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Biomedical subjects

A Lam

Publications and source records attributed to A Lam.

At least 19 recordsLinked to original sources
PubMed2006

Matrix metalloproteinases contribute to endotoxin and interleukin-1beta induced vascular dysfunction.

BACKGROUND AND PURPOSE: The acute vascular inflammatory dysfunction associated with endotoxaemia may reflect an imbalance between matrix metalloproteinases (MMPs) and their natural inhibitors (TIMPs), induced by the endotoxin. This possibility was tested in rat aortic tissue. EXPERIMENTAL APPROACHES: Tone induced by phenylephrine in aortic rings was measured after exposure in vitro to ambient lipopolysaccharide (LPS) or the proinflammatory cytokine interleukin-1beta (IL-1beta) for 6h, with or without MMP inhibitors (doxycycline or GM6001). Gelatinase and MMP activities, TIMP proteins and contractility were measured in aortae taken from rats 6h after receiving LPS in vivo. KEY RESULTS: Inhibition of MMP prevented the loss of phenylephrine-induced tone in aortic rings after LPS or IL-1beta. IL-1beta also increased release of MMP-2 activity from aortic tissue. In aortae exposed in vivo to LPS, net gelatinase, MMP-9 activities and TIMP-1 protein levels were increased, whereas TIMP-4 was reduced. These aortae were hypocontractile to both phenylephrine and KCl. Hypocontractility was partially reversed by doxycycline ex vivo. CONCLUSIONS AND IMPLICATIONS: MMP inhibitors ameliorate vascular hyporeactivity induced by either LPS or IL-1beta in vitro. LPS in vivo alters the balance between MMPs and TIMPs, contributing to vascular dysfunction which is partially reversed by MMP inhibitors. Vascular MMPs are activated as a result of LPS or IL-1beta-induced stress and contribute to the hyporeactivity of blood vessels to vasoconstrictors.

Animals↗
PubMed2006

The placentas of patients with severe acute respiratory syndrome: a pathophysiological evaluation.

AIMS: The pathology of the placentas delivered from pregnant women who had severe acute respiratory syndrome (SARS) in Hong Kong was studied. METHODS: The pathology of the placentas was retrospectively studied in detail and compared with control sets. The clinical data of the women and neonates were also reviewed. RESULTS: A total of seven placentas were studied. The placentas from two women convalescent from SARS in the first trimester were normal. In three placentas delivered in the acute stage of SARS, there were increases in intervillous or subchorionic fibrin which might be related to disturbances in maternal placental blood flow due to the hypoxic respiratory disease. Extensive fetal thrombotic vasculopathy (FTV) with sharply demarcated zones of avascular fibrotic villi was noted in the placentas of two patients convalescent from SARS in the third trimester. Both pregnancies had intrauterine growth retardation, oligohydramnios and newborns small for gestation. The aetiology of the FTV might be related to thrombotic tendency due to SARS or placental hypoxia. CONCLUSIONS: This report highlights placental pathology that was probably the result of pathophysiological alteration of the maternal fetal unit during SARS. Further studies are required to delineate the relationship between severe maternal respiratory disease, placental pathology and pregnancy outcome.

Adult↗
PubMed2006

Ultrasonographic demonstration of a type 1 omphalomesenteric duct remnant.

The vitelline or omphalomesenteric duct malformations constitute a rare group and are seen in only 2% of people. The malformations can take the form of a patent duct, a cyst, a fistula, or a sinus. They may or may not be symptomatic depending on the type of malformation. We present ultrasonographic features of a patent omphalomesenteric duct remnant in a 3-week-old boy who presented to our hospital with a non-healing umbilical lesion. Ultrasound can prove beneficial in the work-up of such cases.

Hernia, Umbilical↗
PubMed2006

Ingested foreign body mimicking an appendicolith in a child.

We describe an unusual case of a child who had ingested sand and stones and presented with signs and symptoms suggestive of appendicitis. Plain radiographs revealed calcific opacities in the right iliac fossa simulating appendicoliths. At surgery and histopathology a small sealed off perforation of the terminal ileum with hard concretions in the wall was observed.

