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Biomedical subjects

A Acharya

Publications and source records attributed to A Acharya.

At least 19 recordsLinked to original sources

Brain abscess due to Scedosporium apiospermum in a non immunocompromised child.

Scedosporium apiospermum is a filamentous fungi that commonly causes cutaneous infection. In certain circumstances, S. apiospermum can also cause invasive disease, which can involve the central nervous system (CNS). When the CNS becomes involved, treatment is difficult, therapeutic options are limited and the prognosis is poor. Early identification and treatment can decrease the mortality rate. Here we present a case of brain abscess with chronic suppurative otitis media, caused by S. apiospermum. This is the first such case report from Nepal. We could identify the organism only post mortem. We could not save the patient, probably due to delay in diagnosis.

Aminoglycosides↗

Anaesthesia-related maternal mortality.

Complications of anaesthesia leading to death in young pregnant women might be prevented if more experienced personnel could be entrusted with the job. The contribution of anaesthesia to maternal mortality in the United Kingdom is 1.7 per million pregnancies with almost similar incidence from United States. The commonest single factor responsible for anaesthesia-related death is difficult or failed intubation. A pregnant woman with a potentially difficult airway should receive aspiration prophylaxis (mechanical or pharmacological) as soon as operative delivery is anticipated. Anaesthetists should make a plan that comes into effect as soon as failure to view the larynx or to intubate the trachea becomes evident. Unsuspected difficult airway can be managed if the skill of the anaesthetists is of high standard. Pulmonary aspiration is one cause of death in obstetric anaesthesia. Regurgitation and vomiting prevention can minimise pulmonary aspiration. In regional anaesthesia, local anaesthetics toxicity is another cause of concern. This should be tackled with some safe local anaesthetics. Preventing a high spinal or epidural block involves ways to detect inadvertent injection of local anaesthetic into the cerebrospinal fluid. Postoperative care after anaesthesia in obstetric cases is very important.

Anesthesia, Conduction↗

Caudal additives in pediatrics: a comparison among midazolam, ketamine, and neostigmine coadministered with bupivacaine.

Single-shot "kiddie caudal" with bupivacaine alone is losing popularity because of its duration of 4-8 h. In a prospective randomized double-blind clinical study, we assessed and compared the efficacy of ketamine, midazolam, and neostigmine coadministered with bupivacaine in a caudal epidural to provide intraoperative and postoperative pain relief. Eighty children (ASA status I) aged 5-10 yr undergoing unilateral inguinal herniotomy were allocated randomly in equal numbers (n = 20) into 4 groups to receive a caudal injection of 0.25% bupivacaine (1 mL/kg) with or without ketamine (0.5 mg/kg), midazolam (50 microg/kg), and neostig-mine (2 microg/kg), after the induction of standardized general anesthesia without premedication. Monitoring for pain, sedation, postoperative nausea/vomiting, dizziness, and pruritus was performed by anesthesiologists blinded to the study allocation. The time to first analgesic administration (paracetamol syrup) was longer (P < 0.05) in the bupivacaine-neostigmine group and the bupivacaine-midazolam group than in the other groups. Undesirable effects, such as emesis, pruritus, and dizziness, were comparable in all groups. However, the incidence of hallucination was more frequent in the bupivacaine-ketamine group compared with the other groups. This study shows that single-shot caudal coadministration of bupivacaine-neostigmine and bupivacaine-midazolam was associated with an extended duration of postoperative pain relief.

Anesthesia Recovery Period↗

Management of intracapsular femoral neck fractures in the elderly; is it time to rethink our strategy?

We reviewed 100 adult patients who had a traumatic intracapsular femoral fracture internally fixed prior to 1998, with full clinical and radiological data available. End points were complete clinical and radiological union of the fracture, non-union, avascular necrosis or fixation failure. The incidence of non-union and avascular necrosis was found to be 13 and 11%, respectively. The following factors did not influence the development of avascular necrosis or non-union; fracture displacement, screws inserted (two or three), osteoporosis, parallelism of screws, presence of screws in each "quadrant" and the experience or seniority of the surgeon. The factors influencing a poor outcome were the age of the patient at injury, reduction gap at the fracture site, alignment after reduction of the fracture especially on AP view and having all screw threads crossing beyond the fracture site. We conclude that the incidence of non-union and avascular necrosis following fixation of femoral neck fractures in our study is less than generally reported with no statistical difference between displaced and undisplaced fractures. Traditional fixation factors such as screw position and number do not seem to significantly affect the outcome with the quality of reduction being most important. Thus, the majority of patients under the age of 70 with displaced intracapsular fracture should be considered for internal fixation.

Age Factors↗

Physicochemical investigations of microemulsification of coconut oil and water using polyoxyethylene 2-cetyl ether (Brij 52) and isopropanol or ethanol.

