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Biomedical subjects

S Hariharan

Publications and source records attributed to S Hariharan.

At least 19 recordsLinked to original sources
PubMed2006

Design of estradiol loaded PLGA nanoparticulate formulations: a potential oral delivery system for hormone therapy.

Estradiol (E2), a highly lipophilic molecule with good oral absorption but poor oral bioavailability, was incorporated into poly(lactide-co-glycolide) (PLGA) nanoparticles to improve its oral bioavailability. Nanoparticles were prepared by using polyvinyl alcohol (PVA) or didodecyldimethylammonium bromide (DMAB) as stabilizer, leading to negatively (size 410.9+/-39.4 nm) and positively (size 148.3+/-10.7 nm) charged particles, respectively. Both preparations showed near zero order release in vitro with about 95% drug being released within 45 and 31 days for PVA and DMAB, respectively. In situ intestinal uptake studies in male Sprague-Dawley (SD) rats showed higher uptake of DMAB stabilized nanoparticles. Following oral administration to male SD rats, E2 could be detected in blood for 7 and 2 days from DMAB and PVA stabilized nanoparticles, respectively. Histopathological examination and blood counts indicated the absence of inflammatory response. These data suggest that DMAB stabilized PLGA nanoparticles have great potential as carriers for oral delivery of estradiol.

Animals↗
PubMed2006

Nonclinical toxicology study of recombinant-plasmid DNA anti-rabies vaccines.

The absence of standard guidelines from National and International regulatory agencies for the safety evaluation of biotechnology products challenges the ingenuity of toxicologists. At present, the development of standard pre-clinical toxicology protocols for such products is on an individual case basis. The present investigation is an attempt to evaluate the safety profile of the first indigenously developed DNA based anti-rabies vaccine in India. The test compounds were DNA rabies vaccine [DRV (100 microg)] and combination rabies vaccine (CRV (100 microg DRV and 1/50 dose of cell culture vaccine)), intended for clinical use by intramuscular route on 1, 7, 14 and 28 day. As per the regular mandatory requirements, the study has been designed to undertake acute (single dose--10 days), sub-chronic (repeat dose--28 days) and chronic (intended clinical dose--120 days) toxicity tests using three dose levels viz. therapeutic, average (2 x therapeutic dose) and highest dose (10 x therapeutic dose) exposure in Swiss Albino mice. The selection of the rodent model viz. Swiss Albino mice is based on affinity and rapid higher antibody response during the efficacy studies. Apart from physical, physiological, clinical, hematological and histopathology profiles of all target organs, the tier-I immunotoxicity parameters have also been monitored. There were no observational adverse effects even at levels of 10x therapeutic dose administration of DRV and CRV. The procedure also emphasizes on the designing of protocols for the products developed by recombinant technique.

Animals↗
PubMed2006

BK virus nephritis after renal transplantation.

BK viremia and nephritis are increasing problems in renal transplant recipients. The exact cause of the increasing prevalence of this condition remains poorly understood. Increasing prevalence has been correlated with newer immunosuppressive agents and the decline in acute rejection rates in recent years. The clinical manifestation varies from the asymptomatic state of viremia and nephritis to clinical renal dysfunction. The diagnosis of this infection is based on the combination of the presence of urinary decoy cells, virus in the urine/blood, and typical renal histological findings of interstitial nephritis. Routine post-transplant screening for BK viremia and viruria prior to the occurrence of nephritis and the reduction in immunosuppressive therapy for subjects with viremia appear to be attractive approaches. The treatment of BKV nephritis (BKVN) consists of reduction in immunosuppressive therapy and antiviral therapy with cidofovir or leflunomide or a combination of both. Approximately 30-60% of subjects with BKVN experienced irreversible graft failure. However, in recent years, the combinations of early detection, prompt diagnosis, and appropriate reduction in immunosuppressive therapy have been associated with better outcome. The pathogenesis of BK virus infection in renal transplant recipients needs to be explored. The source of BKV infection (donor as opposed to recipient), the role of host humoral, and cellular immunity to BKV, and the role of alloimmune activation in renal graft to the occurrence of nephritis are discussed in this review.

Antibodies, Viral↗
PubMed2006

Sustained release nanoparticulate formulation containing antioxidant-ellagic acid as potential prophylaxis system for oral administration.