Appendicitis↗
PubMed2005

Laparoscopic or transanal repair of rectocele? A retrospective matched cohort study.

PURPOSE: The aim of the study was to analyze the functional and physiologic outcome of patients undergoing laparoscopic rectocele repair compared to a matched cohort undergoing transanal repair. METHODS: Forty patients with a rectocele who had undergone laparoscopic pelvic floor repair by a laparoscopic gynecologist were matched for age and rectocele size with 40 patients who had undergone a transanal repair by a colorectal surgeon. All patients had clinical evidence of a symptomatic rectocele. All patients were assessed postoperatively with a quality of life (SF-36) score, a modified St. Mark's continence score, a urinary dysfunction score, a Watt's sexual dysfunction score, and a linear analog patient satisfaction score. Fifteen patients in each group had also undergone preoperative and postoperative anal manometry. RESULTS: At 44 months median follow-up, the transanal approach resulted in significantly more patients reporting bowel symptom alleviation (P < 0.002) and higher patient satisfaction (P < 0.003). The bowel symptom improvement was also sustained over a significantly longer period (P < 0.03). Only 11 patients (28 percent) in the laparoscopic group reported more than 50 percent improvement in their bowel symptoms compared to 25 patients (63 percent) in the transanal group. On univariate analysis of 50 percent bowel symptom improvement, a larger rectocele (P < 0.009), transanal repair (P < 0.02), and presenting with obstructive defecation rather than fecal incontinence (P < 0.03) were statistically significant. Rectocele size (P < 0.012) and treatment cohort (P < 0.006) remained significant on multivariate analysis. Postoperatively, bowel symptom alleviation correlated with patient satisfaction in both groups (P < 0.015). Although not statistically significant, five patients (13 percent) in the transanal group developed postoperative fecal incontinence, which was associated with a low maximum anal resting pressure preoperatively that was further diminished postoperatively (P > 0.06). Only one patient (3 percent) in the laparoscopic group reported a decline in fecal continence, but four patients (10 percent) reported worsening of their symptoms of obstructed defecation. Postoperative dyspareunia was reported by 24 patients in total (30 percent), with significantly more in the transanal group (P > 0.05). CONCLUSIONS: The transanal repair results in a statistically greater alleviation of bowel symptoms and greater patient satisfaction scores. However, this approach may have a greater degree of functional co-morbidity than the laparoscopic rectocele repair.

Adult↗
PubMed2005

Diagnostic accuracy of surgeon-performed focused abdominal sonography (FAST) in blunt paediatric trauma.

AIM: To study the diagnostic accuracy and clinical efficacy of surgeon-performed focused abdominal sonography (FAST) in paediatric blunt abdominal trauma (BAT). MATERIALS AND METHOD: This was a prospective, single blinded study conducted at The Children's Hospital at Westmead Sydney (CHW). All patients with BAT that justified a trauma call activated on presentation to the Emergency Department (ED) had a FAST performed by the Trauma Fellow. The attending surgical team was blinded to the result of the FAST. An independent radiologist reviewed the FAST pictures, and the findings were compared with computerised tomography (CT), ultrasound (US), laparotomy and the clinical outcome of the patient. Sensitivity, specificity and predictive values were calculated. RESULTS: A total of 85 patients (39 M; 26 F) were enrolled in the study between February 2002 and January 2003. The age ranged between 4 months and 16 years. The mean Injury Severity Score (ISS) was 6 (range 1-38). FAST was performed in a mean time of 3 min. Inter-rater agreement was 96%. FAST was positive in nine as confirmed by a CT scan of the abdomen. Three patients underwent laparotomy, two for bowel injuries and one for a Grade III liver laceration. Of the remaining 76, 19 had a CT, which showed evidence of intra-abdominal injury in seven patients. There were two false negative studies resulting in a sensitivity of 81%, specificity of 100%, negative predictive value of 97%, positive predictive value of 100% and an accuracy of 97%. CONCLUSIONS: Surgeon-performed FAST for BAT was safe and accurate with a high specificity. It would seem a potentially valuable tool in the evaluation of paediatric blunt trauma victims for free fluid within the peritoneal cavity.