The microemulsification of coconut oil/polyoxyethylene 2-cetyl ether/2-propanol or ethanol/water was investigated. The phase behaviors of the mixed system were examined. The shear viscosity at different temperatures was measured to derive activation parameters for the viscous flow. The diffusion coefficient of the microemulsions at different compositions was determined by the DLS method. The energetics of solubilization of water into oil + Brij + alkanol as well as of oil into water + Brij + alkanol forming w/o and o/w microemulsions, respectively, were calorimetrically determined.

Journal Article↗

Physicochemical investigations on microemulsification of eucalyptol and water in presence of polyoxyethylene (4) lauryl ether (Brij-30) and ethanol.

The microemulsification of eucalyptol/polyoxyethylene(4)lauryl ether (Brij-30)/ethanol/water has been investigated. The phase behaviours of the mixed system in pseudoternary and tetrahedral representations have been examined to understand the topological nature of the multicomponent mixtures. Phase volumes of the heterogeneous combinations have been estimated to understand the mixing efficacy of the combinations. Shear viscosities of different monophasic compositions have been measured at different shear rates and temperatures, and the activation parameters for the viscous flow have been evaluated. The dimensions of the nanodispersions of w/o and o/w types, their diffusion coefficients and the polydispersity have been determined by the DLS method. The energetics of solubilisation (dissolution) of water in oil+Brij-30+ethanol as well as oil in water+Brij-30+ethanol forming w/o and o/w microemulsions, respectively, have been calorimetrically determined. Considering the phase separation point to be the point of maximum solubility, the energetic parameters (enthalpy, free energy and entropy) of the microemulsification process have been estimated.

Calorimetry↗

S-adenosyl-L-methionine is required for DNA cleavage by type III restriction enzymes.

The requirement of S-adenosyl-L-methionine (AdoMet) in the cleavage reaction carried out by type III restriction-modification enzymes has been investigated. We show that DNA restriction by EcoPI restriction enzyme does not take place in the absence of exogenously added AdoMet. Interestingly, the closely related EcoP15I enzyme has endogenously bound AdoMet and therefore does not require the addition of the cofactor for DNA cleavage. By employing a variety of AdoMet analogs, which differ structurally from AdoMet, this study demonstrates that the carboxyl group and any substitution at the epsilon carbon of methionine is absolutely essential for DNA cleavage. Such analogs could bring about the necessary conformational change(s) in the enzyme, which make the enzyme proficient in DNA cleavage. Our studies, which include native polyacrylamide gel electrophoresis, molecular size exclusion chromatography, UV, fluorescence and circular dichroism spectroscopy, clearly demonstrate that the holoenzyme and apoenzyme forms of EcoP15I restriction enzyme have different conformations. Furthermore, the Res and Mod subunits of the EcoP15I restriction enzyme can be separated by gel filtration chromatography in the presence of 2 M NaCl. Reconstitution experiments, which involve mixing of the isolated subunits, result in an apoenzyme form, which is restriction proficient in the presence of AdoMet. However, mixing the Res subunit with Mod subunit deficient in AdoMet binding does not result in a functional restriction enzyme. These observations are consistent with the fact that AdoMet is required for DNA cleavage. In vivo complementation of the defective mod allele with a wild-type mod allele showed that an active restriction enzyme could be formed. Furthermore, we show that while the purified c2-134 mutant restriction enzyme is unable to cleave DNA, the c2-440 mutant enzyme is able to cleave DNA albeit poorly. Taken together, these results suggest that AdoMet binding causes conformational changes in the restriction enzyme and is necessary to bring about DNA cleavage.

Alleles↗

Development of WHO guidelines on generalized cost-effectiveness analysis.

The growing use of cost-effectiveness analysis (CEA) to evaluate specific interventions is dominated by studies of prospective new interventions compared with current practice. This type of analysis does not explicitly take a sectoral perspective in which the costs and effectiveness of all possible interventions are compared, in order to select the mix that maximizes health for a given set of resource constraints. WHO guidelines on generalized CEA propose the application of CEA to a wide range of interventions to provide general information on the relative costs and health benefits of different interventions in the absence of various highly local decision constraints. This general approach will contribute to judgements on whether interventions are highly cost-effective, highly cost-ineffective, or something in between. Generalized CEAs require the evaluation of a set of interventions with respect to the counterfactual of the null set of the related interventions, i.e. the natural history of disease. Such general perceptions of relative cost-effectiveness, which do not pertain to any specific decision-maker, can be a useful reference point for evaluating the directions for enhancing allocative efficiency in a variety of settings. The proposed framework allows the identification of current allocative inefficiencies as well as opportunities presented by new interventions.

Cost-Benefit Analysis↗

Selective estrogen receptor modulators suppress mesangial cell collagen synthesis.

