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Biomedical subjects

K Das

Publications and source records attributed to K Das.

At least 91 records · Page 5Linked to original sources
PubMed1999

Performance and potential impact of a chest pain prediction rule in a large public hospital.

PURPOSE: To evaluate the performance of a previously validated prediction rule for patients presenting to the emergency department with chest pain and the potential impact of the rule on triage decisions. SUBJECTS AND METHODS: In a prospective cohort study, physician investigators interviewed consecutive patients admitted for suspected acute ischemic heart disease (n = 207) by emergency department attending physicians who had not used the prediction rule. We measured the accuracy of the rule in predicting cardiac complications in these patients, and compared actual triage decisions with those that might have been recommended by use of the prediction rule. We also measured comorbid illnesses among patients stratified as very low risk by the prediction rule, as well as the effect of standardizing the definition of unstable angina and interpretation of electrocardiograms (ECG) on the rule's sensitivity and specificity. RESULTS: Overall, the rate of major cardiac complications (4.3%) was similar to that reported in the original study (3.6%). The prediction rule performed well in predicting these complications in our patients (area under receiver operating characteristic curve 0.84 versus 0.80 in the original study; difference 0.04, 95% confidence interval [CI] -0.07, 0.14). Standardized definitions of unstable angina and interpretation of ECGs improved the specificity of the prediction rule in predicting complications (55% versus 47%; difference 8%, 95% CI 1.5%, 13.7%). The prediction rule recommended admission to telemetry units in 65 fewer patients than actually occurred (31% of the entire cohort). None of these patients had major complications. A substantial minority of "very low risk" patients (27%) had comorbid illnesses requiring inpatient treatment. CONCLUSIONS: This independent validation of the prediction rule suggests that it can improve triage decisions for patients admitted with suspected acute ischemic heart disease. Additional studies are needed to test prospectively the performance of the prediction rule in actual decision making, its acceptance by clinicians, and its cost effectiveness.

Adult↗
PubMed1999

Neuroprotective effects of brain-derived neurotrophic factor in seizures during development.

Although the immature brain is highly susceptible to seizures, it is more resistant to seizure-induced neuronal loss than the adult brain. The developing brain contains high levels of neurotrophins which are involved in growth, differentiation and survival of neurons. To test the hypothesis that neurotrophins may protect the developing brain from seizure-induced neuronal loss, brain-derived neurotrophic factor up-regulation was blocked by intracerebroventricular infusion of an 18mer antisense oligodeoxynucleotide sequence to brain-derived neurotrophic factor in 19-day-old rats using micro-osmotic pumps. Control rats were infused with sense or missense oligodeoxynucleotide. Status epilepticus was induced by intraperitoneal administration of kainic acid 24 h after the start of oligodeoxynucleotide infusion. Seizure duration was significantly increased in the antisense oligodeoxynucleotide plus kainic acid group compared to groups that received kainic acid alone or kainic acid plus sense or missense oligodeoxynucleotide. There was no difference between groups in the latency to forelimb clonus. A twofold increase in brain-derived neurotrophic factor levels was observed in the hippocampus 20 h following kainic acid-induced seizures. This kainic acid-induced increase was absent in animals receiving infusion of antisense oligodeoxynucleotide to brain-derived neurotrophic factor at time of seizure induction. Hippocampi of rats in this group (antisense oligodeoxynucleotide plus kainic acid) showed a loss of CA1 and CA3 pyramidal cells and hilar interneurons. This neuronal loss was not dependent upon seizure duration since animals injected with diazepam to control seizure activity in the antisense plus kainic acid group also showed similar neuronal loss. Administration of kainic acid or infusion of antisense alone did not produce any cell loss in these regions. Induction of seizures at postnatal day 20, in the presence or absence of antisense oligonucleotide, did not produce an impairment in learning and memory when tested 15 days later in the Morris water maze. The hippocampi of these animals did not show any synaptic reorganization as assessed by growth-associated protein-43 immunostaining and Timm staining. Our findings confirm prior studies demonstrating that seizures in the immature brain are associated with little, if any, cell loss. However, when seizure-induced increase in brain-derived neurotrophic factor is blocked, seizures do result in neuronal loss in the developing brain. Thus, brain-derived neurotrophic factor appears to provide protection against kainic acid seizure-induced neuronal damage in the developing brain.

