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Biomedical subjects

L Lam

Publications and source records attributed to L Lam.

At least 19 recordsLinked to original sources

Epidemiological analysis of tongue cancer in South Australia for the 24-year period, 1977-2001.

BACKGROUND: Tongue cancer (141 ICD-9) is the most common intra-oral malignancy in Western countries. In recent decades, reported tongue cancer incidence and mortality rates have increased both in Europe and in the United States, whilst survival has not improved. This study aimed to determine the epidemiology and survival trends of tongue cancer in South Australia over the 24-year period from 1977 to 2001. METHODS: Population-based data for tongue cancer were provided by the Central Cancer Registry Unit of the Epidemiology Branch of the South Australian Department of Health. Age-standardized incidence and mortality rates for males and females were calculated. Kaplan-Meier survival analysis was conducted according to time periods, age, sex and tongue sub-sites. Cox regression analysis was used to determine factors that influenced survival. RESULTS: During this 24-year period, 611 cases of tongue cancer (398 males, 213 females) were reported, the majority of which were squamous cell carcinomas. The most common age of diagnosis was 65-69 years in males and 60-64 years in females. Fifty cases (8.18 per cent of all tongue cancer cases) occurred in patients 40 years or younger. The most common cancer sub-sites reported were 'unspecified site' (48.45 per cent), lateral border (25.53 per cent) and base (18.49 per cent) of the tongue. The age-standardized incidence and mortality rates for males and females in South Australia were relatively low and stable, and there was no significant improvement in survival of tongue cancer over this period. Significant predictors for survival were sex, age and tongue sub-sites, with male, advanced age and base of tongue associated with poorer survival. CONCLUSIONS: Tongue cancer is an important health issue associated with poor survival. Early detection and diagnosis is important in order to improve survival rate for this malignancy.

Adult↗

A cohort study of 20,822 young drivers: the DRIVE study methods and population.

BACKGROUND AND OBJECTIVE: Research on young drivers directly linking risk factors to serious injury and death outcomes is required. The DRIVE Study was established to facilitate this aim. This paper outlines the study methods and describes the population that has been recruited, in order to demonstrate that the necessary heterogeneity in risk factors has been attained. DESIGN, SETTING AND PARTICIPANTS: Drivers aged 17-24 years holding their first-stage provisional driver's licence from New South Wales, Australia, were recruited into a prospective cohort study. The participants were contacted by mail and asked to complete the study questionnaire at an online site or via a mailed questionnaire. Baseline data collection involved a questionnaire with questions to drivers about their training, risk perception, driver behavior, sensation-seeking behavior and mental health. Participants gave consent for prospective data linkage to their data on licensing, crashes and injuries, held in routinely collected databases. RESULTS: 20 822 drivers completed the baseline questionnaire, of whom 45.4% were men, 74.3% resided in capital cities and 25.7% in regional or remote areas. The recruited study population showed a wide variation in the risk factors under examination. For example, almost 40% of drivers reported drinking alcohol at hazardous levels and about 32% of participants seemed to be at a high or very high risk of psychological distress. Participants reported a mean of 67.3 h (median 60 h) of supervised driver training while holding their learner's permit. CONCLUSIONS: The DRIVE Study has a robust study design aimed at minimizing bias in the collection of outcome data. Analyses of baseline data showed substantial heterogeneity of risk factors in the study population. Subsequent prospective linkages comparing relative differences in exposures at baseline with the outcomes of interest have the potential to provide important new information needed to develop targeted interventions aimed at young drivers.

Accidents, Traffic↗

A case of takotsubo cardiomyopathy: transient left ventricular apical ballooning.

A 78-year-old woman was admitted to hospital with central chest pain and the electrocardiographic and cardiac marker changes typical of acute anterior myocardial infarction. Coronary angiography revealed normal epicardial coronary arteries, and left ventriculography showed apical akinesis as well as basal hyperkinesis. This is a case of transient left ventricular apical ballooning or takotsubo cardiomyopathy, possibly attributable to catecholamine-mediated myocardial stunning.

