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Biomedical subjects

A Lam

Publications and source records attributed to A Lam.

At least 19 recordsLinked to original sources

Measurement of the positive muon anomalous magnetic moment to 0.7 ppm.

A higher precision measurement of the anomalous g value, a(mu)=(g-2)/2, for the positive muon has been made at the Brookhaven Alternating Gradient Synchrotron, based on data collected in the year 2000. The result a(mu(+))=11 659 204(7)(5)x10(-10) (0.7 ppm) is in good agreement with previous measurements and has an error about one-half that of the combined previous data. The present world average experimental value is a(mu)(expt)=11 659 203(8)x10(-10) (0.7 ppm).

Journal Article↗

Role of outer ring carboxylates of the rat skeletal muscle sodium channel pore in proton block.

Voltage-gated Na+ current is reduced by acid solution. Protons reduce peak Na+ conductance by lowering single channel conductance and shift the voltage range of gating by neutralizing surface charges. Structure-function studies identify six carboxyls and a lysine in the channel's outer vestibule. We examined the roles of the superficial ring of carboxyls in acid block of Na(v)1.4 (the rat skeletal muscle Na+ channel isoform) by measuring the effects of their neutralization or their substitution by lysine on sensitivity to acid solutions, using the two-micropipette voltage clamp in Xenopus oocytes. Alteration of the outer ring of carboxylates had little effect on the voltage for half-activation of Na+ current, as if they are distant from the channels' voltage sensors. The mutations did not abolish proton block; rather, they all shifted the pK(a) (-log of the dissociation constant) in the acid direction. Effects of neutralization on pK(a) were not identical for different mutations, with E758Q > D1241A > D1532N > E403Q. E758K showed double the effect of E758Q, and the other lysine mutations all produced larger effects than the neutralizing mutations. Calculation of the electrostatic potential produced by these carboxylates using a pore model showed that the pK(a) values of carboxylates of Glu-403, Glu-758, and Asp-1532 are shifted to values similar to the experimentally measured pK(a). Calculations also predict the experimentally observed changes in pK(a) that result from mutational neutralization or introduction of a positive charge. We propose that proton block results from partial protonation of these outer ring carboxylates and that all of the carboxylates contribute to a composite Na+ site.

Animals↗

Safety and comfort during sedation for diagnostic or therapeutic procedures.

Sedation during diagnostic or therapeutic procedures must be safe and comfortable for patients. To achieve this, additional suitably qualified staff must be available throughout the procedure to administer sedation and monitor the patient. Anaesthesiologists possess the necessary knowledge and skills to perform sedation safely but are often unavailable. Non-anaesthesiologists performing sedation should be fully trained in the physiology of sedation, the pharmacology of sedatives and analgesics, the monitoring of patients, and in airway support, ventilatory care, and cardiopulmonary resuscitation. The presence of an anaesthesiologist is desirable when dealing with patients at high-risk of complications. Good sedation practice involves presedation assessment and optimal selection of patients, careful monitoring and support from dedicated staff, and adherence to recovery and discharge criteria.

Adult↗

Effect of contact time and inhibitor concentration on the affinity mediated adsorption of cells to surfaces.

Cell detachment by shear stress under conditions of laminar flow was used to investigate the effect of incubation time and soluble binding competitors on affinity mediated cell/surface interactions. Fractional attachment between yeast and a Concanavalin A (Con A) coated surface was studied as a function of adhesion time prior to exposure to shear in a parallel plate flow chamber. Two, four and sixteen hours adhesion times gave rise to significantly different fractional attachment profiles, with four hours giving greater cell retention.The effect of dextran as a competitive displacer of pre-attached cells was also examined using a number of exposure regimes. While the presence of dextran in the displacement buffer led to higher fractional displacement of pre-attached cells, this effect was magnified if an equilibration period between dextran solution and pre-attached cells was allowed before detachment was attempted. The decline in fractional attachment increased with incubation time up to 30 min, with longer periods resulting in a smaller effect. Pre-incubation of the Con A surface with dextran prior to the introduction of cells led to a 60% reduction in attachment.Attempts to determine critical shear values were complicated by the presence of a tightly bound cell fraction of approximately 15% that was not removed at the highest shear values used.