Animals↗
PubMed1999

Comparative effects of intravenous ketorolac and pethidine on perioperative analgesia and postoperative nausea and vomiting (PONV) for paediatric strabismus surgery.

BACKGROUND: Corrective strabismus surgery is associated with moderate pain and a very high incidence of postoperative nausea and vomiting (PONV). Ketorolac tromethamine, a nonsteroidal anti-inflammatory drug, is a popular analgesic in adults. There are only limited published data on the use of intravenous ketorolac for paediatric analgesia perioperatively. This study evaluated and compared the emetic and analgesic effect of ketorolac with pethidine and its suitability for this kind of surgery. METHODS: Following institutional ethics committee approval and parental consent, 52 ASA class I children of age 2.5 to 15 yr were randomised to receive either ketorolac 0.9 mg kg-1 or pethidine 0.5 mg kg-1 given intravenously (i.v.). A blinded observer assessed recovery by Steward's method immediately after arrival at the post anaesthesia care unit (PACU), pain by validated Objective Pain Score (OPS) at 0 h, 1/2 h and 1 h after arrival at the PACU and PONV by Numeric Rank Score at specified time intervals. RESULTS: There were no differences in demographic data, anaesthesia time or surgery duration. Recovery scores, OPS and postoperative analgesic requirement were similar in both groups. PONV at various time intervals for the first 24 h, occurred more frequently in the pethidine group as compared to the ketorolac group (P < 0.001) There were no side effects observed with either drug. CONCLUSION: Ketorolac in a dose of 0.9 mg kg-1 i.v. at the induction of anaesthesia is as effective as pethidine 0.5 mg kg-1 i.v. as an analgesic and is associated with significantly less PONV.

Adolescent↗
PubMed1999

Null mutation of the murine ATP7B (Wilson disease) gene results in intracellular copper accumulation and late-onset hepatic nodular transformation.

The Atp7b protein is a copper-transporting ATPase expressed predominantly in the liver and to a lesser extent in most other tissues. Mutations in the ATP7B gene lead to Wilson disease, a copper toxicity disorder characterized by dramatic build-up of intracellular hepatic copper with subsequent hepatic and neuro-logical abnormalities. Using homologous recombination to disrupt the normal translation of ATP7B, we have generated a strain of mice that are homozygous mutants (null) for the Wilson disease gene. The ATP7B null mice display a gradual accumulation of hepatic copper that increases to a level 60-fold greater than normal by 5 months of age. An increase in copper concentration was also observed in the kidney, brain, placenta and lactating mammary glands of homo-zygous mutants, although milk from the mutant glands was copper deficient. Morphological abnormalities resembling cirrhosis developed in the majority of the livers from homozygous mutants older than 7 months of age. Progeny of the homozygous mutant females demonstrated neurological abnormalities and growth retardation characteristic of copper deficiency. Copper concentration in the livers of the newborn homozygous null mutants was decreased dramatically. In summary, inactivation of the murine ATP7B gene produces a form of cirrhotic liver disease that resembles Wilson disease in humans and the 'toxic milk' phenotype in the mouse.

Adenosine Triphosphatases↗
PubMed1999

Approaches to the sellar and parasellar region: anatomic comparison of the microscope versus endoscope.