Aged↗

Adolescent versus adult responses to vertical spinal loading.

This study compared the vertical spinal creep response between adolescent and adult males. Thirty healthy male subjects, 15 adolescents (aged 12 to 16 years) and 15 adults (aged 30 to 57 years) were measured. Spinal creep was measured continuously over 25 min under loaded and unloaded conditions using a seated stadiometer that controlled spinal posture. Both adolescent and adult subjects showed significant increase in vertical spinal creep with time but the magnitude of vertical spinal creep was significantly greater in adolescent than in the adult subjects.

Adolescent↗

Granular flows through vertical pipes controlled by an electric field.

The flow of granular nickel particles moving down vertical pipes from a hopper in the presence of a local, horizontal ac electric field is studied experimentally. The flow is initiated by opening the bottom outlet of the pipe after the pipe is fully filled with particles from the hopper. The mass of particles flowing out of the pipe is measured as a function of time by an electronic balance. The time dependence of the steady-state flow rate Q, under each fixed voltage V, is obtained. Depending on the magnitude of V, two types of flow behaviors are observed. For low V ( or =V(c)), no interface exists and the whole region between the hopper and the electrodes are densely filled; only one constant flow rate Q(A2) is observed. (The precise meaning of Q(A2) and Q(B) are defined in the text.) The steady-state flow rates Q(A2) and Q(B) measured for each V, are plotted as a function of V. The flow rate Q(A2) is a monotonically decreasing function of V, which can be approximately fitted by a power law, with an exponent of -0.8, while Q(B) is found to be voltage independent. These features result from a competition between the blocking effect of the electric-field region and the gravity-driven pushing effect from the hopper outlet. The local electric field is able to retard the downward movement of a dense column existing above it, but is ineffective in doing so when the column above is dilute in density.

Journal Article↗

Extensive repertoire of membrane-bound and soluble dendritic cell-specific ICAM-3-grabbing nonintegrin 1 (DC-SIGN1) and DC-SIGN2 isoforms. Inter-individual variation in expression of DC-SIGN transcripts.

Expression in dendritic cells (DCs) of DC-SIGN, a type II membrane protein with a C-type lectin ectodomain, is thought to play an important role in establishing the initial contact between DCs and resting T cells. DC-SIGN is also a unique type of human immunodeficiency virus-1 (HIV-1) attachment factor and promotes efficient infection in trans of cells that express CD4 and chemokine receptors. We have identified another gene, designated here as DC-SIGN2, that exhibits high sequence homology with DC-SIGN. Here we demonstrate that alternative splicing of DC-SIGN1 (original version) and DC-SIGN2 pre-mRNA generates a large repertoire of DC-SIGN-like transcripts that are predicted to encode membrane-associated and soluble isoforms. The range of DC-SIGN1 mRNA expression was significantly broader than previously reported and included THP-1 monocytic cells, placenta, and peripheral blood mononuclear cells (PBMCs), and there was cell maturation/activation-induced differences in mRNA expression levels. Immunostaining of term placenta with a DC-SIGN1-specific antiserum showed that DC-SIGN1 is expressed on endothelial cells and CC chemokine receptor 5 (CCR5)-positive macrophage-like cells in the villi. DC-SIGN2 mRNA expression was high in the placenta and not detectable in PBMCs. In DCs, the expression of DC-SIGN2 transcripts was significantly lower than that of DC-SIGN1. Notably, there was significant inter-individual heterogeneity in the repertoire of DC-SIGN1 and DC-SIGN2 transcripts expressed. The genes for DC-SIGN1, DC-SIGN2, and CD23, another Type II lectin, colocalize to an approximately 85 kilobase pair region on chromosome 19p13.3, forming a cluster of related genes that undergo highly complex alternative splicing events. The molecular diversity of DC-SIGN-1 and -2 is reminiscent of that observed for certain other adhesive cell surface proteins involved in cell-cell connectivity. The generation of this large collection of polymorphic cell surface and soluble variants that exhibit inter-individual variation in expression levels has important implications for the pathogenesis of HIV-1 infection, as well as for the molecular code required to establish complex interactions between antigen-presenting cells and T cells, i.e. the immunological synapse.

