Trichosporon asahii. Blood-stream infection in a non-cancer patient receiving combination antifungal therapy.
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Accidents, Occupational↗
Biomedical subjects
A Bedi
Publications and source records attributed to A Bedi.
The effects of subanaesthetic concentrations of xenon in volunteers.
This study reports the subjective, psychomotor and physiological properties of subanaesthetic concentrations of xenon. Ten healthy male volunteers received either xenon or nitrous oxide in a randomised crossover study design. The subjects breathed either xenon (Xe) or nitrous oxide (N2O) from a closed circuit breathing system, according to a randomised, double-blind protocol. The concentration of xenon required to produce sedation, ranged between 27 and 45% (median 35%). All subjects completed the xenon protocol. Subjects were tested using the Critical Flicker Fusion test and derived electroencephalogram parameters, however, neither test was found to reliably predict sedation. The respiratory rate decreased markedly during sedation with xenon. The subjects did not experience any airway irritability (coughing, breath-holding or laryngospasm) during administration of either gas. One subject required anti-emetic treatment in the N2O group compared to none in the Xe group. Eight subjects reported that they found sedation with xenon pleasant and preferable to nitrous oxide. Xenon sedation was well tolerated and was not associated with any adverse physiological effects, however, it was reported to be subjectively dissimilar to nitrous oxide.
Adult↗
Xenon has no effect on cytokine balance and adhesion molecule expression within an isolated cardiopulmonary bypass system.
BACKGROUND: Although almost inert chemically, xenon is not unreactive biologically. It interacts with receptors involved in the expression of cytokines and adhesion molecules. The effect of xenon on the immune function in whole blood has not been studied. METHODS: We examined the effects of 70% xenon in oxygen on cytokine balance and expression of adhesion molecules in an isolated cardiopulmonary bypass (CPB) system, which simulates an evolving inflammatory response. Whole blood from 10 healthy male volunteers was circulated in a CBP system supplied with either 70% xenon in oxygen, or oxygen-enriched air - FO(2)=0.3 (control). We took samples of blood after 30, 60 and 90 min of simulated CBP. We measured interleukin (IL)-1beta, tumour necrosis factor (TNF)alpha, IL-8, IL-10, IL-1ra and TNF-sr-2 levels, and the expression of HLA-DR and the adhesion molecules L-selectin, CD18 and CD11b on monocytes, granulocytes and lymphocytes. RESULTS: IL-8 concentrations were increased significantly, TNF-sr-2 concentrations decreased significantly and IL-10 levels decreased during bypass. There were no significant differences between the groups for any measured variable. CONCLUSION: In an isolated CPB system, xenon and oxygen-enriched air had similar effects on cytokine production and expression of adhesion molecules.
Aged↗
Successful defibrillation in the prone position.
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Electric Countershock↗
Overexpression of a dominant-negative signal transducer and activator of transcription 3 variant in tumor cells leads to production of soluble factors that induce apoptosis and cell cycle arrest.
Gene therapy of B16 tumors with a dominant-negative signal transducer and activator of transcription (Stat3) variant, designated Stat3beta, results in inhibition of tumor growth and tumor regression. Although only 10-15% of the tumor cells are transfected in vivo, the Stat3beta-induced antitumor effect is associated with massive apoptosis of B16 tumor cells, indicative of a potent bystander effect. Here, we provide evidence that blocking Stat3 signaling in B16 cells results in release of soluble factors that are capable of inducing apoptosis and cell cycle arrest of nontransfected B16 cells. RNase protection assays using multi-template probes specific for key physiological regulators of apoptosis reveal that overexpression of Stat3beta in B16 tumor cells induces the expression of the apoptotic effector, tumor necrosis factor-related apoptosis-inducing ligand. These in vitro results suggest that the observed in vivo bystander effect leading to tumor cell growth inhibition is mediated, at least in part, by soluble factors produced as a result of overexpression of Stat3beta in tumor cells.
3T3 Cells↗
Regulation of death receptor expression and TRAIL/Apo2L-induced apoptosis by NF-kappaB.
TRAIL (tumour-necrosis factor-related apoptosis ligand or Apo2L) triggers apoptosis through engagement of the death receptors TRAIL-R1 (also known as DR4) and TRAIL-R2 (DR5). Here we show that the c-Rel subunit of the transcription factor NF-kappaB induces expression of TRAIL-R1 and TRAIL-R2; conversely, a transdominant mutant of the inhibitory protein IkappaBalpha or a transactivation-deficient mutant of c-Rel reduces expression of either death receptor. Whereas NF-kappaB promotes death receptor expression, cytokine-mediated activation of the RelA subunit of NF-kappaB also increases expression of the apoptosis inhibitor, Bcl-xL, and protects cells from TRAIL. Inhibition of NF-kappaB by blocking activation of the IkappaB kinase complex reduces Bcl-x L expression and sensitizes tumour cells to TRAIL-induced apoptosis. The ability to induce death receptors or Bcl-xL may explain the dual roles of NF-kappaB as a mediator or inhibitor of cell death during immune and stress responses.
