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Biomedical subjects

T Lam

Publications and source records attributed to T Lam.

At least 19 recordsLinked to original sources

Twenty-year audit of percutaneous liver biopsy in a major Australian teaching hospital.

BACKGROUND: To examine the changes in indications, patient characteristics, safety and outcomes in consecutive patients undergoing percutaneous core liver biopsies in a major Australian teaching hospital over a period of two decades. METHODS: A retrospective audit was carried out on all percutaneous core liver biopsies from a single institution between 1996 and 2005. This was combined with 10 years of data already reported on for the years 1986-1995 to detect trends in indications and outcomes. RESULTS: Medical records from 1398 patients were included for analysis. Over a 20-year period, the most common indications for liver biopsy were hepatitis C (37.8%), hepatitis B (26.4%) and abnormal liver function tests (22.2%). Twelve major complications (1.0%) were seen; 10 episodes of haemorrhage, 1 bile leak and 1 visceral perforation. Seven of these patients had an abnormal baseline coagulation profile; a significant risk for major haemorrhage (P < 0.001), resulting in three deaths. All deaths occurred in inpatients with major comorbidities. Minor complications occurred in 13.6% of patients, with multiple passes a significant risk factor. Whereas the overall major and minor complication rates were independent of operator experience inadequate specimens were more frequently obtained by the registrar. CONCLUSION: This large series extending over two decades shows that despite advances in biopsy techniques, the rates of both minor and major complications remain significant. Of particular concern are the procedure-related deaths. Identifying factors that may increase risk requires further scrutiny and careful patient selection needs to be undertaken.

Adolescent↗

Performance characteristics of a microMOSFET as an in vivo dosimeter in radiation therapy.

The commercially available microMOSFET dosimeter was characterized for its dosimetric properties in radiotherapy treatments. The MOSFET exhibited excellent correlation with the dose and was linear in the range of 5-500 cGy. No measurable effect in response was observed in the temperature range of 20-40 degrees C. No significant change in response was observed by changing the dose rate between 100 and 600 monitor units (MU) min(-1) or change in the dose per pulse. A 3% post-irradiation fading was observed within the first 5 h of exposure and thereafter it remained stable up to 60 h. A uniform energy response was observed in the therapy range between 4 MV and 18 MV. However, below 0.6 MeV (Cs-132), the MOSFET response increased with the decrease in energy. The MOSFET also had a uniform dose response in 6-20 MeV electron beams. The directional dependence of MOSFET was within +/-2% for all the energies studied. The inherent build-up of the MOSFET was evaluated dosimetrically and found to have varying water equivalent thickness, depending on the energy and the side of the beam entry. At depth, a single calibration factor obtained by averaging the MOSFET response over different field sizes, energies, orientation and depths reproduced the ion chamber measured dose to within 5%. The stereotactic and the penumbral measurements demonstrated that the MOSFET could be used in a high gradient field such as IMRT. The study showed that the microMOSFET dosimeter could be used as an in vivo dosimeter to verify the dose delivery to the patient to within +/-5%.

Algorithms↗

The effect of applying a pipe-joint lubricant to connect ductile iron pipe on off-flavors in drinking water distribution systems.

This study was used to help define the contribution to taste and odor problems caused by the application of a pipe-joint lubricant to connect ductile iron pipe in drinking water distribution systems. Tyton Joint Lubricant (TJL) was studied. The lubricant produced odors that are continually oxidized by chlorine or oxygen. The mechanism of oxidative rancidity, one of the major causes of food spoilage is the apparent mechanism of oxidation. The odors produced by the lubricant were characterized by a Flavor Profile Analysis (FPA) panel as well as GC/MS and Sensory GC analysis. The most common odors perceived in the TJL water samples for the first six days were waxy/oily and soapy odors with a rancid oil, odor note. The waxy/oily and soapy odors decreased with time in the chlorine medium as the rancid oily odor note increased. Numerous aldehydes, ketones, alcohols and borneol compounds, produced from the lubricants, were tentatively identified and linked to the odors perceived by the FPA panel.

Equipment Design↗

A new technology for the treatment of mercury contaminated water and soils.