OBJECTIVE: Traditionally, surgical approaches to the sellar region require the use of the operating microscope. Over the past decade endoscopic surgery has gained much popularity because of advances in optics and illumination. Endoscopic surgery of the sellar region has been performed successfully. The goal of the present study was to quantify the amount of exposure to the sellar and suprasellar region that the endoscope provides versus the microscope, with three different anterior approaches to the sellar region. METHODS: The transethmoidal, endonasal-transsphenoidal, and sublabial-transsphenoidal approaches were performed on 14 formalin-fixed cadaver heads with a 0 degrees endoscope and repeated with the operative microscope. The distances of relevant surgical landmarks and the amount of exposure superior and anterior to the dorsum sella, as well as the lateral exposure, were measured. The mean distances were then used to calculate the volume of exposure for each of the approaches. RESULTS: It was found that the endoscope provided greater view than the operating microscope in all three approaches. The difference was statistically significant using a paired Student t test and a signed-rank test (P<.001). CONCLUSION: The authors believe that endoscopic surgery of the sellar region can be performed safely and effectively, while providing the surgeon with a view that is superior to that afforded by the operating microscope.

Cadaver↗
PubMed1999

Profile of non-compressive myelopathy in eastern India: a 2-year study.

Eighty-two patients with non-compressive myelopathy have been studied from July 1994 to June 1996 in Bangur Institute of Neurology and S.S.K.M. Hospital, Calcutta, of which 48 patients were men and 34 patients were women. Presentation was acute in 40 patients (48.78%), subacute in 7 (8.53%), chronic in 27 (32.92%) and history of relapse and remission in 8 (9.75%) patients. Preceding as well as simultaneous fever was observed in 16 cases (19.5%); vaccination (anti-rabies) in 1 case (1.21%); drug abuse in 1 case (1.21%); arthralgia-myalgia and rash in 2 cases (2.42%) and history of electrocution in 2 cases (2.42%). Only pyramidal tract involvement was present in 24 cases (29.26%) and remaining 58 cases (70.73%) had pyramidal tract affection with other sites of involvement. CSF study carried out in 60 cases, revealed rise of protein in 31 (37.8%); oligoclonal band had been detected in 6 (7.31%), pleocytosis in 18 cases (21.95%) and increased IgG index greater than 6.66 in 2 cases (2.42%). CT myelogram done in 23 cases revealed no abnormality. MRI study carried out in 59 cases showed myelomalacia in 1 (1.21%); demyelination plaque in 14 cases (17.07%); atrophy of cord in 3 (3.65%); infarction of cord in 1 (1.21%) and in 40 cases (48.78%) no abnormality could be detected. Etiological diagnosis could be established in 59 (71.95%) cases such as transverse myelitis or myelopathy (post infectious) in 24 (29.26%); demyelination in 16 (19.51%); vascular and vasculitis in 3 (3.65%); toxic in 1 (1.21%); physical (electrocution) in 2 cases (2.42%). In the remaining 23 cases (28.04%) no aetiological factors could be found.

Adult↗
PubMed1999

Photophysics of hypericin and hypocrellin A in complex with subcellular components: interactions with human serum albumin.

Time-resolved fluorescence and absorption measurements are performed on hypericin complexed with human serum albumin, HSA (1:4, 1:1 and approximately 5:1 hypericin: HSA complexes). Detailed comparisons with hypocrellin A/HSA complexes (1:4 and 1:1) are made. Our results are consistent with the conclusions of previous studies indicating that hypericin binds to HSA by means of a specific hydrogen-bonded interaction between its carbonyl oxygen and the N1-H of the tryptophan residue in the IIA subdomain of HSA. (They also indicate that some hypericin binds nonspecifically to the surface of the protein.) A single-exponential rotational diffusion time of 31 ns is measured for hypericin bound to HSA, indicating that it is very rigidly held. Energy transfer from the tryptophan residue of HSA to hypericin is very efficient and is characterized by a critical distance of 94 A, from which we estimate a time constant for energy transfer of approximately 3 x 10(-15) s. Although it is tightly bound to HSA, hypericin is still capable of executing excited-state intramolecular proton (or hydrogen atom) transfer in the approximately 5:1 complex, albeit to a lesser extent than when it is free in solution. It appears that the proton transfer process is completely impeded in the 1:1 complex. The implications of these results for hypericin (and hypocrellin A) are discussed in terms of the mechanism of intramolecular excited-state proton transfer, the mode of binding to HSA and the light-induced antiviral and antitumor activity.