Journal Article↗

Intracellular mechanisms of TRAIL: apoptosis through mitochondrial-dependent and -independent pathways.

Tumor necrosis (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family of cytokines that promotes apoptosis. TRAIL induces apoptosis via death receptors (DR4 and DR5) in a wide variety of tumor cells but not in normal cells. The objectives of this study are to investigate the intracellular mechanisms by which TRAIL induces apoptosis. The death receptor Fas, upon ligand binding, trimerizes and recruits the adaptor protein FADD through the cytoplasmic death domain of Fas. FADD then binds and activates procaspase-8. It is unclear whether FADD is required for TRAIL-induced apoptosis. Here we show that the signaling complex of DR4/DR5 is assembled in response to TRAIL binding. FADD and caspase-8, but not caspase-10, are recruited to the receptor, and cells deficient in either FADD or caspase-8 blocked TRAIL-induced apoptosis. In addition, TRAIL initiates the activation of caspases, the loss of mitochondrial transmembrane potential (Deltapsi(m)), the cleavage of BID, and the redistribution of mitochondrial cytochrome c. Treatment of Jurkat cells with cyclosporin A delayed TRAIL-induced Deltapsi(m), caspase-3 activation and apoptosis. Similarly, Overexpression of Bcl-2 or Bcl-X(L) delayed, but did not inhibit, TRAIL-induced Deltapsi(m) and apoptosis. In contrast, XIAP, cowpox virus CrmA and baculovirus p35 inhibited TRAIL-induced apoptosis. These data suggest that death receptors (DR4 and DR5) and Fas receptors induced apoptosis through identical signaling pathway, and TRAIL-induced apoptosis via both mitochondrial-dependent and -independent pathways.

Adaptor Proteins, Signal Transducing↗

Antenatal prediction of hypertrophic pyloric stenosis.

This is the first reported case where the diagnosis of hypertrophic pyloric stenosis (HPS) was entertained in the antenatal period and the neonate was followed up in the postnatal period on a prospective basis until the HPS became manifest.

Adult↗

Pre-eclampsia: a predisposing factor for neonatal venous sinus thrombosis?

Neonatal venous sinus thrombosis is a well-recognized, but infrequently diagnosed, cause of neonatal encephalopathy. Previous reports have tended to omit reference to the importance of maternal factors in predisposing the infant to this condition. This report, in which eight patients with neonatal venous sinus thrombosis are presented, will reveal a strong association between pre-eclampsia, prothrombotic disorders, and neonatal venous sinus thrombosis. Contrary to previously published reports, there is a high likelihood of neurodevelopmental residua after this condition.

Adult↗

Co-composting of soybean residues and leaves in Hong Kong.

The goal of this project was to evaluate the feasibility of co-composting of soybean residues and leaves and the effects of turning frequency on compost quality. Soybean residues were mixed with leaves and sawdust in 1:1:3 (w/w wet weight) for achieving a C/N ratio of about 30. Three heaps of about 4 m3 of compost mixtures were prepared receiving a turning frequency of daily (pile A), 3-day (pile B) and weekly (pile C) turning. Different turning frequencies did not significantly affect the changes in pH and volatile solids throughout the composting period. High turning frequency caused a lower electrical conductivity and NH4-N contents as well as a shorter duration of thermophilic phase, because of a high heat loss by evaporation and volatilization of ammonia in the pile. The highest C decomposition of 4% occurred in the pile with a 3-day turning period, which coincided with the higher-nitrogen content in this treatment. All treatments with different turning frequencies reached maturation at 63 days as indicated by the soluble organic carbon, soluble NH4-N, C/N ratio and cress seed germination index. However, increasing the aeration during composting period was beneficial in accelerating the maturation process. Taking into consideration less labour and lower operation costs as compared to daily turning, it can be suggested that a 3-day turning frequency would be more appropriate for reaching acceptable quality of compost and ease in operation.