A new technology has been developed for the treatment of contaminated water and soils with lignin derivatives. It has been demonstrated that this technology can be used in the process of removal of high levels of mercury from water, and in the immobilization of leachable mercury in contaminated soils. Lignin derivatives contain an abundance of oxygen-containing functional groups such as phenolic, carboxyl, sulfonyl, alcoholic and enolic structures, which will form lignin-metal macromolecular complexes with high stability through ionic and coordinate covalent bonding. This feature is the basis for the application of lignin derivatives in the removal of metal contaminants from water and in the immobilization of leachable metal in soils or sediments. Tests have confirmed that lignin derivatives are capable of combining with a variety of metal ions including chromium, copper, lead, zinc, mercury, nickel and aluminum. In the new water treatment process, lignin derivatives are dissolved in mercury contaminated water to complex mercury in an exceptionally stable form of a lignin-mercury colloid. The lignin-mercury colloid is then coagulated through the addition of a flocculating agent such as ferric chloride. Under optimized conditions, a dean effluent is produced with a residual mercury level of less than 1 microg l(-1), together with a ferric sludge that is not leachable by TCLP, EPA Method 1311. In the new soil stabilization process, a new solid adsorbent of ferric-lignin is blended with mercury contaminated soil. This solid adsorbent can stabilize the soil by complexing with mercury and, thereby, greatly reduce the TCLP mercury of soil.

Adsorption↗

Application of ferric sludge to immobilize leachable mercury in soils and concrete.

A Hg-contaminated site in B.C. Province, Canada was caused by the previous operation of Hg-cell in chlor-alkali process for over 25 years. The soils and groundwater at the site are highly contaminated with mercury. An analysis of groundwater at the site has shown that most of the mercury is bonded with humic and fulvic acids (HFA) in colloidal form. The Hg-HFA colloids can be completely removed from the groundwater with ferric chloride treatment under optimized process conditions to form ferric sludge (FS), which is rendered non-leachable by standard TCLP (Toxicity Characteristic Leaching Procedure) test. The effluent discharged from a clarifier has achieved mercury levels of < 0.5 microkg l(-1). The studies of mercury adsorption characteristics of FS show it has low mercury leachability by TCLP, and great mercury adsorption capability. This feature is the basis for the application of FS to immobilization of leachable Hg-contaminants in solid wastes. Full-scale stabilization tests of Hg-contaminated soil have been carried out, and the time-based stability of the treated soil has been monitored by TCLP over a period of 60 days. All the results have shown a small variation in TCLP mercury levels within a range of 10-40 microg l(-1). Based on these results and with the approval of the B.C. Ministry of the Environment, 1850 tons of Hg-contaminated soils and 260 tons of Hg-contaminated concrete fines have been treated, stabilized with FS, and disposed in a non-hazardous waste disposal site.

Ferric Compounds↗

Competency-based student self-assessment on a surgery rotation.

BACKGROUND: Although self-assessment is an essential component of self-directed adult learning, few data exist regarding the ability of medical students to perform this important task. Therefore, the purpose of this study was to evaluate the ability of medical students to perform self-assessment during a third-year surgery clerkship. METHODS: Sixty-eight (34 male, 34 female) third-year medical students assessed their progress at the midpoint of an 8-week surgery clerkship using an 11-item, competency-based evaluation. Students compared perceptions of their performance with a faculty member's assessment using the identical evaluation form. RESULTS: Male students tended to overestimate their midclerkship performance compared with faculty formative and summative evaluations (3.31 +/- 0.03 vs 3.23 +/- 0.03 and 3.28 +/- 0.03) although this did not reach statistical significance. Female students significantly underestimated their midclerkship performance compared with faculty formative and summative evaluations (3.06 +/- 0.03 vs 3.40 +/- 0.03 and 3.45 +/- 0.03, P < 0.05 vs faculty evaluations). Preclerkship academic performance (first- and second-year grade point averages and NBME Part 1 scores) was not predictive of student self-assessment. Finally, women statistically outperformed men on the surgery clerkship (86.6% +/- 0.75 vs 83.2% +/- 1.20, P < 0.05 vs male students). CONCLUSIONS: Female students tend to underestimate their midclerkship performance compared with male students on a surgery rotation. Despite lower self-assessment, female students actually outperform male students. Women may underreport their capabilities when compared with men as a result of gender differences in socialization. These gender differences in self-assessment may be important to recognize when faculty provide feedback to students.