Anthracenes↗
PubMed1999

Fluorescence properties of recombinant tropomyosin containing tryptophan, 5-hydroxytryptophan and 7-azatryptophan.

Tropomyosin mutants containing either tryptophan (122W), 5-hydroxytryptophan (5OH122W) or 7-azatryptophan (7N122W) have been expressed in Escherichia coli and their fluorescence properties studied. The fluorescent amino acids were located at position 122 of the tropomyosin primary sequence, corresponding to a solvent-exposed position c of the coiled-coil heptapeptide repeat. The emission spectrum of the probe in each mutant is blue-shifted slightly with respect to that of the probe in water. The fluorescence anisotropy decays are single exponential, with a time constant of 2-3 ns while the fluorescence lifetimes of the probes incorporated into the proteins, in water, are nonexponential. Because tryptophan in water has an intrinsic nonexponential fluorescence decay, it is not surprising that the fluorescence decay of 122W is well described by a triple exponential. The fluorescence decays in water of the nonnatural amino acids 5-hydroxytryptophan and 7-azatryptophan (when emission is collected from the entire band) are single exponential. Incorporation into tropomyosin induces triple-exponential fluorescence decay in 5-hydroxytryptophan and double-exponential fluorescence decay in 7-azatryptophan. The range of lifetimes observed for 5-hydroxyindole and 5-hydroxytryptophan at high pH and in the nonaqueous solvents were used as a base with which to interpret the lifetimes observed for the 5OH122W and indicate that the chromophore exists in several solvent environments in both its protonated and unprotonated forms in 5OH122W.

5-Hydroxytryptophan↗
PubMed1998

Structure and functional implications of the polymerase active site region in a complex of HIV-1 RT with a double-stranded DNA template-primer and an antibody Fab fragment at 2.8 A resolution.

The structure of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) complexed with a 19-mer/18-mer double-stranded DNA template-primer (dsDNA) and the Fab fragment of monoclonal antibody 28 (Fab28) has been refined at 2.8 A resolution. The structures of the polymerase active site and neighboring regions are described in detail and a number of novel insights into mechanisms of polymerase catalysis and drug inhibition are presented. The three catalytically essential amino acid residues (Asp110, Asp185, and Asp186) are located close to the 3' terminus of the primer strand. Observation of a hydrogen bond between the 3'-OH of the primer terminus and the side-chain of Asp185 suggests that the carboxylate of Asp185 could act as a general base in initiating the nucleophilic attack during polymerization. Nearly all of the close protein-DNA interactions involve atoms of the sugar-phosphate backbone of the nucleic acid. However, the phenoxyl side-chain of Tyr183, which is part of the conserved YMDD motif, has hydrogen-bonding interactions with nucleotide bases of the second duplex base-pair and is predicted to have at least one hydrogen bond with all Watson-Crick base-pairs at this position. Comparison of the structure of the active site region in the HIV-1 RT/dsDNA complex with all other HIV-1 RT structures suggests that template-primer binding is accompanied by significant conformational changes of the YMDD motif that may be relevant for mechanisms of both polymerization and inhibition by non-nucleoside inhibitors. Interactions of the "primer grip" (the beta12-beta13 hairpin) with the 3' terminus of the primer strand primarily involve the main-chain atoms of Met230 and Gly231 and the primer terminal phosphate. Alternative positions of the primer grip observed in different HIV-1 RT structures may be related to conformational changes that normally occur during DNA polymerization and translocation. In the vicinity of the polymerase active site, there are a number of aromatic residues that are involved in energetically favorable pi-pi interactions and may be involved in the transitions between different stages of the catalytic process. The protein structural elements primarily responsible for precise positioning of the template-primer (including the primer grip, template grip, and helices alphaH and alphaI of the p66 thumb) can be thought of functioning as a "translocation track" that guides the relative movement of nucleic acid and protein during polymerization.

