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Biomedical subjects

P K Dubey

Publications and source records attributed to P K Dubey.

At least 19 recordsLinked to original sources

Prediction of successful epidural catheter placement by a 'cold test'.

We tested the hypothesis that the patients' feeling of cold sensation down the back during epidural drug administration through the epidural catheter was a reliable predictor of correct epidural catheter placement. In a prospective study of 80 patients, an epidural catheter was placed in the lumbar epidural space. During epidural drug injection, patients were asked to report feeling of the cold sensation in their back by pressing a bell. After 15 minutes, the patients were assessed for cold sensation in the thoracic to sacral dermatomes bilaterally and the dermatomal block recorded. Of 80 patients, three had inadvertent dural puncture. Seventy-two of 77 patients reported feeling cold sensation in their back during local anaesthetic injection, and all had successful epidural blockade. Of the five patients who did not report any cold sensation, three had failed epidural block and two successful epidural block. There were no false positive results. Of three patients who had inadvertent dural puncture and had normal saline 5 ml injected through the Tuohy needle, none reported cold sensation. The perception of cold sensation in the back during epidural administration of a test dose and/or subsequent full dose of local anaesthetic is useful in predicting successful epidural catheter placement.

Adult↗

RGD-anchored magnetic liposomes for monocytes/neutrophils-mediated brain targeting.

Negatively charged magnetic liposomes were prepared using soya lecithin (Soya PC), cholesterol and phosphatidyl serine (PS) for their preferential presentation to circulating blood phagocytes (monocytes and neutrophils). PS ratio was optimized in terms of drug and magnetite loading, in vitro magnetic responsiveness and ex vivo monocytes/neutrophils uptake. RGD peptide was covalently coupled to the negatively charged liposomes composed of PC, cholesterol, PS and phopsphatidyl ethanolamine (PE) via carbodiimide-mediated coupling. In vivo cellular sorting study under magnetic guard indicated an increase in relative count of neutrophils and monocytes. Results suggest that selective uptake of RGD-anchored magnetic liposomes by these cells imparts them magnetic property. High levels of a model drug diclofenac sodium was quantified in target organ brain. In case of negatively charged uncoated magnetic liposomes brain levels of the drug was 5.95-fold compared to free drug and 7.58-fold in comparison to non-magnetic formulation, while for RGD-coated magnetic liposomes this ratio was 9.1-fold compared to free drug solution, 6.62-fold compared to non-magnetic RGD-coated liposomes and 1.5-fold when compared to uncoated magnetic liposomes. Liver uptake was significantly bypassed (37.2% and 48.3% for uncoated and RGD-coated magnetic liposomes, respectively). This study suggested the potential of negatively charged and RGD-coated magnetic liposomes for monocytes/neutrophils-mediated active delivery of drugs to relatively inaccessible inflammatory sites, i.e. brain. The study opens a new perspective of active delivery of drugs for a possible treatment of cerebrovascular diseases.

Animals↗

Impurity profile study of repaglinide.

Three unknown impurities and a byproduct in repaglinide bulk drug at levels below 0.1% (ranging from 0.05 to 0.1%) were detected by a simple isocratic reversed-phase high performance liquid chromatography (HPLC) method. These impurities were isolated from crude sample of repaglinide using reversed-phase preparative high performance liquid chromatography. Based on the spectroscopic data (IR, NMR and MS) the structures of these impurities (I, II and IV) and byproduct (III) were characterised as 4-carboxymethyl-2-ethoxy-benzoic acid (I), 4-cyclohexylaminocarbamoylmethyl-2-ethoxy-benzoic acid (II), 1-cyclohexyl-3-[3-methyl-1-(2-piperidin-1-yl-phenyl)-butyl]-urea (IV) and 1,3-dicyclohexyl urea (III), respectively. Their synthesis and formation is discussed.

Carbamates↗

A validated chiral HPLC method for the enantiomeric separation of Linezolid on amylose based stationary phase.