Adult↗

GABAergic neurons that pioneer hippocampal area CA1 of the mouse: morphologic features and multiple fates.

Dramatic changes occur in the expression of glutamic acid decarboxylase (GAD67) immunoreactivity in mouse hippocampus during postnatal development. Most striking is the presence of a dense population of immunopositive cells in stratum radiatum and stratum oriens in area CA1 during the first postnatal week. Between days 5 and 10, these cells disappear and the GAD67 immunoreactivity begins to resemble that of adulthood. These neurons are considered pioneer cells, and studies were undertaken to determine their fate. Between days 5 and 50, area CA1 doubles in size; however, the loss of cells expressing GAD67 mRNA cannot be explained solely by dilution resulting from hippocampal growth. In stratum radiatum, cell loss is particularly dramatic. Although between days 5 and 15, many cells seem to migrate from stratum radiatum to its border with stratum lacunosum-moleculare, both fate maps of pioneer cells labeled with bromodeoxyuridine (BrdU) on embryonic day 13 (E13) and in situ DNA end-labeling studies suggest that some cells die by means of programmed cell death. However, not all pioneer cells die, because many cells labeled with BrdU on E13 are present in adulthood and express markers for and have anatomic features of hippocampal interneurons. In conclusion, events that underlie the age-dependent disappearance of gamma-aminobutyric acid (GABA) -ergic pioneer cells are complex and cannot be completely explained by dilution in an expanding neuropile. Although some GABAergic pioneer cells likely undergo programmed cell death during the first postnatal weeks, others relocate within hippocampal laminae and terminally differentiate into the interneurons of adulthood.

Aging↗

Evidence for a susceptibility gene, SLEV1, on chromosome 17p13 in families with vitiligo-related systemic lupus erythematosus.

Both systemic lupus erythematosus (SLE) and vitiligo are autoimmune disorders that have strong evidence of complex genetic contributions to their etiology, but, to date, efforts using genetic linkage to find the susceptibility genes for either phenotype have met with limited success. Since autoimmune diseases are thought to share at least some of their genetic origins, and since only a small minority (16 of 92) of the European-American pedigrees multiplex for SLE in our collection have one or more affected members with vitiligo, we hypothesized that these pedigrees might be more genetically homogeneous at loci important to both SLE and vitiligo and, hence, have increased power for detection of linkage. We therefore evaluated genomewide microsatellite-marker-scan data for markers at an average marker density of approximately 11 cM in these 16 European-American pedigrees and identified a significant linkage at 17p13, where the maximum multipoint parametric LOD score was 3.64 (P<4.3x10(-5)) and the nonparametric linkage score was 4.02 (P<2.8x10(-5)), respectively. The segregation behavior of this linkage suggests a recessive mode of inheritance with a virtually homogeneous genetic effect in these 16 pedigrees. These results support the hypotheses that SLE and vitiligo may share important genetic effects and that sampling on the basis of clinical covariates dramatically improves power to identify genetic effects.

Chromosome Mapping↗

Abnormal balance in the angiopoietin-tie2 system in human brain arteriovenous malformations.

Brain arteriovenous malformations (BAVMs) are congenital vascular lesions that often present as cerebral hemorrhage in young adults. The variable nature of the clinical course, especially with respect to spontaneous hemorrhage, recurrence, growth, and regression, suggests that BAVMs are lesions with active angiogenesis and vascular remodeling. We examined mRNA and protein expression of angiopoietin 1 (Ang1) and Ang2 by semiquantitative reverse transcriptase-polymerase chain reaction, in situ hybridization, and Western blot in BAVMs and control brains obtained from temporal lobectomy for medically intractable seizures. Although Ang1 mRNA levels were similar in BAVMs and controls, Ang1 protein levels were 30% lower in BAVMs than in controls. Ang2 mRNA levels were 40% higher and Ang2 protein levels were 8-fold higher in BAVMs than in controls. In situ hybridization showed that the Ang2 mRNA was localized to the perivascular area in BAVMs. This abnormal balance in the Ang-Tie2 system may, in part, explain the aberrant vascular phenotype in BAVMs.