Adult↗

Melanoma of the clavicular region: multimodal treatment.

HYPOTHESIS: Treatment for melanoma that has metastasized to the supraclavicular nodes should be intensive and use a multimodality approach. DESIGN: Retrospective analysis of clinical records. SETTING: Six primary care centers, 2 of which were referral centers. PATIENTS: Eighteen patients diagnosed as having a rare pattern of advanced melanoma metastatic to the clavicular region. INTERVENTION: Combined radiotherapy, chemotherapy, and thorough surgical excision of the affected nodal basins. MAIN OUTCOME MEASURE: Length of survival from time of diagnosis and treatment to time of follow-up. RESULTS: Median survival among the 18 patients was 28 months with a 22% survival rate at 5 years after diagnosis. Among patients who received radiotherapy to the clavicular node basin, mean length of survival was 88.7 months with a 50% 5-year survival rate compared with a mean length of survival of 33.8 months and an 8.3% 5-year survival rate in patients who did not receive radiotherapy (P<.001). Mean survival among patients who had supraclavicular node dissection was 45.8 months with a 23.1% survival rate at 5 years after diagnosis, compared with a mean survival of 52 months and a 20% 5-year survival rate among patients who did not receive therapeutic lymphadenectomy. Of the 11 patients who had therapeutic lymphadenectomy, 2 also received radiotherapy to the supraclavicular nodal basin and continued to be disease-free at 82 and 130 months. All long-term survivors had been treated with intra-arterial chemotherapy. CONCLUSION: In a series of patients with malignant melanoma metastatic to the clavicular lymph nodes, multimodality treatment using radiotherapy, chemotherapy, and thorough surgical excision of affected nodal basins provided an appreciable 5-year survival rate.

Adult↗

A novel carbohydrate:acceptor oxidoreductase from Microdochium nivale.

A Microdochium nivale carbohydrate:acceptor oxidoreductase was purified, cloned, heterologously expressed, and characterized. The gene encoding the protein showed one intron, and the ORF showed a sequence with low homology (< or = 25% identity or 65% similarity) to other known flavin-containing carbohydrate oxidases. The maturation of the protein required the cleavage of a tetrameric propeptide in addition to an 18 amino-acid signal peptide. The enzyme was found to have a relative molecular mass of 55 000 Da, an isoelectric point of 9, and one FAD per protein. It could oxidize mono-, oligo-, or polymeric saccharides, and transfer their electrons to O2 or other acceptors. When D-glucose served as electron-donating substrate, an activity of 2 s(-1) was observed at pH 5.5 and 23 degrees C. Among various oligosaccharides, the enzyme preferred tetrameric dextrins, indicating a favorable interaction of four linked glucose units with the substrate pocket. The unique structure and ability of oxidizing oligo/polymeric saccharides suggest a promising prospect of this enzyme for various industrial/medicinal applications.

Alcohol Oxidoreductases↗

Enzymatic and electrochemical oxidation of N-hydroxy compounds. Redox potential, electron-transfer kinetics, and radical stability.

A series of N-hydroxyacetanilide and 1-hydroxybenzotriazole analogues derivatized by various functional substituents were studied with regard to redox potential, oxidation by laccase, oxidative stability, and correlation to the electronic and steric properties of the substituents. It was found that substituents carrying conjugative/pi-electron function influenced the redox potential more than substituents carrying inductive/sigma-electron function, and that the electron-transfer from an N-hydroxy moiety to laccase was significantly affected by the redox potential. Electron-withdrawing substituents tended to reduce the electron density on the N-hydroxy group, leading to higher redox potential and lower oxidation rate. Bulky substitution or absence of N-phenyl tended to increase the Km of the N-hydroxy group, leading to lower oxidation rate. Oxidized N-hydroxy compounds were stabilized by N-phenyl or N-carbonyl group, but not by N-azo or highly strained structure. Potential implication of these effects on laccase-based, N-hydroxy compound-mediated biocatalysis is discussed.