Biodegradation, Environmental↗

Comparison of tissue injury between laparosonic coagulating shears and electrosurgical scissors in the sheep model.

STUDY OBJECTIVE: To compare laparosonic coagulating shears (LCS), which use ultrasonic energy, and unipolar diathermy scissors with respect to depth of tissue injury. DESIGN: Prospective observational study (Canadian Task Force classification I). SETTING: A reproduced surgical setting. SUBJECTS: An anesthetized sheep. INTERVENTION: We laparoscopically harvested uterine horn and bowel tissue. MEASUREMENTS AND MAIN RESULTS: Tissue was transected while hemostasis was maintained. Two pathologists examined tissue independently, and each was blinded as to the instrument used for harvesting. Clinical characteristics and tissue injury created by the instruments were compared. CONCLUSION: Subjectively, LCS appeared to produce less smoke plume than diathermy scissors. It also produced greater tissue damage than unipolar electrosurgery on settings of 35 W cut and 30 W coagulate.

Animals↗

Laparoscopic presacral neurectomy: a review.

Dysmenorrhea can be a severe and debilitating symptom in many women. Although most women may find adequate relief of symptoms from pharmacological approaches, there remain a few with resistant pain. Presacral neurectomy, although technically challenging, may be offered after other approaches are unsuccessful. The operation is now performed increasingly by the laparoscopic approach, which has revived this operation in some centers. The anatomy, technique, and indications as well as a review of the literature supporting this operation are reviewed. The potential complications of this operation are discussed also.

Autonomic Denervation↗

Deeply infiltrating endometriosis: implications, diagnosis, and management.

Deeply infiltrating endometriosis was described in the early part of the last century. Only recently, has there become a greater awareness and understanding of this form of endometriosis aided in part by advances in laparoscopic surgical technology in techniques. The clinical implications of the disease as well as diagnosis and current management are reviewed.

Endometriosis↗

Laparoscopic presacral neurectomy - retrospective series.

A retrospective audit of medical records was conducted for one surgeon (AL). All patients who underwent laparoscopic presacral neurectomy for severe midline dysmenorrhoea were identified. Details of the preoperative symptoms, clinical findings and operative records were studied. Improvement of dysmenorrhoea was assessed according to a pain scale. Twelve patients who had a laparoscopic presacral neurectomy performed were identified. Eight patients reported significant improvement of symptoms, with a further two reporting mild improvement. Two patients failed to show any improvement of symptoms. We believe that the role of laparoscopic presacral neurectomy should be limited to patients with severe midline dysmenorrhoea not responding to the medical therapy. It may be a supplementary procedure to laparoscopic resection of endometriosis or adhesiolysis.

Adult↗

Measurement of midfemoral shaft geometry: repeatability and accuracy using magnetic resonance imaging and dual-energy X-ray absorptiometry.