Adolescent↗

Subclinical renal injury induced by transient cyclosporine exposure is associated with salt-sensitive hypertension.

Cyclosporine use is highly associated with the development of salt-sensitive hypertension. We hypothesized that subtle renal injury induced by cyclosporine could lead to salt sensitivity. Cyclosporine nephropathy was induced by treatment for 4 weeks with cyclosporine (15 mg/kg/day) on a low sodium (0.05%) diet, followed by stopping cyclosporine and placement on a high sodium (4%) diet for 4 additional weeks. Control groups included a group treated with cyclosporine (15 mg/kg/day) on a normal salt diet in which nephropathy does not develop, and a vehicle-treated group. A fourth group received half-dose of cyclosporine (8 mg/kg/day) on a low sodium diet, which results in mild nephropathy. Biopsies were obtained at the end of the cyclosporine administration (4 week) and at sacrifice (8 week), and blood pressure and renal function were measured. Rats treated with cyclosporine for 4 weeks on a low sodium diet developed classic features of tubulointerstitial disease and arteriolopathy; these changes were absent in the cyclosporine/normal salt group and in the vehicle group. At 4 weeks, all groups were switched to a high salt diet; only the rats with nephropathy developed hypertension. The degree of hypertension correlated closely with the degree of tubulointerstitial injury (r=0.85) and with the severity of the arteriolopathy (r=0.9) (p<0.0.1). Importantly, renal function (creatinine clearance) was normal in all groups at 8 weeks, documenting that the hypertension could not be attributed to cyclosporine-mediated alterations in glomerular filtration rate (GFR). One mechanism by which cyclosporine induces hypertension is the induction of subtle renal microvascular and tubulointerstitial disease. This mechanism is not dependent on GFR and may persist even after the cyclosporine is discontinued.

Animals↗

Proprioceptive modulation of hip flexor activity during the swing phase of locomotion in decerebrate cats.

This study examined the influence of proprioceptive input from hip flexor muscles on the activity in hip flexors during the swing phase of walking in the decerebrate cat. One hindlimb was partially denervated to remove cutaneous input and afferent input from most other hindlimb muscles. Perturbations to hip movement were applied either by 1) manual resistance or assistance to swing or by 2) resistance to hip flexion using a device that blocked hip flexion but allowed leg extension. Electromyographic recordings were made from the iliopsoas (IP), sartorius, and medial gastrocnemius muscles. When the hip was manually assisted into flexion, there was a reduction in hip flexor burst activity. Conversely, when hip flexion was manually resisted or mechanically blocked during swing, the duration and amplitude of hip flexor activity was increased. We also found some specificity in the role of afferents from individual hip flexor muscles in the modulation of flexor burst activity. If the IP muscle was detached from its insertion, little change in the response to blocking flexion was observed. Specific activation of IP afferent fibers by stretching the muscle also did not greatly affect flexor activity. On the other hand, if conduction in the sartorius nerves was blocked, there was a diminished response to blocking hip flexion. The increase in duration of the flexor bursts still occurred, but this increase was consistently lower than that observed when the sartorius nerves were intact. From these results we propose that during swing, feedback from hip flexor muscle afferents, particularly those from the sartorius muscles, enhances flexor activity. In addition, if we delayed the onset of flexor activity in the contralateral hindlimb, blocking hip flexion often resulted in the prolongation of ipsilateral flexor activity for long periods of time, further revealing the reinforcing effects of flexor afferent feedback on flexor activity. This effect was not seen if conduction in the sartorius nerves was blocked. In conclusion, we have found that hip flexor activity during locomotion can be strongly modulated by modifying proprioceptive feedback from the hip flexor muscles.

Animals↗

Absorption and tissue distribution of zeaxanthin and lutein in rhesus monkeys after taking Fructus lycii (Gou Qi Zi) extract.