Amino Acid Sequence↗
PubMed1998

Structures of Tyr188Leu mutant and wild-type HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor HBY 097: inhibitor flexibility is a useful design feature for reducing drug resistance.

The second generation Hoechst-Bayer non-nucleoside inhibitor, HBY 097 (S-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3, 4-dihydroqui noxalin-2(1H)-thione), is an extremely potent inhibitor of HIV-1 reverse transcriptase (RT) and of HIV-1 infection in cell culture. HBY 097 selects for unusual drug-resistance mutations in HIV-1 RT (e.g. Gly190Glu) when compared with other non-nucleoside RT inhibitors (NNRTIs), such as nevirapine, alpha-APA and TIBO. We have determined the structure of HBY 097 complexed with wild-type HIV-1 RT at 3.1 A resolution. The HIV-1 RT/HBY 097 structure reveals an overall inhibitor geometry and binding mode differing significantly from RT/NNRTI structures reported earlier, in that HBY 097 does not adopt the usual butterfly-like shape. We have determined the structure of the Tyr188Leu HIV-1 RT drug-resistant mutant in complex with HBY 097 at 3.3 A resolution. HBY 097 binds to the mutant RT in a manner similar to that seen in the wild-type RT/HBY 097 complex, although there are some repositioning and conformational alterations of the inhibitor. Conformational changes of the structural elements forming the inhibitor-binding pocket, including the orientation of some side-chains, are observed. Reduction in the size of the 188 side-chain and repositioning of the Phe227 side-chain increases the volume of the binding cavity in the Tyr188Leu HIV-1 RT/HBY 097 complex. Loss of important protein-inhibitor interactions may account for the reduced potency of HBY 097 against the Tyr188Leu HIV-1 RT mutant. The loss of binding energy may be partially offset by additional contacts resulting from conformational changes of the inhibitor and nearby amino acid residues. This would suggest that inhibitor flexibility can help to minimize drug resistance.

Antiviral Agents↗
PubMed1998

Mutational analysis of caveolin-induced vesicle formation. Expression of caveolin-1 recruits caveolin-2 to caveolae membranes.

Caveolae are vesicular organelles with a characteristic uniform diameter in the range of 50-100 nm. Although recombinant expression of caveolin-1 is sufficient to drive caveolae formation, it remains unknown what controls the uniform diameter of these organelles. One hypothesis is that specific caveolin-caveolin interactions regulate the size of caveolae, as caveolin-1 undergoes two stages of self-oligomerization. To test this hypothesis directly, we have created two caveolin-1 deletion mutants that lack regions of caveolin-1 that are involved in directing the self-assembly of caveolin-1 oligomers. More specifically, Cav-1 delta61-100 lacks a region of the N-terminal domain that directs the formation of high molecular mass caveolin-1 homo-oligomers, while Cav-1 deltaC lacks a complete C-terminal domain that is required to allow caveolin homo-oligomers to interact with each other, forming a caveolin network. It is important to note that these two mutants retain an intact transmembrane domain. Our current results show that although Cav-1 delta61-100 and Cav-1 deltaC are competent to drive vesicle formation, these vesicles vary widely in their size and shape with diameters up to 500-1000 nm. In addition, caveolin-induced vesicle formation appears to be isoform-specific. Recombinant expression of caveolin-2 under the same conditions failed to drive the formation of vesicles, while caveolin-3 expression yielded caveolae-sized vesicles. These results are consistent with the previous observation that in transformed NIH 3T3 cells that lack caveolin-1 expression, but continue to express caveolin-2, no morphologically distinguishable caveolae are observed. In addition, as caveolin-2 alone exists mainly as a monomer or homo-dimer, while caveolins 1 and 3 exist as high molecular mass homo-oligomers, our results are consistent with the idea that the formation of high molecular mass oligomers of caveolin are required to regulate the formation of uniform caveolae-sized vesicles. In direct support of this notion, regulated induction of caveolin-1 expression in transformed NIH 3T3 cells was sufficient to recruit caveolin-2 to caveolae membranes. The ability of caveolin-1 to recruit caveolin-2 most likely occurs through a direct interaction between caveolins 1 and 2, as caveolins 1 and 2 are normally co-expressed and interact with each other to form high molecular mass hetero-oligomers containing both caveolins 1 and 2.

