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Biomedical subjects

Piyush Gupta

Publications and source records attributed to Piyush Gupta.

At least 37 records · Page 2Linked to original sources

Retinopathy of prematurity--risk factors.

OBJECTIVE: Improved survival of low birth weight, premature babies have increased the incidence of retinopathy of prematurity. This hospital-based, prospective, study was undertaken to determine its incidence and risk factors in our neonatal unit. METHODS: Neonates with gestational age < or = 35 weeks and/or birth weight < or = 1500 gm born over a one-year period were examined by indirect ophthalmoscopy between 2 to 4 weeks after birth, and followed up till retinal vascularisation was complete. Maternal and neonatal risk factors were noted and data analyzed by statistical package SPSS-10.0. RESULTS: Sixty babies were thus examined. The incidence of retinopathy was 21.7% in the cohort, 33.3% in babies < or = 32 weeks gestation and 36.4% in babies weighing < or = 1250 gm. Oxygen (p=0.01), sepsis (p=0.04) and apnoea (p=0.02) were independent risk factors. Retinopathy was significantly more severe in babies with hyaline membrane disease (p=0.02) and lower birth weight (p=0.02). Severe disease was never seen before 6.5 weeks of age. CONCLUSION: Indirect ophthalmoscopy should be performed at 4 weeks of post natal age in all preterm babies with birth weight < or = 1500 gm, and intensified in the presence of risk factors like oxygen administration, apnoea and septicemia.

Apnea↗

Stability and solubility of celecoxib-PVP amorphous dispersions: a molecular perspective.

PURPOSE: The purpose of the current study is to evaluate the solubility advantage offered by celecoxib (CEL) amorphous systems and to characterize and correlate the physical and thermodynamic properties of CEL and its amorphous molecular dispersions containing poly(vinylpyrrolidone) (PVP). METHODS: The measurement of crystalline content, glass transition temperatures, and enthalpy relaxation was performed using differential scanning calorimetry. Solubility and dissolutions studies were conducted at 37 degrees C to elucidate release mechanisms. Further, the amorphous systems were characterized by polarized light microscopy and X-ray powder diffraction studies. RESULTS: The PVP content has a prominent effect on the stability and solubility profiles of amorphous systems. A dispersion of 20% w/w PVP with CEL resulted in a maxima in terms of solubility enhancement and lowering of relaxation enthalpy. The release of drug from amorphous molecular dispersions was found to be drug-dependent and independent of the carrier. CONCLUSIONS: The solubility enhancement and enthalpy relaxation studies with respect to PVP concentration helped in a better prediction of role of carrier and optimization of concentration in the use of solid dispersions or amorphous systems. The drug release mechanism is drug-controlled rather than carrier-controlled.

Algorithms↗

Amorphous drug delivery systems: molecular aspects, design, and performance.

The biopharmaceutical properties-especially the solubility and permeability-of a molecule contribute to its overall therapeutic efficacy. The newer tools of drug discovery have caused a shift in the properties of drug-like compounds, resulting in drugs with poor aqueous solubility and permeability, which offer delivery challenges, thus requiring considerable pharmaceutical manning. The modulation of solubility is a more viable option for enhancing bioavailability than permeability, because of the lack of "safe" approaches to enhance the latter. Solid-state manipulation in general, and amorphization in particular, are preferred ways of enhancing solubility and optimizing delivery of poorly soluble drugs. This review attempts to address the diverse issues pertaining to amorphous drug delivery systems. We discuss the various thermodynamic phenomenon such as glass transition, fragility, molecular mobility, devitrification kinetics, and molecular-level chemical interactions that contribute to the ease of formation, the solubility advantage, and the stability of amorphous drugs. The engineering of pharmaceutical alloys by solubilizing and stabilizing carriers, commonly termed solid dispersions, provide avenues for exploiting the benefits of amorphous systems. Carrier properties, mechanisms of drug release, and study of release kinetics help to improve the predictability of performance. The review also addresses the various barriers in the design of amorphous delivery systems, use of amorphous form in controlled release delivery systems, and their in vivo performance.

Adjuvants, Pharmaceutic↗

A randomized trial of eutectic mixture of local anesthetics during lumbar puncture in newborns.

