Publications by authors named "Girish Chandra"

44 Publications

Longitudinally centered embossed structure in the locking compression plate for biodegradable bone implant plate: a finite element analysis.

Comput Methods Biomech Biomed Engin 2021 Sep 6:1-16. Epub 2021 Sep 6.

Department of Mechanical Engineering, Maulana Azad National Institute of Technology, Bhopal, Madhya Pradesh, India.

In the current revolution of internal fixation implant in orthopaedics, a biodegradable implant is the most awaited and exceptional medical device where biodegradable material has paid more attention to the success of a biodegradable implant than the design of a biodegradable bone implant plate. By far, LCP is the most traditionally used implant plate (using non-biodegradable material) because of its experimental success, but not with qualified biodegradable material (Mg-alloy). This lack of mechanical performance is a major drawback that can be rectified by better structural design. This will help avoid few other problems as well. Therefore, with proper consideration, the LCP has been added to a semicircular filleted longitudinally centered embossed (LCE) structure to enhance overall mechanical performance that can help emphasize mechanical support even after continuous degradation when applied in a physiological environment. For mechanical verification of this advanced design of biodegradable bone implant plate, four-point bending test (4PBT) and axial compression test (ACT) have been performed using FEM on LCELCP, LCP, continuously degraded (CD)-LCELCP, and CD-LCP. LCELCP showed reduced stress of about 22% and 10% in 4PBT and ACT, respectively, compared to LCP. CD-LCELCP is safe during ACT over 6 months of continuous degradation when the degradation rate is assumed to be 4 mm/year. These results also ensured accuracy using mesh convergence and also mesh checked for quality assurance. Overall, LCELCP can be considered as a biodegradable bone implant plate because of its superior performance, if its ultimate validation is carried out through animal/human trials as future work.
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http://dx.doi.org/10.1080/10255842.2021.1970145DOI Listing
September 2021

Design approaches and challenges for biodegradable bone implants: a review.

Expert Rev Med Devices 2021 Jul 14;18(7):629-647. Epub 2021 Jun 14.

Department of Mechanical Engineering, Maulana Azad National Institute of Technology, Bhopal, Madhya Pradesh, India.

: Biodegradable materials have been at the forefront of cutting-edge research and offer a truly viable option in the designing and manufacturing of bone implants in biomedical engineering. Most research regarding these materials has focused on their biological characteristics and mechanical behavior vis-à-vis nonbiodegradable (NB) materials; but the design aspects and parametric configurations of biodegradable bone implant have somehow not received as much attention as they deserved.: This review aims to develop insight into the parametrically conceptualized design of biodegradable bone implant and takes into due consideration the characteristics of bone-biodegradable implant interface (BBII), design techniques employed for conventionally used bone implants to optimize parameters using standard test methods, traditional design, and finite element analysis approaches for implant and healing behavior, manufacturing techniques, real-time surgical simulations, and so on.: Some successful and conventionally used NB bone implants do not dissolve or degrade with time and require removal through a complicated surgery after fulfilling the intended objectives. These bone implants should be reconceptualized and designed with an appropriate biodegradable material while paying due attention to all factors/parameters involved and striking a balance between these factors with the ultimate objective of fulfilling all desired orthopedic requirements.
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http://dx.doi.org/10.1080/17434440.2021.1935875DOI Listing
July 2021

Design and analysis of biodegradable buttress threaded screws for fracture fixation in orthopedics: a finite element analysis.

Biomed Phys Eng Express 2021 May 26;7(4). Epub 2021 May 26.

Department of Mechanical Engineering, Maulana Azad National Institute of Technology, Bhopal-462003, India.

Screws made up of non-biodegradable materials (Ti-alloy, etc.) have been used since long for temporary joining/fixation in applications involving skeleton damage or bone fracture. These screws need to be removed after complete healing as their sustained presence results in many complications, such as - micro-fracturing, stress shielding, etc. The removal of these screws is a little difficult too as it may result in the healed bone getting broken/damaged again. These problems can be overcome by employing metallic implants (plate, screws, etc.) made up of biodegradable metallic materials (Mg-alloy, etc.). Such implants exhibit optimal mechanical performance, are biocompatible, have adequate biodegradation rates, and rely on a unique design. Internal fracture fixation makes usage of screws with or without an accompanying plate. Buttress-threaded screws are the most frequently used ones. These screws must have the capacity to bear usually occurring loads and hold fractured segments of bone all through the process of healing. Finite element analysis (FEA) is an effective technique used for testing and validation of desired characteristics for Mg-based biodegradable buttress-threaded screw (BBTS). The characteristics of interest include maximum possible pullout resistance to tightly hold segments of bone, torsional ability for tightening or tapping, bending ability during providing plate support by screw head, and resistance to combined loading (tensile/compressive and bending) during the self-support stage using merely the screw(s). According to test results and subsequent validation through discretization error and convergence plot, BBTS made up of Mg-alloy are found safe for regular applications under usually encountered impact loads. Topological optimization and vibration analysis are also performed wherein it is observed that design of BBTS is good enough for possible usage in fracture fixation in orthopaedics.
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http://dx.doi.org/10.1088/2057-1976/ac00d1DOI Listing
May 2021

Cure lies in nature: medicinal plants and endophytic fungi in curbing cancer.

3 Biotech 2021 Jun 12;11(6):263. Epub 2021 May 12.

School of Applied Sciences, Suresh Gyan Vihar University, Jaipur, Rajasthan 302017 India.