Animals↗
The in vitro performance of carbon dioxide absorbents with and without strong alkali apparatus.
We report the in vitro longevity of a conventional soda lime carbon dioxide absorbent and an absorbent free from strong alkali (Amsorb). Although the times taken to breakthrough of carbon dioxide (> 0.5%) within an in vitro low flow breathing system were shorter with the alkali-free absorbent, we found that the size and shape of the absorbent container was the major factor in determining the efficiency of the carbon dioxide absorbents.
Absorption↗
Prolonged QRS duration (QRS >/=170 ms) and left axis deviation in the presence of left bundle branch block: A marker of poor left ventricular systolic function?
BACKGROUND: Left bundle branch block (LBBB) is commonly associated with structural heart disease and left ventricular dysfunction. We propose that the QRS duration and degree of left-axis deviation (LAD) identify significant left ventricular systolic dysfunction in patients with LBBB. METHODS: In this prospective study the ejection fraction (EF) of 300 consecutive patients with LBBB was evaluated by echocardiography. The relationship between QRS duration and LAD (axis between -30 degrees and -90 degrees ) and EF were derived. RESULTS: There was no significant difference in age, sex, presence of ischemic or nonischemic cardiomyopathy and valvular heart disease, and EF among the patients with or without LAD. The EF of patients with QRS >/=170 milliseconds with LAD (n = 20) and without LAD (n = 18) was 25% +/- 16% and 23% +/- 13%, respectively (P =.71). The mean EF (24% +/- 10%) of the patients with a QRS duration of >/=170 milliseconds (n = 38) was significantly lower than the mean EF (36% +/- 16%) of the patients with a QRS duration of <170 milliseconds (n = 262, P <.015). The QRS duration also had a significant (P <.001) inverse correlation with EF (R = 0.37, adjusted R (2) = 0.13, SE of estimate = 16.21). However, the QRS axis was not significantly correlated with EF and did not have added predictive value. CONCLUSIONS: The QRS duration has a significant inverse relationship with EF and prolongation of QRS duration (>/=170 milliseconds) in the presence of LBBB is a marker of significant left ventricular systolic dysfunction. The presence of LAD in LBBB does not signify a further decrease in EF.
Bundle-Branch Block↗
Inhalational anaesthesia.
Sevoflurane and desflurane have important advantages over isoflurane and halothane. Disadvantages, which the clinician should keep in mind, include the degradation of both agents by soda lime under certain circumstances during closed circuit anaesthesia. As a result compound A and carbon monoxide (CO) may be generated in soda lime canisters and may be inhaled by patients. The extent to which this constitutes a significant problem during routine anaesthesia in humans is not clear. Recent developments in absorbent technology have the potential to reduce any hazard to negligible proportions. Other undesirable properties of the newer inhalation agents include agitation with sevoflurane in children and cardiovascular and airway effects with desflurane.
Journal Article↗
Acute renal infarction secondary to left ventricular thrombus, masquerading as a renal calculus--a case report and brief review of literature.
Acute embolic renal infarction is an entity that is often misdiagnosed as a renal calculus because of similar presenting symptoms. This leads to delay in the initiation of treatment and to increased morbidity. Few case reports exist relating cardiac emboli to acute renal infarction. The authors present a patient with a renal embolism secondary to left ventricular thrombus. A brief review of the literature highlighting the importance of clinical suspicion in making an accurate diagnosis, the utility of various diagnostic studies, and comparison of various treatment options is presented.
Aged↗
'The metabolism of tumours': 70 years later.
Otto Warburg's classic treatise on the reprogramming of tumour metabolism from oxidative to glycolytic metabolism was published in London in 1930. Although the Warburg effect is one of the most universal characteristics of solid tumours, the molecular basis for this phenomenon has only recently been elucidated by studies indicating that increased expression of genes encoding glucose transporters and glycolytic enzymes in tumour cells is mediated by the transcription factors c-MYC and HIF-1. Whereas c-myc is a direct target for oncogenic mutations, expression of hypoxia-inducible factor 1 (HIF-1) is indirectly up-regulated via gain-of-function mutations in oncogenes and loss-of-function mutations in tumour suppressor genes that result increased HIF-1alpha protein expression and/or increased HIF-1 transcriptional activity in a cell-type-specific manner. As a result of genetic alterations and intratumoral hypoxia, HIF-1alpha is overexpressed in the majority of common human cancers relative to the surrounding normal tissue. In human breast cancer and brain tumours, HIF-1alpha overexpression is strongly correlated with tumour grade and vascularity.