Two chiral HPLC methods namely method A and method B were developed for the separation of enantiomers of Linezolid. The mobile phases containing hexane, 2-propanol and trifluoro acetic acid (TFA) in the ratio (80:20:0.1, v/v/ v); hexane, ethanol and TFA in the ratio (65:35:0.1, v/v/v) were used in method A and method B, respectively. The assay results of the two methods were checked in terms of F-test variance ratio and found to be less than the table value, confirming their good precision. The enantiomeric separation of Linezolid on different chiral stationary phases was investigated. The two enantiomers of Linezoild were well resolved on a Chiralpak AD, an amylose based stationary phase. Preparative chiral HPLC was carried out to obtain pure (+) enantiomer of Linezolid from its racemate. The method A was extensively validated and found to be robust. The chiral assay of Linezolid in bulk and pharmaceutical formulations (tablet) were found to be 100.4 +/- 0.4 and 101.2 +/- 1.4%, respectively at 95% confidence interval. The percentage recovery of (+) enantiomer (chiral impurity) was found to be 99.2 +/- 1.9 at 95% confidence interval. The limit of detection and limit of quantification of (+) enantiomer were found to be 123 and 374 ng/ml, respectively for 10 microl injection volume.

Acetamides↗

Impurity profile study of loratadine.

Three unknown impurities in loratadine bulk drug at levels below 0.1% (ranging from 0.05 to 0.1%) were detected by a simple isocratic reversed-phase high performance liquid chromatography (HPLC). These impurities were isolated from mother liquor sample of loratadine using reversed-phase preparative HPLC. Based on the spectral data (IR, NMR and MS) the structures of these impurities were characterized as 11-(N-carboethoxy-4-piperidylidene)-6,11-dihydro-5H-benzo(5,6) cyclopenta(1,2-b)-pyridine (I), 8-bromo-11-(N-carboethoxy-4-piperidylidene)-6,11-dihydro-5H-benzo(5,6) cyclopenta (1,2-b)-pyridine (II) and 8-chloro-11-(N-carboethoxy-4-piperidylidene)-5H-benzo(5,6) cyclopenta (1,2-b)-pyridine (III). The synthesis of these impurities was discussed.

Chromatography, High Pressure Liquid↗

Isolation and characterization of process-related impurities in linezolid.

Two unknown impurities in linezolid bulk drug at levels below 0.1% (ranging from 0.05 to 0.1%) were detected by a simple isocratic reverse phase high performance liquid chromatography (HPLC). These impurities were isolated from crude sample of linezolid using reverse phase preparative HPLC. Based on the spectroscopic data (IR, NMR and MS) the structures of the impurities were characterized as (S)-N-[[-(3-(3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl] acetate(I) and (S)-N-[[-(3-(3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl] chloride(II). The synthesis from an unambiguous route and the formation of impurities was discussed.

Acetamides↗

Isolation and characterisation of process-related impurities in rofecoxib.

Two unknown impurities in rofecoxib bulk drug at levels below 0.1% were detected by a simple isocratic reverse phase high performance liquid chromatography (HPLC). These impurities were isolated from crude sample of rofecoxib using reverse phase preparative HPLC. (1)H, (13)C and Mass spectroscopic investigations revealed the structures of the impurities as 4-[4-(methylsulphonyl)phenyl]-3-phenyl-5-hydroxyfuran-2-one (I) and 4-[4-(methylsulphonyl)phenyl]-3-phenyl-2,5-furandione (II), respectively. These structures were further confirmed by prepared synthetic standards of the impurities. The tentative mechanism for the formation of these impurities was discussed.

Anti-Inflammatory Agents, Non-Steroidal↗

Anesthetic considerations in a patient with visceral leishmaniasis.

PURPOSE: To describe the anesthetic problems in a patient with visceral leishmaniasis undergoing general anesthesia. CLINICAL FEATURES: A 17-yr-old man with visceral leishmaniasis was booked for emergency appendectomy. He received parentral sodium stibogluconate 600 mg per day. The patient was pale, afebrile and had hepatosplenomegaly. Preoperative investigations showed a hemoglobin of 6.2 g.dL(-1), platelet count of 80 x 10(9).L(-1) and serum albumin of 2.1 g.dL(-1). The electrocardiogram and chest x-ray were normal. Anesthesia was induced with 100 microg fentanyl and 50 mg propofol iv and tracheal intubation was facilitated with 3 mg vecuronium iv. Maintenance of anesthesia was done with intermittent positive pressure ventilation using 50% nitrous oxide and 0.4% isoflurane in oxygen. Reversal of neuromuscular blockade was achieved with 1.0 mg neostigmine and 0.2 mg atropine iv. 50 mg tramadol iv every six hours was used for postoperative analgesia. The perioperative course was uneventful. CONCLUSION: Patients with visceral leishmaniasis have problems unique to them that may influence the anesthetic management. Of particular concern to an anesthesiologist are the presence of hematological abnormalities (anemia, leukopenia, thrombocytopenia), and hypoalbuminic malnutrition. The combination of low hemoglobin and thrombocytopenia may necessitate blood component therapy perioperatively. Drugs affecting coagulation should be used judiciously. Hypoalbuminemia may adversely affect the pharmacokinetics of agents that are highly protein bound. The anesthetic management in a patient with visceral leishmaniasis may be further complicated by the presence of coexisting infections like pneumonia and tuberculosis. Leishmaniasis is a recognized complication of infection with human immunodeficiency virus.