Success of targeted cancer treatment modalities has generated an ambience of plausible cure for cancer. However, cancer remains to be the major cause of mortality across the globe. The emergence of chemoresistance, relapse after treatment and associated adverse effects has posed challenges to the present therapeutic regimes. Thus, investigating new therapeutic agents of natural origin and delineating the underlying mechanism of action is necessary. Since ages and still in continuum, the phytochemicals have been the prime source of identifying bioactive agents against cancer. They have been exploited for isolating targeted specific compounds to modulate the key regulating signaling pathways of cancer pathogenesis and progression. Capsaicin (alkaloid compound in chilli), catechin, epicatechin, epigallocatechin and epigallocatechin-3-gallate (phytochemicals in green tea), lutein (carotenoid found in yellow fruits), Garcinol (phenolic compound present in kokum tree) and many other naturally available compounds are also very valuable to develop the drugs to treat the cancer. An alternate repository of similar chemical diversity exists in the form of endophytic fungi inhabiting the medicinal plants. There is a high diversity of plant associated endophytic fungi in nature which are potent producers of anti-cancer compounds and offers even stronger hope for the discovery of an efficient anti-cancer drug. These fungi provide various bioactive molecules, such as terpenoids, flavonoids, alkaloids, phenolic compounds, quinines, steroids etc. exhibiting anti-cancerous property. The review discusses the relevance of phytochemicals in chemoprevention and as modulators of miRNA. The perspective advocates the imperative role of anti-cancerous secondary metabolites containing repository of endophytic fungi, as an alternative route of drug discovery.
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http://dx.doi.org/10.1007/s13205-021-02803-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116431PMC
June 2021

-adenosyl-L-homocysteine Hydrolase: Its Inhibitory Activity Against and Development of Malaria Drugs.

Mini Rev Med Chem 2021 ;21(7):833-846

Department of Bioinformatics, School of Earth, Biological and Environmental Science, Central University of South Bihar, Gaya, Bihar, India.

Parasite Plasmodium falciparum is continuously giving a challenge to human beings by changing itself against most of the antimalarial drugs and its consequences can be seen in the form of a huge number of deaths each year especially in the poor and developing country. Due to its drug resistance ability, new drugs are regularly needed to kill the organism. Many new drugs have been developed based on different mechanisms. One of the potential mechanisms is to hamper protein synthesis by blocking the gene expression. S-Adenosyl-L-homocysteine (SAH) hydrolase is a NAD+ dependent tetrameric enzyme, which is responsible for the reversible hydrolysis of AdoHcy to adenosine and L-homocysteine, has been recognized as a new target for antimalarial agents since the parasite has a specific SAH hydrolase. The inhibition of SAH hydrolase causes the intracellular accumulation of S-Adenosyl-L-homocysteine, elevating the ratio of SAH to S-adenosylmethionine (SAM) and inhibiting SAM-dependent methyltransferase that catalyzes methylation of the capped structure at the 5'-terminus of mRNA, and other methylation reaction which is essential for parasite proliferation. In other words, S-Adenosyl-Lhomocysteine hydrolase regulates methyltransferase reactions. In this way, SAH hydrolase inhibitors can be used for the treatment of different diseases like malaria, cancer, viral infection, etc. by ultimately stopping the synthesis of protein. Many antiviral drugs have been synthesized and marketed which are based on the inhibition of SAH hydrolase. This review summarises the development of SAH inhibitors developed over the last 20 years and their potentiality for the treatment of malaria.
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http://dx.doi.org/10.2174/1389557521666201218155321DOI Listing
August 2021

Design of a biodegradable plate for femoral shaft fracture fixation.

Med Eng Phys 2020 07 17;81:86-96. Epub 2020 May 17.

Department of Mechanical Engineering, Maulana Azad National Institute of Technology, Bhopal 462003, Madhya Pradesh, India.

Biodegradable materials have been generating increasing bit of interest in biomedical applications and associated research. The evolution of implants made up of such materials (Mg-alloys, etc.) has the potential to be a game changer in fracture surgeries. These implants are essentially made up of a plate and a number of screws. In orthopaedic applications, they offer the biggest advantage of complete degradation after successfully supporting the fractured bone for the desired period. They may provide some nutrients that accelerate the healing process while simultaneously ensuring adequate mechanical stability. This article essentially focuses on design of a biodegradable implant plate for femoral shaft fracture, taking into consideration the dimensional accuracy of the plate, uniform biodegradation rate and adequate mechanical stability of the plate across the entire process span. The design of a biodegradable implant plate and associated specified screws that support the plate, fitted over two segments for fixation of femoral shaft fracture, has been made on the basis of femur's standard dimensions, optimized plate dimensions and uniform biodegradation rate. A confirmation regarding the safe design of the implant plate is obtained through computational structural analysis. The implant plate design turns out to be safe at specific optimized dimensions for a human being weighing 80 Kg, at corresponding loading and boundary conditions. For average monthly degradation of the plate across a period of six months, the factor of safety comes out to be more than unity. The implant plate eventually goes through complete degradation 3-6 months after the completion of the healing process and this is where the plate thickness plays a significant role.
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http://dx.doi.org/10.1016/j.medengphy.2020.05.010DOI Listing
July 2020

Fatal ruptured ectopic pregnancy - a case report.

Med Leg J 2019 Mar 29;87(1):38-41. Epub 2018 Nov 29.

Department of Forensic Medicine, M.S. Ramaiah Medical College, Bangalore, India.

A 26-year-old unmarried female with a history of acute abdominal pain and bleeding per vagina was brought unresponsive to the hospital. She was in shock on arrival and could not be resuscitated. Death was registered as a medico-legal case. Further investigation by the police revealed that she had amenorrhoea for eight weeks and had tested positive for pregnancy. She had consumed abortion pills purchased from a local pharmacist without consulting a doctor and had developed acute abdominal pain after 48 h. Autopsy revealed a ruptured ectopic pregnancy (tubal type).
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http://dx.doi.org/10.1177/0025817218795337DOI Listing
March 2019

Design, synthesis and anticancer activity of fluorocyclopentenyl-purines and - pyrimidines.

Eur J Med Chem 2018 Jul 5;155:406-417. Epub 2018 Jun 5.

Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 151-742, South Korea. Electronic address:

Based on the potent anticancer activity of 6'-fluorocyclopentenyl-cytosine 2b in phase IIa clinical trials for the treatment of gemcitabine-resistant pancreatic cancer, we carried out a systematic structure-activity relationship study of 6'-fluorocyclopentenyl-pyrimidines 3a-i and -purines 3j-o to discover novel anticancer agents. We also synthesized the phosphoramidate prodrug 3p of adenine derivative 1b to determine if the anticancer activity depended on the inhibition of DNA and/or RNA polymerase in cancer cells and/or on the inhibition of S-adenosylhomocysteine (SAH) hydrolase. All of the synthesized pyrimidine nucleosides exhibited much less potent anticancer activity in vitro than the cytosine derivative 2b, acting as RNA and/or DNA polymerase inhibitor, indicating that they could not be efficiently converted to their triphosphates for anticancer activity. Among all the synthesized purine nucleosides, adenine derivative 1b and N-methyladenine derivative 3k showed potent anticancer activity, showing equipotent inhibitory activity as the positive control, neplanocin A (1a) or Ara-C. However, the phosphoramidate prodrug 3p showed less anticancer activity than 1b, indicating that it did not act as a RNA and/or DNA polymerase inhibitor like 2b. This result also demonstrates that the anticancer activity of 1b largely depends on the inhibition of histone methyltransferase, resulting from strong inhibition of SAH hydrolase. The deamination of the N-amino group, the addition of the bulky alkyl group at the N-amino group, or the introduction of the amino group at the C2 position almost abolished the anticancer activity.
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http://dx.doi.org/10.1016/j.ejmech.2018.06.003DOI Listing
July 2018

Association of -330 interleukin-2 gene polymorphism with oral cancer.

Indian J Med Res 2017 Dec;146(6):730-737

Department of Anaesthesiology, King George's Medical University, Lucknow, India.

Background & Objectives: Cytokines play an important role in the development of cancer. Several single-nucleotide polymorphisms (SNPs) of cytokine genes have been reported to be associated with the development and severity of inflammatory diseases and cancer predisposition. This study was undertaken to evaluate a possible association of interleukin 2 (IL-2) (- 330A>C) gene polymorphisms with the susceptibility to oral cancer.

Methods: The SNP in IL-2 (-330A>C) gene was genotyped in 300 oral cancer patients and in similar number of healthy volunteers by polymerase chain reaction (PCR)-restriction fragment length polymorphism and the association of the gene with the disease was evaluated.

Results: IL-2 (-330A>C) gene polymorphism was significantly associated with oral cancer whereas it was neither associated with clinicopathological status nor with cancer pain. The AC heterozygous genotype was significantly associated with oral cancer patients as compared to controls [odds ratio (OR): 3.0; confidence interval (CI): 2.14-4.20; P<0.001]. The C allele frequency was also significantly associated with oral cancer (OR: 1.80; CI: 1.39-2.33; P<0.001). IL-2 (-330A>C) gene polymorphism was also associated with oral cancer in tobacco smokers and chewers.

Interpretation & Conclusions: Our results showed that oral cancer patients had significantly higher frequency of AA genotype but significantly lower frequency of AC genotype and C allele compared to controls. The IL-2 AC genotype and C allele of IL-2 (-330A>C) gene polymorphisms could be potential protective factors and might reduce the risk of oral cancer in Indian population.
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http://dx.doi.org/10.4103/ijmr.IJMR_1949_15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926344PMC
December 2017

Silence of male child sexual abuse in India: Qualitative analysis of barriers for seeking psychiatric help in a multidisciplinary unit in a general hospital.

Indian J Psychiatry 2017 Apr-Jun;59(2):202-207

Department of Psychiatry, JSS Medical College, Mysore, Karnataka, India.

Introduction: In 2007, Ministry of Women and Child Welfare, supported by United Nations Children's Fund, save the children and Prayas conducted a study to understand the magnitude of child abuse in India, they found that 53.22% children faced one or more forms of sexual abuse; among them, the number of boys abused was 52.94%.

Aim: The aim of this study was to explore the barriers for seeking psychiatric help by qualitative analysis of stake holders of male victims of child abuse.

Materials And Methods: All the statements made by the stakeholders regarding psychiatric assessment and treatment were recorded in each referral made to the psychiatrist. Semistructured interviews and in-depth interviews were conducted to explore the topic of understanding the need for psychiatric treatment to the victims.

Results: Collaborative child response unit, a multidisciplinary team, to tackle child sexual abuse in a general hospital received three referrals of male child abuse among the 27 referrals in 20 months. The main theme of the barrier that was generated by interviewing the stakeholders of male child victims of abuse was the misconception of superiority of a male victim due to gender (patriarchy) an expectation that he will outgrow the experience. In-depth interviews of three cases of homosexual abuse explored the theme.

Conclusion: Patriarchy is oppressing male children and acts as a barrier to seek psychiatric help in collaborative child response unit.
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http://dx.doi.org/10.4103/psychiatry.IndianJPsychiatry_195_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547862PMC
August 2017

Dexmedetomidine as an Anesthetic Adjuvant in Intracranial Surgery.

Anesth Essays Res 2017 Apr-Jun;11(2):309-313

Department of Anaesthesia, Mayo Institute of Medical Sciences, Barabanki, Uttar Pradesh, India.

Background: The basic principle of neuroanesthesia is to provide hemodynamic stability, provision of optimal operative conditions, maintenance of cerebral perfusion pressure, and cerebral oxygenation.

Aim: This study was undertaken to see the effect of dexmedetomidine infusion on hemodynamics and its ability to act as an anesthetic adjuvant in patients undergoing supratentorial tumor surgery.

Setting And Design: Prospective randomized control double blind study.

Subjects And Methods: In this study, we compared two groups with 25 patients in each group. Group C patients received saline infusion during surgery and 4 μg/kg of fentanyl intravenously (i.v.) at the induction and at pin head application. Group D patients received dexmedetomidine infusion during surgery at the rate of 0.4 μg/kg/h and 2 μg/kg of fentanyl i.v. at the induction and at pin head application.

Statistical Analyses Used: Parametric data were analyzed using Student's -test. The categorical data were studied using Chi-squared test or Fisher's test as appropriate.