Abdominal Injuries↗
PubMed2005

Desmoplastic infantile ganglioglioma: a questionably benign tumour.

Desmoplastic infantile ganglioglioma is a rare intracranial tumour of childhood that involves the cerebral cortex and the leptomeninges. We report two patients with desmoplastic infantile gangliogliomas and multiple cerebrospinal metastases. To our knowledge, only two similar cases have been reported in the published literature. Pathologically, this rare intracranial tumour shows glial and ganglionic differentiation, accompanied by an extreme desmoplastic reaction. These are low-grade neoplasms that are questionably benign.

Brain Neoplasms↗
PubMed2005

Outcomes in persistent hyperplastic primary vitreous.

AIMS: To report outcomes in cases of persistent hyperplastic primary vitreous (PHPV) and examine factors predictive of visual acuity in patients selected for surgery. METHODS: Retrospective case series of 55 eyes in 50 patients presenting between 1990 and 2001 at the Children's Hospital, Westmead. 33 eyes underwent surgery aimed at visual rehabilitation. RESULTS: In surgical patients, median age at surgery was 77 days, and median age at final follow up was 28 months. Six (18%) achieved a visual acuity at final follow up of 6/60 or better and eight (24%) achieved acuity of less than 6/60 to counting finger vision inclusive. Those undergoing surgery before 77 days were approximately 13 times more likely to obtain a visual acuity of counting fingers or better than those operated later (p = 0.01). Neither posterior segment PHPV nor post-surgical glaucoma was a significant predictor of outcome in this selected group. CONCLUSION: Early surgery aimed at rehabilitation markedly improves the likelihood of useful visual outcome in selected eyes with PHPV.

Eye Abnormalities↗
PubMed2004

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

The anomalous magnetic moment of the negative muon has been measured to a precision of 0.7 ppm (ppm) at the Brookhaven Alternating Gradient Synchrotron. This result is based on data collected in 2001, and is over an order of magnitude more precise than the previous measurement for the negative muon. The result a(mu(-))=11 659 214(8)(3) x 10(-10) (0.7 ppm), where the first uncertainty is statistical and the second is systematic, is consistent with previous measurements of the anomaly for the positive and the negative muon. The average of the measurements of the muon anomaly is a(mu)(exp)=11 659 208(6) x 10(-10) (0.5 ppm).

Journal Article↗
PubMed2003

Remote glucosyltransferase-microparticle vaccine delivery induces protective immunity in the oral cavity.

Intranasally administered dental caries vaccines show significant promise for human application. Alternate mucosal routes may be required, however, to induce caries-protective salivary IgA antibody in children with respiratory diseases. Since rectal mucosa contains inductive lymphoid tissue, we hypothesized that the rectal route could be used to induce salivary immunity to mutans streptococcal glucosyltransferase (GTF), resulting in protective immunity to experimental dental caries. We first explored the ability of glucosyltransferase, incorporated into polylactide-co-glycolide (PLGA) microparticles (MP), and administered rectally together with mucosal adjuvant, to induce a salivary IgA antibody response. Groups of Sprague-Dawley rats (6/group) were immunized rectally on days 0, 7, 14 and 21 with a) GTF-MP alone, b) GTF-MP with cholera toxin, c) GTF-MP with detoxified mutant Escherichia coli toxin (dLT), or d) sham immunized with PLGA and cholera toxin. An additional group was immunized intranasally with GTF-MP alone. Saliva and nasal washes of all intranasally immunized rats contained IgA antibody to glucosyltransferase on day 28. Salivary IgA antibody was also detected in 7/12 rats rectally immunized with GTF-MP and cholera toxin or dLT, although responses were lower than those obtained by intranasal immunization. Most fecal extracts from rectally delivered GTF-MP plus cholera toxin or dLT rats contained IgA antibody to GTF-MP. Low levels of fecal IgA antibody were detected in 3/6 intranasally immunized rats and 2/6 rats rectally immunized with GTF-MP alone. We then examined the extent to which salivary IgA antibody induced by the rectal route could be protective. At 25, 31 and 38 days of age, two groups of female Sprague-Dawley rats (13/group) were rectally immunized with GTF-MP and cholera toxin or with empty microparticles and cholera toxin (sham group). A third group was intranasally immunized with GTF-MP alone. After demonstrating salivary IgA responses to GTF in most GTF-immunized rats, all animals were infected with streptomycin-resistant Streptococcus sobrinus and placed on diet 2000. After 79 days of infection, total caries on molar surfaces were lower in both rectally (7.9 +/- 1.0) and intranasally (7.1 +/- 0.9; P < 0.0.03) immunized groups compared with the sham-immunized group (11.9 +/- 1.6). Smooth surface caries were significantly lower (P < 0.05) in both rectally and intranasally immunized groups. These results support the interconnectedness of the mucosal immune system and indicate that rectal immunization with GTF-MP, together with adjuvant, or intranasal immunization with GTF-MP alone, can induce protective levels of salivary antibody in rats.