Cell Hypoxia↗
Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha.
The switch to an angiogenic phenotype is a fundamental determinant of neoplastic growth and tumor progression. We demonstrate that homozygous deletion of the p53 tumor suppressor gene via homologous recombination in a human cancer cell line promotes the neovascularization and growth of tumor xenografts in nude mice. We find that p53 promotes Mdm2-mediated ubiquitination and proteasomal degradation of the HIF-1alpha subunit of hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor that regulates cellular energy metabolism and angiogenesis in response to oxygen deprivation. Loss of p53 in tumor cells enhances HIF-1alpha levels and augments HIF-1-dependent transcriptional activation of the vascular endothelial growth factor (VEGF) gene in response to hypoxia. Forced expression of HIF-1alpha in p53-expressing tumor cells increases hypoxia-induced VEGF expression and augments neovascularization and growth of tumor xenografts. These results indicate that amplification of normal HIF-1-dependent responses to hypoxia via loss of p53 function contributes to the angiogenic switch during tumorigenesis.
Adenocarcinoma↗
Postoperative nausea and vomiting following 8% sevoflurane anaesthesia.
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Anesthesia, Closed-Circuit↗
Philadelphia chromosome-negative engraftment after autologous transplantation with granulocyte-macrophage colony-stimulating factor for chronic myeloid leukemia.
Autologous bone marrow transplantation (BMT) has not been curative in chronic myeloid leukemia (CML), because of the inability to purge CML from the autograft and the absence of the allogeneic T cell-mediated antileukemic activity. However, recent advances demonstrate that normal progenitors can be selected from CML marrows by a variety of techniques, including isolation by their small size. Furthermore, we found that myeloid growth factors have a potent antileukemic effect against CML progenitors in vitro by inducing their terminal differentiation. Based on these data, we initiated a trial of autologous BMT in patients with high-risk CML. Autografts were processed in an attempt to enrich for normal progenitors, first by isolating small cells by counterflow centrifugal elutriation and then incubating them in granulocyte-macrophage colony-stimulating factor (GM-CSF) for 72 hours. After a conditioning regimen of busulfan and cyclophosphamide, all patients received GM-CSF daily for 2 months. The median age of the 13 patients in the trial was 45 years (range 17-56 years). The median duration of disease before BMT was 24 months (range 13-72 months). Eight patients were in chronic phase (CP), and five were in accelerated phase (AP). All patients failed to achieve a cytogenetic response to interferon-alpha and were 100% Philadelphia chromosome (Ph)+ before BMT. There were three transplant-related deaths, all AP patients. All of the remaining 10 patients engrafted with some degree of Ph- hematopoiesis; despite high-risk features, nine patients engrafted 100% Ph-. All patients relapsed cytogenetically at a median of 6 months (range 4-22 months). These results demonstrate that autologous BMT can consistently induce complete Ph- engraftment in CP patients. GM-CSF appears to produce a clinical antileukemic effect against CML after autologous BMT.
Adolescent↗
Peribulbar anaesthesia: a double-blind comparison of three local anaesthetic solutions.
A prospective, randomised, double-blinded study comparing three agents for peribulbar anaesthesia is reported. Sixty patients undergoing extracapsular cataract extraction under local anaesthesia were randomly allocated to receive peribulbar anaesthesia with lignocaine 2% with adrenaline; prilocaine 3% with felypressin 0.03 IU.ml-1 or 2% lignocaine and 0.5% bupivacaine in a ratio of 1:1, using a standardised two-injection technique. The pain of injection, time of onset of the block and the operating conditions at the start and finish of surgery were assessed. Peribulbar anaesthesia using lignocaine 2% was significantly more painful than the other solutions. The onset of anaesthesia adequate for surgery was similar in all three groups. Prilocaine 3% with felypressin was associated with the greatest number of blocks providing total akinesia of the eye. Inadequate duration of anaesthesia was seen in only one case; the solution used for this block was 2% lignocaine.
Aged↗
Reduced basal ganglia blood flow and volume in pre-symptomatic, gene-tested persons at-risk for Huntington's disease.