Results: The vitals remained within 20% of baseline in both groups during the study period except at the time of extubation where the rise in heart rate was more than 20% in control group. The requirement of thiopentone for induction was significantly less in dexmedetomidine group. In dexmedetomidine group, less number of patients required intraoperative fentanyl ( < 0.05), and the time to rescue analgesic was also more in Group D ( < 0.05).

Conclusion: Dexmedetomidine infusion started before surgery maintains hemodynamic stability intraoperatively and is effective in attenuating the cardiovascular responses to intubation, skull pin application, and extubation. It decreases the requirement of other anesthetic agents as well.
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http://dx.doi.org/10.4103/0259-1162.194555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490096PMC
July 2017

Evaluation of Fastrach Laryngeal Mask Airway as an Alternative to Fiberoptic Bronchoscope to Manage Difficult Airway: A Comparative Study.

J Clin Diagn Res 2017 Jan 1;11(1):UC09-UC12. Epub 2017 Jan 1.

Professor, Department of Anaesthesiology, King George's Medical University , Lucknow, Uttar Pradesh, India .

Introduction: Awake intubation via Fiberoptic Bronchoscope (FB) is the gold standard for management of difficult airway but patients had to face problems like oxygen desaturation, tachycardia, hypertension and anxiety due to awake state. This study was conducted to assess feasibility of Fastrach Laryngeal Mask Airway (FLMA) to manage difficult airway as a conduit for intubation as well as for ventilation.

Materials And Methods: After ethical approval and informed consent, 60 patients with difficult airway were randomly enrolled in FB group and FLMA group. In FB group, patients were sedated with midazolam/fentanyl. Airway anaesthetization of oropharynx was done with xylocaine spray and viscous and larynx and trachea by superior laryngeal nerve block and transtracheal block respectively. In FLMA group, initially patients were induced with propofol for FLMA insertion then succinylcholine was given for Tracheal Intubation (TI). The first TI attempt was done blindly via the FLMA and all subsequent attempts were performed with fiberoptic guidance. Haemodynamic monitoring was done during induction, intubation, immediately post insertion and there after at five minutes interval for 30 minutes.

Results: All patients in the FLMA group were successfully ventilated (100%). In both the groups 28 (93.33%) patients were successfully intubated. However, first/second/third attempt intubation rate in FLMA vs FB group was 15 (50%) vs 13 (43.3%), 8 (26.66%) vs 10 (33.33%) and 5 (16.66%) in both groups respectively. Patients in the FLMA group were more satisfied with their method of TI and had lesser complications (p<0.05).

Conclusion: So the FLMA may be a better technique for management of patients with difficult airways.
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http://dx.doi.org/10.7860/JCDR/2017/22001.9284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324468PMC
January 2017

Barriers and Challenges in Seeking Psychiatric Intervention in a General Hospital, by the Collaborative Child Response Unit, (A Multidisciplinary Team Approach to Handling Child Abuse) A Qualitative Analysis.

Indian J Psychol Med 2017 Jan-Feb;39(1):12-20

Department of Forensic Medicine, MSR Medical College, Bengaluru, Karnataka, India.

Child abuse is a serious criminal act against children in our country and punishable according to protection of children from sexual offenses act 2012. No one agency has the ability to respond completely to the abuse. Hence a multidisciplinary team approach was developed in India. Aim is to narrate the collaborative effort among the multiple disciplines in a general hospital to deliver child protection services and explore the barriers to integrate psychiatric services.

Methodology: Members of the team were recruited from different disciplines and trained by experts. A mission statement, protocol to assess the victims and provide treatment was formulated as an algorithm. The barriers to psychiatric treatment among the stakeholders were analyzed using framework method of qualitative analysis. Results (After 20 months) the unit received 27 referrals in 20 months, 24 females, and 3 males. Age of the victims was between 8 months and 17 years. Two cases found to be physically abused. Penetrative sexual abuse was found in 23 cases, pregnant victims were 4. Most referrals were by police, trafficking found in 6 cases.

Discussion: It was possible to provide multidisciplinary care to the victims and families. Recurrent themes of barriers to psychiatric treatment were stigma, victim blaming; focus on termination of pregnancy, minimization of abuse in males by stakeholders. Conclusion is collaboration needs more effort to integrate psychiatric services but can minimize the reduplication of services.
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http://dx.doi.org/10.4103/0253-7176.198957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5329985PMC
March 2017

Sudden death due to aortic dissection in early pregnancy - a case report.

Med Leg J 2017 Sep 16;85(3):162-164. Epub 2017 Feb 16.

Department of Forensic Medicine, MS Ramaiah Medical College, Bangalore, India.

Forensic pathologists come across many deaths due to natural causes which are sudden. Sudden natural deaths in females who are pregnant warrant thorough investigation and a medico-legal autopsy to rule out any foul play. Here, we report a case of 21-year-old primigravida in her first trimester who suddenly complained of severe chest pain and was brought dead to the hospital with no history suggestive of prior natural disease. At autopsy, the death was attributed to dissection of ascending aorta.
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http://dx.doi.org/10.1177/0025817217694108DOI Listing
September 2017

Genetic polymorphism of interleukin-10 (-A592C) among oral cancer with squamous cell carcinoma.

Arch Oral Biol 2017 May 7;77:18-22. Epub 2017 Jan 7.

Department of Anaesthesiology, King George Medical University, UP, Lucknow, India. Electronic address:

Objective: Interleukin-10 (IL-10) is a pleiotropic cytokine with either immunosuppressive or immunostimulative activities. It has been reported that in cancer, the promoter region polymorphism of IL-10 (-A592C) alters both the expression and serum levels of this cytokine. In the present study, we have addressed the question as to whether the single nucleotide polymorphisms (SNPs) at positions -592 A/C in the IL-10 gene promoter, could predispose an individual to oral squamous cell carcinoma (OSCC).

Design: We analyzed the genotype of the IL-10 (-A592C) gene, in 250 histopathologically confirmed OSCC patients and similar number of healthy volunteers taken as controls, in an Indian population by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Allele and genotype frequencies were analyzed by the Student's t-test and the chi-squared test, and strength of associations by the odds ratio (OR) with 95% confidence intervals.