PURPOSE: To study serum and tissue levels of zeaxanthin and lutein after feeding rhesus monkeys an extract of Fructus lycii (gou qi zi). METHODS: A carotenoid-containing fraction (P1) from an extract of F. lycii (equivalent to 2.2 mg zeaxanthin) was fed to three rhesus monkeys for 6 weeks as a daily dietary supplement through a nasogastric tube. Three other monkeys were fed with the vehicle (olive oil) similarly for 4 weeks as a control. Another three animals were fed with normal diet only. All animals were killed 4 hours after the last dose. Samples of serum, liver, spleen, brain, and retina were analyzed for zeaxanthin and lutein by high-pressure liquid chromatography. RESULTS: The basal levels of zeaxanthin and lutein in the monkey sera were 3.0 +/- 1.6 ng/ml (range, 2.3-4.8) and 31.5 +/- 12.2 ng/ml (range, 22.3-42.5), respectively. Serum levels of zeaxanthin and lutein in the P1-fed group were significantly higher than those of vehicle control (P<0.05). Besides the retina, the liver had the highest zeaxanthin and lutein levels, whereas the levels in the brain were undetectable. P1 supplement appeared to elevate zeaxanthin levels in liver and spleen. The level of lutein was higher than that of zeaxanthin in the maculae of rhesus monkeys. However, there were no detectable carotenoids in the peripheral and the equatorial regions of the monkey retina. P1 treatment elevated zeaxanthin density but not lutein in the macula. CONCLUSIONS: Serum levels and macular density of zeaxanthin was raised by feeding a carotenoid-containing fraction of F. lycii. Therefore, F. lycii is a good dietary source of zeaxanthin supplement.

Animals↗

Time to clinical response: an outcome of antibiotic therapy of febrile neutropenia with implications for quality and cost of care.

PURPOSE: To determine whether antibiotic regimens with similar rates of response differ significantly in the speed of response and to estimate the impact of this difference on the cost of febrile neutropenia. METHODS: The time point of clinical response was defined by comparing the sensitivity, specificity, and predictive values of alternative objective and subjective definitions. Data from 488 episodes of febrile neutropenia, treated with either of two commonly used antibiotics (coded A or B) during six clinical trials, were pooled to compare the median time to clinical response, days of antibiotic therapy and hospitalization, and estimated costs. RESULTS: Response rates were similar; however, the median time to clinical response was significantly shorter with A-based regimens (5 days) compared with B-based regimens (7 days; P =.003). After 72 hours of therapy, 33% of patients who received A but only 18% of those who received B had responded (P =.01). These differences resulted in fewer days of antibiotic therapy and hospitalization with A-based regimens (7 and 9 days) compared with B-based regimens (9 and 12 days, respectively; P <.04) and in significantly lower estimated median costs ($8,491 v $11,133 per episode; P =.03). Early discharge at the time of clinical response should reduce the median cost from $10,752 to $8,162 (P <.001). CONCLUSION: Despite virtually identical rates of response, time to clinical response and estimated cost of care varied significantly among regimens. An early discharge strategy based on our definition of the time point of clinical response may further reduce the cost of treating non-low-risk patients with febrile neutropenia.

Adult↗

Novel hippocampal interneuronal subtypes identified using transgenic mice that express green fluorescent protein in GABAergic interneurons.

The chief inhibitory neurons of the mammalian brain, GABAergic neurons, are comprised of a myriad of diverse neuronal subtypes. To facilitate the study of these neurons, transgenic mice were generated that express enhanced green fluorescent protein (EGFP) in subpopulations of GABAergic neurons. In one of the resulting transgenic lines, called GIN (GFP-expressing Inhibitory Neurons), EGFP was found to be expressed in a subpopulation of somatostatin-containing GABAergic interneurons in the hippocampus and neocortex. In both live and fixed brain preparations from these mice, detailed microanatomical features of EGFP-expressing interneurons were readily observed. In stratum oriens of the hippocampus, EGFP-expressing interneurons were comprised almost exclusively of oriens/alveus interneurons with lacunosum-moleculare axon arborization (O-LM cells). In the neocortex, the somata of EGFP-expressing interneurons were largely restricted to layers II-IV and upper layer V. In hippocampal area CA1, two previously uncharacterized subtypes of interneurons were identified using the GIN mice: stratum pyramidale interneurons with lacunosum-moleculare axon arborization (P-LM cells) and stratum radiatum interneurons with lacunosum-moleculare axon arborization (R-LM cells). These newly identified interneuronal subtypes appeared to be closely related to O-LM cell, as they selectively innervate stratum lacunosum-moleculare. Whole-cell patch-clamp recordings revealed that these cells were fast-spiking and showed virtually no spike frequency accommodation. The microanatomical features of these cells suggest that they function primarily as "input-biasing" neurons, in that synaptic volleys in stratum radiatum would lead to their activation, which in turn would result in selective suppression of excitatory input from the entorhinal cortex onto CA1 pyramidal cells.