The aim of this study was to examine basal ganglia volumes and regional cerebral blood flow in asymptomatic subjects at-risk for Huntington's disease who had undergone genetic testing. We determined which measures were the best 'markers' for the presence of the mutation and for the onset of symptoms. Twenty subjects who were Huntington's disease gene mutation-positive and 24 Huntington's disease gene mutation-negative participants, all of whom had a parent with genetically confirmed Huntington's disease, and were therefore 50% at-risk for inheriting the Huntington's disease gene mutation, were included in the study. To evaluate basal ganglia structure and function, MRI and single photon emission computed tomography (SPECT) were used. Quantitative measures of regional volumes and relative measures of regional perfusion were calculated. SPECT and MRI scans were co-registered so that MRI anatomy could be used accurately to place SPECT regions. Estimated years-to-onset in the mutation-positive subjects was calculated based on a regression formula that included gene (CAG)(n) repeat length and parental age of onset. Changes in imaging measures in relation to estimated years-to-onset were assessed. The imaging measure that was most affected in mutation-positive subjects was putamen volume. This was also the measure that correlated most strongly with approaching onset. In subjects >/=7 years from estimated onset age, the putamen volume measures were similar to those of the mutation-negative subjects. However, in subjects </=6 years from estimated onset age, there were dramatic reductions in putamen volume, resulting in >90% discrimination from both the far-from-onset and the mutation-negative subjects. Caudate volume and bicaudate ratio also showed a significant decline in the close-to-onset subjects, although to a lesser degree than putamen volume reductions. Furthermore, SPECT basal ganglia perfusion deficits were observed in mutation-positive subjects. Imaging markers of neuropathological decline preceding clinical onset are important for assessing the effects of treatments aimed at slowing the course of Huntington's disease. The current study suggests that quantitative assessment of basal ganglia may provide a means to track early signs of decline in individuals with the Huntington's disease gene mutation prior to clinical onset.
Adult↗
Amsorb: a new carbon dioxide absorbent for use in anesthetic breathing systems.
BACKGROUND: This article describes a carbon dioxide absorbent for use in anesthesia. The absorbent consists of calcium hydroxide with a compatible humectant, namely, calcium chloride. The absorbent mixture does not contain sodium or potassium hydroxide but includes two setting agents (calcium sulphate and polyvinylpyrrolidine) to improve hardness and porosity. METHODS: The resultant mixture was formulated and subjected to standardized tests for hardness, porosity, and carbon dioxide absorption. Additionally, the new absorbent was exposed in vitro to sevoflurane, desflurane, isoflurane, and enflurane to determine whether these anesthetics were degraded to either compound A or carbon monoxide. The performance data and inertness of the absorbent were compared with two currently available brands of soda lime: Intersorb (Intersurgical Ltd., Berkshire, United Kingdom) and Dragersorb (Drager, Lubeck, Germany). RESULTS: The new carbon dioxide absorbent conformed to United States Pharmacopeia specifications in terms of carbon dioxide absorption, granule hardness, and porosity. When the new material was exposed to sevoflurane (2%) in oxygen at a flow rate of 1 l/min, concentrations of compound A did not increase above those found in the parent drug (1.3-3.3 ppm). In the same experiment, mean +/-SD concentrations of compound A (32.5 +/- 4.5 ppm) were observed when both traditional brands of soda lime were used. After dehydration of the traditional soda limes, immediate exposure to desflurane (60%), enflurane (2%), and isoflurane (2%) produced concentrations of carbon monoxide of 600.0 +/- 10.0 ppm, 580.0 +/- 9.8 ppm, and 620.0 +/-10.1 ppm, respectively. In contrast, concentrations of carbon monoxide were negligible (1-3 ppm) when the anhydrous new absorbent was exposed to the same anesthetics. CONCLUSIONS: The new material is an effective carbon dioxide absorbent and is chemically unreactive with sevoflurane, enflurane, isoflurane, and desflurane.
Absorption↗
p53-mediated repression of nuclear factor-kappaB RelA via the transcriptional integrator p300.
The p53 tumor suppressor gene plays an instrumental role in transcriptional regulation of target genes involved in cellular stress responses. p53-dependent transactivation and transrepression require its interaction with p300/CBP, a coactivator that also interacts with the RelA subunit of nuclear factor-kappaB. We find that p53 inhibits RelA-dependent transactivation without altering RelA expression or inducible kappaB-DNA binding. p53-mediated repression of RelA is relieved by p300 overexpression and the increased RelA activity conferred by p53-deficiency is counteracted by either transactivation domain-deficient p300 fragments that bind RelA or a transdominant mutant of IkappaB alpha. Our results suggest that p53 can regulate diverse kappaB-dependent cellular responses.
CREB-Binding Protein↗