Results: The genotype and allele distribution of IL-10 (-A592C) gene polymorphism was significantly different between OSCC cases and controls (genotype AA vs AC: OR 2.87; 95 % CI 1.50-5.48; p=0.0016 and AA vs CC: OR 4.08; 95 % CI 1.98-8.41; p=0.0002). The -592 C alleles were found to be significantly different among OSCC cases and controls (OR: 1.44, 95% CI: 1.12-1.85, p<0.0051).

Conclusions: The IL-10 gene promoter region (-592) A/C polymorphism is significantly associated with reduced risk of OSCC. The OSCC group had a significantly greater frequency of genotype AA as compared to control group.
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http://dx.doi.org/10.1016/j.archoralbio.2016.12.011DOI Listing
May 2017

Comparison between Thoracic Epidural Block and Thoracic Paravertebral Block for Post Thoracotomy Pain Relief.

J Clin Diagn Res 2016 Sep 1;10(9):UC08-UC12. Epub 2016 Sep 1.

Senior Resident, Department of Anaesthesiology, King George's Medical University , Lucknow, Uttar Pradesh, India .

Introduction: Postoperative pain after thoracotomy is being considered one of the most severe pain and if not treated well, can result in various respiratory and other complications.

Aim: Present study was conducted with the aim to compare continuous thoracic epidural infusion with continuous paravertebral infusion for postoperative pain using Visual Analogue Scale (VAS) score and four point observer ranking. The secondary outcomes measured were pulmonary functions and any complication like hypotension, bradycardia, nausea, vomiting, urinary retention and neurological complications if any.

Materials And Methods: Sixty patients of age group 18-60 years posted for anterolateral thoracotomy surgery for lung resection were randomised either to epidural or paravertebral group in this randomised prospective double blind study. In Epidural group 7.5ml bolus of 0.125% Bupivacaine with 50μg Fentanyl and in Paravertebral group 15ml bolus of 0.125% Bupivacaine with 50μg Fentanyl was given 30 minutes before the anticipated end of surgery. Bolus dose was followed by infusion of 0.125% Bupivacaine with 2μg/ml Fentanyl at the rate of 5 ml/hr in both groups. Parameters noted were Mean Arterial Pressure (MAP), Heart Rate (HR), Oxygen Saturation (SpO), Arterial Blood Gas (PaCO, P/F ratio), Visual Analogue Scale (VAS) and Four Point Observer Ranking Scale (FPORS) for pain, number of sensory segments blocked (by checking for pinprick sensation), requirement of infusion top ups and rescue analgesia (Tramadol), pre and postoperative pulmonary function test {(Forced Expiratory Volume (FEV), Forced Vital Capacity (FVC), FEV/FVC, Peak Expiratory Flow Rate (PEFR)} and complications from start of infusion till 24 hours in the postoperative period.

Results: Both the techniques were effective in relieving pain but pain relief was significantly better with epidural. Postoperatively, HR, SpO, P/F ratio and PaCO were comparable between group E and P. There was significant decline in FeV, FVC, FeV/FVC and PEFR in postoperative period as compared to preoperative value in both the groups. Hypotension and bradycardia were more in group E.

Conclusion: Both the techniques, continuous thoracic epidural block and continuous thoracic paravertebral block were effective for post-thoracotomy pain relief; however, epidural block provides better pain relief. The incidence of sympatholytic complications was more in epidural group. The effect on respiratory mechanics was equivalent. Hence, paravertebral block can be used in post thoracotomy pain relief in those patients where thoracic epidural is contraindicated.
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http://dx.doi.org/10.7860/JCDR/2016/19159.8489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072054PMC
September 2016

Glue sniffing.

Med Leg J 2017 Mar 30;85(1):38-42. Epub 2016 Sep 30.

Department of Forensic Medicine, M.S. Ramaiah Medical College, Bangalore, India.

Inhalant abuse refers to the inhalation of volatile substances for their euphoric effects. Glues and adhesives have been abused inhalants for decades and so the term "glue sniffing" attached to the habit. These days many substances used are not adhesives and the most accurate title of "solvent abuse" has been given to this widespread and dangerous habit. The various methods of inhalational abuse include huffing, bagging, dusting, glading, and sniffing. We report one such case of a 22-year-old male who was found in an unresponsive state at his residence with a plastic cover around his head and empty tubes of "Fevibond" glue beside him. He died on the way to hospital. At autopsy, conjunctival and visceral congestion were found with pulmonary edema and petechiae over visceral pericardium. The viscera were analyzed, and the presence of toluene in his liver and blood was reported.
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http://dx.doi.org/10.1177/0025817216671106DOI Listing
March 2017

Transdermal Buprenorphine Patches for Postoperative Pain Control in Abdominal Surgery.

J Clin Diagn Res 2016 Jun 1;10(6):UC05-8. Epub 2016 Jun 1.

Professor, Department of Anaesthesiology, King George's Medical University , U.P., Lucknow, India .

Introduction: Buprenorphine is a semi-synthetic derivative of thebaine; its low concentration is sufficient to provide effective pain relief.

Aim: To evaluate the efficacy of transdermal buprenorphine patch in postoperative pain management.

Materials And Methods: After ethical approval and taking informed consent from the patients, they were randomized into three groups (n=30 in each group) using a computer generated random number table. Group A: placebo patch; Group B: buprenorphine (10mg) patch and Group C: buprenorphine (20mg) patch. Haemodynamic and analgesic effects were compared by using analysis of variance (ANOVA) followed by Turkey's post hoc test. The proportion of side effects was compared using the Chi-square test.

Results: Haemodynamic changes were not statistically different in all the three groups A, B and C, whereas at the end of surgery VAS score of Group A subjects was significantly higher (4.93±0.98) as compared to Group B (1.73±0.64) and Group C (1.40±0.50). On 2(nd) postoperative day, no pain was reported by the Group C patients and on 4(th) day after surgery, no pain was reported by Group B patients.