The aim of the present work was to develop ellagic acid (EA) loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles for oral administration. PLGA nanoparticles were prepared by a method based on the concept of emulsion-diffusion-evaporation by using polyethylene glycol (PEG) 400 as a cosolvent for solubilizing the drug. While developing this method, didodecyldimethylammomium bromide (DMAB) and polyvinyl alcohol (PVA), alone and in combination with chitosan (CS) were employed. DMAB stabilized particles were the smallest of all the formulations with a particle size of 148.5 nm. PVA alone gave particles of 269.7 nm but a blend with CS (80:20) resulted in an increase in particle size (359.6 +/- 23.6 nm). Initial release of EA from nanoparticles in pH 7.4 phosphate buffer was rapid, followed by a slower sustained release. Release rates followed the order PVA > PVA-CS > DMAB. Release rate from the PLGA-DMAB particles was slowest, which is attributed to higher hydrophobicity of DMAB as compared to PVA, preventing diffusion of drug out of polymeric matrix. Insolubility of CS at alkaline pH could have retarded the release in case of PVA-CS system. In situ intestinal permeability study of pure drug and the drug encapsulated in nanoparticles prepared using PVA, PVA-CS blend and DMAB as stabilizer in rats showed 66, 75, 73 and 87% permeation, respectively. EA showed good free radical scavenging effect in a yeast cell culture model as well as in a cell free system.

Animals↗
PubMed2006

Characteristics of patients requiring prolonged length of stay in a surgical intensive care unit in Barbados.

OBJECTIVE: To evaluate the clinical characteristics and costs incurred for patients who stayed for a prolonged period in a surgical intensive care unit (ICU). DESIGN AND METHODS: Data of all patients admitted to a surgical ICU in Barbados during the period of two years from July 1999 to June 2001 were prospectively collected. Demographic data, diagnoses on admission and Acute Physiology and Chronic Health Evaluation (APACHE II) score were recorded. Costs for treatment were calculated from using a cost block model. The characteristics of patients who had a prolonged stay (> 14 days) were compared with a concurrent cohort of patients who stayed less than 14 days. RESULTS: Of 438 admissions, 58 (13.2%) stayed in the ICU for more than two weeks. The overall age, hospital outcome, APACHE II scores in the prolonged stay group were significantly higher than that of the patients who stayed less than two weeks. Cost analysis showed about six times more expenditure in the long stay patients (dollar US 3800 vs dollar US 24000). Of the prolonged stay ICU patients, 29.2% would have required only a step-down unit due to less severity of illness as evidenced by their low mean APACHE II scores [7.3 +/- 2.6 (SD)] compared to overall mean APACHE II score 10.7 +/- 7.5 (SD). CONCLUSION: The study highlighted the need for a step-down unit and a protocol to transfer eligible patients to such a unit.

APACHE↗
PubMed2006

Knowledge, attitudes and practice of medical students at the Cave Hill Campus in relation to ethics and law in healthcare.

OBJECTIVES: The purpose of this study is to assess the knowledge, attitudes and practices among medical students in relation to medical ethics and law. The results of the study will be a useful guide to tutors of medical students and curricula designers. METHODS: A thirty-item self-administered questionnaire about knowledge of law and ethics, and the role of an ethics committee in the healthcare system was devised, tested and distributed to all levels of students and staff at the Queen Elizabeth Hospital in Barbados (a tertiary care teaching hospital) in 2003. The data from the completed questionnaires were entered into an SPSS database and analyzed using frequency and multiple cross-tabulation tables. RESULTS: Completed responses were obtained from 55 (96%) of the medical students. Medical students generally attested to the importance of ethical knowledge but felt that they knew little of the law. Students varied widely as regards the frequency with which they saw ethical or legal problems, with a quarter seeing them infrequently, but another quarter seeing them every day. They received their knowledge from multiple sources and particularly from lectures/seminars, and found case conferences the most helpful. Only a few students felt that text books had been helpful. Students were generally knowledgeable about most ethical issues, but many had uncertainties on how to deal with religious differences in treating patients, on the information to be given to relatives, and how violent patients should be treated. CONCLUSIONS: The results of the study highlight that medical students felt an inadequacy of knowledge of law as it pertains to their chosen career Since most of their knowledge of law was obtained from lectures, these should be reviewed and other avenues of tuition explored. The study also highlights the need to identify the minority of students who have problems with their ethical knowledge and to devise means whereby any deficiencies can be discussed and modified.