Catalysis↗

Saturation of, and competition for entry into, the apical secretory pathway.

To investigate mechanisms of apical sorting in the secretory pathway of epithelial cells, we expressed varying amounts of the 165 amino acid isoform of vascular endothelial growth factor (VEGF(165)) and transforming growth factor beta1 (TGF-beta1) via replication defective adenoviruses. Apical sorting of both proteins was efficient at low expression levels but saturated or was reversed at high expression levels. High expression levels of TGF-beta1 were effective at competing VEGF(165) out of the apical pathway; however, VEGF(165) did not compete out TGF-beta1. Tunicamycin inhibition experiments showed that the apical polarity of VEGF(165) was independent of N-glycosylation. We conclude that the apical sorting of these two molecules is a saturable, signal-mediated process, involving competition for apical sorting receptors. The sorting of the two proteins does not appear to involve N-glycans as sorting signals, or lectin sorters. The observations are particularly relevant to gene therapy because they demonstrate that overexpression of a transgene can result in undesirable missorting of the encoded protein.

Adenoviridae↗

Memory and organizational strategies in chronic and acute schizophrenic patients.

The memory profile of acute and chronic schizophrenic patients was examined according to the information processing model, with which encoding, retention and retrieval processes of these patients were compared. The effects of an external organizational strategy on their verbal learning and memory were also examined. Twenty chronic and 20 acute schizophrenic patients were tested with a list learning task consisting of a random (i.e., words presented randomly) and a blocked (i.e., words presented in clusters) word-list. The schizophrenic patients, as compared with age- and education-matched normal control subjects, demonstrated impaired learning, and the duration of their illness was not a significant factor in the severity of their learning impairment. However, the acute and chronic schizophrenic patients seem able to retain most of the newly acquired materials, regardless of the presentation format, after 30 min. In addition, the learning and subjective organizational strategy of the chronic patients, but not that of the acute patients, improved significantly by the blocked presentation. However, semantic organization could facilitate both the chronic and acute schizophrenic patients to retain more newly learned items.

Acute Disease↗

Specificities of heparin-binding sites from the amino-terminus and type 1 repeats of thrombospondin-1.

Interactions of heparin with intact human thrombospondin-1 (TSP1) and with two heparin-binding fragments of TSP1 were characterized using chemically modified heparins, a vascular heparan sulfate proteoglycan, and a series of heparin oligosaccharides prepared by partial deaminative cleavage. The avidity of TSP1 binding increased with oligosaccharide size, with plateaus at 4 to 6 and at 8 to 10 monosaccharide units. The dependence on oligosaccharide size for binding to the recombinant amino-terminal heparin-binding domain of TSP1 was the same as that of the intact TSP1 molecule but differed from that of a synthetic heparin-binding peptide from the type 1 repeats, suggesting that the interaction between intact TSP1 and heparin is primarily mediated by the amino-terminal domain. Based on activities of chemically modified heparins, binding to TSP1 depended primarily on 2-N- and 6-O-sulfation of glucosamine and to a lesser degree on 2,3-O-sulfation and the carboxyl residues of the uronic acids. In contrast, all of these modifications were required for binding of heparin to the type 1 repeat peptides. Affinity purification of heparin octasaccharides on immobilized TSP1 type 1 repeat peptides revealed a preference for oligosaccharides containing the disaccharide sequence IdoA(2-OSO(3))alpha1-4-GlcNS(6-OSO(3)). Binding of these oligosaccharides to the peptide required the Trp residues. These data demonstrate that the heparin-binding specificities of intact TSP1 and peptides from the type 1 repeats overlap with that of basic fibroblast growth factor (FGF2) and are consistent with the ability of these TSP1-derived molecules to inhibit FGF2-stimulated angiogenesis.