Conclusion: The transdermal buprenorphine patch (20mg) was effective in attenuating postoperative pain, maintaining haemodynamic stability requiring no rescue analgesia, with fewer postoperative rescue analgesic requirements in low dose of buprenorphine patch (10mg) group.
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http://dx.doi.org/10.7860/JCDR/2016/18152.7982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963743PMC
June 2016

Establishing a deceased donor program in north Indian region: lessons learnt.

Clin Transplant 2016 May 18;30(5):633-40. Epub 2016 Apr 18.

Department of Human Organ Transplant, KGMU, Luknow, India.

Introduction: Living-related donors are the source of almost all organ transplants in India. However, these donations fall far short of current needs, and there remains a huge disparity between demand and supply of organs. In the last five yr, a consistent increase in deceased donor transplant activity has been observed in some southern Indian states. This report describes our experience of establishing a new deceased donor program in the state of Uttar Pradesh in north India.

Methods: We describe our experience on counseling families of all brain-dead patients admitted to our center from October 2013 to September 2014 and data on retrieving and transplanting organs.

Results: A total of 99 brain-dead patients were identified, of which 67 were medically eligible as donors. Fourteen patients developed cardiac arrest before the counseling could begin. Only eight families agreed for multi-organ donation.

Conclusion: Lack of consensus among the family members, mistrust of the medical system, fear of mutilation of the body, and delay in the funeral were identified as the main reasons behind negative consent. Conversely, mass media campaign, proper ICU care of brain-dead patients, rapport with the family and streamlining all medico legal processes were associated with positive consent.
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http://dx.doi.org/10.1111/ctr.12730DOI Listing
May 2016

Association of Genetic Polymorphism in the Interleukin-8 Gene with Risk of Oral Cancer and Its Correlation with Pain.

Biochem Genet 2016 Feb 10;54(1):95-106. Epub 2015 Dec 10.

Department of Biochemistry, King George's Medical University, Lucknow, UP, 226003, India.

Oral cancer is a multifactorial disease process and involves complex interactions between gene to gene and gene to environmental factors. Interleukin 8 (IL-8), a pro-inflammatory cytokine, having angiogenic activity with elevated expression in tumor cells, is reported to play an essential role in oral cancer development. This study was conducted with the aim to investigate the role of IL-8 (-A251T) gene polymorphism in susceptibility, progression, and self-reporting pain in oral cancer. The single nucleotide polymorphisms of the IL-8 (-A251T) gene were screened in 300 patients with oral cancer and 300 healthy controls, by polymerase chain reaction-restriction fragment length polymorphism. Genotype and allele frequencies were evaluated by chi-square test and odds ratio (OR) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. The results of the study demonstrated that IL-8 (-A251T) gene polymorphism was significantly associated with susceptibility of oral cancer, whereas its correlation with clinico-pathological status or pain due to oral cancer could not be established. The AT heterozygous (OR 5.31; CI 3.38-8.34; p 0.0001) and AA homozygous (OR 2.89; CI 1.76-4.75; p 0.0001) had a greater risk for oral cancer compared to TT homozygous. Furthermore, significantly increased values of A allele frequencies compared to T allele were observed in all patients (OR 1.56; CI 1.24-1.96; p 0.0002). Tobacco chewing and smoking were also found to influence the development of oral cancer and increased the incidence of pain in oral cancer patients. The findings of this study suggest that the IL-8 (-A251T) gene polymorphism may be associated with increased risk of oral cancer.
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http://dx.doi.org/10.1007/s10528-015-9704-yDOI Listing
February 2016

Structure-Activity Relationships of Neplanocin A Analogues as S-Adenosylhomocysteine Hydrolase Inhibitors and Their Antiviral and Antitumor Activities.

J Med Chem 2015 Jun 5;58(12):5108-20. Epub 2015 Jun 5.

†Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.

On the basis of the potent inhibitory activity of neplanocin A (1) against S-adenosylhomocysteine (AdoHcy) hydrolase, we analyzed the comprehensive structure-activity relationships by modifying the adenine and carbasugar moiety of 1 to find the pharmacophore in the active site of the enzyme. The introduction of 7-deazaadenine instead of adenine eliminated the inhibitory activity against the AdoHcy hydrolase, while 3-deazaadenine maintained the inhibitory activity of the enzyme, indicating that N-7 is essential for its role as a hydrogen bonding acceptor. The substitution of hydrogen at the 6'-position with fluorine increased the inhibitory activity of the enzyme. The one-carbon homologation at the 5'-position generally decreased the inhibitory activity of the enzyme, indicating that steric repulsion exists. A molecular docking study also supported these experimental data. In this study, 6'-fluoroneplanocin A (2) was the most potent inhibitor of AdoHcy hydrolase (IC50 = 0.24 μM). It showed a potent anti-VSV activity (EC50 = 0.43 μM) and potent anticancer activity in all the human tumor cell lines tested.
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http://dx.doi.org/10.1021/acs.jmedchem.5b00553DOI Listing
June 2015

Association of interleukin-6 genetic polymorphisms with risk of OSCC in Indian population.

Meta Gene 2015 Jun 15;4:142-51. Epub 2015 May 15.

Department of Biochemistry, King George's Medical University, UP, Lucknow, India.

Purpose: Interleukin-6 (IL-6) encodes a cytokine protein, which causes inflammation, maintains immune homeostasis and plays an essential role in oral pathogenesis. The aim of this study was to evaluate the association between IL-6 (- 174 and - 572) G/C promoter gene polymorphisms and risk of OSCC among Indians.

Methods: Single nucleotide polymorphism in IL-6 genes was genotyped in OSCC patients and healthy controls by PCR-RFLP method. Genotype and allele frequencies were analyzed by chi-square test and strength of associations by odds ratio with 95% confidence intervals.

Results: Frequency distribution of IL-6 (- 174) G/C gene polymorphism was significantly associated with OSCC patients in comparison to healthy controls (OR: 0.541, CI: 0.356-0.822; p: 0.004. However, frequency of IL-6 (- 572) G/C gene polymorphism was not significantly associated with OSCC patients (p > 0.05).