3T3 Cells↗
PubMed1998

Results of a genome-wide genetic screen for panic disorder.

Panic disorder is characterized by spontaneous and recurrent panic attacks, often accompanied by agoraphobia. The results of family, twin, and segregation studies suggest a genetic role in the etiology of the illness. We have genotyped up to 23 families that have a high density of panic disorder with 540 microsatellite DNA markers in a first-pass genomic screen. The thirteen best families (ELOD > 6.0 under the dominant genetic model) have been genotyped with an ordered set of markers encompassing all the autosomes, at an average marker density of 11 cM. Over 110,000 genotypes have been generated on the whole set of families, and the data have been analyzed under both a dominant and a recessive model, and with the program SIBPAIR. No lod scores exceed 2.0 for either parametric model. Two markers give lod scores over 1.0 under the dominant model (chromosomes 1p and 20p), and four do under the recessive model (7p, 17p, 20q, and X/Y). One of these (20p) may be particularly promising. Analysis with SIBPAIR yielded P values equivalent to a lod score of 1.0 or greater (i.e., P < .016, one-sided, uncorrected for multiple tests) for 11 marker loci (2, 7p, 8p, 8q, 9p, 11q, 12q, 16p, 20p and 20q).

Adolescent↗
PubMed1998

Posterolateral approach for decompression with anterior and posterior fusion: a less invasive surgical technique for stabilization of the thoracic spine. Case report.

The goals of surgery in unstable thoracic fractures or tumors involving the thoracic spine are neural decompression, correction of deformity, and stabilization. Several different approaches can be used to achieve these goals. The anterior, combined anterior and posterior, and more recently thoracoscopic approaches are well described in the literature and are extremely effective in achieving the goals mentioned. However, they do carry with them significant morbidity and mortality rates in patients who are elderly, who have associated medical problems, or for whom there are contraindications to thoracic surgery. The authors believe the posterolateral approach is a viable alternative that is reasonably well tolerated in this select patient population. One can achieve circumferential neural decompression as well as anterior and posterior arthrodesis through a single incision. Most neurosurgeons are familiar with the anatomical landmarks and technical steps in the posterolateral approach, and the authors believe it is a less invasive method that can be especially useful and should not be overlooked in this subgroup of patients.

Journal Article↗
PubMed1998

Results of clinically downstaging cervical cancer in a cytological screening programme.

The study was aimed at clinically downstaging cancer of the cervix during a cytological Screening Programme to find out whether such a strategy may help in yielding a large number of early cases of cancer. A cohort of 6,178 women with different cervical lesions were cytologically examined from April 1971 at Queen Mary's Hospital, Lucknow, India. The 8,718 asymptomatic women with healthy cervices were taken as controls. The incidence of cervical dysplasia and malignancy in the study group was found to be 11.2% and 1.9%, which was statistically highly significant compared to control values of 3.3% and 0.02%, respectively. Dysplastic smears were seen maximally in women whose cervix bled to the touch, and the rate of cervical cancer was high in women with suspicious cervix. Dysplastic smears were seen frequently in all age and parity groups, but malignancy was common in women of high age (over 30 years) and high parity (two and above). The incidence of three sexually transmitted diseases, namely Trichomonas vaginalis, Herpes simplex, and condyloma revealed highly significant values, especially in women whose cervix bled to the touch. The study highlights the strategy of clinically downstaging cervical cancer, which is very useful in detecting a large number of dysplasia and frank malignancy cases and also the presence of any associated sexually transmitted pathogens whose treatment would aid in restricting the rising incidence of the dreaded disease in this country.

Adolescent↗