Action Potentials↗

Chimeric anti-CD20 (IDEC-C2B8) monoclonal antibody sensitizes a B cell lymphoma cell line to cell killing by cytotoxic drugs.

More than 50% of patients with aggressive B lymphomas and the majority of patients with low grade lymphomas are not cured by current therapeutic strategies. The lymphomas express the B cell antigen CD20 on the cell surface and this antigen serves as target for antibody-directed therapies. Clinical studies with encouraging results have been underway with the use of a chimeric anti-CD20 antibody (IDEC-C2B8), consisting of human IgG1-6 constant regions and variable regions from the murine monoclonal anti-CD20 antibody IDEC-2B8. This study investigated the potential anti-tumor therapeutic value of combination treatment with anti-C2B8 and cytotoxic drugs. The in vitro study examined the sensitizing effect of C2B8 antibody on the DHL-4 B lymphoma line to various cytotoxic agents. Cytotoxicity was determined by the MTT assay. Surface and cytoplasmic proteins were determined by flow cytometry. Pretreatment of DHL-4 with C2B8 resulted in inhibition of cell proliferation and cell death and a fraction of the cells underwent apoptosis. While the DHL-4 tumor cells were relatively resistant to several cytotoxic drugs, pretreatment with C2B8 rendered the cells sensitive to TNF-alpha, ricin, diphtheria toxin (DTX), adriamycin and cisplatin but not to VP-16. Chemosensitization of DHL-4 tumor cells was not due to downmodulation of either the MDR-1 or bcl-2 gene products. However, treatment of DHL-4 with C2B8 inhibited TNF-alpha secretion. These findings demonstrate that C2B8 antibody potentiates the sensitivity of DHL-4 tumor cells to several cytotoxic agents. Further, the findings suggest that combination treatments with C2B8 antibody and drugs may be of clinical benefit in the treatment of patients with resistant aggressive B lymphomas.

Animals↗

Gore-Tex patch repair of the anterior rectus sheath in free rectus abdominis muscle and myocutaneous flaps.

Reconstruction of the breast and other tissues by the free transverse rectus abdominis myocutaneous (TRAM) flap is an accepted, reliable technique with a high success rate. Closure of the anterior rectus sheath defect that results from this flap and the related rectus abdominis muscle-only (RAM) free flap has been the subject of debate, since hernia formation is considered a risk. Some authors prefer direct closure, while others recommend a variety of synthetic mesh reinforcements. We have reviewed 81 patients from a consecutive series of free TRAM and RAM flaps performed by one surgeon (Pennington) over an 8-year period. The majority of patients had repair of the anterior rectus sheath with a 1-mm-thick synthetic patch of polytetrafluoroethylene (Gore-Tex), used in 52 of 71 patients having the TRAM flap and 4 of 10 patients having the RAM flap. There were 5 wound infections (6.2 percent) overall, 3 of which occurred in the Gore-Tex group (5.4 percent). In all 3 of the latter patients, Gore-Tex was removed, although usually only after some months. Even after patch removal, no hernias developed subsequently. The two other infections occurred in patients with a Prolene mesh patch and no patch, respectively. One hernia was found in 71 patients with TRAM flaps, and that was in a patient in whom no patch was used. No hernias occurred in 52 TRAM flap patients with Gore-Tex patches. Hernia formation was noted in 6 of 10 RAM flap patients, although only 1 hernia occurred in the 4 patients with Gore-Tex patches. We conclude that the 1-mm polytetrafluoroethylene (Gore-Tex) patch is a satisfactory method for repair of the anterior rectus sheath after harvesting of either free RAM or TRAM flaps. Even if removal of the patch is required because of infection, the risk of subsequent hernia formation appears minimal.

Abdominal Muscles↗