Conclusion: The genotype GC and allele C of IL-6 (- 174) G/C gene polymorphism play a significant role in OSCC susceptibility.
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http://dx.doi.org/10.1016/j.mgene.2015.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436510PMC
June 2015

Compressed sensing methods for DNA microarrays, RNA interference, and metagenomics.

J Comput Biol 2015 Feb 28;22(2):145-58. Epub 2015 Jan 28.

1 TCS Innovation Labs , Tata Consultancy Services, Hyderabad, Andhra Pradesh, India .

Compressed sensing (CS) is a sparse signal sampling methodology for efficiently acquiring and reconstructing a signal from relatively few measurements. Recent work shows that CS is well-suited to be applied to problems in genomics, including probe design in microarrays, RNA interference (RNAi), and taxonomic assignment in metagenomics. The principle of using different CS recovery methods in these applications has thus been established, but a comprehensive study of using a wide range of CS methods has not been done. For each of these applications, we apply three hitherto unused CS methods, namely, l1-magic, CoSaMP, and l1-homotopy, in conjunction with CS measurement matrices such as randomly generated CS m matrix, Hamming matrix, and projective geometry-based matrix. We find that, in RNAi, the l1-magic (the standard package for l1 minimization) and l1-homotopy methods show significant reduction in reconstruction error compared to the baseline. In metagenomics, we find that l1-homotopy as well as CoSaMP estimate concentration with significantly reduced time when compared to the GPSR and WGSQuikr methods.
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http://dx.doi.org/10.1089/cmb.2014.0244DOI Listing
February 2015

Association of TNF-α (-238 and -308) promoter polymorphisms with susceptibility of oral squamous cell carcinoma in North Indian population.

Cancer Biomark 2015 ;15(2):125-31

Department of Biochemistry, King George's Medical University, Lucknow, India.

Background: The pro-inflammatory cytokines play an essential role in immune response and are involved in a variety of inflammatory and infectious disease. Tumor necrosis factor alpha (TNF-α) gene polymorphism has been a potential determinant of susceptibility to various types of cancer.

Objective: To evaluate the association of TNF-α gene promoter (-238) G/A and (-308) G/A polymorphisms with the susceptibility of OSCC patients in North Indian population.

Methods: A total 272 patients with OSCC and 185 healthy volunteers were genotypes for the TNF-α (-238) G/A and (-308) G/A gene polymorphism. Genotypes were identified by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). Genotype frequencies were evaluated by Chi-square test and Odds ratio (OR) relative risk.

Results: TNF-α (-238) G/A polymorphism was significantly associated with OSCC patients as compared to healthy volunteers (GG vs. GA: OR=0.3500, 95% CI=0.1289-09502; p=0.036; G vs. A: OR=0.3589 1.477, 95% CI=0.1335-0.9652; p=0.0386). No significant association was found in TNF-α (-308) G/A gene polymorphism with OSCC patients and controls.

Conclusions: We conclude that the TNF-α (-238) G/A polymorphism was significantly associated with OSCC however TNF-α (-308) G/A polymorphism was not associated in OSCC patients.
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http://dx.doi.org/10.3233/CBM-140444DOI Listing
February 2016

Effects of interleukin-18 promoter (C607A and G137C) gene polymorphisms and their association with oral squamous cell carcinoma (OSCC) in northern India.

Tumour Biol 2014 Dec 15;35(12):12275-84. Epub 2014 Nov 15.

Department of Anaesthesiology, King George's Medical University, Lucknow, Uttar Pradesh, 226003, India.

Interleukin-18 (IL-18) is one of the immunomodulatory cytokines that plays an important role in cellular functions against tumor development and progression. IL-18 (-607) C/A and (-0137) G/C gene promoter polymorphisms and their haplotypes variants are associated with risk of various cancers. We evaluated a possible association of IL-18 (-607) C/A and (-137) G/C gene promoter polymorphisms in the susceptibility to oral squamous cell carcinoma (OSCC). A total number of 272 patients with OSCC and 185 healthy volunteers were genotyped for the IL-18 (-607) C/A and (-137) G/C polymorphism. Polymorphism variants were examined by using tetra-primer amplification refractory mutation system (T-ARMS). Genotype frequencies were evaluated by chi-square test and odds ratio (OR) relative risk. IL-18 (-137) G/C gene polymorphism was significantly associated with the risk of OSCC as compared to healthy volunteers (genotype GG vs GC: OR 2.238; 95 % CI 1.455-3.441; p = 0.0003 and allele G vs C: OR 1.984; 95 % CI 1.335-2.947; p = 0.0007). The genotype and allele frequencies of the IL-18 promoter -607 C/A polymorphism in OSCC patients were not significantly different than that in healthy controls (p > 0.05). Our results suggest that IL-18 -137 G/C polymorphism is significantly associated with the progression of oral cancer but -607 C/A polymorphism is not associated with this.
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http://dx.doi.org/10.1007/s13277-014-2538-0DOI Listing
December 2014

A comparative evaluation of analgo-sedative effects of oral dexmedetomidine and ketamine: a triple-blind, randomized study.

Paediatr Anaesth 2014 Dec 25;24(12):1252-9. Epub 2014 Jul 25.

Department of Pediatric and Preventive Dentistry, King George's Medical University, Lucknow, India.

Background: Use of sedative agents for difficult to manage children during dental procedures has been indicated for years, but neither the agent nor the route has been found to be ideal.

Objectives: The aim of the study was to evaluate and compare the efficacy and safety of oral dexmedetomidine (D) and ketamine (K) in producing moderate sedation among uncooperative pediatric dental patients.

Methods: This prospective, triple-blind, randomized comparative study included 112 ASA grade I children of both sexes aged 3-10 years, who satisfied all the inclusion criteria. They were randomly divided into four groups and ketamine 8 mg·kg(-1) (K) or dexmedetomidine 3 μg·kg(-1) (D1), 4 μg·kg(-1) (D2) and 5 μg·kg(-1) (D3) were given orally. Similar dental procedures were performed in these patients, and effects of these drugs were assessed in terms of changes in vital signs, onset and duration of sedation, analgesia, and amnesia. Secondary outcomes such as level of sedation, behavior, adverse effects, and overall success were also measured.