Adult↗
PubMed2005

Analytical methods for assay of ellagic acid and its solubility studies.

Ultra-violet (UV) spectrophotometric and high performance liquid chromatographic methods for quantitative determination of ellagic acid (EA), an antioxidant were developed. The analytical methods were validated for linearity, accuracy, intra- and inter-day variability, and precision. EA was eluted using a polyethylene glycol (PEG) column with mobile phase composed of acetonitrile and 5 mM potassium dihydrogen orthophosphate buffer pH 2.5 (80:20, v/v). The UV and high performance liquid chromatography (HPLC) methods have lower detection limits of 0.2 and 0.1 microg/ml, respectively. Because of the increasing pharmaceutical interest in phytochemicals and their solubility problems, solubility studies for EA were also carried out. Various organic solvents and surfactants were screened for assessing solubility of EA and the compound was found to be soluble in some pharmaceutically acceptable solvents like triethanolamine, polyethylene glycol 400 and N-methyl pyrrollidone (NMP). Aqueous and pH dependent solubility of EA were determined using UV and HPLC methods, respectively.

Antioxidants↗
PubMed2005

Conversion of stable kidney transplant recipients from a twice daily Prograf-based regimen to a once daily modified release tacrolimus-based regimen.

UNLABELLED: Modified release (MR) tacrolimus is an extended release formulation administered once daily (qD). The purpose of this pharmacokinetic (PK) study was to evaluate tacrolimus exposure in stable kidney transplant recipients converted from Prograf twice a day to MR tacrolimus qD. METHODS: This was an open-label, multicenter study with a crossover design. Eligible patients were 18 to 65 years of age, more than 6 months posttransplant with stable renal function, and received stable Prograf doses more than 2 weeks prior to enrollment. Patients received Prograf twice a day through day 7; 24-hour PK profiles were obtained on days 1 and 7. Patients were converted to the same milligram-for-milligram daily dose of MR tacrolimus qD in the morning on day 8; 24-hour PK profiles were obtained for MR tacrolimus on days 8, 14, and 21. Laboratory and safety parameters were also evaluated. RESULTS: Most patients (67 of 70) completed all 5 PK profiles. The 90% confidence intervals (CI) for the MR tacrolimus vs Prograf comparison at steady state (days 14 and 21 vs days 1 and 7) were 90.7 and 99.4 for AUC0-24 and 82.7 and 91.9 for Cmin. MR tacrolimus was well tolerated with a safety profile comparable to that of Prograf. AUC0-24 was highly correlated to Cmin for Prograf (day 1, r = 0.80; day 7, r = 0.84) and MR tacrolimus (day 14, r = 0.92; day 21, r = 0.86). Renal function remained stable after conversion to MR tacrolimus. CONCLUSION: The steady state PK of MR tacrolimus are equivalent to Prograf after a milligram-for-milligram conversion in stable kidney transplant recipients. The results provide evidence to support a safe 1:1 conversion from Prograf twice a day to MR tacrolimus.

Adult↗
PubMed2005

Evaluation of the reasons for cancellations and delays of surgical procedures in a developing country.

Data on all patients scheduled to have elective and emergency surgeries during the period of 6 weeks from September 1999 to October 1999 were prospectively collected to determine scheduled starting times, actual starting times, completion times, causes for delays and cancellations. Of 840 procedures scheduled during the study period, 594 (71%) were available for analysis. Eighty-nine per cent of cancellations occurred in patients undergoing elective surgery. The common causes of cancellations were non-availability of beds in recovery room (RR) (15%), patients not showing up (9%), improper pre-operative patient preparation (13%), unavailability of nurses (11%) and anaesthetists (8%). Twenty-three per cent of the cancellations were day cases. Public patients were cancelled more frequently than private patients. Surgical procedures started on time in only 7% of patients. The most common cause of delay was due to delayed transport of patients to the operating theatre (17%). Optimal utilisation of operating theatres in our situation may be effected by increasing the bed-strength of ICUs to free the RR, proper pre-operative work up, adequate counselling of day-care surgery patients and efficient floor management of the operating theatre.

Appointments and Schedules↗
PubMed2005

Outcome of elderly patients undergoing open-heart surgery in a developing country.