Amino Acid Sequence↗

The effects of a seamless model of management on the quality of care for emergency department patients.

The aim of this study was to examine the effectiveness of the seamless model of management on the quality of care for emergency department (ED) patients. This was a pre- and postintervention study of comparing post intervention data with the baseline on several variables of interest. The intervention was the seamless model of ED management, designed and implemented as a response to the challenge of increasing work load at the ED. Information on patients' waiting times, critical care performance, patients' satisfaction and staff morale was collected at baseline and postintervention for comparison. The results indicated significant improvements on all outcome measures were found postintervention. The average waiting time reduced by 40%, from 92.1 to 55.3 min, as well as the time to craniotomy from 120 to 45 min for more severe patients. Complaints from patients were reduced by 80% and staff morale had improved with a 48% reduction in sick days and a 80% reduction in staff resignations. Ambulatory patients presenting to the department saw a 20% improvement in their waiting time. We report a successful restructuring process that used routinely collected clinical and administrative data to highlight problems. Using these data and through a systematic planning process, appropriate strategies for restructuring were developed by emergency staff in partnership with the hospital executive. Significant improvements in waiting time and patient care were clearly demonstrated.

Attitude of Health Personnel↗

Increased responses of glucagon and glucose production to hypoglycemia with intraperitoneal versus subcutaneous insulin treatment.

The study aim was to investigate the effect of the route of insulin treatment on the glucagon and glucose production (GP) responses to hypoglycemia in the diabetic rat. Experiments were performed in 4 groups of rats: (1) streptozotocin (STZ)-induced diabetic, untreated (D, n = 7), (2) diabetic treated with subcutaneous insulin (DSC, n = 8), (3) diabetic treated with intraperitoneal insulin (DIP, n = 6), and (4) normal control (N, n = 10). Slow-release insulin implants were used in DSC and DIP rats for 10 to 14 days (3 U/d). A hyperinsulinemic (120 pmol x kg(-1) x min(-1) insulin)-hypoglycemic (glycemia = 2.5 +/- 0.1 mmol/L) clamp following an isoglycemic basal period was performed in 5-hour fasted rats. Basal plasma glucose was normalized in both DSC and DIP rats; however, in DSC but not DIP rats, glucose normalization required peripheral hyperinsulinemia. Tracer-determined GP, which was elevated in D rats, was completely normalized in DIP but only partially corrected in DSC rats. Basal glucagon levels were similar in all groups. During hypoglycemia, GP was suppressed in D rats (delta, -28.9 +/- 5.0 micromol x kg(-1) x min(-1), moderately increased in DSC rats (delta, 6.1 +/- 5.6, P < .01 v D), but markedly increased in DIP and N rats (delta, 34.5 +/- 4.5 for DIP and 16.8 +/- 2.8 for N; P < .01 vD, P < .05 for DIP v DSC or N). Plasma glucagon increased 6-fold in N (945 +/- 129 pg/mL), only doubled in D (424 +/- 54), and tripled in DSC (588 +/- 83), but increased 5-fold in DIP rats (1,031 +/- 75, P < .05 v D and DSC). We conclude that in STZ-diabetic rats, (1) intraperitoneal but not subcutaneous insulin treatment normalizes basal GP, and (2) intraperitoneal insulin treatment as compared with subcutaneous treatment alleviates peripheral hyperinsulinemia and results in increased glucagon and GP responses to hypoglycemia.

Animals↗

Comparison of serologic assays and PCR for diagnosis of human herpesvirus 8 infection.