Results: The onset of sedation was significantly rapid with K and D3 as compared to D1 and D2. Recovery from sedation was fastest in group D1. Intra- and postoperative analgesia and anterograde amnesia were highest with K and least with D1, while D3 produced analgesia comparable to K. In K treated group, vomiting was observed in five patients and two patients exhibited emergence phenomenon. Overall, highest success rate was observed in D3 group.

Conclusions: Given by oral route, the novel sedative dexmedetomidine provides dose-dependent effective analgo-sedation, comparable to ketamine, with less adverse effects.
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http://dx.doi.org/10.1111/pan.12493DOI Listing
December 2014

Aortic dissection complicated with haemothorax - an autopsy report.

Med Leg J 2015 Mar 30;83(1):40-2. Epub 2014 May 30.

Department of Forensic Medicine, M.S. Ramaiah Medical College, Bangalore, India.

In a forensic setting, haemothorax is usually seen in cases of trauma. The main non-traumatic cause for haemothorax is an intrathoracic rupture of an acute aortic dissection or an aortic aneurysm that is almost always fatal. Here we present one such case of sudden natural death caused by rupture of an acute aortic dissection. The deceased was a middle-aged, unidentified male who was subjected to autopsy at the Department of Forensic Medicine, M.S. Ramaiah Medical College, after having been brought in dead to the hospital. It is a type III DeBakey dissection as it originates in the descending aorta and it is quite unusual that a rare retrograde extension was also observed.
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http://dx.doi.org/10.1177/0025817213517349DOI Listing
March 2015

Aortic dissection complicated with haemothorax - an autopsy report.

Med Leg J 2015 Mar 30;83(1):40-2. Epub 2014 May 30.

Department of Forensic Medicine, M.S. Ramaiah Medical College, Bangalore, India.

In a forensic setting, haemothorax is usually seen in cases of trauma. The main non-traumatic cause for haemothorax is an intrathoracic rupture of an acute aortic dissection or an aortic aneurysm that is almost always fatal. Here we present one such case of sudden natural death caused by rupture of an acute aortic dissection. The deceased was a middle-aged, unidentified male who was subjected to autopsy at the Department of Forensic Medicine, M.S. Ramaiah Medical College, after having been brought in dead to the hospital. It is a type III DeBakey dissection as it originates in the descending aorta and it is quite unusual that a rare retrograde extension was also observed.
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http://dx.doi.org/10.1177/0025817213517349DOI Listing
March 2015

Synthesis and anti-renal fibrosis activity of conformationally locked truncated 2-hexynyl-N(6)-substituted-(N)-methanocarba-nucleosides as A3 adenosine receptor antagonists and partial agonists.

J Med Chem 2014 Feb 5;57(4):1344-54. Epub 2014 Feb 5.

Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul 151-742, Korea.

Truncated N(6)-substituted-(N)-methanocarba-adenosine derivatives with 2-hexynyl substitution were synthesized to examine parallels with corresponding 4'-thioadenosines. Hydrophobic N(6) and/or C2 substituents were tolerated in A3AR binding, but only an unsubstituted 6-amino group with a C2-hexynyl group promoted high hA2AAR affinity. A small hydrophobic alkyl (4b and 4c) or N(6)-cycloalkyl group (4d) showed excellent binding affinity at the hA3AR and was better than an unsubstituted free amino group (4a). A3AR affinities of 3-halobenzylamine derivatives 4f-4i did not differ significantly, with Ki values of 7.8-16.0 nM. N(6)-Methyl derivative 4b (Ki = 4.9 nM) was a highly selective, low efficacy partial A3AR agonist. All compounds were screened for renoprotective effects in human TGF-β1-stimulated mProx tubular cells, a kidney fibrosis model. Most compounds strongly inhibited TGF-β1-induced collagen I upregulation, and their A3AR binding affinities were proportional to antifibrotic effects; 4b was most potent (IC50 = 0.83 μM), indicating its potential as a good therapeutic candidate for treating renal fibrosis.
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http://dx.doi.org/10.1021/jm4015313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954500PMC
February 2014

Comparative study of intrathecal hyperbaric versus isobaric ropivacaine: A randomized control trial.

Saudi J Anaesth 2013 Jul;7(3):249-53

Department of Anaesthesia, King George's Medical University, Lucknow, Uttar Pradesh, India.

Background: Hyperbaric ropivacaine produce more reliable sensory and motor block, with faster onset, better quality of muscles relaxation than isobaric ropivacaine. So, this study was designed to compare the efficacy of hyperbaric ropivacaine with isobaric ropivacaine in patients undergoing lower abdominal surgery.

Methods: A randomized controlled double blind study in two groups of patients. group A (n=35) received 3 ml of isobaric ropivacaine 6 mg/ml (18 mg). Group B (n=35) received 3 ml of hyperbaric ropivacaine 6 mg/ml (18 mg). The onset and duration of sensory block at dermatome level T10, maximum upper and lower spread of sensory block, intensity, and duration of motor block were recorded.

Statistical Analysis: Block characteristics were compared using the two-tailed Mann - Whitney U-test. The proportion of side effects was compared using the Chi-square test.

Results: The median time of onset of sensory block at the T10 dermatome was 4.4±1.3 min in group B and 6.0±1.03 min in group A. The median time to maximum block height was 16.7±3.7 min in group A and 12.03±1.96 min in group B. The median duration of complete motor recovery (B0) was significantly shorter in the heavy ropivacaine group (166.5±11.7 min) compared with the isobaric ropivacaine group (192.9±9.6 min).

Conclusions: Intrathecal hyperbaric ropivacaine provides more rapid, adequate, and good quality of sensory and motor block with rapid post-operative recovery as compare to isobaric ropivacaine.
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http://dx.doi.org/10.4103/1658-354X.115326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757795PMC
July 2013
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