
Ann Hum Biol ; 42(1): 97-100, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25117664

RESUMO

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) encoded by DPYD gene is the major enzyme involved in metabolism of 5-flurouracil (5-FU), a pyrimidine analogue used in cancer chemotherapy. Although very effective as a cancer therapeutic drug, if not rapidly metabolized, 5-FU may prove lethal. Single nucleotide variants (SNVs) within DPYD that modulate DPD enzyme activity contribute to 5-FU toxicity. STUDY: This study looked for DPYD SNVs common in the Indian population that might be associated with variable DPD activity and drug toxicity. To achieve this, sequencing analysis was performed of all 23 exons and flanking intronic regions of the DPYD gene in a cohort of 50 healthy adult Indians. This study detected 22 SNVs including intronic, synonymous and non-synonymous changes in the DPYD gene, of which six have not been documented before. Allelic frequency was calculated for the observed variants and linkage disequilibrium (LD) analysis was performed on variants with frequency ≥0.1 to identify haplotypes. CONCLUSIONS: This study provides a brief overview of the genetic polymorphism in DPYD in Indians and emphasizes the need for a large scale extensive study to establish markers associated with the frequently observed variable drug metabolism.


Assuntos
Di-Hidrouracila Desidrogenase (NADP)/genética , Fluoruracila/metabolismo , Adulto , Sequência de Bases , Feminino , Fluoruracila/toxicidade , Frequência do Gene , Humanos , Inativação Metabólica , Índia , Masculino , Polimorfismo Genético , Análise de Sequência de DNA , População Branca/genética
18.
Minim Invasive Surg ; 2014: 654607, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24693423

RESUMO

Background. Gastroesophageal reflux disease currently accounts for the majority of esophageal pathologies. This study is an attempt to help us tackle the diagnostic and therapeutic challenges of this disease. This study specifically focuses on patients in the urban Indian setup. Materials and Methods. This study was a prospective interventional study carried out at a teaching public hospital in Mumbai from May 2010 to September 2012. Fifty patients diagnosed with gastroesophageal reflux disease (confirmed by endoscopy and esophageal manometry) were chosen for the study. Results. Fifty patients were included in the study. Twenty patients showed symptomatic improvement after three months and were thus managed conservatively, while 30 patients did not show any improvement in symptoms and were eventually operated. Conclusion. We suggest that all patients diagnosed to have gastroesophageal reflux disease should be subjected to 3 months of conservative management. In case of no relief of symptoms, patients need to be subjected to surgery. Laparoscopic Toupet's fundoplication is an effective and feasible surgical treatment option for such patients, associated with minimal side effects. However, the long-term effects of this form of treatment still need to be evaluated further with a larger sample size and a longer followup.

19.
Eye Contact Lens ; 39(6): 410-2, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24045832

RESUMO

PURPOSE: To describe a patient with Exophiala jeanselmei keratitis and to review the prior cases reported in the literature. METHODS: We report one patient with keratitis after remote injury and chronic steroid use and review the six prior reported cases. RESULTS: Culture plates from corneal scraping revealed growth of the dematiaceous fungi, E. jeanselmei, a rare causative organism of ocular infection. The patient underwent therapy with topical and intracameral antifungals and subsequently required a corneal transplant. Biopsy of the donor graft confirmed the diagnosis of E. jeanselmei. This is the first reported case to use intracameral antifungal agents and the first biopsy proven case. Half of reported cases experienced associated trauma, and severity was generally related to delay in diagnosis. CONCLUSIONS: Trauma and chronic topical steroid use contributed to the development of severe keratitis in this patient. Patients on chronic steroids should be monitored closely. Topical, subconjunctival, and intracameral antifungals have all been effective in treating this pathogen. If diagnosed and treated early, E. jeanselmei keratitis can have a good visual outcome.


Assuntos
Exophiala/isolamento & purificação , Infecções Oculares Fúngicas/microbiologia , Ceratite/microbiologia , Adulto , Lesões da Córnea , Corpos Estranhos no Olho/complicações , Humanos , Masculino
20.
Gene ; 524(1): 35-9, 2013 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-23612254

RESUMO

Cytidine deaminase (CDA) is the major enzyme involved in metabolism of gemcitabine, a pyrimidine analog widely used for chemotherapy of solid tumors. While only low amounts of administered gemcitabine undergo intracellular phosphorylation into active forms and involve in antineoplastic activities, majority of it is rapidly inactivated by CDA and excreted to avoid drug toxicity. Knowledge of the genetic polymorphisms mildly effecting cellular activity of the enzyme CDA is therefore crucial to understanding drug-induced toxicities associated with gemcitabine. Functional significance and allele frequencies for common SNPs including 79A>C (*2) and 208G>A (*3) have been reported in various ethnic populations including Caucasian, African, Korean and Japanese. However, such studies have not been reported in any Indian sub-population. In the present study, conventional polymerase chain reaction (PCR) based amplification using gene specific primers and Sanger sequencing were performed to identify CDA variants in 50 healthy individuals from Indian sub-population. Established common variant 79A>C known to reduce CDA activity was observed at a frequency of 0.14 in the study cohort. In addition to other known variants, one novel variant, c.325-209T>C was detected at a frequency of 0.06. Genetic variants in CDA gene and their frequencies established in our study hold value in pharmacogenetics.


Assuntos
Povo Asiático/genética , Citidina Desaminase/genética , Etnicidade/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Coortes , Análise Mutacional de DNA , Ativação Enzimática , Frequência do Gene , Marcadores Genéticos , Genética Populacional , Humanos , Índia , Íntrons , Neoplasias/enzimologia , Neoplasias/genética , Projetos Piloto , Reação em Cadeia da Polimerase
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...