A variety of assays for the diagnosis human herpesvirus 8 (HHV-8) infection have been reported. We compared several such assays with a panel of 88 specimens from human immunodeficiency virus (HIV)-infected patients with Kaposi's sarcoma (KS) (current-KS patients; n = 30), HIV-infected patients who later developed KS (later-KS patients; n = 13), HIV-infected patients without KS (no-KS patients; n = 25), and healthy blood donors (n = 20). PCR assays were also performed with purified peripheral blood mononuclear cells (PBMCs) to confirm positive serologic test results. The order of sensitivity of the serologic assays (most to least) in detecting HHV-8 infection in current-KS patients was the mouse monoclonal antibody-enhanced immunofluorescence assay (MIFA) for lytic antigen (97%), the orfK8.1 peptide enzyme immunoassay (EIA) (87%), the orf65 peptide EIA (87%), MIFA for latent antigen (83%), the Advanced Biotechnologies, Inc., EIA (80%), and the orf65 immunoblot assay (80%). Combination of the results of the two peptide EIAs (combined peptide EIAs) increased the sensitivity to 93%. For detection of infection in later-KS patients, the MIFA for lytic antigen (100%), the orfK8.1 peptide EIA (85%), and combined peptide EIAs (92%) were the most sensitive. Smaller percentages of no-KS patients were found to be positive (16 to 56%). Most positive specimens from the current-KS and later-KS groups were positive by multiple assays, while positive specimens from the no-KS group tended to be positive only by a single assay. PCR with PBMCs for portions of the HHV-8 orf65 and gB genes were positive for less than half of current-KS and later-KS patients and even fewer of the no-KS patients. The concordance between serologic assays was high. We propose screening by the combined peptide EIAs. For specimens that test weakly positive, we recommend that MIFA for lytic antigen be done. A positive result with a titer of >/=1:40 would be called HHV-8 positive. A negative or low titer would be called HHV-8 negative. If a population has a high percentage of persons who test positive by the combined peptide EIAs, then a MIFA could be performed with the negative specimens to determine if any positive specimens are being missed. Alternatively, if a population has a low percentage that test positive, then a MIFA could be performed with a subset of the negative specimens for the same reason. As described above, only a titer of >/=1:40 would be considered HHV-8 positive.

Algorithms↗

Percutaneous interventional strategies in the treatment of chronic total coronary occlusions.

Chronic total coronary occlusions which make up 10% to 20% of all interventional procedures in high-volume centres remain a vexing problem for invasive cardiologists for 2 main reasons. First, they are only successfully recanalised in about 60% of attempts with most failures resulting from an inability to cross the lesions. Laser guidewire appears to be a promising innovation in overcoming this obstacle. Second, after initially successful recanalisation with conventional balloon angioplasty (PTCA), a high restenosis rate (range, 45% to 75%) is observed. Stent placement, by conferring maximal luminal expansion, appears to have resolved this problem to a large extent; both observational and randomised studies indicate that after stent placement, restenosis rate is at least halved that of PTCA.

Angioplasty, Balloon, Coronary↗

A breakdown of event schemas in patients with schizophrenia: an examination of their script for dining at restaurants

Event schemas, the conceptualization of past experience, in schizophrenic patients were examined based upon script theory. Forty schizophrenic patients and 40 age- and education-matched normal control subjects participated in this study. This experiment consisted of three tasks. In the recall task, subjects recalled a typical scenario of going to a formal restaurant. In the frequency judgment task, subjects determined whether the given events happen frequently, occasionally or rarely in a restaurant. In the sequencing task, the subjects put the randomly presented events in the correct order. The responses of the schizophrenic patients in the recall task, when compared with those of the normal control subjects, had significantly fewer concepts and a greater proportion of highest-frequency concepts. In addition, the sequence of their responses was less accurate than that of normal individuals. This abnormality is unlikely due primarily to a retrieval deficit (i.e. generating fewer concepts in the recall task) given that their performances on the frequency judgment and sequencing tasks, tasks that require less retrieval effort, were consistent with those of the recall task. These results suggest that event schemas in schizophrenic patients contain little detailed information and are incoherent in organization.

Journal Article↗