Adolescent↗

Internal jugular vein occlusion test for rapid diagnosis of misplaced subclavian vein catheter into the internal jugular vein.

BACKGROUND: During subclavian vein catheterization, the most common misplacement of the catheter is cephalad, into the ipsilateral internal jugular vein (IJV). This can be detected by chest radiography. However, after any repositioning of the catheter, subsequent chest radiography is required. In an effort to simplify the detection of a misplaced subclavian vein catheter, the authors assessed a previously published detection method. METHODS: One hundred adult patients scheduled for subclavian vein cannulation were included in this study. After placement of subclavian vein catheter, chest radiography was performed. While the x-ray film was being processed, the authors performed an IJV occlusion test by applying external pressure on the IJV for approximately 10 s in the supraclavicular area and observed the change in central venous pressure and its waveform pattern. The observations thus obtained were compared with the position of catheter in chest radiographs, and the sensitivity and specificity of this method were evaluated using a 2 x 2 table. RESULTS: In 96 patients, subclavian vein cannulation was successfully performed. In four patients, cannulation was unsuccessful; therefore, these patients were excluded from the study. There were six misplacements of venous catheters as detected by radiography. In five (5.2%) patients, the catheter tip was located in the ipsilateral IJV, and in one (1.02%), the catheter tip was located in the contralateral subclavian vein. In the patients who had a misplaced catheter into the IJV, IJV occlusion test results were positive, with an increase of 3-5 mmHg in central venous pressure, whereas the test results were negative in patients who had normally placed catheters or misplacement of a catheter other than in the IJV. There were no false-positive or false-negative test results. CONCLUSION: The IJV occlusion test successfully detects the misplacement of subclavian vein catheter into the IJV. However, it does not detect any other misplacement. The test may allow avoidance of repeated exposure to x-rays after catheter insertion and repositioning.

Adult↗

Preparation, characterization and in vitro antimicrobial activity of metronidazole bearing lectinized liposomes for intra-periodontal pocket delivery.

Liposomes constructed of egg phosphatidylcholine (EPC), cholesterol (Chol) and stearoylamine (SA) were coated with lectin (Concanavalin-A). These lectinized liposomes were found to retain the ligand binding activity of surface coated concanavalin A (Con-A) as demonstrated by bovine submaxillary mucin (BSM) binding assay. Moreover the ligand specificity of Con-A was maintained even after coating the liposome surface because the presence of competing sugar alpha-methyl mannoside, significantly inhibited the interaction of lectinized liposomes and BSM. The significance of divalent cations for these interactions was studied. The Con-A coating was found to be stable in simulated salivary fluids (SSF, pH 7.2) and under various pH conditions. In vitro targeting studies of lectinized liposomes with gram-negative bacilli (Streptococcus mutans) that harbor in the periodontal pocket (biofilm) demonstrated nearly 100% bacterial growth inhibition (% BGI). The antimicrobial effect was maintained for 360 min. The results were compared with metronidazole bearing plain (protein free/uncoated) liposomes and the free drug at the same dose levels. Mechanisms involved are also discussed. These observations suggest that liposomes coated with lectin (Con-A) were able to maintain the sugar affinity and specificity of the associated ligand and could be targeted to the surface 'glyco-calyx' of bacterial bio-film.

Anti-Bacterial Agents↗

Venous oxygen embolism due to hydrogen peroxide irrigation during posterior fossa surgery.

Hazards of application of hydrogen peroxide to semiclosed space are well known. We present a case of suspected gas embolism following hydrogen peroxide irrigation of the surgical field during posterior fossa surgery in the prone position. Severe cardiovascular collapse occurred when the wound was irrigated with hydrogen peroxide solution. Generation of pressure gradient leads to absorption of a considerable amount of oxygen giving rise to features of venous gas embolism. Although the case was associated with an uneventful recovery, use of hydrogen peroxide for securing hemostasis should be avoided.

Absorption↗