Although macroscopic geometric architecture is an important determinant of bone strength, there is limited published information relating to the validation of the techniques used in its measurement. This study describes new techniques for assessing geometry at the midfemur using magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry (DXA) and examines both the repeatability and the accuracy of these and previously described DXA methods. Contiguous transverse MRI (Philips 1.5T) scans of the middle one-third femur were made in 13 subjects, 3 subjects with osteoporosis. Midpoint values for total width (TW), cortical width (CW), total cross-sectional area (TCSA), cortical cross-sectional area (CCSA), and volumes from reconstructed three-dimensional (3D) images (total volume [TV] and cortical volume [CVol]) were derived. Midpoint TW and CW also were determined using DXA (Lunar V3.6, lumbar software) by visual and automated edge detection analysis. Repeatability was assessed on scans made on two occasions and then analyzed twice by two independent observers (blinded), with intra- and interobserver repeatability expressed as the CV (CV +/- SD). Accuracy was examined by comparing MRI and DXA measurements of venison bone (and Perspex phantom for MRI), against "gold standard" measures made by vernier caliper (width), photographic image digitization (area) and water displacement (volume). Agreement between methods was analyzed using mean differences (MD +/- SD%). MRI CVs ranged from 0.5 +/- 0.5% (TV) to 3.1 +/- 3.1% (CW) for intraobserver and 0.55 +/- 0.5% (TV) to 3.6 +/- 3.6% (CW) for interobserver repeatability. DXA results ranged from 1.6 +/- 1.5% (TW) to 4.4 +/- 4.5% (CW) for intraobserver and 3.8 +/- 3.8% (TW) to 8.3 +/- 8.1% (CW) for interobserver variation. MRI accuracy was excellent for TV (3.3 +/- 6.4%), CVol (3.5 +/- 4.0%), TCSA (1.8 +/- 2.6%), and CCSA (1.6 +/- 4.2%) but not TW (4.1 +/- 1.4%) or CW (16.4 +/14.9%). DXA results were TW (6.8 +/- 2.7%) and CW (16.4 +/- 17.0%). MRI measures of geometric parameters of the midfemur are highly accurate and repeatable, even in osteoporosis. Both MRI and DXA techniques have limited value in determining cortical width. MRI may prove valuable in the assessment of surface-specific bone accrual and resorption responses to disease, therapy, and variations in mechanical loading.

Absorptiometry, Photon↗

Failure of Bcl-2 to block mitochondrial dysfunction during TRAIL-induced apoptosis. Tumor necrosis-related apoptosis-inducing ligand.

Tumor necrosis (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family of cytokines that promotes apoptosis. TRAIL induces apoptosis in a wide variety of tumor cells but not in normal cells. Oncogene Bcl-2 can protect cells from apoptosis induced by various stress stimuli. However, it is not clear whether Bcl-2 can regulate TRAIL-induced apoptosis. The objective of this study was to investigate whether Bcl-2 can regulate apoptosis induced by TRAIL. TRAIL initiates the activation of caspases, the loss of mitochondrial transmembrane potential (Delta psi(m)), and the redistribution of mitochondrial cytochrome c. TRAIL has no effect on Delta psi(m) and apoptosis in Jurkat cells deficient in either FADD or caspase-8, suggesting both FADD and caspase-8 are required for TRAIL signaling. Overexpression of Bcl-2 delays, but does not inhibit, TRAIL-induced Delta psi(m), cytochrome c release from mitochondria and apoptosis, whereas etoposide-induced apoptosis is blocked by Bcl-2. XIAP, cowpox virus CrmA and baculovirus p35 inhibits TRAIL-induced apoptosis. These data suggest that TRAIL can be used to kill Bcl-2 positive cells that can not be killed by other class of chemotherapeutic drugs.

Apoptosis↗

[Cataract surgery with posterior chamber lens implantation in Senegalese children less than 15 year-old].

PURPOSE: To assess short and medium term outcomes of cataract surgery with intraocular lens implantation in Senegalese children less than fifteen years. METHODS: From 1992 to 1997, 50 eyes of 40 children between the age of 5 months and 14 years, suffering from cataract were operated. Some of them were seen untill 2000. Twenty-seven cataracts were congenital, 19 were traumatic, 2 were from corticosteroid side effects, 1 after uveitis, and 1 had no determined cause. Thirty-one had manual extracapsular surgery and 19 ultrasound cataract surgery. They all have a standard single-piece PMMA intraocular lens of 21 to 22 diopters, 12.0-12.5mm long, under the ciliaris silcus (34 cases) or in the capsular bag (16). The results were noted in the first week, at one month, at 3 months, and after. RESULTS: Exudative reactions were frequent in the anterior chamber: 20% of the eyes had such reactions during the operation, especially when a manual extracapsular extraction was performed, and 34% soon after operation. The reactions were generally revealed with one month of survey. Corticosteroids used before and after surgery reduced inflammation disorders but seemed to speed up the onset of secondary cataract. Posterior capsule opacification was observed in the first week after surgery. It increased from 45% at 3 months to 74% at 1 year and 100% after 3 years. Intraocular cristal lens implants are well tolerated with limited complications. Fifty-seven percent of the operated eyes we observed after 3 years had 30/60 or better visual acuity. CONCLUSION: Despite fairly frequent inflammation and secondary cataract, posterior chamber lens implantation in children is well tolerated. This suggest that, as in adults, intraocular lens implant would be the best treatment for aphakia.