To evaluate and compare the outcome of open-heart surgery in elderly patients with a concurrent group of younger patients in a developing country, data of all adult patients who underwent open-heart surgery during the period of 3 years from January 1999 to December 2001 were collected prospectively. Demographic data such as age and gender, other data such as preoperative diagnoses, comorbid illnesses, type of surgery, time of cardio-pulmonary bypass, length of stay and hospital outcome were recorded. The characteristics of patients above the age of 65 years were compared with a concurrent cohort of patients aged less than 65 years. One hundred and forty-five adult patients underwent open-heart surgeries in 3 years, and the overall mortality rate was 4.8%. The much common surgeries were coronary artery bypass grafting, valve repair/replacement surgery and surgery for adult congenital heart diseases. Forty-five (31%) patients were above the age of 65 years. The mortality rate was 2.2% for patients who were aged 65 years and above, in comparison with that of the concurrent cohort of younger patients (6%). This was probably because of more number of surgeries for congenital heart diseases in the latter group. However, even with other surgeries such as coronary artery bypass grafting, the elderly group of patients did equally well as the younger group. Elderly patients tolerate cardiac surgery well, and age should not be an exclusive criterion to decide against open-heart surgery.

Adolescent↗
PubMed2004

Autopsy-proven Creutzfeldt-Jakob disease in a patient with a negative 14-3-3 assay and nonspecific EEG and MRI.

Detection of 14-3-3 protein in cerebrospinal fluid (CSF), in combination with findings on electroencephalography (EEG) and magnetic resonance imaging (MRI), is a highly sensitive and specific diagnostic test for sporadic Creutzfeldt-Jakob disease (CJD) in patients premortem. We present a case of classic, sporadic CJD, confirmed on autopsy and by Western blot. However, all routine premorbid testing was negative, the CSF was negative for the 14-3-3 protein, EEG did not show periodic sharp wave complexes (PSWC), and MRI failed to show hyperintense signal in the basal ganglia. Thus, laboratory support for the diagnosis of CJD was not obtained premortem. The chances of all three diagnostic testing modalities to be negative in a single case of sporadic CJD are extremely remote. Autopsy with neuropathologic confirmation remains the only definitive way to make a diagnosis of CJD.

14-3-3 Proteins↗
PubMed2004

Dexamethasone therapy in patients with brain tumors--a focus on tapering.

Administration of corticosteriods in brain tumor patients requires an understanding of the physiology of the adrenal system and desired patient response. Close attention to other concomitant medications will ensure adequate amounts of all drugs, including dexamethasone. Nurses need to assess patients' tolerance of dexamethasone, discuss these findings with physicians and pharmacists, and educate both patients and family members on doses and tapering schedules tailored to individual patient needs.

Brain Neoplasms↗
PubMed2004

Mortality of patients following hip fractures in Barbados.

A retrospective study of all patients admitted with hip fractures to the Queen Elizabeth Hospital in Barbados from January 1996 to December 1998 was conducted. There were 110 patients who had sustained either a femoral neck or peri-trochanteric fracture. The mean age was 80.7 years and 71.8% of the patients were women. Mortality at six months in 110 patients was 32.7% and 41.2% at 12 months in 102 patients. Forty-nine patients had open reduction and internal fixation of their fractures, forty-five patients were treated with Austin Moore prostheses and one patient had excisional arthroplasty. Patients with pre-operative cardiac abnormalities had a significantly higher mortality (60%) at 12 months (p = 0.028). There was a linear correlation between age and mortality with mortality increasing with age. The length of time from admission to surgical procedure had no significant influence on mortality. Hip-fracture patients with cardiac abnormalities should be carefully evaluated and stabilized pre-operatively.

Adult↗
PubMed2003

Molecular analysis of astrocytomas presenting after age 10 in individuals with NF1.