Administration, Rectal↗
PubMed2003

Clinical and economic impacts of latanoprost 0.005% in first-line treatment of open-angle glaucoma and ocular hypertension in France.

PURPOSE: To assess the cost-effectiveness of treatment strategies that utilize first-line latanoprost compared to those based on initial beta-blocker therapy in patients with open-angle glaucoma (OAG) or ocular hypertension (OH) in France. METHODS: The study was based on a decision-analytic model that was populated with data from a retrospective chart review. A hypothetical cohort of patients newly diagnosed with OAG and/or OH was assessed over a period of 2 and 3 years. For each treatment strategy 10,000 patients were assumed. RESULTS: First-line latanoprost therapy was significantly more effective than initial treatment with a beta-blocker, providing more days of intraocular pressure (IOP) control primarily due to its longer time until initial treatment failure. Latanoprost's higher acquisition cost was largely offset by reductions in costs associated with surgical procedures. The additional cost for latanoprost was estimated at approximately 41 Euro and 27 Euro over 2 and 3 years, respectively. The incremental cost per day of IOP control when latanoprost was used as first-line strategy compared to the first-line beta-blocker strategy was 0.82 Euro and 0.36 Euro over 2 and 3 years, respectively. CONCLUSIONS: These results provide compelling evidence that first-line latanoprost therapy can provide superior clinical outcomes at a small additional cost in actual clinical practice.

Antihypertensive Agents↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

Ultrasonography of plantar soft tissues thickness in young people with diabetes.

AIMS: The aims of this study were to examine soft tissue changes in the skin and plantar aponeurosis of young people with Type 1 diabetes mellitus (T1DM) and to evaluate any relationship between any soft tissue changes, arch length, limited joint mobility (LJM) and plantar pressure. METHODS: The thickness of the skin on the plantar surface of the foot and plantar aponeurosis were examined using ultrasound in 216 young people with diabetes and 57 controls. Foot length, arch length, joint mobility, peak pressure and pressure time integrals were evaluated. RESULTS: Skin was not significantly thicker in the diabetic subjects. The plantar aponeurosis was significantly thicker in the diabetic subjects and was associated with foot size, male gender and subtalar joint (ST) LJM (P < 0.01). Males were nearly three times more likely to have thickened plantar aponeurosis. CONCLUSION: Soft tissue thickening in young people with T1DM affects the deeper structures on the plantar surface of the foot rather than the skin. Thickening of the plantar aponeurosis was associated with LJM at the ST joint and male gender, but was not associated with plantar pressure or arch height changes. Plantar aponeurosis thickening does not appear to alter foot mechanics in young people with T1DM.

Adolescent↗
PubMed2002

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↗
PubMed2001

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↗
PubMed2001

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↗