Cataract Extraction↗

Altered patterns of gene expression in response to myocardial infarction.

The use of cDNA microarrays has made it possible to simultaneously analyze gene expression for thousands of genes. Microarray technology was used to evaluate the expression of >4000 genes in a rat model of myocardial infarction. More than 200 genes were identified that showed differential expression in response to myocardial infarction. Gene expression changes were monitored from 2 to 16 weeks after infarction in 2 regions of the heart, the left ventricle free wall and interventricular septum. A novel clustering program was used to identify patterns of expression within this large set of data. Unique patterns were revealed within the transcriptional responses that illuminate changes in biological processes associated with myocardial infarction.

Animals↗

Application of in vitro-in vivo correlations (IVIVC) in setting formulation release specifications.

An in vitro-in vivo correlation (IVIVC) was established for an osmotic controlled-release dosage form by deconvolution using data from an immediate-release treatment as the characteristic response. The established IVIVC was evaluated internally (predicting data used to develop the IVIVC) and externally (predicting data not originally included in developing the IVIVC), and the application of the IVIVC in product development was demonstrated. The estimated in vivo dissolution profile compared favorably with the in vitro drug release profile. Good agreement was demonstrated between the estimated and observed cumulative drug release across the entire time course (level A correlation) with low (<10%) predictive error for both C(max) and AUC(infinity). External validation using lots not initially included in the model development compared very well with the observed in vivo profile, with mean prediction errors less than 10% for both C(max) and AUC(infinity). The proposed method demonstrates a schema for developing IVIVCs using data from biostudies routinely conducted during formulation development. The method should facilitate product optimization and can support setting in vitro dissolution specification.

Algorithms↗

CTGF expression is induced by TGF- beta in cardiac fibroblasts and cardiac myocytes: a potential role in heart fibrosis.

Connective tissue growth factor (CTGF) is a cysteine-rich protein induced by transforming growth factor beta (TGF- beta) in connective tissue cells. CTGF can trigger many of the cellular processes underlying fibrosis, such as cell proliferation, adhesion, migration and the synthesis of extracellular matrix; however, its role in acute and chronic cardiac injury is not fully understood. Here, we show that TGF- beta is a specific inducer of CTGF expression in both cardiac fibroblasts and cardiac myocytes. The activity of a CTGF promoter-based reporter construct correlated with endogenous CTGF expression, suggesting that TGF- beta induces CTGF expression most likely by activating its promoter. Upregulation of CTGF coincided with an increase in fibronectin, collagen type I and plasminogen activator inhibitor-1 production. Forskolin, a stimulator of cyclic AMP, blocked TGF- beta induced CTGF expression and reduced the basal level of CTGF, whereas an inhibitor that blocks the MAP kinase signaling pathway (PD 98059) significantly enhanced TGF- beta induced CTGF expression. Furthermore, we found that both TGF- beta and CTGF mRNAs were significantly elevated in the left ventricles and septa of rat hearts 2-16 weeks following myocardial infarction. This correlated well with concomitant increases in fibronectin, and type I and type III collagen mRNA levels in these animal hearts. Significant upregulation of CTGF was also detected in human heart samples derived from patients diagnosed with cardiac ischemia. Based on these findings, we propose that CTGF is an important mediator of TGF- beta signaling in the heart and abnormal expression of this gene could be used as a diagnostic marker for cardiac fibrosis.

Adult↗