OBJECTIVE: To determine the efficacy of a topical anesthetic cream, eutectic mixture of local anesthetics (EMLA), in alleviating pain associated with lumbar puncture in newborns. DESIGN: Randomized double-blind placebo-controlled trial. SETTING: Neonatal intensive care unit of a university teaching hospital. Patients Sixty consecutive newborns (gestational age, >or=34 weeks) undergoing diagnostic lumbar puncture. Intervention Topical application of 1 g of EMLA or placebo 60 to 90 minutes before lumbar puncture. MAIN OUTCOME MEASURES: Heart rate, transcutaneous oxygen saturation level, and total behavioral score recorded on a video camera and graded according to the Neonatal Facial Coding System. RESULTS: Compared with baseline, all newborns experienced pain as evidenced by increased heart rate, decreased oxygen saturation level, and total behavioral score (all within-groups differences were significant using repeated-measures analysis of variance; P<.001) during the procedure. Compared with placebo, EMLA significantly attenuated the pain response as shown by a lower mean +/- SE heart rate (per minute), particularly at needle insertion (EMLA: 159.3 +/- 2.3; placebo: 175.2 +/- 2.7; P<.001) and needle withdrawal (EMLA: 153.8 +/- 2.6; placebo: 167.3 +/- 2.5; P<.001), and a lower mean +/- SE total behavioral score, again at insertion (EMLA: 4.0 +/- 0.3; placebo: 5.0 +/- 0.0; P =.004) and withdrawal (EMLA: 1.8 +/- 0.3; placebo: 3.9 +/- 0.3; P<.001). There was no statistically significant difference between groups with regard to oxygen saturation level. CONCLUSIONS: Lumbar puncture in newborns produces pain responses. Eutectic mixture of local anesthetics is an efficacious agent for reducing the pain associated with needle insertion and withdrawal during lumbar puncture in newborns.

Anesthetics, Combined↗

Life span of peripheral intravenous cannula in a neonatal intensive care unit of a developing country.

The use of peripheral intravenous cannulas (IVCs) in the care of sick newborns is a common practice. IVCs, priced five times higher than conventional steel needles, can be more cost effective if insight is available on the variables affecting their life span in situ. The present report summarizes the efforts made to ascertain these factors in a neonatal intensive care unit (NICU) of a developing country. A total of 186 peripheral IVCs (24-gauge teflon) were used in 78 newborns amounting to 7,583 hours of IV therapy (mean, 40.8 hr per cannula; range, 1-136 hr). Of these, 25 cannulas were removed selectively and 84, 50, 17, and 10 were removed for swelling, dislodgement/leakage, blockage, and local erythema, respectively. The median survival time of IVC as expressed by Kaplan-Meir survival analysis was 40 hours (SE, 2.49; 95% confidence interval, 35.12-44.88). Birth weight, gestation, application of splint, fluid and glucose infusion rate, site of cannulation, and administration of ampicillin, gentamicin, amikacin, vancomycin, phenobarbitone, blood products, or calcium gluconate did not influence the median life span of IVCs. Children receiving cefotaxime had a significantly lower median survival time as compared with those not receiving it (36 vs 47 hours, p =.007). Median survival time of IVCs in our set-up was comparable with those in developed countries and was not governed by the cannula or patient variables. Cefotaxime use led to decreased survival of IVCs; though this effect appeared to be related to the mode of administration rather than to the drug per se.

Catheterization, Peripheral↗

Characterization of solid-state forms of celecoxib.

This study deals with the generation and characterization of various solid-state forms of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor. The drug was subjected to polymorphic screen using different solvents to explore the possibility of existence of different solid forms. N,N-Dimethyl acetamide (DMA) and N,N-dimethyl formamide (DMF) yielded solvates in 1:1 stoichiometric ratio. Quench cooling of the melt resulted in amorphous form of the drug. All these solid-state forms were characterized by thermoanalytical (DSC, TGA, HSM), crystallographic (XRD), microscopic (polarized, SEM), spectroscopic (FTIR), and elemental analysis techniques. Solubility and van't Hoff studies were carried out for their thermodynamic interpretation. Influence of morphology of different solid-state forms on flow behavior was also investigated. Molecular modeling studies were used to elucidate the interaction between solute and solvent molecules in the solvate.