Estrogen receptor modulators (SERMs) are "designer drugs" that exert estrogen-like actions in some cells but not in others. We examined the effects of the SERMs LY-117018 (an analog of raloxifene) and tamoxifen on mesangial cells synthesis of type I and type IV collagen. We found that LY-117018 and tamoxifen suppressed mesangial cell type IV collagen gene transcription and type IV collagen protein synthesis in a dose-dependent manner, with a potency identical to that of estradiol. Type I collagen synthesis was also suppressed by LY-117018 in a dose-dependent manner with a potency identical to that of estradiol but greater than that of tamoxifen. Genistein, which selectively binds to estrogen receptor-beta in nanomolar concentrations, suppressed type I and type IV collagen synthesis, suggesting that estrogen receptor-beta mediates the effects of estrogen on collagen synthesis. Because matrix accumulation is central to the development of glomerulosclerosis, second-generation SERMs may prove clinically useful in ameliorating progressive renal disease without the adverse effects of estrogen on reproductive tissues.

Angiotensin II↗

Mycophenolate mofetil therapy for lupus nephritis refractory to intravenous cyclophosphamide.

Intravenous (i.v.) cyclophosphamide has been the treatment of choice for diffuse proliferative glomerulonephritis (DPGN) in patients with systemic lupus erythematosus (SLE). However, there is little guidance in the medical literature about what to do when this therapy fails. Mycophenolate mofetil (MMF), a new immunosuppressive agent, has been used successfully in patients with solid organ transplants and rheumatoid arthritis. We report two patients with diffuse proliferative glomerulonephritis who responded favorably to MMF therapy after i.v. cyclophosphamide failed.

Adult↗

Heparin-releasable lipoprotein lipase activity is increased in cardiomyocytes after culture.

The activity of lipoprotein lipase (LPL) in adult rat heart cardiomyocytes after overnight culture on laminin-coated plates for 18-22 h was compared with enzyme activity in freshly isolated cardiomyocytes. LPL activity in cellular homogenates from cultured cardiomyocytes and freshly isolated cells was 240 and 233 nmol oleate released h-1.mg-1 protein, respectively. LPL specific activity (mU/ng LPL protein) was 0.07 in cultured cells compared with 0.42 in freshly isolated cells, indicating an increased content of inactive LPL mass after overnight culture. The heparin-induced release of LPL activity into the medium of cultured cardiomyocytes (198 nmol.h-1.mg-1) was much greater than heparin-releasable LPL (HR-LPL) activity (59 nmol.h-1.mg-1) from freshly isolated cells. HR-LPL activity from cultured cardiomyocytes was dependent on serum (16.3-fold activation) and was inhibited by high ionic strength (1 M NaCl) and by a polyclonal antibody to LPL. Cultured cardiomyocytes also had more immunodetectable LPL on the cell surface compared with freshly isolated cardiomyocytes, consistent with increased HR-LPL activity. Therefore, overnight culture may permit cardiomyocytes time to recover from the stress of isolation by increasing the content of LPL on the cell surface.

Animals↗

A methodology for specifying PET VOI's using multimodality techniques.

Volume-of-interest (VOI) extraction for radionuclide and anatomical measurements requires correct identification and delineation of the anatomical feature being studied. We have developed a toolset for specifying three-dimensional (3-D) VOI's on a multislice positron emission tomography (PET) dataset. The software is particularly suited for specifying cerebral cortex VOI's which represent a particular gyrus or deep brain structure. A registered 3-D magnetic resonance image (MRI) dataset is used to provide high-resolution anatomical information, both as oblique two-dimensional (2-D) sections and as volume renderings of a segmented cortical surface. VOI's are specified indirectly in two dimensions by drawing a stack of 2-D regions on the MRI data. The regions are tiled together to form closed triangular mesh surface models, which are subsequently transformed into the observation space of the PET scanner. Quantification by this method allows calculation of radionuclide activity in the VOI's, as well as their statistical uncertainties and correlations. The methodology for this type of analysis and validation results are presented.

Brain↗

Fatty acids reduce heparin-releasable LPL activity in cultured cardiomyocytes from rat heart.

Varying glucose and fatty acid (FA) concentrations in the medium of cultured cardiomyocytes from adult rat hearts were tested for effects on lipoprotein lipase (LPL) activity. Glucose (5.5, 11, and 25 mM in the culture medium for 18-22 h) had no effect on either heparin-releasable LPL (HR-LPL) or on cellular LPL (C-LPL) activities. When cardiomyocytes were cultured overnight with 60 microM oleate, HR-LPL activity was reduced to 20% of control, with no change in C-LPL activity or total C-LPL mass. Similar results (HR-LPL and C-LPL activities) were obtained with 60 microM concentrations of palmitate and myristate; linoleate and eicosapentaenoate did reduce C-LPL activity, but the decrease in HR-LPL activity was much greater. Oxfenicine, an FA oxidation inhibitor, did not alter the inhibitory effect of 60 microM oleate on HR-LPL. Short-term incubations (1 and 3 h) of cultured cardiomyocytes with 60 microM oleate did not displace LPL into the medium. Immunodetectable LPL on the cell surface of oleate-treated cultured cardiomyocytes was increased compared with control cells, but heparin treatment released the same amount of LPL mass that had reduced catalytic activity.

Animals↗