BACKGROUND: Fifteen to 20% of children with neurofibromatosis type 1 (NF1) develop low-grade astrocytomas. Although brain tumors are less common in teenagers and adults with NF1, recent studies have suggested that patients with NF1 are at a significantly increased risk of developing astrocytomas. OBJECTIVE: S: To investigate the genetic basis for astrocytoma development in patients with NF1 beyond the first decade of life. METHODS: The authors performed molecular genetic analyses of 10 NF1-associated astrocytomas representing all World Health Organization (WHO) malignancy grades using fluorescence in situ hybridization, loss of heterozygosity, immunohistochemistry, and direct sequencing. RESULTS: Later-onset NF1-associated astrocytomas, unlike histologically identical sporadic astrocytomas, exhibit NF1 inactivation, supporting a direct association with NF1 rather than a chance occurrence. Furthermore, some of these astrocytomas have homozygous NF1 deletion. In addition, genetic changes observed in high-grade sporadic astrocytomas, including TP53 mutation and CDKN2A/p16 deletion, are also seen in NF1-associated high-grade astrocytomas. CONCLUSIONS: Neurofibromatosis type 1-associated astrocytomas occurring in patients older than 10 years exhibit genetic changes observed in sporadic high-grade astrocytomas. Patients with neurofibromatosis type 1 and germline NF1 deletions may be at risk for developing late-onset astrocytomas.

Adolescent↗
PubMed2002

Outcome evaluation in a surgical intensive care unit in Barbados.

The performance of the Acute Physiology and Chronic Health Evaluation II scoring system was prospectively assessed in the surgical intensive care unit at the Queen Elizabeth Hospital, Barbados. A total of 309 patients admitted consecutively during a 2-year period (1999-2001) were evaluated. Demographic data, diagnosis, Acute Physiology and Chronic Health Evaluation II score, duration of stay and hospital outcome were recorded. The predicted mortality for every patient and the costs incurred were also calculated. The overall observed mortality rate was 15.9% while the mean predicted mortality rate for our case-mix was 16.4%, which is comparable to results from developed countries. The cost incurred per patient was much lower at $13,636 (Barbados), compared to the patients' cost in North America ($60,000 Barbados).

APACHE↗
PubMed2001

Risk factors for renal allograft survival from pediatric cadaver donors: an analysis of united network for organ sharing data.

BACKGROUND: The shortage of cadaveric donors for kidney transplantation has prompted many centers to use cadaver kidneys from pediatric donors. Use of kidneys from pediatric donors has been shown to have a lower graft survival. METHODS: Recipients receiving cadaver kidneys from pediatric and adult donors between 1988 and 1995 were analyzed. The data were obtained from United Network of Organ Sharing database. The actuarial kidney transplant graft survival was estimated by the Kaplan-Meier method. A logistic regression analysis was used to identify various risk factors for 1-year graft failure. Odds ratios (OR) were estimated for various risk factors. RESULTS: Kidney transplant survival rates for donor age <18 years (n=12,838) at 1, 2, 3, 4, and 5 years were 81.5%, 76.3%, 71.3%, 66.4%, and 61.7%, respectively. The corresponding results for adult donors from age 18 to 50 years (n=35, 442) were 83.5%, 78.4%, 73.1%, 67.9%, and 62.4%, respectively, Log-rank test P<0.01. Pediatric donors were further divided into three groups according to donor age: group I (0-5 years), group II (6-11 years), and group III (12-17 years). The actuarial survival rates for 1, 3, and 5 years for group I (n=2198) were 73.6%, 63.3%, and 55.6%, respectively. The corresponding values for group II (n=2873) were 78.0%, 67.5%, and 57.8% and for group III (n=7767) were 85%, 75.0%, and 64.8%, respectively, P<0.01. Although the recipients of group I had lower graft survival, en bloc grafts (n=751) had much better 1-, 3-, and 5-year graft survival rates (76.3%, 67.7%, and 60.7%, respectively) compared with single grafts (n=1447; 72.2%, 61.1%, and 53.2%, P=0.02) from donors 0 to 5 years. Graft thrombosis as a cause of graft failure was seen in 10% of group I compared with 6% in group II and 5% in group III. In group I, lower OR were seen when an en bloc transplant was performed (0.688, P<0.01) and when donor body weight was>15 kg (0.547, P<0.01). However, OR were elevated in recipients of previous transplants (1.556, P<0.01), with prolonged cold ischemic time (1.097, P=0.03), for black recipients (1.288, P=0.03), and for recipients with body mass index> or =25 (1.286, P=0.02). Progressive increase in the donor age was associated with lower OR in group II (0.894, P<0.01). CONCLUSIONS: (1) Overall, poorer graft survival was seen in pediatric donor transplants, (2) transplant kidney survival with en bloc kidneys was better than a single kidney from donors 0-5 years, (3) progressive increase in donor age was associated with improved graft survival when the donors were 6-11 years, whereas progressive increase in donor weight was associated with improved graft survival when the donors were 0-5 years.

Adolescent↗