Celecoxib↗

Brainstem auditory evoked responses in term small for gestational age newborn infants born to undernourished mothers.

Our aim was to assess the effect of intrauterine growth retardation on neurosensory development by evaluating brainstem auditory evoked responses (BAER) in term small for gestational age (SGA) newborn infants born to undernourished mothers. This prospective clinical study included 25 singleton healthy SGA newborn infants born between 38 and 41 weeks to undernourished mothers (weight <45kg, height <145cm, haemoglobin <8g/dl, and serum albumin <2.5g/dl). An equal number of age- and sex-matched appropriate for gestational age newborn infants born to healthy mothers served as controls. Mothers with other risk factors and newborns with complications during delivery or immediate newborn period were excluded. BAER was recorded within first 3 days of life. Interpeak latency (IPL), absolute peak latency (APL) and amplitudes of various waveforms were determined and compared between the groups. No statistically significant differences were observed for the mean interpeak and absolute latencies between term SGA and AGA infants (p>0.05). The absolute peak latency (wave V) and central conduction time (I-V interval) were borderline prolonged in the study group compared with controls (p=0.051 and 0.088 respectively). Using multiple regression analysis, maternal haemoglobin was identified to be the only parameter having a negative correlation with both IPL (waves I-V) (F[1,46]=4.12, p=0.048) and APL (wave V) (F[1,46]=5.80, p=0.02). Maternal undernourishment may have a minor effect on intrauterine development of the auditory brainstem. Maternal haemoglobin is the only factor significantly associated with these changes.

Brain Stem↗

Neonatal plantar response revisited.

OBJECTIVE: To evaluate plantar response in the early neonatal period in normal, term, healthy newborn infants. This was a prospective study set in the postnatal ward of a tertiary care hospital. METHODS: The plantar response was elicited in 256 healthy, term, appropriate-for-gestational-age neonates during their first 7 days of life, utilizing the thumb-nail-drag method. The response was tested daily at intervals of 24 h, until the neonate was discharged. A total of 597 observations were made, and the responses were classified as extensor, flexor or equivocal. RESULTS: The overall plantar response was found to be predominantly extensor (73.8%), followed by equivocal (17.3%) and, finally, flexor (8.9%). The plantar response was bilaterally extensor in 72.5%, bilaterally equivocal in 14.2%, and bilaterally flexor in 7.7% of observations, respectively. Asymmetrical plantar response was elicited in 5.4% of observations. No difference was observed in individual categories based on age (<12 h, 12.1-24 h, 24.1-72 h, 72.1 h-7 days) and site of response (right/left foot). CONCLUSION: The plantar response in healthy, term neonates is predominantly extensor. Further, the relatively high frequency of asymmetrical and symmetrical flexor responses limits its clinical usefulness in the early neonatal period.

Humans↗

Disseminated nocardiosis in an immunocompetent child.

We report a 2-month-old child with a disseminated Nocardia farcinica infection that presented with suppurative lymphatic abscess. The child did not have any predisposing factors and responded to treatment with co-trimoxazole and amikacin. This is first case report of disseminated nocardiosis caused by Nocardia farcinica in an immunocompetent child.

Abscess↗

Safety of oral use of nimesulide in children: systematic review of randomized controlled trials.

BACKGROUND: Nimesulide has been widely used to treat fever in children. Due to reports of adverse drug reactions, discontinuation or modification of its use has been suggested. OBJECTIVE: To evaluate the safety of oral use of nimesulide in children. DESIGN: Systematic review of published randomized controlled trials. SEARCH STRATEGY: Electronic searches of databases (PubMed, Cochrane, Toxnet) for relevant trials upto January 2003 using specified key words. The studies were also identified by searching the references of available meta-analyses and review articles, and bibliography of pertinent references. INCLUSION CRITERIA: Randomized controlled trials in children (less than or equal to 18 years of age) comparing the use of oral nimesulide with placebo or other antipyretic, anti-inflammatory or analgesic agents. OUTCOME: The primary outcome variable included the commonly encountered adverse effects of nimesulide therapy, i.e., hypothermia, abdominal symptoms, gastrointestinal bleeding, and elevated liver enzymes. DATA COLLECTION AND ANALYSIS: One of the authors developed a questionnaire and independently extracted data on methods, type of participants, interventions and outcomes. The meta-analysis was conducted using pooled relative risk with 95% confidence intervals, with random effects model assumption. RESULTS: We identified 16 trials that fulfilled the inclusion criteria. These included 1254 subjects, with mean age between 22 -140 months. Nimesulide was primarily used for its antipyretic (10 trials) or anti-inflammatory and analgesic activity (4 trials). One study each evaluated the symptomatic improvement in ARI and bronchial asthma. The control group included administration of placebo (3 studies), paracetamol (9 studies), and ketoprofen, naproxen, mefanemic acid and aspirin in one study each. The pooled effect sizes of various adverse events as compared between nimesulide and different control groups were: hypothermia (RR: 1.055; 95% CI: 0.184 - 6.047; P = 0.952), abdominal symptoms (RR: 0.464; 95% CI: 0.264 - 0.816; P = 0.008), gastrointestinal bleeding (RR: 0.914; 95% CI: 0.236 - 3.543; P = 0.896), and asymptomatic liver enzyme elevation (RR: 2.678; 95% CI, 0.558-12.853; P = 0.218). Cutaneous and renal adverse effects were not seen in any of the included studies. CONCLUSION: Oral nimesulide is as safe or unsafe as other analgesics-antipyretics for short-term use (less than or equal to 10 d) in children. The drug is best avoided in known or suspected liver disease; caution is warranted while prescribing nimesulide concomitantly with other hepatotoxic drugs. There is limited data for drawing concrete inferences below the age of six months.

Administration, Oral↗

Hydrogels: from controlled release to pH-responsive drug delivery.

Hydrogels are one of the upcoming classes of polymer-based controlled-release drug delivery systems. Besides exhibiting swelling-controlled drug release, hydrogels also show stimuli-responsive changes in their structural network and hence, the drug release. Because of large variations in physiological pH at various body sites in normal as well as pathological conditions, pH-responsive polymeric networks have been extensively studied. This review highlights the use of hydrogels (a class of polymeric systems) in controlled drug delivery, and their application in stimuli-responsive, especially pH-responsive, drug release.

Delayed-Action Preparations↗

Weekly vs daily iron and folic acid supplementation in adolescent Nepalese girls.

OBJECTIVE: To compare the effectiveness of weekly vs daily iron and folic acid supplementation for control of anemia in adolescent Nepalese girls. DESIGN: Randomized controlled trial. SETTING: A Government Girl School in Dharan, Nepal, an urban foothill town that is 305 m above sea level. SUBJECTS: Consecutive healthy adolescent girls (n = 209, median age 15 years) randomized to 3 groups matched for age, anthropometry, and personal and sociodemographic characteristics. Of 209 subjects, 181 completed the trial. Two girls had adverse reactions to treatment and were excluded. INTERVENTION: Group A (n = 70) received a 350-mg ferrous sulfate and 1.5-mg folic acid combination once daily for 90 to 100 days. Group B (n = 67) received the tablet under supervision once a week for 14 weeks. Group C (n = 72) did not receive any drugs. OUTCOME VARIABLE: Presupplementation and postsupplementation differences in prevalence of anemia and change in hematocrit. RESULTS: Prevalence of anemia (defined as hematocrit <36%) declined from 68.6% and 70.1% in groups A and B to 20% and 13.4%, respectively, postsupplementation (P<.001), whereas the prevalence in group C changed little (68.1% to 65.3%, P =.81). There was a significant rise in the mean hematocrit of both supplemented groups (group A, 32.9% +/- 3.5% to 41.0% +/- 5.6%, P<.001; group B, 33.2% +/- 3.6% to 40.4% +/- 4.9%, P<.001) but no appreciable change in controls (34.2% +/- 2.9% to 34.1% +/- 3.3%, P =.91). Net change in mean hematocrit in both the supplementation groups was comparable (P =.57). CONCLUSIONS: The prevalence of anemia in adolescent Nepalese girls is high. Supervised iron and folic acid therapy once a week is an effective alternative to daily administration and helps lower the prevalence of anemia in adolescent girls.

Adolescent↗